Recent Cochrane Systematic Review Research Articles

O-005 The ToF-study - comparing the cumulative live birth rate of blastocyst-stage versus cleavage-stage embryo transfers in good prognosis IVF patients: a multicenter randomized controlled trial.

Abstract Study question Does blastocyst-stage embryo transfer in fresh and frozen cycles improve the cumulative live birth rate (cLBR) compared with cleavage-stage embryo transfer in IVF/ICSI treatments? Summary answer In good prognosis IVF patients (≥4 available embryos), a blastocyst-stage transfer policy did not result in a significant higher cLBR compared to cleavage-stage transfer policy. What is known already A recent Cochrane systematic review and meta-analysis concluded that fresh blastocyst-stage transfer in IVF/ICSI treatments is associated with higher rates of pregnancy in comparison to fresh transfer of cleavage-stage embryos. However, it is unknown whether a blastocyst-transfer policy also improves the cumulative live birth rate, i.e. the live birth rate derived from fresh and frozen-thawed embryo transfers following a single oocyte retrieval, in comparison to a cleavage-stage transfer policy in IVF/ICSI. Study design, size, duration In this multicenter randomized controlled trial women were randomly allocated to blastocyst-stage transfers (blastocyst group - fresh embryo transfer on day 5 after oocyte retrieval followed by vitrification of remnant blastocysts on day 5 and 6 following local criteria) or cleavage-stage transfers (cleavage-stage group - fresh embryo transfer on day 3 after oocyte retrieval followed by embryo cryopreservation on day 3 or 4). Randomization was stratified for age (≥36 or < 36 years). Participants/materials, setting, methods Women with a good prognosis after IVF/ICSI (defined as presenting ≥4 available embryos on day 2 of embryo culture), during their first, second, or third treatment cycle, were included. The primary outcome was the cLBR per oocyte retrieval, including associated frozen-thawed embryo transfers within 12 months after randomization (or 17 months during the COVID pandemic). Risk ratios (RR) with 95% CI adjusted for age group were calculated using log-linear binominal regression. Main results and the role of chance A total of 1202 women from 21 Dutch centers were randomly assigned to blastocyst-stage transfers (N = 599) or cleavage stage transfers (N = 603) between 2018 and 2021. At submission of this abstract, data on the primary outcome was available for 1153 (95.9%) women, 577 women in the blastocyst-stage group and 576 women in the cleavage-stage group. The cumulative live birth rate was 58.2% (336/577 women) in the blastocyst-stage group and 57.3% (330/576 women) in the cleavage stage group (RR 1.022, 95% CI 0.844-1.237; p = 0.825). The live birth rate after fresh embryo transfer was 38.0% (219/577 women) versus 29.9% (172/576 women) in the blastocyst-stage group and cleavage-stage group respectively (RR 1.282, 95% CI 1.017-1.615 p = 0.035). Interaction was found between age and day of transfer with a higher cumulative live birth rate and a higher live birth rate after fresh transfer in women of 36 years or older in the blastocyst group. Analyses on other IVF treatment outcomes, obstetrical or neonatal outcomes, patient burden, and cost effectiveness are ongoing. Limitations, reasons for caution Outcomes are only applicable for treatments of women with at least four embryos available on day two of embryo culture. Wider implications of the findings A blastocyst-stage embryo transfer policy did not result in a significant higher cumulative live birth rate in comparison to a cleavage-stage embryo transfer policy in IVF/ICSI treatments. Further research into the interaction of age with outcomes is warranted. Trial registration number NTR7034

Telerehabilitation Training to Facilitate Improved Reading Ability with New Magnification Devices for Low Vision.

This pilot study provides some insight about the potential benefits of telerehabilitation training to improve the reading ability of adults with low vision using magnifiers, to spur future work with larger groups. Telerehabilitation services can be implemented clinically to facilitate access to follow-up care for low vision. A recent Cochrane systematic review revealed that there are no published visual function outcomes for telerehabilitation with handheld magnification devices for low vision; thus, this study aimed to provide evidence for its preliminary efficacy. One to 4 months after receiving a new magnification device (i.e., handheld or stand optical magnifier or portable electronic magnifier), 14 adult low vision patients (with any visual acuity level or ocular diagnosis) received two training sessions at home via telerehabilitation with their vision rehabilitation provider located remotely in-office. Telerehabilitation included a loaner smartphone for Zoom videoconferencing with remote control access software. The Minnesota Low-Vision Reading Test was administered during each of the telerehabilitation sessions to assess near reading (acuity and speed) with the new magnifier. Mean reading acuity with the magnifier was 0.17 logMAR across subjects before training at telerehabilitation session 1, which significantly improved to 0.09 on average a few weeks later at telerehabilitation session 2 (95%confidence interval, -0.001 to -0.16; P = .047). Logarithm reading speed with the magnifier for the reading acuity level at session 1 improved significantly by 0.18 log words per minute on average for the same text size at session 2 (95% confidence interval, 0.06 to 0.29; P = .002). With the magnifier at session 2, 71% of participants gained at least 0.1 log unit in reading acuity, and half improved by >0.01 in log reading speed; all participants with increased reading speed also improved in reading acuity ( P = .02). These preliminary data support that telerehabilitation can enhance reading ability and efficiency with newly prescribed magnifiers as an alternative option to in-office vision rehabilitation.

P-159 The role of Embryo transfer medium containing high concentrations of hyaluronic acid on IVF outcome: A systematic review and meta-analysis

Abstract Study question Does embryo transfer medium containing high concentrations of hyaluronic acid (HA) increase In Vitro Fertilisation (IVF) success rate? Summary answer Embryo transfer medium containing high concentration of HA has increased the live birth (LBR) and clinical pregnancy rate (CPR) whilst decreasing the miscarriage rate. What is known already The recent Cochrane systematic review reported low to moderate evidence to support the use of high concentration hyaluronic acid (HA) in the treatment group. Previous studies have also shown no effect of high concentration HA on frozen embryo transfer (FET) rate and have identified the supplementation of the transfer media with HA to have no significance on adverse effect rate. Study design, size, duration A literature search was performed on three online databases: Ovid Medline, PsychInfo and Central Cochrane. 1162 citations were retrieved and after screening abstracts and titles 1099 citations were removed and a following 37 removed after screening full texts. This left 26 publications for the review. Bias was assessed for in RCTs using Cochrane collaboration tool of bias and STROBE for observational studies. Meta-analysis was performed using Review manager identifying the risk ratio (RR) and heterogeneity. Participants/materials, setting, methods In the review, 6304 participants in the treatment group and, 5965 in the control group were included. The primary outcomes was LBR and secondary outcomes were CPR; miscarriage rate; multiple pregnancy rate; ectopic pregnancy and congenital abnormalities. A subgroup analysis was performed looking into the outcome based on the stage of embryos transferred, the exposure time to the transfer medium and difference between frozen and fresh embryo transfer. Main results and the role of chance There was a significant increase in LBR (RR: 1.25; 95% CI 1.17 to 1.33) with use of high concentration HA and this positive effect was seen in both cleavage stage and blastocyst transfer cycles. CPR was also higher (RR: 1.16 (95% CI 1.10 to 1.22), while Miscarriage rate was significantly reduced (RR: 0.75; 95% CI 0.66 to 0.85) in the treatment group. Multiple pregnancy rate were higher in the study group (RR: 1.33; 95% CI: 1.16 to 1.53), although one study had a large influence on these results. The ectopic pregnancy rates (RR: 0.62; 95% CI 0.19 to 1.99) and congenital abnormalities (RR: 0.84; 95% CI 0.37 to 1.92) were similar. On subgroup analysis, the higher LBR was seen only for fresh cycles (RR: 1.2; 95% CI 1.1 to 1.3) but were similar for frozen embryo transfer (RR: 0.99; 95% CI 0.8 to 1.24). Further, LBR were higher in both short (10 minutes) and long exposure (>10 minutes) groups (RR: 1.32; 95% CI 1.19 to 1.45 and RR: 1.23; 95% CI 1.14 to 1.33 respectively. Limitations, reasons for caution The high heterogeneity across the studies may increase the risk of bias in the results. Inclusion of observational studies also has an inherent risk of selection bias. The review did not have a restrictive exclusion criterion resulting in inclusion of patients from a large demographic, limiting the specificity of results. Wider implications of the findings The data from this review support the use of embryo transfer medium containing high concentration of HA during fresh IVF cycles but not for frozen cycles. However, a large RCT is warranted particularly for selected groups like women of advanced maternal age and those with recurrent implantation failure. Trial registration number Not applicable

Dimethylarginines in Children after Anti-Neoplastic Treatment.

Background and Objectives: According to a recent Cochrane systematic review, renal impairment can develop in 0–84% of childhood cancer survivors in the future. The renal function impairment in this patient group can be related to nephrectomy, nephrotoxic agents therapy, abdominal radiotherapy, and combinations of these treatment methods. In this study, in a population of patients after anti-neoplastic therapy, with particular emphasis on patients after Wilms’ tumour treatment, we compared new substances which play role in the chronic kidney disease (CKD) pathogenesis (asymmetric dimethylarginine—ADMA, symmetric dimethylarginine—SDMA) with standard renal function markers (e.g., creatinine and cystatin C in serum, creatinine in urine, etc.) to assess the usefulness of the former. Materials and Methods: Eighty-four children, without CKD, bilateral kidney tumours, congenital kidney defects, or urinary tract infections, with a minimum time of 1 year after ending anti-neoplastic treatment, aged between 17 and 215 months, were divided into three groups: group 1—patients after nephroblastoma treatment (n = 21), group 2—after other solid tumours treatment (n = 44), and group 3—after lymphoproliferative neoplasms treatment (n = 19). The patients’ medical histories were taken and physical examinations were performed. Concentrations of blood urea nitrogen (BUN), creatinine, cystatin C, C-reactive protein (CRP), ADMA, and SDMA in blood and albumin in urine were measured, and a general urine analysis was performed. The SDMA/ADMA ratio, albumin–creatine ratio, and estimated glomerular filtration rate (eGFR) were calculated. eGFR was estimated by three equations recommended to the paediatric population by the KDIGO from 2012: the Schwartz equation (eGFR1), equation with creatinine and urea nitrogen (eGFR2), and equation with cystatin C (eGFR3). Results: Both the eGFR1 and eGFR2 values were significantly lower in group 1 than in group 3 (eGFR1: 93.3 (83.1–102.3) vs. 116.5 (96.8–126.9) mL/min/1.73 m2, p = 0.02; eGFR2: 82.7 (±14.4) vs. 94.4 (±11.9) mL/min/1.73 m2, p = 0.02). Additionally, there were weak positive correlations between SDMA and creatinine (p < 0.05, r = 0.24), and cystatin C (p < 0.05, r = 0.32) and weak negative correlations between SDMA and eGFR1 (p < 0.05, r = −0.25), eGFR2 (p < 0.05, r = −0.24), and eGFR3 (p < 0.05, r = −0.32). Conclusions: The usefulness of ADMA and SDMA in the diagnosis of renal functional impairment should be assessed in further studies. eGFR, calculated according to equations recommended for children, should be used in routine paediatric practice.

Is there still a place for methotrexate in severe psoriatic arthritis?

The management of psoriatic arthritis (PsA) has long been equated with that of rheumatoid arthritis (RA), particularly because methotrexate (MTX) was found efficient in RA in the 1990s. However, results of collective evidence-based medicine, included and argued in this narrative review, do not currently support the use of MTX as first-line therapy in severe PsA. A recent Cochrane systematic review examining the efficacy of MTX in PsA concluded that low-dose MTX was only slightly more effective than placebo. Questions about a structural effect of MTX in PsA remains non-elucidated. Even if tolerance data on MTX are more consensual and adverse events generally non-severe, subjective side effects such as fatigue might lead to MTX withdrawal based on the patient’s decision. PsA patients with axial disease, radiographic lesions, and extensive and disabling skin or joint involvement should receive early treatment with targeted therapy and no longer with MTX. Finally, the usefulness of MTX combined with targeted therapies is limited. MTX does not affect efficacy but only seems to increase the therapeutic maintenance of monoclonal TNF inhibitors. This narrative review may help clarify the place of MTX in PsA management. It allows for reflection on the evolution of current concepts and practices.

Group-based pelvic floor muscle training for all women during pregnancy is more cost-effective than postnatal training for women with urinary incontinence: cost-effectiveness analysis of a systematic review

What is the most cost-effective way of providing pelvic floor muscle training (PFMT) to prevent or treat postpartum incontinence? Meta-analysis and cost-effectiveness analysis of models of care included in a recent Cochrane systematic review. Pregnant and postnatal women. Supervised PFMT for preventing or treating urinary and/or faecal incontinence. Postpartum urinary or faecal incontinence. We examined the comparative incremental cost effectiveness of different approaches to successfully prevent or cure one case of incontinence. Costs were valued in Australian dollars using publicly available market rates and enterprise agreements as of 2019. Comparisons involving group-based treatment approaches were subject to sensitivity analyses where the numbers of patients attending each group were varied to identify thresholds where recommendations change. Seventeen trials were included for meta-analysis. Three models of care were clinically effective: individually supervised PFMT during pregnancy to prevent urinary incontinence (Model 1), group-based PFMT during pregnancy to prevent or treat urinary incontinence (Model 2) and individually supervised postnatal PFMT to treat urinary incontinence and prevent or treat faecal incontinence (Model 3). The health service costs per urinary incontinence case prevented or cured were $768 for Model 1, and $1,970 for Model 3. However, Model 2 generated a cost saving of $14 if there were eight participants per session, with greater savings if more participants attend. The health service cost per faecal incontinence case prevented or cured was $2,784 (Model 3). Providing group-based PFMT for all women during pregnancy is likely more efficient than individual PFMT for incontinent women postnatally; however, providing PFMT for postnatal women with urinary incontinence should not be discounted because of the added known benefit for preventing and treating faecal incontinence.

Yoga for the primary prevention of cardiovascular disease: Summary of a Cochrane review

This column is one of a series published periodically in EXPLORE on recent Cochrane systematic reviews. Cochrane is an international non-profit organization that prepares systematic reviews of randomized controlled trials of a wide range of interventions. The Cochrane Complementary Medicine Field, which coordinates this column, is a group within Cochrane that is dedicated to facilitating the production and dissemination of Cochrane systematic reviews focused on complementary, alternative, and integrative medicine interventions. The Field is supported by the National Center for Complementary & Integrative Health of the National Institutes of Health under award number R24AT001293. For additional information on Cochrane and the Cochrane Complementary Medicine Field please contact L. Susan Wieland, PhD at swieland@som.umaryland.com.

Prophylactic Antibiotics in Cirrhotic Patients With Upper Gastrointestinal Bleeding.

Cirrhotic patients often develop bleeding from gastric or esophageal varices that occur secondary to portal hypertension. Gastrointestinal (GI) bleeding is fatal in approximately 20% of these episodes and bacterial infections are an important contributor to this mortality. Patients with cirrhosis are also known to have impaired immune function and also at higher risk of translocation of bacteria from the gut into the bloodstream.1 Therefore, the administration of prophylactic antibiotics during the bleeding event might help prevent such infections.

Molluscum Contagiosum

ABSTRACT Molluscum contagiosum (MC) is a common dermatology condition affecting the worldwide population. MC is caused by the MC virus, a member of the Poxviridae family. The virus predominantly affects children, sexually active adolescents and young adults, individuals involved in contact sports, and immunocompromised individuals. The condition is self-limited and will eventually clear spontaneously without treatment. Many individuals do elect treatment, and management strategies are discussed along with potential side effects. Selected treatment outcomes printed in a recent Cochrane systematic review are summarized.

Oral magnesium supplementation for leg cramps in pregnancy-An observational controlled trial.

Oral magnesium for leg cramps treatment in pregnancy is a controversial issue according to recent Cochrane systematic review. This study aims to evaluate the efficacy of Mg++ supplementation in leg cramps treatment in pregnancy. This observational clinical trial studied 132 pregnant women with leg cramps in the first trimester of pregnancy. At baseline, 74 (56.3%) had two leg cramps episodes per week, 28 (21.1%) three episodes, 13 (9.8%) four episodes and 9 (6.8%) five or more episodes. They were randomized 1:1 to 300 mg/day of oral Mg++ citrate (n = 66) or placebo (n = 66). The primary outcome was the frequency of leg cramps episodes per week reported by pregnant women. Secondary outcomes were the ocurrence of leg cramps and oral magnesium side effects. 130 pregnant women completed the study and the two groups were comparable according to some sociodemographic and clinical characteristics. After 4 weeks of intervention it was observed a 28.4% (39/132) (CI 95%: 20.9-37.0) reduction of leg cramps in all participants and no difference between the two groups was found; reduction of 27.2% (18/66) (CI 95%: 17.0-39.6) in Mg++ group and 32.8% (21/66) (CI 95%: 21.6-45.7) in the placebo group. The OR of leg cramps was 1.3 (CI 95%: 0.6-2.9), p = 0.527, taking the placebo group as reference. Among pregnant women who remained with leg cramps the mean of leg cramps episodes per week showed no significance difference between the Mg++ and placebo groups; t-student test: p = 0.408. Four pregnant women showed gastrointestinal side effects; 2 in each group had nauseas and diarrhoea. Oral magnesium supplementation during pregnancy did not reduce the ocurrence and frequency of episodes of leg cramps.

Optimising the Management of Late Term Pregnancies: Inconclusive Evidence and High Induction Rates Affect Quality of Care for Women

(BMJ. 2019;364:1681) Most pregnant women want clear and accurate evidence-based information to help them make decisions about their labor and delivery experience. When confronted with a “postterm” pregnancy, which poses increased risks for women and their babies, this information is especially important. A recent Cochrane systematic review reported that induction at or beyond the due date was associated with fewer perinatal deaths, neonatal admissions to intensive care, and cesarean sections but more operative vaginal births when compared with expectant management. This editorial discussed previous studies and the current study by Keulen and colleagues.

Identifying Effective Behavior Change Techniques for Alcohol and Illicit Substance Use During Pregnancy: A Systematic Review.

BackgroundDuring pregnancy, consuming alcohol and using illicit drugs can have serious health implications for both mother and child. Behavioral change interventions, especially those underpinned by theoretical constructs, can be effective in reducing harmful substance use among pregnant women.PurposeTo understand what type of behavior change mechanisms could be useful in reducing alcohol consumption or achieving abstinence from illicit drug use during pregnancy, this review aimed to identify behavior change techniques (BCTs), the smallest, active components of interventions that may be effective. It also aimed to establish the extent that psychosocial-based theories were used to inform intervention design.MethodsTo identify eligible randomized controlled trials (RCTs), five databases were searched electronically from the end search dates of the most recent Cochrane systematic reviews on behavioral interventions for each behavior, until March 2018. Within the RCTs, intervention descriptions were analyzed for BCT content and extent of theory use in the intervention design process and outcome measurements, in each trial, was established. “Effectiveness percentages,” the number of times a BCT had been a component of an effective intervention divided by the total number of interventions it had been used in, were calculated for BCTs used in two or more trials.ResultsIncluding all RCTs from the Cochrane reviews, and those published subsequently, nine alcohol and six illicit drug trials were identified. Interventions tested in four alcohol RCTs and no illicit drugs RCTs showed positive results. Subsequent data were extracted for alcohol consumption trials only. Thirteen BCTs showed “potential effectiveness” for alcohol consumption. Six of nine included alcohol trials reported using theory but not extensively.ConclusionsAction planning, behavioral contract, prompts/cues, self-talk, offer/direct toward written material, problem solving, feedback on behavior, social support (unspecified), information about health consequences, behavior substitution, assess current readiness and ability to reduce excess alcohol consumption, goal setting (behavior), and tailor interactions appropriately are BCTs that could be useful in helping reduce alcohol consumption among pregnant women.

A critical appraisal of gabapentinoids for pain in cancer patients.

Gabapentinoids are frequently used in the management of cancer pain. In recent Cochrane systematic reviews, although there was an abundance of evidence relating to non-cancer pain, only a few studies related to cancer pain. This review summarizes recent randomised controlled trials (RCTs) evaluating the use of gabapentinoids for tumour-related (as monotherapy or part of combination therapy) and treatment-related pain. For tumour-related pain, ten out of thirteen studies showed statistically significant benefits in favour of gabapentinoids. When used, as part of monotherapy or combination therapy, benefits were observed in five out of six studies evaluating gabapentin, and in six out of eight studies evaluating pregabalin. For treatment-related pain, none of the four studies (two gabapentin, two pregabalin) showed statistically significant benefits in favour of gabapentinoids. Unfortunately, many of the studies included were limited by small sample size, lack of blinding, and inadequate follow-up. More and better quality studies are required, although it may be challenging to accomplish in this patient population. Gabapentinoids may offer benefits to cancer patients with pain, but careful titration and monitoring of adverse effects is necessary.

Pulmonary rehabilitation in patients with an acute exacerbation of chronic obstructive pulmonary disease.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are one of the most common causes of emergency hospital admission and place great burden upon healthcare systems. Furthermore, AECOPD represent an important life event for patients, and are associated with significant reductions in physical activity, skeletal muscle function, exercise tolerance and health-related quality of life. Pulmonary rehabilitation, an intervention comprising supervised exercise-training and education, may counteract these negative consequences and target modifiable risk factors for hospital readmission. A recent Cochrane systematic review included 20 randomized controlled trials comparing pulmonary rehabilitation after exacerbation of COPD versus conventional care. Overall, the evidence supports moderate to large effects on health-related quality of life and exercise capacity. However, there is substantial heterogeneity across studies, and more recent studies have been more equivocal, including around hospital readmissions, particularly when rehabilitation is started in the inpatient setting. In this narrative review, we examine the rationale for pulmonary rehabilitation following AECOPD with a particular focus on skeletal muscle function, review the current evidence for pulmonary rehabilitation in the AECOPD setting, and identify areas that require future research, including the structure and nature of the intervention, improving uptake and adherence, and the role of alternative rehabilitation strategies for patients with AECOPD.

Making Sense of Data Analytic Techniques used in a Cochrane Systematic Review

Systematic reviews have developed over the past 40 years as a method for integrating findings from the available studies relating to clinical problems and interventions into one publication. Systematic reviews employ a variety of data analytic techniques including meta-analysis, which combines treatment effects across disparate studies in order to produce a truer estimate of treatment effect. The Cochrane Collaboration was established in order to facilitate access to high-quality evidence and specifies stringent guidelines for the production of systematic reviews. A Cochrane Systematic Review (CSR) includes consideration of the risk-of-bias of the selected studies in reaching conclusions. A recent CSR is used as an example to demonstrate the process of conducting a CSR, the data analytic methods employed and the assumptions made when employing these methods. There is a discussion of issues the reader will need to be aware of when considering the findings of a CSR and how this might differ from other systematic reviews including some consideration of how CSRs apply to the brain impairment literature.

The Health Promoting Schools Framework: Known Unknowns and an Agenda for Future Research.

The World Health Organization's Health Promoting Schools (HPS) framework is a whole-school approach to promoting health that recognizes the intrinsic relationship between health and education. Our recent Cochrane systematic review found HPS interventions produced improvements in a number of student health outcomes. Here we reflect on what this review was not able to tell us: in other words, what evidence is missing with regard to the HPS approach. Few HPS interventions engage with schools' "core business" by examining impacts on educational outcomes. Current evidence is dominated by obesity interventions, with most studies conducted with children rather than adolescents. Evidence is lacking for outcomes such as mental or sexual health, substance use, and violence. Activities to engage families and communities are currently weak and unlikely to prompt behavioral change. The HPS approach is largely absent in low-income settings, despite its potential in meeting children's basic health needs. Intervention theories are insufficiently complex, often ignoring upstream determinants of health. Few studies provide evidence on intervention sustainability or cost-effectiveness, nor in-depth contextual or process data. We set out an agenda for future school health promotion research, considering implications for key stakeholders, namely, national governments, research funders, academics, and schools.

Factors that impact on the use of mechanical ventilation weaning protocols in critically ill adults and children: a qualitative evidence-synthesis.

Factors that impact on the use of mechanical ventilation weaning protocols in critically ill adults and children: a qualitative evidence-synthesis.

Complexities and Perplexities: A Critical Appraisal of the Evidence for Soil-Transmitted Helminth Infection-Related Morbidity.

Background: Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative evidence is required to justify large-scale deworming programmes. A recent Cochrane systematic review, which influences Global Burden of Disease (GBD) estimates for STH, has again called into question the evidence for deworming benefit on morbidity due to STH. In this narrative review, we investigate in detail what the shortfalls in evidence are. Methodology/Principal Findings: We systematically reviewed recent literature that used direct measures to investigate morbidity from STH and we critically appraised systematic reviews, particularly the most recent Cochrane systematic review investigating deworming impact on morbidity. We included six systematic reviews and meta-analyses, 36 literature reviews, 44 experimental or observational studies, and five case series. We highlight where evidence is insufficient and where research needs to be directed to strengthen morbidity evidence, ideally to prove benefits of deworming. Conclusions/Significance: Overall, the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. Urgent investment in studies powered to detect direct morbidity effects due to STH is required.

Prevention of postpartum haemorrhage: cost consequences analysis of misoprostol in low-resource settings.

BackgroundWhile inferior to oxytocin injection in both efficacy and safety, orally administered misoprostol has been included in the World Health Organization Model List of Essential Medicines for use in the prevention of postpartum haemorrhage (PPH) in low-resource settings. This study evaluates the costs and health outcomes of use of oral misoprostol to prevent PPH in settings where injectable uterotonics are not available.MethodsA cost-consequences analysis was conducted from the international health system perspective, using data from a recent Cochrane systematic review and WHO’s Mother-Baby Package Costing Spreadsheet in a hypothetical cohort of 1000 births in a mixed hospital (40 % births)/community setting (60 % births). Costs were estimated based on 2012 US dollars.ResultsUsing oxytocin in the hospital setting and misoprostol in the community setting in a cohort of 1000 births, instead of oxytocin (hospital setting) and no treatment (community setting), 22 cases of PPH could be prevented. Six fewer women would require additional uterotonics and four fewer women a blood transfusion. An additional 130 women would experience shivering and an extra 42 women fever. Oxytocin/misoprostol was found to be cost saving (US$320) compared to oxytocin/no treatment.If misoprostol is used in both the hospital and community setting compared with no treatment (i.e. oxytocin not available in the hospital setting), 37 cases of PPH could be prevented; ten fewer women would require additional uterotonics; and six fewer women a blood transfusion. An additional 217 women would experience shivering and 70 fever. The cost savings would be US$533.Sensitivity analyses indicate that the results are sensitive to the incidence of PPH-related outcomes, drug costs and the proportion of hospital births.ConclusionsOur findings confirm that, even though misoprostol is not the optimum choice in the prevention of PPH, misoprostol could be an effective and cost-saving choice where oxytocin is not or cannot be used due to a lack of skilled birth attendants, inadequate transport and storage facilities or where a quality assured oxytocin product is not available. These benefits need to be weighed against the large number of additional side effects such as shivering and fever, which have been described as tolerable and of short duration.

Triamterene in the Treatment of Hypertension: More Than Just Potassium Sparing?

H ypertension is the most commonly encountered chronic medical condition in primary care practice and is a major risk factor for stroke and coronary artery disease. For decades, thiazide diuretics have been a recommended first line option for antihypertensive therapy. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended thiazides as first line therapy unless a compelling indication existed for another agent. JNC-8 recommends diuretics as one of four acceptable first line options for non-black patients without chronic kidney disease (other options include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, or calcium channel blockers), and as one of two acceptable options for African American patients without chronic kidney disease (the other option is calcium channel blockers). Hypokalemia frequently results from the administration of thiazide diuretics. This effect is more common with chlorthalidone than hydrochlorothiazide (HCTZ) or indapamide, and occurs in a dose dependent fashion. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), one of the largest trials of antihypertensive therapy (n=33,357), mean potassium levels at 4 years fell 0.2 mEq/L among chlorthalidone treated patients, and potassium fell below 3.5 mEq/L in 8.5% of patients at 4 years (as opposed to 1.9 % of amlodipine treated patients). Hypokalemia, when it occurs, usually appears within the first 2 weeks after initiating diuretic therapy. If hypokalemia occurs, clinicians have the option of beginning potassium chloride replacement therapy (typical doses are 20–40 mEq per day for patients with normal renal function), or beginning a potassium sparing diuretic. Potassium sparing diuretics include triamterene and amiloride (epithelial sodium channel inhibitors) and spironolactone and eplerenone (mineralocorticoid receptor antagonists). The choice of potassium replacement or a potassium-sparing diuretic has been typically left to the discretion of the clinician, as no evidence has suggested that the addition of potassium-sparing diuretics provides additional value in terms of blood pressure lowering or a reduction in cardiovascular events. From the patient perspective, a disadvantage of potassium replacement is the requirement to add either large pills that are often difficult to swallow, or a salty tasting solution to the thiazide. No studies exist of triamterene as monotherapy for the treatment of hypertension. In a recent Cochrane systematic review, authors evaluated the blood pressure lowering effect of potassium-sparing diuretics that block the epithelial sodium channel when given in combination with another antihypertensive agent. Only six trials of 496 patients existed; all six studies were performed in the 1980s. Two trials (n=211) evaluated the incremental benefit of triamterene 50mg per day when added to chlorthalidone at 25 to 50 mg per day. The addition of triamterene provided no incremental reduction in systolic blood pressure (−0.01, 95 % CI −3.63 to 3.61), or diastolic blood pressure (+0.20, 95 % CI −2.01 to 2.41), but total sample sizes were too small to draw any meaningful conclusions. In this issue of JGIM, Tu and colleagues queried a large network electronic medical record system to determine the incremental blood pressure lowering effect of triamterene. They identified 17,291 patients with a diagnosis of hypertension over an 8-year period and divided these patients into those with and without a pharmacy claim for triamterene. Patients who received triamterene were more likely to be female or African American, and less likely to have diabetes, coronary artery disease, congestive heart failure, a history of stroke, or chronic obstructive pulmonary disease. A direct comparison of the blood pressure values in these two groups would be confounded by substantial selection bias due to the nonrandom assignment between the groups. Tu et al. used a novel approach to attempt to correct for limitations inherent in these observational data. They used propensity score matching to estimate the probability that a patient would receive a particular treatment, based on logistic regression that adjusted for 14 clinical characteristics. They then stratified patients into quartiles of estimated propensity and compared the recorded blood pressures for those who had or had not received triamterene. They evaluated separately the impact of adding triamterene to HCTZ or to combinations of drugs that included HCTZ. They present no data on chlorthalidone use; in their network, triamterene was most commonly prescribed as a fixed combination pill with HCTZ (initial dose was HCTZ 25 mg daily and triamterene 37.5 mg daily). Published online September 18, 2015