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1.  Sleep disorders in children 
Clinical Evidence  2010;2010:2304.
Introduction
Sleep disorders may affect between 20% and 30% of young children, and include problems getting to sleep (dyssomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for dyssomnias in children? What are the effects of treatments for parasomnias in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 28 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antihistamines; behavioural therapy plus antihistamines, plus benzodiazepines, or plus chloral and derivatives; benzodiazepines alone; exercise; extinction and graduated extinction; 5-hydroxytryptophan; light therapy; melatonin; safety/protective interventions for parasomnias; scheduled waking (for parasomnias); sleep hygiene; and sleep restriction.
Key Points
Sleep disorders may affect between 20% and 30% of young children, and include problems getting to sleep (dyssomnias) or undesirable phenomena during sleep (parasomnias), such as sleep terrors and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.
There is a paucity of evidence about effective treatments for sleep disorders in children, especially parasomnias, but behavioural interventions may be the best first-line approach.
Extinction and graduated extinction in otherwise healthy children with dyssomnia may improve sleep quality and settling, and reduce the number of tantrums and wakenings compared with no treatment. Extinction and graduated extinction in children with physical disabilities, learning disabilities, epilepsy, or attention-deficit disorder with dyssomnia may be more effective at improving settling, reducing the frequency and duration of night wakings, and improving parental sleep compared with no treatment; however, we don't know whether it is more effective in improving sleep duration.Graduated extinction may be less distressing for parents, and therefore may have better compliance.
Sleep hygiene for dyssomnia in otherwise healthy children may be more effective in reducing the number and duration of bedtime tantrums compared with placebo, but we don’t know if it is more effective at reducing night wakenings, improving sleep latency, improving total sleep duration, or improving maternal mood. Sleep hygiene and graduated extinction seem to be equally effective at reducing bedtime tantrums in otherwise healthy children with dyssomnia.We don't know whether sleep hygiene for dyssomnia in children with physical disabilities, learning disabilities, epilepsy, or attention-deficit disorder is effective.
Melatonin for dyssomnia in otherwise healthy children may be more effective at improving sleep-onset time, total sleep time, and general health compared with placebo. Evidence of improvements in dyssomnia with melatonin is slightly stronger in children with physical disabilities, learning disabilities, epilepsy, or attention-deficit disorder.
Little is known about the long-term effects of melatonin, and the quality of the product purchased could be variable as melatonin is classified as a food supplement.
Antihistamines for dyssomnia may be more effective than placebo at reducing night wakenings and decreasing sleep latency, but we don’t know if they are more effective at increasing sleep duration. The evidence for antihistamines in dyssomnia comes from only one small, short-term study.
We don’t know whether behavioural therapy plus antihistamines, plus benzodiazepines, or plus chloral and derivatives, exercise, light therapy, or sleep restriction are effective in children with dyssomnia.
We don’t know whether antihistamines, behavioural therapy plus benzodiazepines or plus chloral and derivatives, benzodiazepines, 5-hydroxytryptophan, melatonin, safety/protective interventions, scheduled waking, sleep hygiene, or sleep restriction are effective in children with parasomnia.
PMCID: PMC3217667  PMID: 21418676
2.  Sleep disorders in children 
Clinical Evidence  2007;2007:2304.
Introduction
Sleep disorders may affect 20-30% of young children, and include excessive daytime sleepiness, problems getting to sleep (dysomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors, and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for dysomnias in children? What are the effects of treatments for parasomnias in children? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antihistamines, behavioural therapy plus benzodiazepines, or plus chloral and derivates, exercise, extinction and graduated extinction, light therapy, melatonin, safety/protective interventions for parasomnias, scheduled waking (for parasomnias), sleep hygiene, and sleep restriction.
Key Points
Sleep disorders may affect 20-30% of young children, and include excessive daytime sleepiness, problems getting to sleep (dysomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors, and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.
There is a paucity of evidence about effective treatments for sleep disorders in children, especially parasomnias, but behavioural interventions may be the best first-line approach.
Extinction and graduated extinction interventions improve settling and reduce night wakes compared with placebo in healthy children, and in children with learning disabilities. Graduated extinction may be less distressing for parents, and therefore may have better compliance.Sleep hygiene interventions may reduce bedtime tantrums in healthy children compared with placebo, with similar effectiveness to graduated extinction.Sleep hygiene plus graduated extinction may reduce bedtime tantrums in children with physical or learning disabilities.We don't know whether combining behavioural therapy with benzodiazepines or with chloral improves sleep or parasomnias.
Melatonin may improve sleep onset and sleep time compared with placebo in healthy children, but we don't know if it is beneficial in children with disabilities, if it improves parasomnias, or what its long-term effects might be. We don't know whether antihistamines, exercise, light therapy, or sleep restriction improve dysomnias or parasomnias in children.We don't know whether safety or protective interventions, scheduled waking, extinction, or sleep hygiene are effective in children with parasomnias.
PMCID: PMC2943792  PMID: 19450298
3.  Insomnia (primary) in older people 
Clinical Evidence  2011;2011:2302.
Introduction
Up to 40% of older adults have insomnia, with difficulty getting to sleep, early waking, or feeling unrefreshed on waking. The prevalence of insomnia increases with age. Other risk factors include psychological factors, stress, daytime napping, and hyperarousal.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug treatments for insomnia in older people? What are the effects of drug treatments for insomnia in older people? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 34 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antidepressants, benzodiazepines, cognitive behavioural therapy (CBT), diphenhydramine, exercise programmes, timed exposure to bright light, zaleplon, zolpidem, and zopiclone.
Key Points
Up to 40% of older adults have insomnia, with difficulty getting to sleep, early waking, or feeling unrefreshed on waking. The prevalence of insomnia increases with age. Other risk factors include medical and psychiatric illnesses, psychological factors, stress, daytime napping, and hyperarousal.Primary insomnia is a chronic and relapsing condition that may increase the risks of accidents.Primary insomnia is chronic insomnia without specific underlying medical, psychiatric, or other sleep disorders. This review only covers primary insomnia in people aged 60 years and over.
Cognitive behavioural therapy (CBT) improves sleep compared with no treatment.
Exercise may improve symptoms compared with no treatment, but evidence is weak.
We don't know whether timed exposure to bright light can improve sleep quality compared with no treatment.
Zaleplon, zolpidem, and zopiclone may improve sleep latency in older people, although long-term effects are unknown, and they may cause adverse effects. Zolpidem and zopiclone may also increase sleep duration and improve sleep quality compared with placebo in the short term.Zaleplon has not been shown to decrease the number of awakenings, and it may cause rebound insomnia after discontinuation of treatment.
Benzodiazepines may improve sleep outcomes compared with placebo or other treatments, but they may cause adverse effects. We don't know what the long-term effects of benzodiazepines are.Benzodiazepines can cause impairment of memory, cognitive function, and psychological function, and rebound insomnia. They may increase the risks of accidents, falls, and hip fractures in older people.
We don't know whether diphenhydramine improves sleep quality in older people.
We don't know whether antidepressants improve sleep outcomes in older people with primary insomnia, as we found no RCTs.
PMCID: PMC3275108  PMID: 22030082
4.  Insomnia in the elderly 
Clinical Evidence  2007;2007:2302.
Introduction
Up to 40% of adults have insomnia, with difficulty getting to sleep, early waking, or feeling unrefreshed on waking. The prevalence of insomnia increases with age. Other risk factors include psychological factors, stress, daytime napping, and hyperarousal.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug treatments for insomnia in elderly people? What are the effects of drug treatments for insomnia in elderly people? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 28 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: benzodiazepines (brotizolam, flurazepam, loprazolam, midazolam, nitrazepam, quazepam, temazepam, and triazolam), cognitive behavioural therapy, diphenhydramine, exercise programmes, timed exposure to bright light, zaleplon, zolpidem, and zopiclone.
Key Points
Up to 40% of adults have insomnia, with difficulty getting to sleep, early waking, or feeling unrefreshed on waking. The prevalence of insomnia increases with age. Other risk factors include psychological factors, stress, daytime napping, and hyperarousal.Primary insomnia is a chronic and relapsing condition that may increase the risks of accidents, and is associated with dementia, depression and falls.
We don't know whether CBT, exercise programmes or timed exposure to bright light can improve sleep quality compared with no treatment.
Zaleplon,zolpidem, and zopiclone may improve sleep latency in elderly people, although long-term effects are unknown, and they are likely to cause adverse effects. Zolpidem and zopiclone may also increase sleep duration and improve sleep quality compared with placebo in the short term.Zaleplon has not been shown to improve sleep duration, number of awakenings, or sleep quality, and may cause rebound insomnia after discontinuation of treatment.
Benzodiazepines may improve sleep outcomes compared with placebo or other treatments, but are likely to cause adverse effects. We don't know what the long-term effects of benzodiazepines are.Benzodiazepines can cause impairment of memory, cognitive and psychological function, and rebound insomnia. They may increase the risks of accidents, falls, and hip fractures in elderly people.
We don't know whether diphenhydramine improves sleep quality in elderly people.
PMCID: PMC2943793  PMID: 19450355
5.  GORD in children 
Clinical Evidence  2008;2008:0310.
Introduction
Gastro-oesophageal regurgitation is considered a problem if it is frequent, persistent, and associated with other symptoms such as increased crying, discomfort with regurgitation, and frequent back arching. A cross-sectional survey of parents of 948 infants attending 19 primary care paediatric practices found that regurgitation of at least one episode a day was reported in 51% of infants aged 0 to 3 months.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatment for symptomatic gastro-oesophageal reflux? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 27 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: domperidone, feed thickeners in infants, H2 antagonists, head elevated sleep positioning, left lateral or prone sleep positioning, metoclopramide, proton pump inhibitors, sodium alginate, surgery, soy formula with added fibre, and weight loss.
Key Points
Reflux of gastric contents into the oesophagus in children causes recurrent vomiting (usually before 6 weeks of age), epigastric and abdominal pain, feeding difficulties, failure to thrive, and irritability. At least half of infants regurgitate feeds at least once a day, but this only causes other problems in about 20% of infants, and most cases resolve spontaneously by 12 to 18 months of age.Risk factors include lower oesophageal sphincter disorders, hiatus hernia, gastric distension, raised intra-abdominal pressure, and neurodevelopmental problems.
Sleeping in the left lateral or prone position may improve oesophageal pH compared with sleeping supine or on the right side, but these positions may increase the risk of SIDS compared with supine sleeping, and their effect on clinically important outcomes is unknown. We don't know whether sleeping in the prone elevated position reduces symptoms compared with the prone horizontal position, or whether weight loss reduces symptoms.
Thickened feeds may reduce the severity and frequency of regurgitation in the short term.
Sodium alginate may reduce the frequency of regurgitation compared with placebo, although studies have given conflicting results. The high sodium content of sodium alginate may make it unsuitable for use in preterm babies.
Metoclopramide may be effective, but studies have given conflicting results and it can cause adverse effects.
We don't know whether domperidone, H2 antagonists, proton pump inhibitors, or surgery reduce symptoms in babies with gastro-oesophageal reflux, and they may cause adverse effects.
Soy-based formula with added fibre may reduce the frequency of regurgitation in infants in the neonatal period compared with cow’s milk infant formulas.
PMCID: PMC2907988  PMID: 19445794
6.  Chronic fatigue syndrome 
Clinical Evidence  2011;2011:1101.
Introduction
Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, cognitive behavioural therapy (CBT), corticosteroids, dietary supplements, evening primrose oil, galantamine, graded exercise therapy, homeopathy, immunotherapy, intramuscular magnesium, oral nicotinamide adenine dinucleotide, and prolonged rest.
Key Points
Chronic fatigue syndrome is characterised by severe, disabling fatigue, and other symptoms including musculoskeletal pain, sleep disturbance, impaired concentration, and headaches. CFS affects between 0.006% and 3% of the population depending on the criteria used, with women being at higher risk than men.
Graded exercise therapy has been shown to effectively improve measures of fatigue and physical functioning. Educational interventions with encouragement of graded exercise (treatment sessions, telephone follow-ups, and an educational package explaining symptoms and encouraging home-based exercise) improve symptoms more effectively than written information alone.
CBT is effective in treating chronic fatigue syndrome in adults. CBT may also be beneficial when administered by therapists with no specific experience of chronic fatigue syndrome, but who are adequately supervised.In adolescents, CBT can reduce fatigue severity and improve school attendance compared with no treatment.
We don't know how effective antidepressants, corticosteroids, and intramuscular magnesium are in treating chronic fatigue syndrome. Antidepressants should be considered in people with affective disorders, and tricyclics in particular have potential therapeutic value because of their analgesic properties.
Interventions such as dietary supplements, evening primrose oil, oral nicotinamide adenine dinucleotide, homeopathy, and prolonged rest have not been studied in enough detail in RCTs for us to draw conclusions on their efficacy.
Based on a single large RCT galantamine seems no better than placebo at improving symptoms of chronic fatigue syndrome.
Although there is some RCT evidence that immunotherapy can improve symptoms compared with placebo, it is associated with considerable adverse effects, and should therefore probably not be offered as a treatment for chronic fatigue.
PMCID: PMC3275316  PMID: 21615974
7.  Chronic fatigue syndrome 
Clinical Evidence  2008;2008:1101.
Introduction
Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (BMJ Clinical evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, cognitive behavioural therapy (CBT), corticosteroids, dietary supplements, evening primrose oil, galantamine, graded exercise therapy, homeopathy, immunotherapy, intramuscular magnesium, oral nicotinamide adenine dinucleotide, and prolonged rest.
Key Points
Chronic fatigue syndrome (CFS) is characterised by severe, disabling fatigue, and other symptoms including musculoskeletal pain, sleep disturbance, impaired concentration, and headaches. CFS affects between 0.006% and 3% of the population depending on the criteria used, with women being at higher risk than men.
Graded exercise therapy has been shown to effectively improve measures of fatigue and physical functioning. Educational interventions with encouragement of graded exercise (treatment sessions, telephone follow-ups, and an educational package explaining symptoms and encouraging home-based exercise) improve symptoms more effectively than written information alone.
CBT is also effective in treating chronic fatigue syndrome. CBT may also be beneficial when administered by therapists with no specific experience of chronic fatigue syndrome, but who are adequately supervised.In adolescents, CBT can reduce fatigue severity and improve school attendance compared with no treatment.
We don't know how effective antidepressants, corticosteroids, and intramuscular magnesium are in treating chronic fatigue syndrome. Antidepressants should be considered in people with affective disorders, and tricyclics in particular have potential therapeutic value because of their analgesic properties.
Interventions such as dietary supplements, evening primrose oil, oral nicotinamide adenine dinucleotide, homeopathy, and prolonged rest have not been studied in enough detail for us to draw conclusions on their efficacy.
A large study has found that galantamine is no better than placebo at improving symptoms of chronic fatigue syndrome.
Although there is some evidence that immunotherapy can improve symptoms compared with placebo, it is associated with considerable adverse effects, and should therefore probably not be offered as a treatment for chronic fatigue.
PMCID: PMC2907931  PMID: 19445810
8.  Obsessive compulsive disorder 
Clinical Evidence  2012;2012:1004.
Introduction
Obsessions or compulsions that cause personal distress or social dysfunction affect about 1% of adult men and 1.5% of adult women. About half of adults with obsessive compulsive disorder (OCD) have an episodic course, whereas the other half have continuous problems. Prevalence in children and adolescents is 2.7%. The disorder persists in about 40% of children and adolescents at mean follow-up of 5.7 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of initial treatments for obsessive compulsive disorder in adults? What are the effects of initial treatments for obsessive compulsive disorder in children and adolescents? What are the effects of maintenance treatment for obsessive compulsive disorder in adults? What are the effects of maintenance treatment for obsessive compulsive disorder in children and adolescents? What are the effects of treatments for obsessive compulsive disorder in adults who have not responded to initial treatment with serotonin reuptake inhibitors (SRIs)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: addition of antipsychotics to serotonin reuptake inhibitors, behavioural therapy alone or with serotonin reuptake inhibitors, cognitive therapy or cognitive behavioural therapy (CBT) (alone or with serotonin reuptake inhibitors), electroconvulsive therapy, optimum duration of maintenance treatment, psychosurgery, serotonin reuptake inhibitors (citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine, or sertraline), and transcranial magnetic stimulation.
Key Points
Obsessions or compulsions that cause personal distress or social dysfunction affect about 1% of adult men and 1.5% of adult women. Prevalence in children and adolescents is 2.7%. About half of adults with obsessive compulsive disorder (OCD) have an episodic course, whereas the other half have continuous problems. Up to half of adults show improvement of symptoms over time. The disorder persists in about 40% of children and adolescents at mean follow-up of 5.7 years.
In adults, CBT and behavioural therapy improve symptoms of OCD compared with a waiting list control or placebo treatments. Behavioural therapy may be as effective at improving symptoms as CBT, but we don't know how they compare with SRIs (SSRIs and clomipramine).
SRIs improve symptoms of OCD in adults compared with placebo. Abrupt withdrawal of SRIs is associated with adverse effects.
We don't know whether combining SRIs and cognitive therapy or behavioural therapy improves symptoms compared with each treatment alone.
We don't know whether electroconvulsive therapy improves symptoms in adults with OCD.
In children and adolescents, CBT and SRIs improve symptoms of OCD. We don't know whether CBT in combination with SRIs is more effective than CBT alone, but it may be more effective than SRIs alone.
We don't know whether behavioural therapy improves symptoms in children and adolescents with OCD.
We don't know which is the most effective SRI to use, or for how long maintenance treatment should continue in adults or children and adolescents.
Adding antipsychotic drugs to SRIs may improve symptoms in adults who did not respond to SRIs alone, although RCTs have given conflicting results.
We don't know whether psychosurgery improves OCD because we found no studies of sufficient quality to assess its effectiveness.
Transcranial magnetic stimulation (rTMS) is not likely to improve symptoms of OCD. The quality of evidence is limited with trials being small.
CAUTION: SSRIs have been associated with an increase in suicidal ideation in children and adolescents.
PMCID: PMC3285220  PMID: 22305974
9.  Venous leg ulcers 
Clinical Evidence  2011;2011:1902.
Introduction
Leg ulcers usually occur secondary to venous reflux or obstruction, but 20% of people with leg ulcers have arterial disease, with or without venous disorders. Between 1.5 and 3.0/1000 people have active leg ulcers. Prevalence increases with age to about 20/1000 in people aged over 80 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of standard treatments, adjuvant treatments, and organisational interventions for venous leg ulcers? What are the effects of advice about self-help interventions in people receiving usual care for venous leg ulcers? What are the effects of interventions to prevent recurrence of venous leg ulcers? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 101 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: compression bandages and stockings, cultured allogenic (single or bilayer) skin replacement, debriding agents, dressings (cellulose, collagen, film, foam, hyaluronic acid-derived, semi-occlusive alginate), hydrocolloid (occlusive) dressings in the presence of compression, intermittent pneumatic compression, intravenous prostaglandin E1, larval therapy, laser treatment (low-level), leg ulcer clinics, multilayer elastic system, multilayer elastomeric (or non-elastomeric) high-compression regimens or bandages, oral treatments (aspirin, flavonoids, pentoxifylline, rutosides, stanozolol, sulodexide, thromboxane alpha2 antagonists, zinc), peri-ulcer injection of granulocyte-macrophage colony-stimulating factor, self-help (advice to elevate leg, to keep leg active, to modify diet, to stop smoking, to reduce weight), short-stretch bandages, single-layer non-elastic system, skin grafting, superficial vein surgery, systemic mesoglycan, therapeutic ultrasound, and topical treatments (antimicrobial agents, autologous platelet lysate, calcitonin gene-related peptide plus vasoactive intestinal polypeptide, freeze-dried keratinocyte lysate, mesoglycan, negative pressure, recombinant keratinocyte growth factor, platelet-derived growth factor).
Key Points
Leg ulcers are usually secondary to venous reflux or obstruction, but 20% of people with leg ulcers have arterial disease, with or without venous disorders.
Compression bandages and stockings heal more ulcers compared with no compression, but we don't know which bandaging technique is most effective. Compression is used for people with ulcers caused by venous disease who have an adequate arterial supply to the foot, and who don't have diabetes or rheumatoid arthritis.The effectiveness of compression bandages depends on the skill of the person applying them.We don't know whether intermittent pneumatic compression is beneficial compared with compression bandages or stockings.
Occlusive (hydrocolloid) dressings are no more effective than simple low-adherent dressings in people treated with compression, but we don't know whether semi-occlusive dressings are beneficial.
Peri-ulcer injections of granulocyte-macrophage colony-stimulating factor may increase healing, but we don't know whether other locally applied agents are beneficial, as we found few trials.
Oral pentoxifylline increases ulcer healing in people receiving compression, and oral flavonoids, sulodexide, and mesoglycan may also be effective. We don't know whether therapeutic ultrasound, oral aspirin, rutosides, thromboxane alpha2 antagonists, zinc, debriding agents, intravenous prostaglandin E1, superficial vein surgery, skin grafting, topical antimicrobial agents, leg ulcer clinics, laser treatment, or advice to elevate legs, increase activity, lose weight, change diet, or give up smoking increase healing of ulcers in people treated with compression. Larval therapy is not likely to be beneficial as it has no impact on healing and is painful.
Compression bandages and stockings reduce recurrence of ulcers compared with no compression, and should ideally be worn for life. Superficial vein surgery may also reduce recurrence, but we don't know whether systemic drug treatment is effective.
PMCID: PMC3275133  PMID: 22189344
10.  Venous leg ulcers 
Clinical Evidence  2008;2008:1902.
Introduction
Leg ulcers usually occur secondary to venous reflux or obstruction, but 20% of people with leg ulcers have arterial disease, with or without venous disorders. Between 1.5 and 3.0/1000 people have active leg ulcers. Prevalence increases with age to about 20/1000 in people aged over 80 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of standard treatments, adjuvant treatments, and organisational interventions for venous leg ulcers? What are the effects of interventions to prevent recurrence of venous leg ulcers? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 80 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: compression bandages and stockings, cultured allogenic (single or bilayer) skin replacement, debriding agents, dressings (cellulose, collagen, film, foam, hyaluronic acid-derived, semi-occlusive alginate), hydrocolloid (occlusive) dressings in the presence of compression, intermittent pneumatic compression, intravenous prostaglandin E1, larval therapy, laser treatment (low-level), leg ulcer clinics, multilayer elastic system, multilayer elastomeric (or non-elastomeric) high-compression regimens or bandages, oral treatments (aspirin, flavonoids, pentoxifylline, rutosides, stanozolol, sulodexide, thromboxane alpha2 antagonists, zinc), peri-ulcer injection of granulocyte-macrophage colony-stimulating factor, short-stretch bandages, single-layer non-elastic system, skin grafting, superficial vein surgery, systemic mesoglycan, therapeutic ultrasound, self-help (advice to elevate leg, advice to keep leg active, advice to modify diet, advice to stop smoking, advice to reduce weight), and topical treatments (antimicrobial agents, autologous platelet lysate, calcitonin gene-related peptide plus vasoactive intestinal polypeptide, freeze-dried keratinocyte lysate, mesoglycan, negative-pressure recombinant keratinocyte growth factor, platelet-derived growth factor).
Key Points
Leg ulcers are usually secondary to venous reflux or obstruction, but 20% of people with leg ulcers have arterial disease, with or without venous disorders.
Compression bandages and stockings heal more ulcers compared with no compression, but we don't know which bandaging technique is most effective. Compression is used for people with ulcers caused by venous disease who have an adequate arterial supply to the foot, and who don't have diabetes or rheumatoid arthritis.The effectiveness of compression bandages depends on the skill of the person applying them.We don't know whether intermittent pneumatic compression is beneficial compared with compression bandages or stockings.
Occlusive (hydrocolloid) dressings are no more effective than simple low-adherent dressings in people treated with compression, but we don't know whether semi-occlusive dressings are beneficial.
Peri-ulcer injections of granulocyte-macrophage colony-stimulating factor may increase healing, but we don't know whether other locally applied agents, or therapeutic ultrasound are beneficial, as we found few studies.
Oral pentoxifylline increases ulcer healing in people receiving compression, and oral flavonoids, sulodexide, and mesoglycan may also be effective. We don't know whether oral aspirin, rutosides, thromboxane alpha2 antagonists, zinc, debriding agents, intravenous prostaglandin E1, superficial vein surgery, skin grafting, leg ulcer clinics, larval therapy, laser treatment, or advice to elevate legs, increase activity, lose weight, change diet, or give up smoking increase healing of ulcers in people treated with compression.
Compression bandages and stockings reduce recurrence of ulcers compared with no compression, and should ideally be worn for life. Superficial vein surgery may also reduce recurrence, but we don't know whether systemic drug treatment is effective.
PMCID: PMC2908003  PMID: 19445798
11.  Genetic Predictors of Response to Serotonergic and Noradrenergic Antidepressants in Major Depressive Disorder: A Genome-Wide Analysis of Individual-Level Data and a Meta-Analysis 
PLoS Medicine  2012;9(10):e1001326.
Testing whether genetic information could inform the selection of the best drug for patients with depression, Rudolf Uher and colleagues searched for genetic variants that could predict clinically meaningful responses to two major groups of antidepressants.
Background
It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.
Methods and Findings
The NEWMEDS consortium, an academia–industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10−8). No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10−8) were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.
Conclusions
No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Genetic and environmental factors can influence a person's response to medications. Taking advantage of the recent advancements in genetics, scientists are working to match specific gene variations with responses to particular medications. Knowing whether a patient is likely to respond to a drug or have serious side effects would allow doctors to select the best treatment up front. Right now, there are only a handful of examples where a patient's version of a particular gene predicts their response to a particular drug. Some scientists believe that there will be many more such matches between genetic variants and treatment responses. Others think that because the action of most drugs is influenced by many different genes, a variant in one of those genes is unlikely to have measurable effect in most cases.
Why Was This Study Done?
One of the areas where patients' responses to available drugs vary widely is severe depression (or major depressive disorder). Prescription of an antidepressant is often the first step in treating the disease. However, less than half of patients get well taking the first antidepressant prescribed. Those who don't respond to the first drug need to, together with their doctors, try multiple courses of treatment to find the right drug and the right dose for them. For some patients none of the existing drugs work well.
To see whether genetic information could help improve the choice of antidepressant, researchers from universities and the pharmaceutical industry joined forces in this large study. They examined two ways to use genetic information to improve the treatment of depression. First, they searched all genes for common genetic variants that could predict which patients would not respond to the two major groups of antidepressants (serotonin reuptake inhibitors, or SRIs, and noradrenaline reuptake inhibitors, or NRIs). They hoped that this would help with the development of new drugs that could help these patients. Second, they looked for common genetic variants in all genes that could identify patients who responded to one of the two major groups of antidepressants. Such predictors would make it possible to know which drug to prescribe for which patient.
What Did the Researchers Do and Find?
The researchers selected 1,790 patients with severe depression who had participated in one of several research studies; 1,222 of the patients had been treated with an SRI, the remaining 568 with an NRI, and it was recorded how well the drugs worked for each patient. The researchers also had a detailed picture of the genetic make-up of each patient, with information for over half a million genetic variants. They then looked for an association between genetic variants and responses to drugs.
They found not a single genetic variant that could predict clearly whether a person would respond to antidepressants in general, to one of the two main groups (SRIs and NRIs), or much better to one than the other. They also didn't find any combination of variants in groups of genes that work together that could predict responses. Combining their data with those from another large study did not yield any robust predictors either.
What Do These Findings Mean?
This study was large enough that it should have been possible to find common genetic variants that by themselves could predict a clinically meaningful response to SRIs and/or NRIs, had such variants existed. The fact that the study failed to find such variants suggests that such variants do not exist. It is still possible, however, that variants that are less common could predict response, or that combinations of variants could. To find those, if they do exist, even larger studies will need to be done.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001326
The National Institute of General Medical Sciences at the US National Institutes of Health has a fact sheet on personalized medicine
PubMed Health at the US National Library of Medicine has a page on major depressive disorder
Wikipedia has pages on major depressive disorder and pharmacogenetics, the study of how genetic variation affects response to certain drugs (note that Wikipedia is a free online encyclopedia that anyone can edit)
The UK National Health Service has comprehensive information pages on depression
doi:10.1371/journal.pmed.1001326
PMCID: PMC3472989  PMID: 23091423
12.  Serious Shortcomings in the Management of Children with Anaphylaxis in Scottish Schools 
PLoS Medicine  2006;3(8):e326.
Background
The United Kingdom incidence of anaphylaxis has increased very sharply over the last decade, with the highest rates of hospital admissions occurring in school-aged children. This raises concerns about the extent to which schools are aware of approaches to the prevention and treatment of anaphylaxis.
Methods and Findings
We undertook a national postal survey of 250 Scottish schools enquiring about approaches to managing children considered to be at risk of anaphylaxis. We obtained responses from 148 (60%) schools, 90 (61%) of which reported having at least one at risk child. Most (80%) schools with children considered to be at risk reported having personalised care plans and invariably reported having at least one member of staff trained in the emergency treatment of anaphylaxis. Access to adrenaline was available on-site in 97% of these schools. However, significantly fewer schools without children considered to be at risk reported having a trained member of staff (48%, p < 0.001), with access to adrenaline being very poor (12%, p < 0.001). Overall, 59% of respondents did not feel confident in their school's ability to respond in an emergency situation.
Conclusions
Most schools with children considered to be at risk of anaphylaxis report using personal care plans and having a member of staff trained in the use of, and with access to, adrenaline. The picture is, however, less encouraging in schools without known at risk children, both in relation to staff training and access to adrenaline. The majority of schools with at risk children have poorly developed strategies for preventing food-triggered anaphylaxis reactions. There is a need for detailed national guidelines for all schools, which the Scottish Executive must now ensure are developed and implemented.
Schools whose officials know that some of their pupils have serious allergies are often prepared to deal with emergencies, but many don't have good plans for exposure prevention. When there is no knowledge of specific pupils at risk, neither preparedness nor prevention efforts are widespread.
Editors' Summary
Background.
Anaphylaxis is a severe allergic reaction that can cause a drop in blood pressure and swelling of the body tissues (swelling of the neck and throat and narrowing of the airways can make it hard to breathe). The reaction can be triggered by foods, such as peanuts or eggs, or by bee stings, natural latex (rubber), and certain drugs such as penicillin. Foods are the most common trigger in children. In the United Kingdom, thousands of people develop anaphylaxis each year, and the number appears to be increasing. If anaphylaxis is severe, a patient will need to be hospitalized, and the highest risk of hospitalization is in school-aged children. About 20 people die each year in the United Kingdom from anaphylaxis. Anaphylaxis can develop both in people known to have a tendency (risk) of getting the condition and in those with no known risk.
Why Was This Study Done?
The researchers wanted to find out how many school children there were in Scotland with a known risk of developing anaphylaxis. They also wanted to know how many schools were taking steps to minimize these children's risk of getting anaphylaxis during school hours (the risk can be reduced, for example, by prohibiting children from sharing food and eating utensils). Finally, they wanted to find out how many schools had the necessary equipment and trained staff to treat a child that develops anaphylaxis on site.
What Did the Researchers Do and Find?
The researchers sent a questionnaire in the mail to 250 Scottish schools. They received replies from 148 schools, of which 90 reported having at least one child with a known risk of developing anaphylaxis. Most of the schools (80%) that had children at risk had at least one staff member trained to treat anaphylaxis, and 97% of these schools had the drug adrenaline (epinephrine) on site, which is a lifesaving medication for treating anaphylaxis. But many of these schools were doing poorly at reducing the risk of anaphylaxis—for example, only one in three of these schools banned the sharing of eating utensils. Another worrying finding was that among the 58 schools that did not have children known to be at risk of anaphylaxis, less than half had a trained member of staff, and only about one in eight of these schools had adrenaline on site.
What Do These Findings Mean?
It is reassuring that most schools in Scotland that have children known to be at risk of anaphylaxis are well equipped to deal with this emergency if it occurs. But many of these schools are not doing enough to reduce the risk of anaphylaxis occurring. It is worrying that schools that don't have children known to be at risk are often very poorly equipped to deal with anaphylaxis. One weakness of this study is that 102 schools never replied to the questionnaire, so we can't know how well prepared these schools are for dealing with anaphylaxis. Nevertheless, the study suggests that there needs to be detailed guidance for all schools in Scotland on preventing and treating anaphylaxis.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030326.
NHS Direct page on anaphylaxis
MedlinePlus page on anaphylaxis
Mayo Clinic page on anaphylaxis
Wikipedia entry on anaphylaxis (note: Wikipedia is a free Internet encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0030326
PMCID: PMC1551918  PMID: 16933965
13.  The Changing “Weightscape” of Bulimia Nervosa 
The American journal of psychiatry  2012;169(10):1031-1036.
Case
Ms. Z, a 35-year-old African-American single woman with a body mass index (BMI) of 37.8 kg/m2 (height 5 feet, 5.5 inches, weight 238 lb.), presents for an evaluation for bulimia nervosa. She was referred to the eating disorders program by her primary care physician who knew about her eating disorder, but was primarily concerned about her weight and blood pressure. Ms. Z has an advanced degree and is employed full time. She has struggled with her eating, weight, and body image since childhood and began binge eating regularly (1–2× week) at age 15. Fasting and self-induced vomiting began in her early twenties, when she achieved her lowest adult BMI of 21.6 kg (weight 130 lb. at age 23). She gained 100 pounds in the past 7 years and currently binges and purges 1–2 times a day. A typical binge consists of a box of cookies, a pint of ice cream, 7 oz. of cheese, two bowls of cereal with 2 cups of milk, and 4 pickles. Ms. Z has seen five therapists to address her eating behaviors and weight concerns and participated in numerous commercial weight loss programs. She states binge eating has always served a self-soothing purpose for her.
Ms. Z has a demanding university-related job that absorbs most of her time. She has few friends and has not been in a romantic relationship for the past five years believing that no one would be interested in a woman of her size. She also claimed that food is more reliable than any man because “it’s always there when you need it and you don’t have to take care of it or stoke its ego.” She spends evenings at home working until she is completely exhausted, heads to the kitchen for an all-out binge, vomits everything up, and then cries herself to sleep. She has never smoked and does not drink alcohol. Current medications prescribed by her primary care physician include Fluoxetine (20 mg), Norvasc (5 mg), and Clonazepam (prn).
What are Ms. Z’s treatment goals? What are her primary care physician’s? Is her medication for bulimia nervosa adequate? How well would cognitive-behavioral therapy for bulimia nervosa address her personal treatment goals? Her physician’s? What challenges might a therapist face having Ms. Z in group therapy for bulimia?
doi:10.1176/appi.ajp.2012.12010147
PMCID: PMC4038540  PMID: 23032383
14.  Wrinkles 
Clinical Evidence  2008;2008:1711.
Introduction
Skin disorders associated with photodamage from ultraviolet light include wrinkles, hyperpigmentation, tactile roughness, and telangiectasia, and are more common in people with white compared with other skin types. Wrinkles are also associated with ageing, hormonal status, smoking, and intercurrent disease.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to prevent and treat skin wrinkles? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: alpha and beta hydroxyl acids, carbon dioxide laser, chemical peel, dermabrasion, facelifts, isotretinoin, natural cartilage polysaccharides (oral or topical), retinyl esters, sunscreens, tazarotene, tretinoin, variable pulse erbium:YAG laser, and vitamin C or E (topical).
Key Points
Skin disorders associated with damage by ultraviolet light include wrinkles, hyperpigmentation, tactile roughness, and telangiectasia, and are more common in white people compared with other skin types. Wrinkles are also associated with ageing, hormonal status, smoking, and intercurrent disease.
We don't know whether sunscreens or topical vitamins C or E prevent wrinkles, as no studies were found.
Exposure to ultraviolet light may be associated with photodamage to the skin. Guidelines suggest that avoiding direct sunlight, either by staying indoors or in the shade, or by wearing protective clothing, is the most effective measure for reducing exposure to ultraviolet light.
We don't know whether topical vitamins C or E improve the appearance of wrinkles, as studies have been small. These vitamins may cause stinging and erythema.
Topical tretinoin improves fine wrinkles compared with placebo cream in people with mild to moderate photodamage, but its effect on coarse wrinkles is unclear. Topical tretinoin may cause itching, burning, erythema, and skin peeling. Isotretinoin cream improves fine and coarse wrinkles compared with vehicle cream in people with mild to severe photodamage, but causes severe irritation of the face in 5%–10% of people.We don't know whether tazarotene is more effective than tretinoin at improving fine and coarse wrinkles in people with moderate photodamage, as studies have given inconclusive results. It can cause burning of the skin.
We don't know whether retinyl esters, topical or oral natural cartilage polysaccharides, alpha or beta hydroxyl acids, or chemical peels are beneficial.
We don't know whether dermabrasion is more effective at improving wrinkles compared with carbon dioxide laser treatment, as studies have given inconclusive results, but adverse effects are common with both treatments, especially erythema. We don't know whether variable pulse erbium:YAG laser treatment or facelifts improve wrinkles, as few studies were found.
PMCID: PMC2907965  PMID: 19445782
15.  Pressure ulcers 
Clinical Evidence  2008;2008:1901.
Introduction
Unrelieved pressure or friction of the skin, particularly over bony prominences, can lead to pressure ulcers in up to a third of people in hospitals or community care, and a fifth of nursing home residents. Pressure ulcers are more likely in people with reduced mobility and poor skin condition, such as older people or those with vascular disease.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive interventions in people at risk of developing pressure ulcers? What are the effects of treatments in people with pressure ulcers? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 60 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: air-filled vinyl boots, air-fluidised supports, alternating pressure surfaces (including mattresses), alternative foam mattresses, constant low-pressure supports, debridement, electric profiling beds, electrotherapy, hydrocellular heel supports, low-air-loss beds (including hydrotherapy beds), low-level laser therapy, low-tech constant low-pressure supports, medical sheepskin overlays, nutritional supplements, orthopaedic wool padding, pressure-relieving overlays on operating tables, pressure-relieving surfaces, repositioning (regular "turning"), seat cushions, standard beds, standard care, standard foam mattresses, standard tables, surgery, therapeutic ultrasound, topical lotions and dressings, topical negative pressure, and topical phenytoin.
Key Points
Unrelieved pressure or friction of the skin, particularly over bony prominences, can lead to pressure ulcers, which affect up to a third of people in hospitals or community care, and a fifth of nursing-home residents. Pressure ulcers are more likely in people with reduced mobility and poor skin condition, such as older people or those with vascular disease.
Alternative foam mattresses (such as viscoelastic foam) reduce the incidence of pressure ulcers in people at risk compared with standard hospital foam mattresses, although we don't know which is the best alternative to use. Low-air-loss beds may reduce the risk of pressure ulcers compared with standard intensive-care beds, but we don't know whether pressure-relieving overlays on operating tables are also beneficial compared with other pressure-relieving surfaces. Medical sheepskin overlays may reduce the risk of pressure ulcers compared with standard care.
Hydrocellular heel supports may decrease the risk of pressure ulcers compared with orthopaedic wool padding, but air-filled vinyl boots with foot cradles and low-air-loss hydrotherapy beds may increase the risk of ulcers compared with other pressure-relieving surfaces. We don't know if other physical interventions, such as alternating pressure surfaces, seat cushions, electric profiling beds, low-tech constant low pressure supports, repositioning, or topical lotions and dressings are effective for preventing pressure ulcers. We also don't know whether pressure ulcers can be prevented by use of nutritional interventions.
In people with pressure ulcers, air-fluidised supports may improve healing compared with standard care, although they can make it harder for people to get in and out of bed independently.
Hydrocolloid dressings may also improve healing rates compared with standard dressings.
We don't know whether healing is improved in people with pressure ulcers by use of other treatments such as alternating pressure surfaces, debriding agents, low-tech constant low pressure supports, low-air-loss beds, seat cushions, dressings other than hydrocolloid, topical phenytoin, surgery, electrotherapy, ultrasound, low level laser therapy, topical negative pressure, or nutritional interventions.
PMCID: PMC2907959  PMID: 19450317
16.  ADHD in children and adolescents 
Clinical Evidence  2011;2011:0312.
Introduction
Prevalence estimates of attention deficit hyperactivity disorder (ADHD) vary according to the diagnostic criteria used and the population sampled. DSM-IV prevalence estimates among school children in the US are 3% to 5%, but other estimates vary from 1.7% to 16.0%. No objective test exists to confirm the diagnosis of ADHD, which remains a clinical diagnosis. Other conditions frequently co-exist with ADHD.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmacological treatments for ADHD in children and adolescents? What are the effects of psychological treatments for ADHD in children and adolescents? What are the effects of combination treatments for ADHD in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 70 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: atomoxetine, bupropion, clonidine, dexamfetamine sulphate, homeopathy, methylphenidate, modafinil, omega-3 polyunsaturated fatty acids, and psychological/behavioural treatment (either alone or in combination with a drug treatment).
Key Points
Core symptoms of ADHD are inattention, hyperactivity, and impulsiveness, although other conditions frequently co-exist with ADHD, including developmental disorders (especially motor, language, social communication, and specific learning disabilities) and psychiatric disorders (especially oppositional defiant and conduct disorder, anxiety, and depressive disorders). Symptoms must be present for at least 6 months, are generally observed in children before the age of 7 years, and cause clinically important impairment in social, academic, or occupational functioning that must be evident in more than one setting.Formal diagnostic criteria are most applicable to boys aged 6 to 12 years, and most research data relate to this group. Pre-school children, adolescents, and females may present less typical features, but similar levels of impairment. Prevalence estimates among school children range from 3% to 5%.
Methylphenidate improves core symptoms in children with ADHD when used alone.
Dexamfetamine and atomoxetine may also reduce symptoms of ADHD.
We don't know how effective any treatment for ADHD is in the long term; people with ADHD may require treatment for many years.
CAUTION: Atomoxetine may cause rare but serious liver injury.
Clonidine and modafinil may improve symptoms of ADHD compared with placebo, but are associated with an increased risk of adverse effects compared with methylphenidate, dexamfetamine, and atomoxetine.
We don't know whether homeopathy, bupropion, or omega-3 polyunsaturated fatty acids are beneficial in the treatment of symptoms of ADHD.
We don't know how effective psychological/behavioural treatments alone are compared with each other or with pharmacological treatments, as we found few high-quality studies. The combination of methylphenidate plus psychological treatment may enhance effectiveness of methylphenidate alone or behavioural treatment alone, but we don't know whether dexamfetamine plus psychological treatment is effective in treatment of ADHD compared with either intervention alone. Long-term outcome for both drug treatment alone and combination treatments is uncertain.We don't know whether parent training in conjunction with teacher involvement is more effective than parent training alone.
PMCID: PMC3217800  PMID: 21718557
17.  ADHD in children and adolescents 
Clinical Evidence  2008;2008:0312.
Introduction
Prevalence estimates of attention deficit hyperactivity disorder (ADHD) vary according to the diagnostic criteria used and the population sampled. DSM-IV prevalence estimates among school children in the US are 3-5%, but other estimates vary from 1.7% to 16.0%. No objective test exists to confirm the diagnosis of ADHD, which remains a clinical diagnosis. Other conditions frequently co-exist with ADHD.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmacological treatments for ADHD in children and adolescents? What are the effects of psychological treatments for ADHD in children and adolescents? What are the effects of combination treatments for ADHD in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 34 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: atomoxetine, bupropion, clonidine, dexamfetamine sulphate, homeopathy, methylphenidate, modafinil, omega 3-polyunsaturated fatty acids, and psychological/behavioural treatment (either alone or in combination with a drug treatment).
Key Points
Core symptoms of ADHD are inattention, hyperactivity, and impulsiveness, although other conditions frequently coexist with ADHD, including developmental disorders (especially motor, language, social communication, and specific learning disabilities) and psychiatric disorders (especially oppositional defiant and conduct disorder, anxiety, and depressive disorders). Symptoms must be present for at least 6 months, are generally observed in children before the age of 7 years, and cause clinically important impairment in social, academic, or occupational functioning which must be evident in more than one setting.Formal diagnostic criteria are most applicable to boys aged 6-12 years, and most research data relate to this group. Preschool children, adolescents, and females may present less-typical features, but similar levels of impairment. Prevalence estimates among school children range from 3% to 5%.
Methylphenidate improves core symptoms and school performance in children with ADHD when used alone.
Dexamfetamine and atomoxetine may also reduce symptoms of ADHD.
We don't know how effective any treatment for ADHD is in the long term; people with ADHD may require treatment for many years.
CAUTION: Atomoxetine may cause rare but serious liver injury.
Clonidine and modafinil may improve symptoms of ADHD compared with placebo, but are associated with an increased risk of adverse effects compared with methylphenidate, dexamfetamine, and atomoxetine.
We don't know whether homeopathy, bupropion, or polyunsaturated fatty acids are beneficial in the treatment of symptoms of ADHD.
We don't know how effective psychological/behavioural treatments alone are compared with each other or with pharmacological treatments, as we found few high-quality studies. The combination of methylphenidate plus psychological treatment may enhance effectiveness of methylphenidate alone or behavioural treatment alone, but we don't know whether dexamfetamine plus psychological treatment is effective in treatment of ADHD compared with either intervention alone. Long-term outcome for both drug treatment alone and combination treatments is uncertain.We don't know whether parent training in conjunction with teacher involvement is more effective than parent training alone.
PMCID: PMC2907929  PMID: 19445793
18.  Female infertility 
Clinical Evidence  2010;2010:0819.
Introduction
About 17% of couples in industrialised countries seek help for infertility, which may be caused by ovulatory failure, tubal damage or endometriosis, or a low sperm count. In developed countries, 80% to 90% of couples attempting to conceive are successful after 1 year and 95% after 2 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for infertility caused by ovulation disorders? What are the effects of treatments for tubal infertility? What are the effects of treatments for infertility associated with endometriosis? What are the effects of treatments for unexplained infertility? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 55 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: clomifene; drug-induced ovarian suppression; gonadotrophin priming of oocytes before in vitro maturation; gonadotrophins; gonadotrophin-releasing hormone agonists plus gonadotrophins; gonadotrophin-releasing hormone antagonists; in vitro fertilisation; intrauterine insemination alone, or combined with gonadotrophins or clomifene; laparoscopic ablation of endometrial deposits; laparoscopic ovarian drilling; laparoscopic removal; metformin; ovarian wedge biopsy; pulsatile gonadotrophin-releasing hormone; selective salpingography plus tubal catheterisation; tamoxifen; tubal flushing; and tubal surgery before in vitro fertilisation.
Key Points
About 17% of couples in industrialised countries seek help for infertility, which may be caused by ovulatory failure, tubal damage or endometriosis, or a low sperm count.
In women with ovulatory disorders, clomifene and metformin increase ovulation and pregnancy rates. There is some evidence that tamoxifen may have similar efficacy to clomifene, but we found no RCTs of sufficient quality comparing tamoxifen with placebo, and it is rarely used nowadays. Gonadotrophins may increase pregnancy rates but may increase ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. Laparoscopic ovarian drilling may be as effective as gonadotrophins. We don't know whether pulsed gonadotrophin-releasing hormone (GnRH), or gonadotrophin priming of oocytes before in vitro maturation increase pregnancy rates.Consensus suggests that in vitro fertilisation may lead to pregnancy, but increases the risks of multiple pregnancy unless single embryo replacement is practised.We don't know whether GnRH agonists plus gonadotrophins increase pregnancy rates compared with gonadotrophins alone but the combination treatment may be associated with an increased risk of OHSS. We don't know how effective GnRH antagonists are because we found few trials.We don't know whether intrauterine insemination alone, or combined with gonadotrophins or clomifene is effective for infertility caused by ovulation disorders.
In women with tubal infertility, tubal flushing may increase pregnancy rates, with oil soluble media possibly more effective than water soluble media; however, we found few trials solely in women with tubal infertility. Tubal surgery before in vitro fertilisation may increase pregnancy rates compared with no treatment in women with hydrosalpinges, but we don't know whether selective salpingography plus tubal catheterisation is beneficial.Consensus suggests that in vitro fertilisation is beneficial.
In women with endometriosis, adding gonadotrophins to intrauterine insemination increases live birth rates compared with no treatment and increases pregnancy rates compared with intrauterine insemination alone. Laparoscopic ablation of endometrial deposits may increase live birth rates compared with diagnostic laparoscopy.Drugs to induce ovarian suppression may not increase pregnancy rates.Consensus suggests that in vitro fertilisation may be beneficial.Tubal flushing with oil-based media may increase live birth rates and pregnancy rates in women with minimal or mild endometriosis.
In women with unexplained infertility, clomifene does not increase live birth rates. It is not better than expectant management. Intrauterine insemination without ovarian stimulation does not result in a significant increase in live birth rates. Intrauterine insemination plus controlled ovarian stimulation may increase pregnancy rates but may increase OHSS and multiple pregnancy. In vitro fertilisation may be beneficial, however, evidence is insufficient to make any conclusions.
PMCID: PMC3217752  PMID: 21406133
19.  Post-traumatic stress disorder 
Clinical Evidence  2010;2010:1005.
Introduction
Post-traumatic stress disorder (PTSD) may affect 10% of women and 5% of men at some stage, and symptoms may persist for several years. Risk factors include major trauma, lack of social support, peritraumatic dissociation, and previous psychiatric history or personality factors.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent PTSD? What are the effects of interventions to treat PTSD? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: affect management; antiepileptic drugs; antihypertensive drugs; benzodiazepines; brofaromine; CBT; drama therapy; eye movement desensitisation and reprocessing; fluoxetine; group therapy; hydrocortisone; hypnotherapy; inpatient treatment programmes; Internet-based psychotherapy; mirtazapine; multiple-session CBT; multiple-session collaborative trauma support; multiple-session education; nefazodone; olanzapine; paroxetine; phenelzine; psychodynamic psychotherapy; risperidone; SSRIs (versus other antidepressants); sertraline; single-session group debriefing; single-session individual debriefing; supportive psychotherapy; supportive counselling; temazepam; tricyclic antidepressants; and venlafaxine.
Key Points
Post-traumatic stress disorder (PTSD) is characterised by disabling symptoms of re-experiencing a traumatic event, avoidance behaviour, and hyperarousal (e.g., irritability or hypervigilance), lasting at least 1 month. PTSD may affect 10% of women and 5% of men at some stage, and symptoms may persist for several years.Risk factors include major trauma, lack of social support, peritraumatic dissociation, and previous psychiatric or personality factors.
Multiple-session trauma-focused CBT may be effective at preventing development of PTSD in people with psychological distress after a traumatic event. However, we don't know whether multiple-session trauma-focused CBT is beneficial for people who have experienced a traumatic event but have not been diagnosed with psychological distress.
We don't know whether antiepileptic drugs, antihypertensive drugs, hydrocortisone, multiple-session collaborative trauma support, multiple-session education, single-session group debriefing, or temazepam are beneficial in preventing PTSD. Single-session individual debriefing may increase the rate of PTSD after a traumatic event compared with no debriefing, and supportive counselling may be less effective than multiple-session CBT at preventing onset of PTSD.
In people with PTSD, trauma-focused CBT improves PTSD symptoms compared with no treatment or with other psychological interventions, including stress management and present-centred therapy. Eye movement desensitisation and reprocessing seems as effective as trauma-focused CBT in the treatment of chronic PTSD. We don't know whether other psychological treatments (affect management, drama therapy, group therapy, hypnotherapy, inpatient treatment regimens, Internet-based psychotherapy, psychodynamic psychotherapy, or supportive psychotherapy) are beneficial in people with PTSD.
Paroxetine may improve symptoms in people with PTSD. However, venlafaxine does not seem effective at improving symptoms, and the benefits of fluoxetine are unclear. We found insufficient good evidence to assess the effects of sertraline, tricyclic antidepressants, or benzodiazepines.We found limited evidence that sertraline and nefazodone may be equally effective at improving symptoms of PTSD, but we don't know how other antidepressants compare with each other in the treatment of PTSD.We don't know whether antiepileptic drugs, antihypertensive drugs, brofaromine, nefazodone, olanzapine, phenelzine, mirtazapine, or risperidone are beneficial in people with PTSD.
PMCID: PMC2907597  PMID: 21718580
20.  Dysmenorrhoea 
Clinical Evidence  2007;2007:0813.
Introduction
Dysmenorrhoea may begin soon after the menarche, after which it often improves with age, or it may originate later in life after the onset of an underlying causative condition. Dysmenorrhoea is common, and in up to 20% of women it may be severe enough to interfere with daily activities.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for dysmenorrhoea? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 34 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupressure, acupuncture, aspirin, behavioural interventions, combined oral contraceptives, compound analgesics, fish oil, herbal remedies, magnesium, magnets, non-steroidal anti-inflammatory drugs, paracetamol, spinal manipulation, surgical interruption of pelvic nerve pathways, thiamine, toki-shakuyaku-san, topical heat, transcutaneous electrical nerve stimulation (TENS), vitamin B12, and vitamin E.
Key Points
Dysmenorrhoea may begin soon after the menarche, where it often improves with age, or may originate later in life after the onset of an underlying causative condition. Dysmenorrhoea is very common, and in up to 20% of women it may be severe enough to interfere with daily activities.Dysmenorrhoea is more likely in women who smoke, and those with an earlier age at menarche or longer duration of menstruation.
NSAIDs, reduce moderate to severe pain in women with primary dysmenorrhoea compared with placebo, but we don't know whether any one NSAID is superior to the others. Aspirin, paracetamol, and compound analgesics may reduce pain in the short term, although few studies have been of good quality.The herbal remedy toki-shakuyaku-san may reduce pain after 6 months compared with placebo, but we don't know whether any other herbal remedy is beneficial. Thiamine and vitamin E may reduce pain compared with placebo in women with primary dysmenorrhoea.
We don't know whether combined oral contraceptives reduce the pain of dysmenorrhoea, as studies have been small and have used products that are no longer available.
Topical heat (about 39 °C) may be as effective as ibuprofen and more effective than paracetamol at reducing pain. High frequency TENS may reduce pain compared with sham TENS, but seems to be less effective than ibuprofen. Acupressure may be more effective than sham acupressure at relieving dysmenorrhoea, and may be as effective as ibuprofen at relieving pain. Spinal manipulation seems to be no more effective than placebo at reducing pain after 1 month in women with primary dysmenorrhoea.We don't know whether acupuncture, relaxation or aerobic exercise, fish oil, magnesium, vitamin B12, surgical interruption of pelvic nerve pathways, or magnets reduce dysmenorrhoea, as few studies have been found.
PMCID: PMC2943779  PMID: 19454059
21.  Pressure ulcers 
Clinical Evidence  2011;2011:1901.
Introduction
Unrelieved pressure or friction of the skin, particularly over bony prominences, can lead to pressure ulcers in up to one third of people in hospitals or community care, and one fifth of nursing home residents. Pressure ulcers are more likely in people with reduced mobility and poor skin condition, such as older people or those with vascular disease.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive interventions in people at risk of developing pressure ulcers? What are the effects of treatments in people with pressure ulcers? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 64 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: air-filled vinyl boots, air-fluidised supports, alternating-pressure surfaces (including mattresses), alternative foam mattresses, constant low-pressure supports, debridement, electric profiling beds, electrotherapy, hydrocellular heel supports, low-air-loss beds (including hydrotherapy beds), low-level laser therapy, low-tech constant-low-pressure supports, medical sheepskin overlays, nutritional supplements, orthopaedic wool padding, pressure-relieving overlays on operating tables, pressure-relieving surfaces, repositioning (regular "turning"), seat cushions, standard beds, standard care, standard foam mattresses, standard tables, surgery, therapeutic ultrasound, topical lotions and dressings, topical negative pressure, and topical phenytoin.
Key Points
Unrelieved pressure or friction of the skin, particularly over bony prominences, can lead to pressure ulcers, which affect up to one third of people in hospitals or community care, and one fifth of nursing home residents. Pressure ulcers are more likely in people with reduced mobility and poor skin condition, such as older people or those with vascular disease.
Alternative foam mattresses (such as viscoelastic foam) reduce the incidence of pressure ulcers in people at risk compared with standard hospital foam mattresses, although we don't know which is the best alternative to use. Low-air-loss beds may reduce the risk of pressure ulcers compared with standard intensive-care beds, and pressure-relieving overlays on operating tables may reduce the risk of pressure ulcer development. Medical sheepskin overlays may reduce the risk of pressure ulcers compared with standard care.
Hydrocellular heel supports may decrease the risk of pressure ulcers compared with orthopaedic wool padding, but air-filled vinyl boots with foot cradles and low-air-loss hydrotherapy beds may increase the risk of ulcers compared with other pressure-relieving surfaces. We don't know if other physical interventions, such as alternating-pressure surfaces, seat cushions, electric profiling beds, low-tech constant-low-pressure supports, repositioning, or topical lotions and dressings are effective for preventing pressure ulcers. We also don't know whether pressure ulcers can be prevented by use of nutritional interventions.
In people with pressure ulcers, air-fluidised supports may improve healing compared with standard care, although they can make it harder for people to get in and out of bed independently.
We don't know whether healing is improved in people with pressure ulcers by use of other treatments such as one specific specialised support surface (including alternating-pressure surfaces, low-tech constant-low-pressure supports, low-air-loss beds, and specific seat cushions) over any other specific specialised support surface, one specific wound dressing over any other specific wound dressing, or with surgery, electrotherapy, ultrasound, low-level laser therapy, topical negative pressure, topical phenytoin, or nutritional interventions.
PMCID: PMC3217823  PMID: 21524319
22.  Online Access to Doctors' Notes: Patient Concerns About Privacy 
Background
Offering patients online access to medical records, including doctors’ visit notes, holds considerable potential to improve care. However, patients may worry about loss of privacy when accessing personal health information through Internet-based patient portals. The OpenNotes study provided patients at three US health care institutions with online access to their primary care doctors’ notes and then collected survey data about their experiences, including their concerns about privacy before and after participation in the intervention.
Objective
To identify patients’ attitudes toward privacy when given electronic access to their medical records, including visit notes.
Methods
The design used a nested cohort study of patients surveyed at baseline and after a 1-year period during which they were invited to read their visit notes through secure patient portals. Participants consisted of 3874 primary care patients from Beth Israel Deaconess Medical Center (Boston, MA), Geisinger Health System (Danville, PA), and Harborview Medical Center (Seattle, WA) who completed surveys before and after the OpenNotes intervention. The measures were patient-reported levels of concern regarding privacy associated with online access to visit notes.
Results
32.91% of patients (1275/3874 respondents) reported concerns about privacy at baseline versus 36.63% (1419/3874 respondents) post-intervention. Baseline concerns were associated with non-white race/ethnicity and lower confidence in communicating with doctors, but were not associated with choosing to read notes or desire for continued online access post-intervention (nearly all patients with notes available chose to read them and wanted continued access). While the level of concern among most participants did not change during the intervention, 15.54% (602/3874 respondents, excluding participants who responded “don’t know”) reported more concern post-intervention, and 12.73% (493/3874 respondents, excluding participants who responded “don’t know”) reported less concern.
Conclusions
When considering online access to visit notes, approximately one-third of patients had concerns about privacy at baseline and post-intervention. These perceptions did not deter participants from accessing their notes, suggesting that the benefits of online access to medical records may outweigh patients’ perceived risks to privacy.
doi:10.2196/jmir.2670
PMCID: PMC3785972  PMID: 24072335
electronic medical records; patient access to records; patient portals; privacy; consumer health informatics; personal health records
23.  Hip fracture 
Clinical Evidence  2010;2010:1110.
Introduction
Between 12% and 37% of people will die in the year after a hip fracture, and 10% to 20% of survivors will move into a more dependent residence.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of surgical interventions in people with hip fracture? What are the effects of perisurgical medical interventions on surgical outcome and prevention of complications in people with hip fracture? What are the effects of rehabilitation interventions and programmes after hip fracture? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 55 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anaesthesia (general, regional); antibiotic regimens; arthroplasty; choice of implant for internal fixation; conservative treatment; co-ordinated multidisciplinary approaches for inpatient rehabilitation of older people; cyclical compression of the foot or calf; early supported discharge followed by home-based rehabilitation; extramedullary devices; fixation (external, internal); graduated elastic compression; intramedullary devices; mobilisation strategies; nerve blocks for pain control; nutritional supplementation (oral multinutrient feeds, nasogastric feeds); perioperative prophylaxis with antibiotics, with antiplatelet agents, or with heparin (low molecular weight or unfractionated); preoperative traction to the injured limb; and systematic multicomponent home-based rehabilitation.
Key Points
Between 12% and 37% of people will die in the year after a hip fracture, and 10% to 20% of survivors will move into a more dependent residence.
Surgery is routinely used in the treatment of hip fracture. Surgical fixation leads to earlier mobilisation and less leg deformity compared with conservative treatment.In people with intracapsular hip fracture, internal fixation is associated with less operative trauma and deep wound sepsis, but is more likely to require subsequent revision surgery, compared with arthroplasty. We don't know the best method for internal fixation, or the best method of arthroplasty, for these fractures. Older fixed nail plates for extramedullary fixation of extracapsular fracture increase the risk of fixation failure compared with sliding hip screws. Short intramedullary cephalocondylic nails, Ender nails, and older fixed nail plates increase the risk of re-operation compared with extramedullary fixation with a sliding hip screw device, but we don't know whether other kinds of extramedullary devices are better than the sliding hip screw. We also don't know how different intramedullary devices compare with each other.
Various perisurgical interventions may be used with the aim of improving surgical outcome and preventing complications. Routine preoperative traction to the injured limb has not been shown to relieve pain or to aid subsequent surgery. Antibiotic prophylaxis reduces wound infections, but we don't know which is the most effective regimen (regimens assessed are antibiotics given on the day of surgery and single-dose antibiotics versus multiple-dose regimens). Antiplatelet agents and heparin reduce the risk of deep vein thrombosis (DVT) when used prophylactically, but both treatments increase the risk of bleeding. We don't know how low molecular weight heparin and unfractionated heparin compare at reducing risk of DVT. Cyclical compression devices also reduce the risk of DVT, but we don't know whether graduated elastic compression stockings are effective. Oral protein and energy multinutrient feeds may reduce unfavourable outcomes after surgery.We don't know whether nerve blocks are effective in reducing pain post-surgery or the pain or requirement for analgesia after surgery. We don't how different anaesthetic regimens compare with each other.We don't know whether nasogastric feeds for nutritional supplementation are effective at improving outcomes after hip fracture.
Various rehabilitation interventions and programmes aim to improve recovery after a hip fracture. Co-ordinated multidisciplinary care may improve outcomes compared with usual care, but we don't know which method is best.We don't know how effective mobilisation strategies, early supported discharge, or multidisciplinary home-based rehabilitation are at improving outcomes after hip surgery.
PMCID: PMC2907602  PMID: 21726483
24.  Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study 
PLoS Medicine  2009;6(8):e1000132.
In a cohort of 6,441 volunteers followed over an average of 8.2 years, Naresh Punjabi and colleagues find sleep-disordered breathing to be independently associated with mortality and identify predictive characteristics.
Background
Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older.
Methods and Findings
We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: ≥30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80–1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality.
Conclusions
Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 1 in 10 women and 1 in 4 men have a chronic condition called sleep-disordered breathing although most are unaware of their problem. Sleep-disordered breathing, which is commonest in middle-aged and elderly people, is characterized by numerous, brief (10 second or so) interruptions of breathing during sleep. These interruptions, which usually occur when relaxation of the upper airway muscles decreases airflow, lower the level of oxygen in the blood and, as a result, affected individuals are frequently aroused from deep sleep as they struggle to breathe. Symptoms of sleep-disordered breathing include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. Affected people can also use special devices to prevent them sleeping on their backs, but for severe sleep-disordered breathing, doctors often recommend continuous positive airway pressure (CPAP), a machine that pressurizes the upper airway through a face mask to keep it open.
Why Was This Study Done?
Sleep-disordered breathing is a serious condition. It is associated with several adverse health conditions including coronary artery disease (narrowing of the blood vessels that supply the heart, a condition that can cause a heart attack) and daytime sleepiness that can affect an individual's driving ability. In addition, several clinic- and community-based studies suggest that sleep-disordered sleeping may increase a person's risk of dying. However, because these studies have been small and have often failed to allow for other conditions and characteristics that affect an individual's risk of dying (“confounding factors”), they provide inconsistent or incomplete information about the potential association between sleep-disordered breathing and the risk of death. In this prospective cohort study (part of the Sleep Heart Health Study, which is researching the effects of sleep-disordered breathing on cardiovascular health), the researchers examine whether sleep-disordered breathing is associated with all-cause mortality (death from any cause) in a large community sample of adults. A prospective cohort study is one in which a group of participants is enrolled and then followed forward in time (in this case for several years) to see what happens to them.
What Did the Researchers Do and Find?
At enrollment, the study participants—more than 6,000 people aged 40 years or older, none of whom were being treated for sleep-disordered breathing—had a health examination. Their night-time breathing, sleep patterns, and blood oxygen levels were also assessed and these data used to calculate each participant's apnea-hypopnea index (AHI)—the number of apneas and hypopneas per hour. During the study follow-up period, 1,047 participants died. Compared to participants without sleep-disordered sleeping, participants with severe sleep-disordered breathing (an AHI of ≥30) were about one and a half times as likely to die from any cause after adjustment for potential confounding factors. People with milder sleep-disordered breathing did not have a statistically significant increased risk of dying. After dividing the participants into subgroups according to their age and sex, men aged 40–70 years with severe sleep-disordered breathing had a statistically increased risk of dying from any cause (twice the risk of men of a similar age without sleep-disordered breathing). Finally, death from coronary artery disease was also associated with sleep-disordered breathing in men but not in women.
What Do These Findings Mean?
These findings indicate that sleep-disordered breathing is associated with an increased risk of all-cause mortality, particularly in men aged 40–70 years, even after allowing for known confounding factors. They also suggest that the increased risk of death is specifically associated with coronary artery disease although further studies are needed to confirm this finding because it was based on the analysis of a small subgroup of study participants. Although this study is much larger than previous investigations into the association between sleep-disordered breathing and all-cause mortality, it has several limitations including its reliance on a single night's measurements for the diagnosis of sleep-disordered breathing. Nevertheless, these findings suggest that clinical trials should now be started to assess whether treatment can reduce the increased risk of death that seems to be associated with this common disorder.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000132.
The US National Heart Lung and Blood Institute has information (including a video) about sleep-disordered breathing (sleep apnea) (in English and Spanish)
The UK National Heath Service also provides information for patients about sleep apnea
MedlinePlus provides links to further information and advice about sleep-disordered breathing (in English and Spanish)
More information on the Sleep Heart Health Study is available
doi:10.1371/journal.pmed.1000132
PMCID: PMC2722083  PMID: 19688045
25.  Menorrhagia 
Clinical Evidence  2012;2012:0805.
Introduction
Menorrhagia limits normal activities, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia, and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall, and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments for menorrhagia? What are the effects of surgical treatments for menorrhagia? What are the effects of endometrial thinning before endometrial destruction in treating menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following medical interventions: combined pill, danazol, etamsylate, gonadorelin analogues, intrauterine progesterone, non-steroidal anti-inflammatory drugs (NSAIDs), progestogens, and the following surgical interventions: dilatation and curettage, endometrial destruction, and hysterectomy.
Key Points
Menorrhagia limits normal activities, and causes anaemia in two-thirds of women with objective menorrhagia (blood loss of 80 mL or more per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia, and with heavy bleeding caused by fibroids, adenomyosis, or use of IUDs.Fibroids have been found in 10% of women with menorrhagia overall, and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus.
NSAIDs, tranexamic acid, and danazol all reduce blood loss compared with placebo. Tranexamic acid and danazol may be more effective than NSAIDs, etamsylate, and oral progestogens at reducing blood loss, but any benefits of danazol must be weighed against the high risk of adverse effects. NSAIDs reduce dysmenorrhoea, and may be as effective at reducing menstrual blood loss as oral progestogens given in the luteal phase, but we don't know how they compare with etamsylate, combined oral contraceptives, intrauterine progestogens, or gonadorelin analogues.We don't know whether combined oral contraceptives, levonorgestrel-releasing intrauterine devices, or gonadorelin analogues are effective at reducing menorrhagia, as few trials were found.
Hysterectomy reduces blood loss and the need for further surgery compared with medical treatments or endometrial destruction, but can lead to complications in up to a third of women. Fewer women reported overall treatment dissatisfaction with hysterectomy. Endometrial destruction is more effective at reducing menorrhagia compared with medical treatment, but complications can include infection, haemorrhage, and uterine perforation.We don't know whether any one type of endometrial destruction is superior, or whether dilatation and curettage has any effect on menstrual blood loss.
Preoperative gonadorelin analogues reduce long-term postoperative moderate or heavy blood loss, and increase amenorrhoea compared with placebo, but we don't know whether oral progestogens or danazol are also beneficial when used preoperatively.
PMCID: PMC3285230  PMID: 22305976

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