Katrina Wyatt

Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review.

BACKGROUND Selective serotonin-reuptake inhibitors (SSRIs) are increasingly being used as first-line therapy for severe premenstrual syndrome (PMS). We undertook a meta-analysis on the efficacy of SSRIs in this disorder. METHODS We searched medical and scientific databases, approached pharmaceutical companies, and reviewed citations of relevant articles to identify 29 studies of the use of SSRIs in PMS. 14 were excluded (no placebo group, preliminary report of included trial, or low quality). 15 randomised placebo-controlled trials were included. Information on study design, participants, drugs used and dosing regimens, outcome measures, side-effects, and sources of funding was extracted. Standardised mean differences between treatment and placebo groups were calculated to obtain an overall estimate of efficacy. The primary outcome measure was a reduction in overall PMS symptoms. FINDINGS The primary analysis included data on 904 women (570 assigned active treatment and 435 assigned placebo, including 101 in crossover trials). The overall standardised mean difference was -1.066 (95% CI -1.381 to -0.750), which corresponds to an odds ratio of 6.91 (3.90 to 12.2) in favour of SSRIs. SSRIs were effective in treating physical and behavioural symptoms. There was no significant difference in symptom reduction between continuous and intermittent dosing or between trials funded by pharmaceutical companies and those independently funded. Withdrawal due to side-effects was 2.5 times more likely in the active-treatment group than in the placebo group. INTERPRETATION SSRIs are an effective first-line therapy for severe PMS. The safety of these drugs has been demonstrated in trials of affective disorder, and the side-effects at low doses are generally acceptable.

Efficacy of vitamin B-6 in the treatment of premenstrual syndrome:systematic review

Objective: To evaluate the efficacy of vitamin B-6 in the treatment of premenstrual syndrome. Design: Systematic review of published and unpublished randomised placebo controlled trials of the effectiveness of vitamin B-6 in the management of premenstrual syndrome. Subjects: Nine published trials representing 940 patients with premenstrual syndrome. Main outcome measures: Proportion of women whose overall premenstrual symptoms showed an improvement over placebo. A secondary analysis was performed on the proportion of women whose premenstrual depressive symptoms showed an improvement over placebo. Results: Odds ratio relative to placebo for an improvement in overall premenstrual symptoms was 2.32 (95% confidence interval 1.95 to 2.54). Odds ratio relative to placebo for an improvement in depressive symptoms was 1.69 (1.39 to 2.06) from four trials representing 541 patients. Conclusion: Conclusions are limited by the low quality of most of the trials included. Results suggest that doses of vitamin B-6 up to 100 mg/day are likely to be of benefit in treating premenstrual symptoms and premenstrual depression.

Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review

Abstract Objective: To evaluate the efficacy of progesterone and progestogens in the management of premenstrual syndrome. Design: Systematic review of published randomised, placebo controlled trials. Studies reviewed: 10 trials of progesterone therapy (531 women) and four trials of progestogen therapy (378 women). Main outcome measures: Proportion of women whose symptoms showed improvement with progesterone preparations (suppositories and oral micronised). Proportion of women whose symptoms showed improvement with progestogens. Secondary analysis of efficacy of progesterone and progestogens in managing physical and behavioural symptoms. Results: Overall standardised mean difference for all trials that assessed efficacy of progesterone (by both routes of administration) was −0.028 (95% confidence interval −0.017 to −0.040). The odds ratio was 1.05 (1.03 to 1.08) in favour of progesterone, indicating no clinically important difference between progesterone and placebo. For progestogens the overall standardised mean was −0.036 (−0.014 to −0.060), which corresponds to an odds ratio of 1.07 (1.03 to 1.11) showing a statistically, but not clinically, significant improvement for women taking progestogens. Conclusion: The evidence from these meta-analyses does not support the use of progesterone or progestogens in the management of premenstrual syndrome. What is already known on this topic The premenstrual syndrome affects about 1.5 million women in the United Kingdom There are numerous treatment options, progesterone being one of the most strongly advocated Progesterone and progestogens are among the most widely prescribed treatments for premenstrual syndrome in the United Kingdom and the United States What this study adds There is no evidence to support the claimed efficacy of progesterone in the management of premenstrual syndrome There is insufficient evidence to make a definitive statement about progestogens, but current evidence suggests that they are not likely to be effective

Determination of total menstrual blood loss

OBJECTIVE To develop and validate a simple method of measuring total menstrual blood loss using a pictorial representation of blood loss, the menstrual pictogram. DESIGN A prospective evaluation of total menstrual blood loss measurement by the menstrual pictogram compared to the alkaline hematin technique. SETTING Academic menorrhagia research clinic. PATIENT(S) One hundred twenty-one women; 62 women complaining of heavy menstrual blood loss, 59 women who considered their menstrual blood loss to be normal. INTERVENTION(S) Participants were asked to complete the menstrual pictogram through the period and collect their feminine hygiene products for an alkaline hematin assessment. MAIN OUTCOME MEASURE(S) Percentage agreement between blood loss measured by the gold standard alkaline hematin method and the menstrual pictogram. Extraneous blood loss was measured using a semiquantitative pictorial method. RESULT(S) The menstrual pictogram had a high level of agreement for blood collected on feminine hygiene products compared with the alkaline hematin method. Some women also lose a significantly large amount of extraneous blood, which is not proportional to the alkaline hematin blood loss assessment. CONCLUSION(S) The menstrual pictogram provides a simple means of measuring menstrual blood loss. It is no longer appropriate to ignore extraneous blood loss, particularly as there is no correlation between extraneous blood loss and that measured on feminine hygiene products.

The effectiveness of GnRHa with and without ‘add‐back’ therapy in treating premenstrual syndrome: a meta analysis

Objective  To determine the effectiveness of gonadotrophin‐releasing hormone analogues (GnRHa) with and without hormonal add‐back therapy in the management of premenstrual syndrome.

The effectiveness and cost-effectiveness of enzyme and substrate replacement therapies: a longitudinal cohort study of people with lysosomal storage disorders.

OBJECTIVES To determine natural history and estimate effectiveness and cost of enzyme replacement therapy (ERT) and substrate replacement therapy (SRT) for patients with Gaucher disease, Fabry disease, mucopolysaccharidosis type I (MPS I), mucopolysaccharidosis type II (MPS II), Pompe disease and Niemann-Pick type C (NPC) disease. DESIGN Cohort study including prospective and retrospective clinical- and patient-reported data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data. SETTING National Specialised Commissioning Group-designated lysosomal storage disorder (LSD) treatment centres in England. PARTICIPANTS Consenting adults and children with a diagnosis of Gaucher disease (n = 272), Fabry disease (n = 499), MPS I (n = 126), MPS II (n = 58), NPC (n = 58) or Pompe disease (n = 93) who had attended a treatment centre in England. INTERVENTIONS ERT and SRT. MAIN OUTCOME MEASURES Clinical outcomes chosen by clinicians to reflect disease progression for each disorder; patient-reported quality-of-life (QoL) data; cost of treatment and patient-reported service-use data; numbers of hospitalisations, outpatient and general practitioner appointments; medication use; data pertaining to associated family/carer costs and QoL impacts. RESULTS Seven hundred and eleven adults and children were recruited. In those with Gaucher disease (n = 175) ERT was associated with improved platelet count, haemoglobin, liver function and reduced risk of enlarged liver or spleen. No association was found between ERT and QoL. In patients with Fabry disease (n = 311) increased time on ERT was associated with small decreases in left ventricular mass and improved glomerular filtration rate, but not with changes in risk of stroke/transient ischaemic attacks or the need for a hearing aid. There was a statistically significant association between duration of ERT use and worsening QoL and fatigue scores. We found no statistical difference in estimates of treatment effectiveness between the two preparations, agalsidase beta (Fabrazyme(®), Genzyme) (n = 127) and agalsidase alpha (Replagal(®), Shire HGT) (n = 91), licensed for this condition. In Pompe disease (n = 77) our data provide some evidence of a beneficial effect on muscle strength and mobility as measured by a 6-minute walk test in adult-onset patients; there were insufficient data from infantile-onset Pompe patients to estimate associations between ERT and outcome. Among subjects with MPS I (n = 68), 42 of the 43 patients with MPS I subtype Hurlers disease had undergone a bone marrow transplant. No significant associations were found between ERT and any outcome measure for the MPS I subtype Scheie disease and heparan sulphate patients. An association between duration of ERT and growth in children was the only statistically significant finding among patients with MPS II (n = 39). There were insufficient data for patients with NPC disease to draw any conclusions regarding the effectiveness of SRT. The current annual cost to the NHS of the different ERTs means that between 3.6 and 17.9 discounted quality-adjusted life-years (QALYs) for adult patients and between 2.6 and 10.5 discounted QALYs for child patients would need to be generated for each year of being on treatment for ERTs to be considered cost-effective by conventional criteria. CONCLUSIONS These data provide further evidence on the effectiveness of ERT in people with LSDs. However, the results need to be interpreted in light of the fact that the data are observational and the relative lack of power due to the small numbers of patients with MPS I, MPS II, Pompe disease and NPC disease. Future work should aim to effectively address the unanswered questions and this will require agreement on a common set of outcome measures and their consistent collection across all treatment centres. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 39. See the HTA programme website for further project information.

A cost–utility analysis of microwave and thermal balloon endometrial ablation techniques for the treatment of heavy menstrual bleeding

Objective  To assess the cost effectiveness of the second‐generation surgical treatments for heavy menstrual bleeding (microwave and thermal balloon endometrial ablation) compared with existing endometrial ablation techniques (transcervical resection and rollerball, alone or in combination) and hysterectomy.

Values associated with public involvement in health and social care research: a narrative review

Much has been written about public involvement (PI) in health and social care research, but underpinning values are rarely made explicit despite the potential for these to have significant influence on the practice and assessment of PI.

Systematic review of the effectiveness of weight management schemes for the under fives

Overweight and obesity in pre‐school children are an increasing problem, with poor diet and exercise habits laying the foundation for serious health risks in later life. Yet most research into childhood obesity has focused on school‐age children. Two previous systematic reviews of pre‐school children have included uncontrolled designs and self‐report outcomes potentially biasing the results in favour of the interventions. We have conducted a systematic review of the effectiveness and cost‐effectiveness of weight management schemes for the under fives restricting the inclusion criteria to controlled trials with objective measures. We found four effectiveness randomized controlled trials of prevention. No treatment or cost‐effectiveness studies were found. Only one study in a Latino community showed a statistically significant advantage from the intervention in a slower rate of increase in body mass index. However, trends in decrease in body mass index and weight loss favoured the intervention groups in other studies. From the studies characteristics we hypothesize that important features to include in future interventions may be; cultural sensitivity, sustained moderate to vigorous exercise, active engagement of the parents in the programme and as role models of healthy living and active engagement of the children in nutrition education. Further randomized controlled trials are needed in this population.

Evidence, theory and context - using intervention mapping to develop a school-based intervention to prevent obesity in children

BackgroundOnly limited data are available on the development and feasibility piloting of school-based interventions to prevent and reduce obesity in children. Clear documentation of the rationale, process of development and content of such interventions is essential to enable other researchers to understand why interventions succeed or fail.MethodsThis paper describes the development of the Healthy Lifestyles Programme (HeLP), a school-based intervention to prevent obesity in children, through the first 4 steps of the Intervention Mapping protocol (IM). The intervention focuses on the following health behaviours, i) reduction of the consumption of sweetened fizzy drinks, ii) increase in the proportion of healthy snacks consumed and iii) reduction of TV viewing and other screen-based activities, within the context of a wider attempt to improve diet and increase physical activity.ResultsTwo phases of pilot work demonstrated that the intervention was acceptable and feasible for schools, children and their families and suggested areas for further refinement. Feedback from the first pilot phase suggested that the 9-10 year olds were both receptive to the messages and more able and willing to translate them into possible behaviour changes than older or younger children and engaged their families to the greatest extent. Performance objectives were mapped onto 3 three broad domains of behaviour change objectives - establish motivation, take action and stay motivated - in order to create an intervention that supports and enables behaviour change. Activities include whole school assemblies, parents evenings, sport/dance workshops, classroom based education lessons, interactive drama workshops and goal setting and runs over three school terms.ConclusionThe Intervention Mapping protocol was a useful tool in developing a feasible, theory based intervention aimed at motivating children and their families to make small sustainable changes to their eating and activity behaviours. Although the process was time consuming, this systematic approach ensures that the behaviour change techniques and delivery methods link directly to the Programmes performance objectives and their associated determinants. This in turn provides a clear framework for process analysis and increases the potential of the intervention to realise the desired outcome of preventing and reducing obesity in children.