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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.  Sleep apnoea 
Clinical Evidence  2009;2009:2301.
Introduction
Sleep apnoea is the popular term for obstructive sleep apnoea-hypopnoea syndrome (OSAHS). OSAHS is abnormal breathing during sleep that causes recurrent arousals, sleep fragmentation, excessive daytime sleepiness, and nocturnal hypoxaemia. Apnoea may be "central", in which there is cessation of inspiratory effort, or "obstructive", in which inspiratory efforts continue but are ineffective because of upper airway obstruction. OSAHS affects up to 4% of men and 2% of women in the USA, with obesity being a major determinant.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment for severe obstructive sleep apnoea-hypopnoea syndrome? What are the effects of treatment for non-severe obstructive sleep apnoea-hypopnoea syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 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 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: nasal continuous positive airway pressure (CPAP); measures aimed at improving compliance with CPAP; oral appliances; and weight loss.
Key Points
Sleep apnoea is the popular term for obstructive sleep apnoea-hypopnoea syndrome (OSAHS). OSAHS is abnormal breathing during sleep that causes recurrent arousals, sleep fragmentation, daytime sleepiness, and nocturnal hypoxaemia. Apnoea may be "central", in which there is cessation of inspiratory effort, or "obstructive", in which inspiratory efforts continue but are ineffective because of upper airway obstruction.OSAHS affects up to 4% of men and 2% of women in the USA, with obesity being a major determinant.
In people with severe OSAHS, nasal CPAP has been shown to reduce daytime sleepiness compared with control treatments. Although effective, it can be difficult getting people to comply with the prescribed CPAP regimen. Compliance seems no better with variations of CPAP, such as automatically titrated CPAP, bi-level positive airway pressure, patient-titrated CPAP, or CPAP plus humidification. We don't know whether educational or psychological interventions may improve compliance with CPAP.
Oral appliances that produce anterior advancement of the mandible seem to be effective in improving sleep-disordered breathing in people with OSAHS (either severe or non-severe). Oral appliances are probably not as effective as CPAP, and we don't know how well they work in the long term.
We found no sufficient evidence judging the effectiveness of weight loss on OSAHS (either severe or non-severe), although there is consensus that advice about weight reduction is an important component of management of OSAHS.
Nasal CPAP also seems beneficial to people suffering from non-severe OSAHS. Nasal CPAP is less acceptable in people with non-severe OSAHS, and we don't know whether measures aimed at improving compliance effectively increase usage.
PMCID: PMC2907765  PMID: 21726484
5.  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
6.  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
7.  Correlation between expectations of recovery and injury severity perception in whiplash-associated disorders 
Objective: To assess the correlation between expectations of recovery and whiplash patients’ perceptions of injury severity using a simplified instrument. Expectations of recovery have been shown to predict rate of recovery from whiplash injury in population-based studies. The perception of having more severe pathology or more ominous diagnostic labels has also been associated with a worse prognosis. Methods: Consecutive patients with whiplash-associated disorder grade 1 or 2, presenting in the acute stage to a primary care centre, were asked “do you think that your injury will…” with response options “get better soon; get better slowly; never get better; don’t know.” Injury severity perception (ISP) was measured with a numerical rating scale which ranged from 0–10, on which subjects were asked to rate how severe (in terms of damage) they thought their injury was. The anchors were labeled “no damage” (0) and “severe, and maybe permanent damage” (10). The primary outcome measure was the correlation between the subject’s ISP score and expectation of recovery. Results: A total of 94 subjects (34 males, 60 females, and mean age (40.6±10.0) years, range 19–60 years) were included. The initial responses to expectation of recovery were: get better soon (29/94); get better slowly (22/94); never get better (11/94); don’t know (32/94). The mean ISP score was 4.9±1.7 (range 2–9 out of 10). There was a high correlation between expectations and ISP scores (Spearman’s rank correlation coefficient 0.68). Those who expected to recover soon and those who expected to get better slowly had the lowest ISP scores. Conclusions: The more slowly whiplash patients expect to recover, or the less sure they are of recovery, the more severe their initial perceptions of injury.
doi:10.1631/jzus.B1100097
PMCID: PMC3150723  PMID: 21796810
Whiplash-associated disorders (WAD); Expectations of recovery; Injury severity perception (ISP)
8.  Obsessive compulsive disorder 
Clinical Evidence  2009;2009:1004.
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 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 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: 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; serotonin reuptake inhibitors (citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine, or sertraline); and optimum duration of maintenance treatment.
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. Behavioural therapy may be as effective at improving symptoms as CBT, but we don't know how they compare with SRIs (SSRIs and clomipramine). Behavioural therapy may be more effective than relaxation.
SRIs improve symptoms of OCD in adults compared with placebo. Abrupt withdrawal of SRIs is associated with adverse effects. SRIs seem more effective at reducing symptoms compared with other antidepressants, including tricyclic antidepressants (other than clomipramine) or MAOIs.We don't know whether SRIs are more effective than venlafaxine.
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.
CAUTION: SSRIs have been associated with an increase in suicidal ideation in children and adolescents.
PMCID: PMC2907809
9.  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
10.  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
11.  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
12.  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
13.  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
14.  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
15.  The secret lives of doctors 
BMJ : British Medical Journal  2008;336(7652):1044.
On the whole, people don’t become doctors because they were destined to do so but because they weren’t good enough at anything else
doi:10.1136/bmj.39570.465266.59
PMCID: PMC2375988  PMID: 18467411
16.  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
17.  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
18.  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
19.  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
20.  The association between active smoking, smokeless tobacco, secondhand smoke exposure and insufficient sleep 
Sleep medicine  2010;12(1):7-11.
Background
Studies have shown that cigarette smoking is associated with sleep disorders in the general population. But studies examining the association between smokeless tobacco use, secondhand smoke exposure and insufficient rest/sleep are limited.
Methods
We examined the association between smoking, smokeless tobacco use (n=83,072), secondhand smoke exposure (n=28,557) and insufficient rest/sleep among adults aged ≥20 years in the state-based 2008 Behavioral Risk Factor Surveillance System. Exposure to secondhand smoke was defined as >1 day of exposure to cigarette smoking either at home or in the workplace in the preceding 7 days. Insufficient rest/sleep was defined as not getting enough rest/sleep everyday in the preceding 30 days.
Results
Compared to never smokeless tobacco users, the odds ratio (OR; 95% confidence interval [CI]) of insufficient rest/sleep was 1.16 (1.00–1.36) and 1.74 (1.37–2.22) among former and current users. Compared to non-smokers/non-smokeless tobacco users, the OR (95% CI) of insufficient rest/sleep for those who were both current smokers and current smokeless tobacco users was 2.21 (1.66–2.94). Regarding secondhand smoke exposure among non-smokers, those with second-hand smoke exposure had higher odds for insufficient rest/sleep than those without. In contrast, the odds of insufficient rest/sleep were similar among current smokers with or without secondhand smoke exposure.
Conclusions
In a multiethnic sample of US adults, compared to non-smokers/non-smokeless tobacco users, those who were both current smokers and current smokeless tobacco users had twice the odds of insufficient sleep. Secondhand smoke exposure was associated with insufficient rest/sleep among non-smokers.
doi:10.1016/j.sleep.2010.09.002
PMCID: PMC3056485  PMID: 21144798
Smokeless tobacco; secondhand smoke; insufficient sleep; BRFSS
21.  Premenstrual syndrome 
Clinical Evidence  2009;2009:0806.
Introduction
Premenstrual symptoms occur in 95% of women of reproductive age. Severe, debilitating symptoms (PMS) occur in about 5% of those women. There is no consensus on how symptom severity should be assessed, which has led to a wide variety of symptoms scales, making it difficult to synthesise data on treatment efficacy. The cyclical nature of the condition also makes it difficult to conduct RCTs.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in women with premenstrual syndrome? What are the effects of hormonal treatments in women with premenstrual syndrome? What are the effects of psychological interventions in women with premenstrual syndrome? What are the effects of physical therapy in women with premenstrual syndrome? What are the effects of dietary supplements in women with premenstrual syndrome? What are the effects of surgical treatments in women with premenstrual syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 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 56 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: acupuncture; alprazolam; bright light therapy; buspirone; chiropractic manipulation; clomipramine; cognitive behavioural therapy (CBT); danazol; endometrial ablation; evening primrose oil; exercise; gonadorelin analogues; hysterectomy; laparoscopic bilateral oophorectomy; magnesium supplements; metolazone; non-steroidal anti-inflammatory drugs (NSAIDs); oestrogens; oral contraceptives; progesterone; progestogens; pyridoxine; reflexology; relaxation; selective serotonin reuptake inhibitors (SSRIs); spironolactone; and tibolone.
Key Points
A woman has premenstrual syndrome (PMS) if she complains of recurrent psychological and/or physical symptoms occurring during the luteal phase of the menstrual cycle, and often resolving by the end of menstruation. Symptom severity can vary between women. Premenstrual symptoms occur in 95% of all women of reproductive age. Severe, debilitating symptoms (PMS) occur in about 5% of those women.There is no consensus on how symptom severity should be assessed, which has led to a wide variety of symptoms scales, making it difficult to synthesise data on treatment efficacy. The cyclical nature of the condition also makes it difficult to conduct RCTs.There is little good evidence for any of the wide range of treatments available, and the selection of treatment is mainly governed by personal choice. The clinician plays a key role in facilitating this choice, and in reassuring women with PMS without coexisting gynaecological problems that there is nothing seriously wrong.
Drug treatments can be effective at reducing premenstrual symptoms, but some are associated with significant adverse effects. There is good evidence that spironolactone improves mood and somatic symptoms in women with PMS. Alprazolam (during the luteal phase), metolazone, and NSAIDs (such as mefenamic acid and naproxen sodium) may also be effective in treating the main physical and psychological symptoms of PMS. Buspirone (luteal or continuous) and gonadorelin analogues seem to improve overall self-rated symptoms. Gonadorelin is effective in improving symptoms, but is associated with serious risks of osteoporosis when used for more than 6 months.Other drug treatments such as clomipramine, danazol, and SSRIs may improve psychological symptoms, but are associated with serious adverse effects.
We don't know whetherprogesterone is effective in reducing symptoms of PMS. There is some evidence thatprogesterone-like drugs reduce premenstrual symptoms, but both progesterone and progesterone-like drugs are associated with several adverse effects. We don't know whether other hormonal treatments such as oestrogen and tibolone are effective in reducing symptoms of PMS. Oral contraceptives containing drospirenone (24/4 schedule [24 out of 28 days]) are likely to be effective in reducing symptoms of PMS.
There is not enough evidence for us to assess the efficacy of CBT in treating the psychological symptoms of PMS.
We also don't know how effective physical therapy techniques (bright light therapy, chiropractic manipulation, exercise, reflexology, relaxation, and acupuncture) are in relieving symptoms of PMS.
We found evidence that pyridoxine (vitamin B6) reduces the overall symptoms of PMS. Calcium supplements may also be effective. We don't know whether other supplements, such as evening primrose oil or magnesium, are a useful treatment for PMS.
Surgery is indicated only if there are coexisting gynaecological problems. There is a consensus that hysterectomy with bilateral oophorectomy or laparoscopic bilateral oophorectomy almost completely eradicate the symptoms of PMS, although we found no RCTs examining this.We don't know whether endometrial ablation has the same effect.
PMCID: PMC2907788
22.  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
23.  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
24.  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
25.  Headache (chronic tension-type) 
Clinical Evidence  2009;2009:1205.
Introduction
Chronic tension-type headache (CTTH) is a disorder that evolves from episodic tension-type headache, with daily or very frequent episodes of headache lasting minutes to days. It affects 4.1% of the general population in the USA, and is more prevalent in women (up to 65% of cases).
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for chronic tension-type headache? What are the effects of non-drug treatments for chronic tension-type headache? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 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 50 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: acupuncture; amitriptyline; analgesics; anticonvulsant drugs; benzodiazepines; botulinum toxin; chiropractic and osteopathic manipulations; cognitive behavioural therapy (CBT); Indian head massage; mirtazapine; relaxation and electromyographic biofeedback; selective serotonin reuptake inhibitor antidepressants (SSRIs); and tricyclic antidepressants (other than amitriptyline).
Key Points
Chronic tension-type headache (CTTH) is a disorder that evolves from episodic tension-type headache, with daily or very frequent episodes, lasting minutes to days. It affects 4.1% of the general population in the USA, and is more prevalent in women (up to 65% of cases).
We found only limited evidence about the treatment of CTTH. Regular analgesics may lead to chronic headache symptoms and reduce the effectiveness of prophylactic treatment. Amitriptyline and mirtazapine may be equally effective in reducing the duration and frequency of CTTH, although amitriptyline may be associated with a less favourable adverse-effect profile.We don't know whether tricyclic antidepressants other than amitriptyline are effective in treating CTTH.We found no evidence examining the effectiveness of noradrenergic and specific serotonergic antidepressants, other than mirtazapine, in CTTH.We don't know whether SSRIs are effective in treating CTTH.We don't know whether benzodiazepines are effective in treating CTTH, and they are commonly associated with significant adverse effects.We found no evidence examining the effectiveness of anticonvulsants, such as sodium valproate, topiramate, and gabapentin, in CTTH. Botulinum toxin does not seem to be a useful treatment for CTTH. It may be associated with several adverse effects, including facial weakness, difficulty in swallowing, and disturbed local sensation.
We don't know whether non-drug treatments, such as CBT, relaxation or electromyographic biofeedback, or acupuncture, are effective in treating CTTH. We don’t know whether chiropractic and osteopathic manipulations are effective in treating CTTH. These treatments have been associated with rare, but very serious, adverse effects; for example, arterial dissection causing stroke, other stroke syndromes, and cerebellar and spinal cord injuries.
PMCID: PMC2907789  PMID: 21696647

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