Treatment selection in multi-arm multi-stage designs: With application to a postpartum haemorrhage trial

Background: Multi-arm multi-stage trials are an efficient, adaptive approach for testing many treatments simultaneously within one protocol. In settings where numbers of patients available to be entered into trials and resources might be limited, such as primary postpartum haemorrhage, it may be necessary to select a pre-specified subset of arms at interim stages even if they are all showing some promise against the control arm. This will put a limit on the maximum number of patients required and reduce the associated costs. Motivated by the World Health Organization Refractory HaEmorrhage Devices trial in postpartum haemorrhage, we explored the properties of such a selection design in a randomised phase III setting and compared it with other alternatives. The objectives are: (1) to investigate how the timing of treatment selection affects the operating characteristics; (2) to explore the use of an information-rich (continuous) intermediate outcome to select the best-performing arm, out of four treatment arms, compared with using the primary (binary) outcome for selection at the interim stage; and (3) to identify factors that can affect the efficiency of the design. / Methods: We conducted simulations based on the refractory haemorrhage devices multi-arm multi-stage selection trial to investigate the impact of the timing of treatment selection and applying an adaptive allocation ratio on the probability of correct selection, overall power and familywise type I error rate. Simulations were also conducted to explore how other design parameters will affect both the maximum sample size and trial timelines. / Results: The results indicate that the overall power of the trial is bounded by the probability of ‘correct’ selection at the selection stage. The results showed that good operating characteristics are achieved if the treatment selection is conducted at around 17% of information time. Our results also showed that although randomising more patients to research arms before selection will increase the probability of selecting correctly, this will not increase the overall efficiency of the (selection) design compared with the fixed allocation ratio of 1:1 to all arms throughout. / Conclusions: Multi-arm multi-stage selection designs are efficient and flexible with desirable operating characteristics. We give guidance on many aspects of these designs including selecting the intermediate outcome measure, the timing of treatment selection, and choosing the operating characteristics

Perceived Barriers to Regular Class Attendance of BCommH Students in University of Community Health, Magway

Education is essential not only for every citizen to survive in dignity but also for nation building. In any education settings, students’ regular class attendance plays a vital role for obtaining good academic achievements. A cross-sectional analytic study was conducted among BCommH students (n=410) of University of Community Health, Magway from October to December 2017 using a mixed method with objectives of exploring their perceived barriers of regular class attendance and possible solutions. Data collected by pretested semi-structured questionnaires were entered into computers and analysed by SPSS software version 18.0 with a significant level of 0.05. Qualitative data were assessed by content analysis. Significant findings related to irregular class attendance were level of previous class [OR = 3.08 (95% CI: 1.6 – 5.91) (p < 0.005)], monthly financial aid from family of MMK 100,000 or more [OR = 2.24 (95% CI: 1.29 – 3.86) (p = 0.003)], travelling pattern to and from campus by other means [OR = 7.76 (95% CI: 2.13 – 28.21) (p < 0.005)] and lunch taking pattern in week days [OR = 1.91 (95% CI: 1.13 – 3.23) (p < 0.025)]. Among the perceived barriers most of students (82.2%) stated illness as a barrier followed by being busy with preparation for examinations (46.4%), getting up late from bed in the morning (41.1%) and lecture room with high indoor temperature (40.5%). In in-depth interviews, students mentioned the reasons of missing classes as weakness in teaching system, their socio-behavioral factors and poor class room conditions. In conclusion the present study unearthed the various perceived barriers and these barriers should be removed by appropriate means including intensive oversight of faculty and staff on the students, reinforced with introduction of time management concepts into curriculum and making teaching learning environment more friendly to and happy for students, leading to more regular attendance among the students finally to achieve their high academic grades

Outcomes after angiography with sodium bicarbonate and acetylcysteine

Background: Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. Methods: Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. Results: The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. Conclusions: Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466.

Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016.

OBJECTIVE: To generate estimates of the global prevalence and incidence of urogenital infection with chlamydia, gonorrhoea, trichomoniasis and syphilis in women and men, aged 15-49 years, in 2016. METHODS: For chlamydia, gonorrhoea and trichomoniasis, we systematically searched for studies conducted between 2009 and 2016 reporting prevalence. We also consulted regional experts. To generate estimates, we used Bayesian meta-analysis. For syphilis, we aggregated the national estimates generated by using Spectrum-STI. FINDINGS: For chlamydia, gonorrhoea and/or trichomoniasis, 130 studies were eligible. For syphilis, the Spectrum-STI database contained 978 data points for the same period. The 2016 global prevalence estimates in women were: chlamydia 3.8% (95% uncertainty interval, UI: 3.3-4.5); gonorrhoea 0.9% (95% UI: 0.7-1.1); trichomoniasis 5.3% (95% UI:4.0-7.2); and syphilis 0.5% (95% UI: 0.4-0.6). In men prevalence estimates were: chlamydia 2.7% (95% UI: 1.9-3.7); gonorrhoea 0.7% (95% UI: 0.5-1.1); trichomoniasis 0.6% (95% UI: 0.4-0.9); and syphilis 0.5% (95% UI: 0.4-0.6). Total estimated incident cases were 376.4 million: 127.2 million (95% UI: 95.1-165.9 million) chlamydia cases; 86.9 million (95% UI: 58.6-123.4 million) gonorrhoea cases; 156.0 million (95% UI: 103.4-231.2 million) trichomoniasis cases; and 6.3 million (95% UI: 5.5-7.1 million) syphilis cases. CONCLUSION: Global estimates of prevalence and incidence of these four curable sexually transmitted infections remain high. The study highlights the need to expand data collection efforts at country level and provides an initial baseline for monitoring progress of the World Health Organization global health sector strategy on sexually transmitted infections 2016-2021

Automated inter-rater reliability assessment and electronic data collection in a multi-center breast cancer study

<p>Abstract</p> <p>Background</p> <p>The choice between paper data collection methods and electronic data collection (EDC) methods has become a key question for clinical researchers. There remains a need to examine potential benefits, efficiencies, and innovations associated with an EDC system in a multi-center medical record review study.</p> <p>Methods</p> <p>A computer-based automated menu-driven system with 658 data fields was developed for a cohort study of women aged 65 years or older, diagnosed with invasive histologically confirmed primary breast cancer (N = 1859), at 6 Cancer Research Network sites. Medical record review with direct data entry into the EDC system was implemented. An inter-rater and intra-rater reliability (IRR) system was developed using a modified version of the EDC.</p> <p>Results</p> <p>Automation of EDC accelerated the flow of study information and resulted in an efficient data collection process. Data collection time was reduced by approximately four months compared to the project schedule and funded time available for manuscript preparation increased by 12 months. In addition, an innovative modified version of the EDC permitted an automated evaluation of inter-rater and intra-rater reliability across six data collection sites.</p> <p>Conclusion</p> <p>Automated EDC is a powerful tool for research efficiency and innovation, especially when multiple data collection sites are involved.</p

Fluctuations in Serum magnesium and Systemic Arterial Blood Pressures during the Menstrual Cycle in young reproductive women

Introduction: The menstrual cycle involves a sequence of structural, functional, and hormonal changes in the reproductive system. This is linked and controlled by cyclical fluctuations in the levels of FSH, LH, estrogen, and progesterone. Because of these cyclical fluctuations, there might also be associated cyclical changes of magnesium and systemic arterial blood pressures during the menstrual cycle. Purpose: To assess the changes in serum magnesium level and systemic arterial blood pressures during the menstrual cycle in young reproductive women. Methodology: the sample population is 40 apparently healthy young reproductive-aged 18- 25years female students from the University of Medicine, Magway participated in this study. Systemic arterial blood pressures were measured by indirect method. The serum magnesium level was measured by spectrophotometry. These measurements were done in the early follicular phase (EF), the peri-ovulatory phase (PO), and the midluteal phase (ML) of the menstrual cycle. The serum magnesium levels were significantly (p <0.001) lower, and the systolic blood pressures were significantly higher (p <0.05) in the PO than the EF and the ML. In the EF, there was a significant negative correlation between serum magnesium level and diastolic blood pressure (r= - 0.374, p <0.05) and mean arterial pressure (r = -0.354, p < 0.05) but no significant correlation with systolic blood pressure. In the PO, there was no significant correlation between serum magnesium level and systemic arterial blood pressures. In the ML, there was significant negative correlation between serum magnesium level and systolic blood pressure (r = -0.651, p <0.001), diastolic blood pressure (r = -0.607, p <0.001), and mean arterial pressure (r = -0.661, p <0.001). Conclusion: The study concludes that serum magnesium level has a negative effect on blood pressure changes and the blood pressure-lowering effect of magnesium. These changes are related to the fluctuation of estrogen levels during the menstrual cycle. KEYWORDS: Serum magnesium, systemic arterial blood pressures, menstrual cycle reproductive syste

Standardised protocol for a prospective cross-sectional multicentre clinic-based evaluation of two dual point-of-care tests for the screening of HIV and syphilis in men who have sex with men, sex workers and pregnant women

Introduction Dual point-of-care tests (POCTs) for detecting antibodies to HIV and syphilis have been developed for use with venous whole blood, serum/plasma or finger-prick capillary whole blood. Several tests are commercially available showing encouraging performance compared with ‘gold-standard’ reference tests in laboratory-based studies. However, data on their performance in the field are limited. This prospective cross-sectional study will conduct a clinic-based evaluation to assess the performance characteristics and acceptability to end-users of two dual HIV/syphilis POCTs for the screening of HIV and syphilis among men who have sex with men (MSM), sex workers (SWs) and pregnant women (PW). This master protocol outlines the overall research approach that will be used in seven countries. Method and analysis MSM, SWs and PW presenting at clinic evaluation sites in high, low and middle-income countries will be enrolled. The (WHO preapproved) POCTs to be evaluated are SD Bioline HIV/Syphilis Duo (Abbott) and Dual Path Platform HIV-Syphilis Assay (Chembio). Finger-prick blood will be collected to perform POCTs and compared with laboratory results (venepuncture blood). Procedures will be carried out by trained healthcare staff and tests performed according to the manufacturers’ directions. Sample size was calculated based on local prevalence of HIV and syphilis. The sensitivity, specificity, positive and negative predictive values for each POCT will be calculated. The study is ongoing with recruitment expected to be completed in all countries by mid to late 2021. Ethics and dissemination This core protocol was independently peer reviewed and approved by the Research Project Review Panel (RP2) of the WHO Department of Sexual and Reproductive Health and Research and by the WHO Ethics Review Committee (ERC). The protocol has been adapted to individual countries and approved by RP2, ERC and institutional review boards at each site. Results will be disseminated through peer-reviewed journals and relevant conferences

Understanding abortion-related complications in health facilities: results from WHO multicountry survey on abortion (MCS-A) across 11 sub-Saharan African countries.

INTRODUCTION: Complications due to unsafe abortions are an important cause of morbidity and mortality in many sub-Saharan African countries. We aimed to characterise abortion-related complication severity, describe their management, and to report women's experience of abortion care in Africa. METHODS: A cross-sectional study was implemented in 210 health facilities across 11 sub-Saharan African countries. Data were collected on women's characteristics, clinical information and women's experience of abortion care (using the audio computer-assisted self-interviewing (ACASI) system). Severity of abortion complications were organised in five hierarchical mutually exclusive categories based on indicators present at assessment. Descriptive bivariate analysis was performed for women's characteristics, management of complications and reported experiences of abortion care by severity. Generalised linear estimation models were used to assess the association between women's characteristics and severity of complications. RESULTS: There were 13 657 women who had an abortion-related complication: 323 (2.4%) women were classified with severe maternal outcomes, 957 (7.0%) had potentially life-threatening complications, 7953 (58.2%) had moderate complications and 4424 (32.4%) women had mild complications. Women who were single, multiparous, presenting ≥13 weeks of gestational age and where expulsion of products of conception occurred prior to arrival to facility were more likely to experience severe complications. For management, the commonly used mechanical methods of uterine evacuation were manual vacuum aspiration (76.9%), followed by dilation and curettage (D&C) (20.1%). Most frequently used uterotonics were oxytocin (50∙9%) and misoprostol (22.7%). Via ACASI, 602 (19.5%) women reported having an induced abortion. Of those, misoprostol was the most commonly reported method (54.3%). CONCLUSION: There is a critical need to increase access to and quality of evidence-based safe abortion, postabortion care and to improve understanding around women's experiences of abortion care

Associated factors for mortality in a COVID-19 colombian cohort : is the third wave relevant when Mu variant was predominant epidemiologically?

Q1Q1Pacientes con COVID-19Objectives: To evaluate the association between Colombia's third wave when the Mu variant was predominant epidemiologically (until 75%) in Colombia and COVID-19 all-cause in-hospital mortality. Methods: In this retrospective cohort, we included hospitalized patients ≥18 years with SARS-CoV-2 infection between March 2020 to September 2021 in ten hospitals from three cities in Colombia. Description analysis, survival, and multivariate Cox regression analyses were performed to evaluate the association between the third epidemic wave and in-hospital mortality. Results: A total of 25,371 patients were included. The age-stratified time-to-mortality curves showed differences according to epidemic waves in patients ≥75 years (log-rank test p = 0.012). In the multivariate Cox analysis, the third wave was not associated with increased mortality relative to the first wave (aHR 0.95; 95%CI 0.84–1.08), but there was an interaction between age ≥75 years and the third wave finding a lower HR for mortality (aHR 0.56, 95%CI 0.36–0.86). Conclusions: We did not find an increase in in-hospital mortality during the third epidemic wave in which the Mu variant was predominant in Colombia. The reduced hazard in mortality in patients ≥75 years hospitalized in the third wave could be explained by the high coverage of SARS-CoV-2 vaccination in this population and patients with underlying conditions.https://orcid.org/0000-0003-1833-1599https://orcid.org/0000-0001-5363-5729https://orcid.org/0000-0001-6964-2229https://orcid.org/0000-0003-3975-2835https://orcid.org/0000-0001-9441-4375Revista Internacional - IndexadaA1N

Following Up on Clinical Recommendations in Transitions from Hospital to Nursing Home

Following up on recommendations made at the time of a hospital discharge is important to patient safety. While data is lacking, specifically around the transition of patient to nursing home, it has been postulated that missed items such as laboratory tests may result in adverse patient outcomes. To determine the extent of this problem, a retrospective cohort study of subjects discharged from an academic medical center and admitted to nursing homes (NH) was followed to determine the type of discharge recommendations and the rate of completion. In addition, for the purpose of generalizability, the 30-day hospital readmission rate was calculated. 152 recommendations were made on 51 subjects. Almost a quarter of the recommendations made by the hospital discharging team were not acted upon. Furthermore, for the majority of those recommendations that were not acted upon, a reason could not be determined. In concert with national data, 20% of the subjects returned to the hospital within 30 days. Further investigation is warranted to determine if an association exists between missed recommendations and hospital readmission from the nursing home setting