Introduction

Dysmenorrhoea may begin soon after the menarche, after which it often improves with age, or it may originate later in life after the onset of an underlying causative condition. Dysmenorrhoea is common, and in up to 20% of women it may be severe enough to interfere with daily activities.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for primary dysmenorrhoea? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 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 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupressure, acupuncture, aspirin, behavioural interventions, contraceptives (combined oral), fish oil, herbal remedies, magnets, non-steroidal anti-inflammatory drugs, paracetamol, progestogens (intrauterine), spinal manipulation, surgical interruption of pelvic nerve pathways, thiamine, toki-shakuyaku-san, topical heat, transcutaneous electrical nerve stimulation (TENS), vitamin B12, and vitamin E.

Key Points

Dysmenorrhoea may begin soon after the menarche, where it often improves with age, or may originate later in life after the onset of an underlying causative condition. Dysmenorrhoea is very common, and in up to 20% of women it may be severe enough to interfere with daily activities.Dysmenorrhoea is more likely in women who smoke, and those with an earlier age at menarche or longer duration of menstruation.

NSAIDs reduce moderate to severe pain in women with primary dysmenorrhoea compared with placebo, but we don't know whether any one NSAID is superior to the others. Simple analgesics such as aspirin and paracetamol may reduce pain in the short term, although few studies have been of good quality.The herbal remedies toki-shakuyaku-san and Iranian herbal remedy (saffron, celery, and anise) may reduce pain compared with placebo. We don't know whether Chinese herbal remedies are beneficial compared with placebo, but we found limited evidence that they may be effective compared with other treatments for dysmenorrhoea. Thiamine and vitamin E may reduce pain compared with placebo in young women with primary dysmenorrhoea.

Combined oral contraceptives may be more effective at reducing pain in women with primary dysmenorrhoea compared with placebo; however, few trials have been of good quality.

Topical heat (about 39 °C) may be as effective as ibuprofen and more effective than paracetamol at reducing pain. High-frequency transcutaneous electrical nerve stimulation (TENS) may reduce pain compared with sham TENS, but seems to be less effective than ibuprofen. Acupressure may be more effective than sham acupressure or no treatment at relieving dysmenorrhoea. Spinal manipulation may be no more effective than placebo at reducing pain after 1 month in women with primary dysmenorrhoea. Relaxation may be better than no treatment at relieving dysmenorrhoea.We don't know whether acupuncture, fish oil, vitamin B12 , magnets, or intrauterine progestogens reduce dysmenorrhoea. Surgical interruption of pelvic nerve pathways is not beneficial in treating dysmenorrhoea, and may be associated with adverse effects including constipation.

In the title benzoyl­hydrazide derivative, C17H18N2O, the dihedral angle between the benzene rings is 88.45 (8)° and the azomethine double bond adopts an E conformation. In the crystal, mol­ecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming a chain along the b axis.

In the title compound, C14H10ClNOS, the dihedral angle between the benzothia­zole ring system and the meth­oxy-substituted benzene ring is 8.76 (16)°. In the crystal, mol­ecules are stacked in columns along the c axis and no significant inter­molecular inter­actions are observed.

Drinking water manganese (WMn) is a potential threat to children’s health due to its associations with a wide range of outcomes including cognitive, behavioral and neuropsychological effects. Although adverse effects of Mn on cognitive function of the children indicate possible impact on their academic achievement little evidence on this issue is available.. Moreover, little is known regarding potential interactions between exposure to Mn and other metals, especially water arsenic (WAs). In Araihazar, a rural area of Bangladesh, we conducted a cross-sectional study of 840 children to investigate associations between WMn and WAs and academic achievement in mathematics and languages among elementary school-children, aged 8–11 years. Data on As and Mn exposure were collected from the participants at the baseline of an ongoing longitudinal study of school-based educational intervention. Annual scores of the study children in languages (Bangla and English) and mathematics were obtained from the academic achievement records of the elementary schools. WMn above the WHO standard of 400 μg/L was associated with 6.4 percentage score loss (95% CI=0.5, 12.3) in mathematics achievement test scores, adjusted for WAs and other sociodemographic variables. We did not find any significant associations between WMn and academic achievement in either language. Neither WAs nor urinary As was significantly related to any of the three academic achievement scores. Our finding suggests that a large number of children in rural Bangladesh may experience deficits in mathematics due to high concentrations of Mn exposure in drinking water.

The title mol­ecule, C10H10N4O2, is almost planar and adopts an E configuration of the azomethine [C=N = 1.298 (2) Å] double bond. The benzene ring is attached to an essentially planar (r.m.s. deviation = 0.0226 Å) amidine moiety (N=CN/Me2), the dihedral angle between the two mean planes being 18.42 (11)°. The cyano group lies in the plane of the benzene ring [the C and N atoms deviating by 0.030 (3) and 0.040 (3) Å, respectively], while the nitro group makes a dihedral angle 5.8 (3)° with the benzene ring. There are two distinct inter­molecular hydrogen bonds, C—H⋯O and C—H⋯N, that stabilize the crystal structure; the former inter­actions result in centrosymmetric dimers about inversion centers resulting in ten-membered rings, while the later give rise to chains of mol­ecules running parallel to the b axis.

In the title mol­ecule, C16H14N4O4, the quinazoline ring is substanti­ally planar (r.m.s. deviation = 0.0129 Å) and forms a dihedral angle of 2.73 (8)° with the benzene ring. The conformation of the mol­ecule is stabilized by an intra­molecular C—H⋯N hydrogen bond. In the crystal, mol­ecules are linked into chains running parallel to the b axis by C—H⋯O hydrogen bonds. In addition, π–π stacking is observed between dimethoxy-substituted and nitro-substituted benzene rings, with centroid–centroid distances in the range 3.6438 (10)–3.7148 (10) Å.

The mol­ecule of the title compound, C14H11ClN2O2 adopts an E conformation of the azomethine double bond and the dihedral angle between the benzene rings is 38.96 (13)°. In the crystal, mol­ecules are linked by N—H⋯O and O—H⋯O (with the ketone O atom as acceptor) and C—H⋯O (with the hy­droxy O atom as acceptor) hydrogen bonds, forming a three-dimensional network.

In the title compound, C16H15N3O, the dihedral angle between the indole ring system (r.m.s. deviation = 0.020 Å) and the phenyl ring is 14.49 (9)°. The mol­ecular conformation is supported by an intra­molecular C—H⋯O inter­action, which closes an S(7) ring. In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds generate R 2 2(8) loops.

In the title compound, C16H14ClNO3S, the dihedral angle between the almost-planar benzothia­zole ring system [maximum deviation = 0.012 (3) Å] and the aromatic ring of the trimeth­oxy­phenyl group is 15.56 (6)°. In the crystal, the mol­ecules are arranged into layers parallel to the bc plane, held together only by weak van der Waals forces.

In the title compound, C15H14O4, the chromone ring system is close to being planar [maximum deviation = 0.015 (2) Å]. The double bond of the ethyl prop-2-enoate chain adopts an E conformation and an intra­molecular C—H⋯O hydrogen bond generates an S6 ring. In the crystal, inversion dimers linked by pairs of C—H⋯O hydrogen bonds generate R 2 2(14) loops. Weak π–π inter­actions [centroid–centroid distance = 3.8493 (12) Å] also occur.

In the title compound, C11H8O3, the benzopyran-4-one or chromone ring system is almost planar, with a maximum deviation of 0.045 (2) Å. The crystal structure is stablized by π–π inter­actions between the benzene and pyran rings of inversion-related mol­ecules stacked along the b axis, with a centroid–centroid distance of 3.5463 (12) Å

In the mol­ecule of the title compound, C14H10ClNO2S, the dihedral angle between the almost planar benzothia­zole ring system [maximum deviation = 0.005 (2) Å] and the benzene ring is 1.23 (9)°. The conformation of the mol­ecule is stabilized by an intra­molecular O—H⋯N hydrogen bond, forming an S(6) ring motif. In the crystal, mol­ecules are linked into layers parallel to the ac plane by C—H⋯O hydrogen bonds and π–π stacking inter­actions [centroid–centroid distance = 3.7365 (12) Å].

In the structure of the title compound, C13H8ClNS, the dihedral angle between the benzothia­zole ring system and the phenyl ring is 7.11 (8)°. In the crystal, mol­ecules are arranged parallel to the c axis.

In the title compound, C15H14O4S, the dihedral angle between the benzene and phenyl rings is 88.74 (10)°. In the crystal, mol­ecules are linked into a three-dimensional network by C—H⋯O hydrogen bonds and π–π stacking inter­actions [centroid–centroid distances = 3.6092 (13)–3.8651 (13) Å].

Human populations throughout much of the world are experiencing unprecedented changes in their relationship to the environment and their interactions with the animals with which so many humans are intimately dependent upon. These changes result not only from human induced changes in the climate, but also from population demographic changes due to wars, social unrest, behavioral changes resulting from cultural mixing, and large changes in land-use practices. Each of these social shifts can affect the maintenance and emergence of arthropod vectors disease or the pathogenic organisms themselves. A good example is the country of Pakistan, with a large rural population and developing urban economy, it also maintains a wide diversity of entomological disease vectors, including biting flies, mosquitoes, and ticks. Pathogens endemic to the region include the agents of piroplasmosis, rickettsiosis, spirochetosis, and viral hemorrhagic fevers and encephalitis. The northwestern region of the country, including the Khyber Pakhtunkhwa Province (KPK), formerly the North-West Frontier Provence (NWFP), and the Federally Administered Tribal Areas (FATA) are mountainous regions with a high degree of habitat diversity that has recently undergone a massive increase in human population density due to an immigrating refugee population from neighboring war-torn Afghanistan. Vector-borne diseases in people and livestock are common in KPK and FATA regions due to the limited use of vector control measures and access to livestock vaccines. The vast majority of people in this region live in abject poverty with >70% of the population living directly from production gained in animal husbandry. In many instances whole families live directly alongside their animal counterparts. In addition, there is little to no awareness of the threat posed by ticks and transmission of either zoonotic or veterinary pathogens. Recent emergence of Crimean–Congo hemorrhagic fever virus in rural populations, outbreaks of Dengue hemorrhagic fever have been reported in the region, and high prevalence of cattle infected and co-infected with multiple species of hemoparasites (Theileria, Babesia, Anaplasma). The emergence of which has followed the increased density of the rural population due to an influx of refugees from violent conflicts in Afghanistan and is exacerbated by an already impoverished society and wide diversity of potential arthropod vectors. These human outbreaks may be exacerbated by episodes of social upheaval but are also tied to the historically close association of people in the region with their livestock and subsequent zoonosis that result from spillover from co-habitation with infected domestic animals.

The title compound, C21H23NO3, is a phenyl­imine derivative of the well known anthelmintic agent α-santonin. The trans-fused cyclo­hexane and γ-lactone rings of the α-santonin ring system adopt chair and envelope conformations, respectively, whereas the hexa­diene ring is approximately planar [maximum deviation = 0.029 (4) Å] and forms a dihedral angle of 62.30 (11)° with the benzene ring. An intra­molecular O—H⋯N hydrogen bond is observed.

The title compound, C21H24N2O2, is a phenyl hydrazine derivative of the well known anthelminthic agent α-santonin, which is composed of three fused rings (benzodieneone, cyclo­hexane and γ-lactone). The cyclo­hexa­dienone ring adopts a boat conformation, the cyclo­hexane ring is in a chair conformation and the trans-fused γ-lactone ring adopts a C-envelope conformation. In the crystal, mol­ecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming chains along the a axis.

The complete mol­ecule of the title compound, C14H16N2S2, is generated by a crystallographic inversion centre. The thio­phene residue is close to being coplanar with the imine group [C—C—C—N torsion angle = 6.5 (2)°], and the conformation about the imine C=N bond [1.281 (2) Å] is E. In the crystal, the three-dimensional architecture is consolidated by C—H⋯N, C—H⋯π and S⋯S [3.3932 (7) Å] inter­actions.

Objective To review the effectiveness and safety of clinical officers (healthcare providers trained to perform tasks usually undertaken by doctors) carrying out caesarean section in developing countries compared with doctors.

Design Systematic review with meta-analysis.

Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, BioMed Central, the Reproductive Health Library, and the Science Citation Index (inception-2010) without language restriction.

Study selection Controlled studies.

Data extraction Information was extracted from each selected article on study characteristics, quality, and outcome data. Two independent reviewers extracted data.

Results Six non-randomised controlled studies (16 018 women) evaluated the effectiveness of clinical officers carrying out caesarean section. Meta-analysis found no significant differences between the clinical officers and doctors for maternal death (odds ratio 1.46, 95% confidence interval 0.78 to 2.75; P=0.24) or for perinatal death (1.31, 0.87 to 1.95; P=0.19). The results were heterogeneous, with some studies reporting a higher incidence of both outcomes with clinical officers. Clinical officers were associated with a higher incidence of wound infection (1.58, 1.01 to 2.47; P=0.05) and wound dehiscence (1.89, 1.21 to 2.95; P=0.005). Two studies accounted for confounding factors.

Conclusion Clinical officers and doctors did not differ significantly in key outcomes for caesarean section, but the conclusions are tentative owing to the non-randomised nature of the studies. The increase in wound infection and dehiscence may highlight a particular training need for clinical officers.

Summary

Evidence-based medicine (EBM) is the clinical use of current best available evidence from relevant, valid research. Provision of evidence-based healthcare is the most ethical way to practise as it integrates up-to-date patient-oriented research into the clinical decision-making to improve patients' outcomes. This article provides tips for teachers to teach clinical trainees the final two steps of EBM: integrating evidence with clinical judgement and bringing about change.

Background: Several reports indicate that drinking water arsenic (WAs) and manganese (WMn) are associated with children’s intellectual function. Very little is known, however, about possible associations with other neurologic outcomes such as motor function.

Methods: We investigated the associations of WAs and WMn with motor function in 304 children in Bangladesh, 8–11 years of age. We measured As and Mn concentrations in drinking water, blood, urine, and toenails. We assessed motor function with the Bruininks-Oseretsky test, version 2, in four subscales—fine manual control (FMC), manual coordination (MC), body coordination (BC), and strength and agility—which can be summarized with a total motor composite score (TMC).

Results: Log-transformed blood As was associated with decreases in TMC [β = –3.63; 95% confidence interval (CI): –6.72, –0.54; p < 0.01], FMC (β = –1.68; 95% CI: –3.19, –0.18; p < 0.05), and BC (β = –1.61; 95% CI: –2.72, –0.51; p < 0.01), with adjustment for sex, school attendance, head circumference, mother’s intelligence, plasma ferritin, and blood Mn, lead, and selenium. Other measures of As exposure (WAs, urinary As, and toenail As) also were inversely associated with motor function scores, particularly TMC and BC. Square-transformed blood selenium was positively associated with TMC (β = 3.54; 95% CI: 1.10, 6.0; p < 0.01), FMC (β = 1.55; 95% CI: 0.40, 2.70; p < 0.005), and MC (β = 1.57; 95% CI: 0.60, 2.75; p < 0.005) in the unadjusted models. Mn exposure was not significantly associated with motor function.

Conclusion: Our research demonstrates an adverse association of As exposure and a protective association of Se on motor function in children.

Summary

Evidence-based medicine (EBM) is an indispensable tool in clinical practice. Teaching and training of EBM to trainee clinicians is patchy and fragmented at its best. Clinically integrated teaching of EBM is more likely to bring about changes in skills, attitudes and behaviour. Provision of evidence-based health care is the most ethical way to practice, as it integrates up-to-date, patient-oriented research into the clinical decision making process, thus improving patients' outcomes. In this article, we aim to dispel the myth that EBM is an academic and statistical exercise removed from practice by providing practical tips for teaching the minimum skills required to ask questions and critically identify and appraise the evidence and presenting an approach to teaching EBM within the existing clinical and educational training infrastructure.

Background: Evidence of neurological, cognitive, and neuropsychological effects of manganese (Mn) exposure from drinking water (WMn) in children has generated widespread public health concern. At elevated exposures, Mn has been associated with increased levels of externalizing behaviors, including irritability, aggression, and impulsivity. Little is known about potential effects at lower exposures, especially in children. Moreover, little is known regarding potential interactions between exposure to Mn and other metals, especially arsenic (As).

Objectives: We conducted a cross-sectional study of 201 children to investigate associations of Mn and As in tube well water with classroom behavior among elementary school children, 8–11 years of age, in Araihazar, Bangladesh.

Methods: Data on exposures and behavioral outcomes were collected from the participants at the baseline of an ongoing longitudinal study of child intelligence. Study children were rated by their school teachers on externalizing and internalizing items of classroom behavior using the standardized Child Behavior Checklist-Teacher’s Report Form (CBCL-TRF).

Results: Log-transformed WMn was positively and significantly associated with TRF internalizing [estimated β = 0.82; 95% confidence interval (CI), 0.08–1.56; p = 0.03], TRF externalizing (estimated β = 2.59; 95% CI, 0.81–4.37; p =0.004), and TRF total scores (estimated β = 3.35; 95% CI, 0.86–5.83; p = 0.008) in models that adjusted for log-transformed water arsenic (WAs) and sociodemographic covariates. We also observed a positive monotonic dose–response relationship between WMn and TRF externalizing and TRF total scores among the participants of the study. We did not find any significant associations between WAs and various scales of TRF scores.

Conclusion: These observations reinforce the growing concern regarding the neurotoxicologic effects of WMn in children.

Background

A recently discovered occult HCV entity reported by various investigators seems to be highly controversial. Especially, the clinical significance of these findings remains uncertain. For optimal outcome of antiviral therapy, investigation of occult HCV needs a broad-based probe in order to investigate the results of viral therapy and its host/viral interaction. The current study was aimed at determining the prevalence of occult HCV in peripheral blood lymphocytes of predominantly genotype 3 HCV-infected patients after completion of antiviral therapy and to investigate long term outcomes in the presence or absence of PBMC positivity.

Method

A total of 151 chronic, antiHCV and serum RNA-positive patients were enrolled in the study. Patients with a complete virological response at the end of treatment were screened for the presence of viral RNA in their PBMCs and were followed for up to one year for the presence of serum and PBMC viral genomic RNA.

Results

Out of 151 patients, 104 (70%) responded to the prescribed interferon treatment and showed viral-clearance from serum. These were screened for the presence of genomic RNA in their PBMCs. Sixteen samples were PBMC-positive for viral RNA at the end of treatment (EOT). All these patients had also cleared the virus from peripheral blood cells after the 6-12 month follow-up study.

Conclusion

True occult hepatitis C virus does not exist in our cohort. Residual viremia at the EOT stage merely reflects a difference in viral kinetics in various compartments that remains a target of immune response even after the end of antiviral therapy and is eventually cleared out at the sustained viral response (SVR).