Sample Size Calculation Research Articles

Study protocol for LOMCAD Trial: Effect of lomerizine hydrochloride to prevent recurrence of cerebral ischemic events in CADASIL patients

ObjectivesCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common monogenic cerebral small vessel diseases. Our previous observational study suggested that lomerizine hydrochloride, a calcium channel blocker approved in Japan in 1999 for the prevention of migraine headaches, is also effective for preventing recurrent ischemic stroke in CADASIL patients. The aim of this study (LOMCAD trial) is to verify the efficacy of lomerizine hydrochloride. Materials and MethodsThis is a multicenter, prospective, single-arm trial, using a historical control for comparison. CADASIL patients with a history of two or more cerebral ischemic events within the last two years will be administered lomerizine hydrochloride (5-mg tablet twice daily) for 24 months. The primary endpoint is symptomatic cerebral ischemic events during the 24-month period. Using our historical data and Bayesian sample size calculation based on a prior predictive distribution, the planned sample size was determined as 20 subjects. ConclusionWe have planned a clinical trial to verify the effectiveness of lomerizine hydrochloride as prophylaxis to prevent recurrent cerebral ischemic events in CADASIL patients. RegistrationThe LOMCAD trial has been registered in the Japan Registry of Clinical Trials (jRCTs051220072, https://jrct.niph.go.jp/latest-detail/jRCTs051220072).

Prevalence of hazardous alcohol consumption and associated factors among HIV-positive pregnant women attending public hospitals in Northwest Ethiopia: a multicentred cross-sectional study

BackgroundAlcohol is a major public health problem in pregnant women due to its harmful effects on pregnancy and adverse birth outcomes. Therefore, assessing the prevalence and the factors associated with...

Assessment of diagnostic accuracy of Gazelle: A point-of-care testing device for screening β-thalassemia trait.

Background & objectives Timely detection of population with β-thalassemia trait (BTT) followed by genetic counselling is an advocated method of preventing the birth of a child with β-thalassemia major. In this study we aim to assess the diagnostic accuracy of Gazelle, a point-of-care (POC) testing device, in screening for BTT in hospital laboratory setting. Methods Standards for Reporting Diagnostic Accuracy (STARD) guidelines were followed in developing study design, recruiting study participants and sample size calculation for the current research. A consecutive sample of 446 participants was recruited for this study and was tested for the reference test Gazelle as well as the gold standard cation exchange high performance liquid chromatography (CE-HPLC). Low serum ferritin levels are known to interfere with the production of HbA2 and in turn lead to false negative results. Hence, the study population was divided into two categories with respect to a cut off value of 15ng/dl of serum ferritin and the results were analyzed. Results Overall diagnostic accuracy of Gazelle for detecting BTT was found to be 95.3 per cent with a confidence interval (CI) of (92.9 - 97.1) and the sensitivity was 94.5 per cent with a 95% CI of (84.8 - 98.8). When analyzed by the serum ferritin level the diagnostic accuracy was found to be 94.7 per cent (91.1% - 97.1%) and 95.7 per cent (91.8% - 98.1%) for participants with serum ferritin level as > 15 ng/ml and < 15 ng/ml, respectively. Interpretation & conclusions This study found Gazelle to be a good screening tool for β-thalassemia trait with high sensitivity, specificity and accuracy. However, it is recommended that the final confirmation of the diagnosis done by a diagnostic test like HPLC or Capillary Zone Electrophoresis (CZE).

Measurement variability of blood-brain barrier permeability using dynamic contrast-enhanced magnetic resonance imaging.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used to quantify the blood-brain barrier (BBB) permeability-surface area product. Serial measurements can indicate changes in BBB health, of interest to the study of normal physiology, neurological disease, and the effect of therapeutics. We performed a scan-rescan study to inform both sample size calculation for future studies and an appropriate reference change value for patient care. The final dataset included 28 healthy individuals (mean age 53.0 years, 82% female) scanned twice with mean interval 9.9 weeks. DCE-MRI was performed at 3T using a 3D gradient echo sequence with whole brain coverage, T1 mapping using variable flip angles, and a 16-min dynamic sequence with a 3.2-s time resolution. Segmentation of white and grey matter (WM/GM) was performed using a 3D magnetization-prepared gradient echo image. The influx constant Ki was calculated using the Patlak method. The primary outcome was the within-subject coefficient of variation (CV) of Ki in both WM and GM. Ki values followed biological expectations in relation to known GM/WM differences in cerebral blood volume (CBV) and consequently vascular surface area. Subject-derived arterial input functions showed marked within-subject variability which were significantly reduced by using a venous input function (CV of area under the curve 46 vs. 12%, p < 0.001). Use of the venous input function significantly improved the CV of Ki in both WM (30 vs. 59%, p < 0.001) and GM (21 vs. 53%, p < 0.001). Further improvement was obtained using motion correction, scaling the venous input function by the artery, and using the median rather than the mean of individual voxel data. The final method gave CV of 27% and 17% in WM and GM, respectively. No further improvement was obtained by replacing the subject-derived input function by one standard population input function. CV of Ki was shown to be highly sensitive to dynamic sequence duration, with shorter measurement periods giving marked deterioration especially in WM. In conclusion, measurement variability of 3D brain DCE-MRI is sensitive to analysis method and a large precision improvement is obtained using a venous input function.

Practice of Fluid and Vasopressor Therapy in Critically Ill Invasively Ventilated Patients (PRoFLUID)-study protocol for an international multicenter observational cohort study.

The practice of intravenous fluid and vasopressor therapy in intensive care unit (ICU) patients, particularly in those who receive invasive ventilation, has been subject to change. Traditional approaches of 'early and liberal fluid administration' and 'late and restrictive vasopressor use' have been challenged, leading to recommendations for giving less fluids and earlier administration of vasopressors. Recommendations for fluid deresuscitation-active fluid removal-are absent. The global approach to fluid and vasopressor therapy in invasively ventilated patients is currently unclear. Our aim is to explore the practice of intravenous fluid and vasopressor therapy in invasively ventilated ICU patients in a study named 'Practice of Fluid and Vasopressor Therapy in Critically Ill Invasively Ventilated Patients' (PRoFLUID). PRoFLUID is an international, multicenter, observational cohort study in critically ill adult patients that are invasively ventilated for more than 24 hours. The outcomes include various aspects of fluid and vasopressor therapy, urine output and cumulative fluid balances. We will also collect duration of ventilation, lengths of stay and mortality in ICU and hospital. We expect to collect granular data on fluid and vasopressor therapy in a sample of at least 2,500 patients. PRoFLUID will provide useful insights into the practice of fluid and vasopressor therapy in invasively ventilated critically ill patients. PRoFLUID also allows us to determine whether geo-economic differences in management of intravenous fluid and vasopressor therapy exist, and allows for analyses of associations of aspects of fluid and vasopressor therapy with outcomes. Last but not least, its findings could feed sample size calculations of future randomized clinical trials of fluid and vasopressor therapy. In conclusion, PRoFLUID will collect data on fluid and vasopressor therapy in invasively ventilated ICU patients worldwide, providing insights that will guide future clinical decisions and randomized trial designs. ClinicalTrials.gov NCT05968066. Registered on August 1, 2023. Intensive care; invasive ventilation; fluid therapy; fluid management; vasopressor.

Tranexamic Acid for reduction of intra- and postoperative TRansfusion requirements in elective Abdominal surgery (TATRA): study protocol for an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized superiority trial with two parallel groups

BackgroundIntra- and postoperative hemorrhage is a relevant problem in major abdominal surgery, leading to acute anemia and necessitating transfusion of packed red blood cells. It is estimated that in 30% of abdominal surgeries, intra- or postoperative transfusion is required. Transfusion potentially has detrimental health effects and poses a considerable socioeconomic burden. Tranexamic acid, a lysine analog inhibiting plasminogen activation and providing clot stability, has been used to reduce hemorrhage. While there is ample evidence in other surgical disciplines, it is almost completely lacking in abdominal surgery.MethodsThis multicenter double-blind parallel group randomized superiority trial will compare tranexamic acid (loading dose 1000 mg over 10 min prior to skin incision, maintenance dose 125 mg/h continuously until skin closure or until 1000 mg have been administered) to placebo in patients ≥ 18 years undergoing elective esophagectomy, gastrectomy, colectomy, rectal resection, pancreatic resection, or hepatectomy. The primary efficacy endpoint is the intra- or postoperative transfusion of at least one unit of packed red blood cells. Key secondary endpoints are the number of transfused units per patient, estimated intraoperative blood loss, postoperative complications/mortality, length of hospital stay, operation/anesthesia time, D-dimer levels, and quality of life. Sample size calculation is based on the assumption that in the control group, 30% of patients require transfusion while the intervention achieves a risk reduction of 33%, reducing the probability to 20%. With a type one error of 5% and a power of 90%, using a two-sided χ2 test, this results in 412 patients per group. Accounting for non-compliance, 425 patients are to be randomized per group. The total trial duration will be 30 months with a recruitment period of 18 months.DiscussionIf the proposed trial yielded positive results, the routine use of tranexamic acid in major abdominal surgery would be supported. This would avoid acute anemia with detrimental effects such as tissue hypoxia and organ injury, as well as the negative immediate and delayed effects of transfusions.Trial registrationEU CT Nr: 2023–509970-43–01, NCT06414031. Registered on 10 May 2024.

Gender differences in the use of an upper-extremity exoskeleton during physically and cognitively demanding tasks- a study protocol for a randomized experimental trial.

Upper limb exoskeletons are recommended to alleviate muscle fatigue, particularly in working conditions inducing musculoskeletal discomfort like overhead work. However, wearing an exoskeleton might introduce cognitive-motor interference, affecting performance. Understanding its neural impact and potential gender differences in design effects is crucial. Therefore, the aim of this study is to examine exoskeleton effects addressing cross-gender comparisons, and exploring the impact on cognitive and physical workload in real-world scenarios. The research questions address the impact of exoskeleton use on muscle synergies, upper body posture, cognitive resources, comfort/discomfort, acceptance and usability. The cross-sectional study integrates a multifactorial mixed-measure design. Participants are grouped by gender (female vs. male) and working condition (with vs. without exoskeleton). Motor performance and underlying neuronal correlates (fNIRS) will be analyzed. Based on an a priori sample size calculation, 80 participants (40 female/40 male) will be recruited. Working performance will be assessed by 1. Physical Performance Task (PILE task) and 2. Precision Task (following the Fitts paradigm), while body postures will be monitored with an Xsens motion capture system. Brain activation will be captured with an fNIRS system comprising 32 active optodes. Postural comfort/discomfort, acceptance, and usability will be reported via standardized questionnaires. The study will gain insights into potential gender differences in exoskeleton use and will contribute to designing and optimizing the implementation of exoskeletons by considering muscle synergies, movement variability and cognitive resource allocation. Additionally, the study also highlights user discomfort, a crucial factor that could impede widespread adoption, particularly among females, in real-world scenarios.

Causes and Reduction Strategies of Research Writing Anxiety among Social Science Undergraduate Students at Mwalimu Nyerere Memorial Academy, Tanzania

This study examined the causes and reduction strategies of research writing anxiety among social science undergraduate students at The Mwalimu Nyerere Memorial Academy (MNMA) in Dar es Salaam, Tanzania. A descriptive research design was adopted to facilitate the collection of quantitative data using a structured close -ended questionnaire. A total of sample size of 168 respondents were determined, using an online sample size calculator. Data was analyzed descriptively using the Statistical Package for Social Science (SPSS) version 19. The findings exhibit a significant prevalence of anxiety among students caused by several factors such as lack of research writing skills, unfamiliarity with academic conventions, and time constraints. Additionally, the study identified several strategies to reduce research writing anxiety, including dedicating a semester for research, selecting appropriate supervisors, allowing more time for research writing, limiting undergraduate students to writing only a proposal and making research an optional module. In light of the prevalence of anxiety among students, the study recommends that university administrators implement targeted support programs, including writing workshops and counseling services, to help students manage and reduce their anxiety levels effectively.

Impact of dental fluorosis on the oral health-related quality of life: a systematic review.

The aim of this systematic review is to investigate the literature to assess the effect of dental fluorosis on the Oral Health-Related Quality of Life (OHRQoL). Included studies were epidemiological investigations, clinical trials, or human studies that directly compared the impact on OHRQoL between individuals with dental fluorosis and those without, utilizing valid OHRQoL assessment tools. The searches were conducted up to March 2024 in databases, including PubMed, Scielo, LILACS, Scopus, Web of Science, Embase, and the Virtual Health Library. Additionally, gray literature sources such as Google Scholar, OpenGrey, Ibict/BDTD, and ProQuest were searched. Reference lists were also manually reviewed for potential eligible studies. The risk of bias in cohort studies was assessed using the Newcastle-Ottawa Scale (NOS), while its modified version was employed for cross-sectional studies. A narrative synthesis of the results was conducted. 16 studies were included in this Systematic Review. In total, 16,314 participants, aged 8 to 18, were assessed across the studies. Most of the included studies were cross-sectional, except for one cohort study. In assessing OHRQoL across different age groups and severities of dental fluorosis, the impact varied. A negative association between dental fluorosis and OHRQoL was found in 9 of the included studies, a positive association was found in 1 study, and no significative association was identified in 6 studies. Limitations in the included studies primarily pertained to cross-sectional designs, with significant issues such as the absence of sample size calculations, lack of non-response rate reporting, limited consideration of confounding factors, and substantial heterogeneity stemming from diverse diagnostic methods and assessment tools. The findings of the systematic review demonstrate a complex and varied relationship between dental fluorosis and OHRQoL in children and adolescents. These conclusions may have limitations in scientific evidence. The findings emphasize the need for further investigations to explore the intricate aspects of this relationship and identify contributing factors to varying outcomes. Dental caries preventive fluoridated measures might be indicated even if there would be a risk for mild dental fluorosis as the fluoridated public water. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under number: CRD42020186552.

Outcomes of acetaminophen infusion on visual analogue scale with varying pain intensity during labour, A randomized controlled trial

Objective: Acetaminophen (Paracetamol) is the most widely used analgesic. We aimed to determine its efficacy in labour with varying pain intensity, to make labour less painful for women. Methods: This randomized controlled trial was conducted on primigravida’s in their active phase of first stage of labour at Pharmacology department of Army Medical College, National University of Medical Sciences in collaboration with Gynecology department of Pak Emirates Military hospital, Rawalpindi. It was a registered trial with trial number of IRCT20220308054220N1. Duration of study was from May 2022 to October 2022. Patients were divided into two groups, Group-I received two doses of I/V 100 ml normal saline whereas Group-II received I/V two doses of 1000 mg acetaminophen in 100 ml normal saline. Calculated sample size was 130, 65 in each group. Visual analogue scale was used as a tool for data measurement. Data was analysed using split plot anova test. Results: Mean VAS in acetaminophen infusion group was found to be less than placebo for 1st dose, but this effect was apparent only one hour after 2nd dose intervention. The difference in means between groups was statistically significant only for 1st dose with p-value of 0.003 (for second dose p-value 0.21). In acetaminophen infusion group, for both doses mean VAS decreased as an immediate effect of drug, but then it increased with time. The difference in VAS between intervals had p-value of &lt;0.001 for 1st dose and 0.005 for 2nd dose. Conclusion: Acetaminophen is an effective non opioid labour analgesic in active phase of first stage of labour. doi: https://doi.org/10.12669/pjms.40.10.8425 How to cite this: Najeeb W, Komal N, Noor M, Khan MA, Chaudry A. Outcomes of acetaminophen infusion on visual analogue scale with varying pain intensity during labour, A randomized controlled trial. Pak J Med Sci. 2024;40(10):2163-2169. doi: https://doi.org/10.12669/pjms.40.10.8425 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Histopathological pattern in endometrial biopsies in reproductive age group and Post-menopausal women.

To identify and analyse the different types and frequencies of morphological pattern in endometrial biopsies along with their associated diagnoses across different age groups. The cross-sectional study was conducted at the Histopathology Section of the Dow Diagnostics Reference and Research Laboratory, Dow University Health Sciences, Karachi, from October 2022 to October 2023. Data was obtained from pre-existing medical record of samples of endometrial biopsies. Open Epi sample size calculator is used for the estimation of sample size. The patients were divided into two aged-based groups; reproductive age ≤45 years in group 1 and postmenopause age ≥46 years in group 2. The histological diagnosis was made by a consultant histopathologist. Of the 430 endometrial biopsies 222(51.6%) were in group 1 and 208(48.4%) were in group 2. In both groups, the most common finding was polyps 271(63%). Malignant changes were found in 12(5.7%) group 2 cases compared to 4(1.8%) group 1 cases. The most common endometrial lesion in both age groups was endometrial polyp. Malignant changes were seen more in postmenopausal women compared to those in the reproductive age group.

A systematic review of sample size estimation accuracy on power in malaria cluster randomised trials measuring epidemiological outcomes

IntroductionCluster randomised trials (CRTs) are the gold standard for measuring the community-wide impacts of malaria control tools. CRTs rely on well-defined sample size estimations to detect statistically significant effects of trialled interventions, however these are often predicted poorly by triallists. Here, we review the accuracy of predicted parameters used in sample size calculations for malaria CRTs with epidemiological outcomes.MethodsWe searched for published malaria CRTs using four online databases in March 2022. Eligible trials included those with malaria-specific epidemiological outcomes which randomised at least six geographical clusters to study arms. Predicted and observed sample size parameters were extracted by reviewers for each trial. Pair-wise Spearman’s correlation coefficients (rs) were calculated to assess the correlation between predicted and observed control-arm outcome measures and effect sizes (relative percentage reductions) between arms. Among trials which retrospectively calculated an estimate of heterogeneity in cluster outcomes, we recalculated study power according to observed trial estimates.ResultsOf the 1889 records identified and screened, 108 articles were eligible and comprised of 71 malaria CRTs. Among 91.5% (65/71) of trials that included sample size calculations, most estimated cluster heterogeneity using the coefficient of variation (k) (80%, 52/65) which were often predicted without using prior data (67.7%, 44/65). Predicted control-arm prevalence moderately correlated with observed control-arm prevalence (rs: 0.44, [95%CI: 0.12,0.68], p-value < 0.05], with 61.2% (19/31) of prevalence estimates overestimated. Among the minority of trials that retrospectively calculated cluster heterogeneity (20%, 13/65), empirical values contrasted with those used in sample size estimations and often compromised study power. Observed effect sizes were often smaller than had been predicted at the sample size stage (72.9%, 51/70) and were typically higher in the first, compared to the second, year of trials. Overall, effect sizes achieved by malaria interventions tested in trials decreased between 1995 and 2021.ConclusionsStudy findings reveal sample size parameters in malaria CRTs were often inaccurate and resulted in underpowered studies. Future trials must strive to obtain more representative epidemiological sample size inputs to ensure interventions against malaria are adequately evaluated.RegistrationThis review is registered with PROSPERO (CRD42022315741).

Comparison of 75 mg versus 150 mg aspirin for the prevention of preterm preeclampsia in high-risk women at a tertiary level hospital: study protocol for a randomized double-blind clinical trial

BackgroundHypertensive disorders of pregnancy (HDP) pose significant risks to maternal and fetal health, with substantial mortality and morbidity rates globally, particularly in developing countries. Pre-eclampsia (PE) accounts for a notable portion of maternal morbidity and mortality, with varied prevalence across regions within countries like India. Despite advancements, disparities in healthcare access persist, influencing outcomes. PE not only affects maternal health during pregnancy but also predisposes women to long-term cardiovascular complications, emphasizing the need for early screening and preventive measures.MethodsThis prospective randomized double-blind clinical trial aims to compare the efficacy and safety of 75 mg versus 150 mg aspirin for preventing preterm pre-eclampsia in high-risk women. Screen-positive women aged 18–45 years with singleton pregnancies between 12 and 16 weeks of gestational age will be enrolled. They will be randomized in a 1:1 ratio to receive either 75 mg or 150 mg of aspirin nightly until 37 weeks of pregnancy or earlier if preterm pre-eclampsia develops. Feto-maternal outcomes, including preterm pre-eclampsia incidence and neonatal and maternal complications, will be assessed. The sample size calculation based on expected proportions of preterm pre-eclampsia in both groups indicates a total of 370 participants (185 per group) accounting for 20% attrition.DiscussionThis prospective randomized double-blind clinical trial aims to compare the effectiveness and safety of two doses of aspirin (75 mg vs 150 mg) in preventing preterm pre-eclampsia in high-risk women. The potential implications of this study are significant, including the optimization of aspirin prophylaxis, the development of evidence-based guidelines, and comprehensive assessment of maternal and fetal outcomes. In conclusion, the results of this study have the potential to significantly impact clinical practice by enhancing maternal and perinatal health outcomes and contributing to evidence-based obstetric care.Trial registrationClinical Trials Registry-India CTRI/2023/12/060983. Trial was registered prospectively on 29 December 2023. Acknowledgement Number REF/2023/12/076358. https://acrobat.adobe.com/id/urn:aaid:sc:AP:15870322-f1f4-4460-900c-6e056ab83a44.

A Prospective Nonrandomized Comparison of Wet Needling Versus Prolotherapy in Myofascial Pain.

The objective was to analyze the difference between prolotherapy and wet needling (WN) for myofascial trigger points (MTrPs) for the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Clinical Global Impression (CGI), and MTrPcount. Patients with myofascial pain for 1.5 years were included based on convenience sampling after a pilot study for sample size calculation. The WNgroup received an injection of bupivacaine 0.5% into the trigger points with WN. Participants in thedextrose prolotherapy (DPT) group received dextrose (25%) plus bupivacaine (0.5%) (1:1) into the same. Outcome measures were recorded at baseline immediatepost-injection, one month, three months, and 24 months. Among the 200 participants, there was no significant difference in the baseline VAS score between the two groups nor for immediate post-VAS. At three months of follow-up, the mean VAS was 6.34 ± 1.44 in the WN group and 1.99 ± 0.89 in the DPT group (p= 0.03). The mean VAS score significantly changed in both groups but favored the DPT group (p= 0.001)and again at 24 months (p= 0.001). The ODI showed a similar trend favoring the DPT group at all intervals. On correlating the VAS score with the ODI score, a statistically significant correlation was seen at one month, favoring the WN group, and at the end of the third month, favoring the DPT group. Both modalities are effective at one month. At three and 24 months, the DPT was significantly more effective in improving the VAS and ODI.

Processing of prosodic cues of uncertainty in autistic and non-autistic adults: a study based on articulatory speech synthesis.

We investigated the prosodic perception of uncertainty cues in adults with Autism Spectrum Disorder (ASD) compared to neurotypical adults (NTC). We used articulatory synthetic speech to express uncertainty in a human-machine scenario by varying the three acoustic cues pause, intonation, and hesitation. Twenty-eight adults with ASD and 28 NTC adults rated each answer for uncertainty, naturalness, and comprehensibility. Both groups reliably perceived different levels of uncertainty. Stimuli were rated as less uncertain by the ASD group, but not significantly. Only when we pooled the recipients' ratings for all three cues, did we find a significant group difference. In terms of reaction time, we observed longer reaction times in the ASD group compared to the neurotypical comparison group for the uncertainty level hesitation & strong intonation, but the differences were not significant after Bonferroni correction. Furthermore, our results showed a significant group difference between the correlation of uncertainty and naturalness, i.e. the correlation in the ASD group is significantly lower than in the NTC group. Obtained effect size estimates can inform sample size calculations in future studies for the reliable identification of group differences. In future work, we would like to further investigate the interaction of all three cues and uncertainty perception. It would be interesting to further vary the duration of the pause and also to use different types of fillers. From a developmental perspective, uncertainty perception should also be investigated in children and adolescents with ASD.

Sample Size Calculation Based on Research Approaches in Animal Studies

Introduction: Sample sizes that are too small can produce inconclusive results, while sample sizes that are too large may raise ethical concerns and produce trivial outcomes. Ethical considerations of sample size calculation in animal studies are essential and researchers should consider the 3R approach. Therefore, accurately calculating the sample size is essential to ensure adequate statistical power and avoid wastage of resources. Methods: The paper presents several innovative approaches for conducting small-scale sampling in animal studies. It includes a comprehensive review of relevant literature, discussing various proposed methods for determining sample size in animal studies Results: In this study, various formulas are available for preparing sample size calculations that are relevant to the research design. These include t-tests (for one sample and two independent/paired samples), ANOVA, ANCOVA, simple/multiple linear regression, as well as proportion studies and studies utilizing correlation coefficients Conclusion: Our aims to equip researchers with formulas for reliable findings and adherence to ethical principles for sample size calculating in animal studies.

Using non-inferiority test of proportions in design of randomized non-inferiority trials with time-to-event endpoint with a focus on low-event-rate setting.

For cancers with low incidence, low event rates, and a time-to-event endpoint, a randomized non-inferiority trial designed based on the logrank test can require a large sample size with significantly prolonged enrollment duration, making such a non-inferiority trial not feasible. This article evaluates a design based on a non-inferiority test of proportions, compares its required sample size to the non-inferiority logrank test, assesses whether there are scenarios for which a non-inferiority test of proportions can be more efficient, and provides guidelines in usage of a non-inferiority test of proportions. This article describes the sample size calculation for a randomized non-inferiority trial based on a non-inferiority logrank test or a non-inferiority test of proportions. The sample size required by the two design methods are compared for a wide range of scenarios, varying the underlying Weibull survival functions, the non-inferiority margin, and loss to follow-up rate. Our results showed that there are scenarios for which the non-inferiority test of proportions can have significantly reduced sample size. Specifically, the non-inferiority test of proportions can be considered for cancers with more than 80% long-term survival rate. We provide guidance in choice of this design approach based on parameters of the Weibull survival functions, the non-inferiority margin, and loss to follow-up rate. For cancers with low incidence and low event rates, a non-inferiority trial based on the logrank test is not feasible due to its large required sample size and prolonged enrollment duration. The use of a non-inferiority test of proportions can make a randomized non-inferiority Phase III trial feasible.

Community perception towards mental illness and help-seeking intention in Southwest Ethiopian Peoples Regional State.

Community perception of mental illness is a collective belief system and attitude about mental disorders; it affects the availability of services, the level of stigma, and the help-seeking intention. This study assessed community perceptions towards mental illness and help-seeking intentions in Southwest Ethiopia. A community-based analytical cross-sectional study was done in Southwest Ethiopian People's Regional State (SWEPRS), from March 1st to June 30th, 2021. All adult individuals >18 years old living in the region were the source population, while all adult >18 years old living in the selected household were the study population. The calculated sample size was 1028. Participants were selected using a multistage sampling technique. A structured, interview-based questionnaire was used to collect the data. The data were entered into Epidata Manager and exported to SPSS for analysis. The response rate for this study was 95.4%. The prevalence of poor perception and unfavorable help-seeking intention of mental illness were 45.8%, 95% CI (42.6, 48.9), and 49.5%, 95% CI (46.4, 52.7) respectively. Being rural [AOR = 1.94 (95% CI:(1.41, 2.66)]c, lack of information [AOR = 4.82(95% CI: (3.39,6.83)], exposure to mental illness [AOR = 4.11(95% CI:(2.64,6.38)] were significantly associated with poor perception of mental illness. Also, gating mental illness information [AOR = 0.40 (95% CI: (0.19, 0.83)], and being exposed to mental illness [AOR = 0.56 (95% CI: (0.41, 0.79)] were significantly associated with unfavorable help-seeking intentions for mental illness. The high prevalence of poor perceptions and unfavorable help-seeking intentions for mental illness can be minimized through providing tailored information regarding the cause, type, and severity of the problem, particularly in the rural areas.

A complex ePrescribing antimicrobial stewardship-based (ePAMS+) intervention for hospitals: mixed-methods feasibility trial results

BackgroundAntibiotic resistant infections cause over 700,000 deaths worldwide annually. As antimicrobial stewardship (AMS) helps minimise the emergence of antibiotic resistance resulting from inappropriate use of antibiotics in healthcare, we developed ePAMS+ (ePrescribing-based Anti-Microbial Stewardship), an ePrescribing and Medicines Administration (EPMA) system decision-support tool complemented by educational, behavioural and organisational elements.MethodsWe conducted a non-randomised before-and-after feasibility trial, implementing ePAMS+ in two English hospitals using the Cerner Millennium EPMA system. Wards of several specialties were included. Patient participants were blinded to whether ePAMS+ was in use; prescribers were not. A mixed-methods evaluation aimed to establish: acceptability and usability of ePAMS+ and trial processes; feasibility of ePAMS+ implementation and quantitative outcome recording; and a Fidelity Index measuring the extent to which ePAMS+ was delivered as intended. Longitudinal semi-structured interviews of doctors, nurses and pharmacists, alongside non-participant observations, gathered qualitative data; we extracted quantitative prescribing data from the EPMA system. Normal linear modelling of the defined daily dose (DDD) of antibiotic per admission quantified its variability, to inform sample size calculations for a future trial of ePAMS+ effectiveness.ResultsThe research took place during the SARS-CoV-2 pandemic, from April 2021 to November 2022. 60 qualitative interviews were conducted (33 before ePAMS+ implementation, 27 after). 1,958 admissions (1,358 before ePAMS+ implementation; 600 after) included 24,884 antibiotic orders.Qualitative interviews confirmed that some aspects of ePAMS+ , its implementation and training were acceptable, while other features (e.g. enabling combinations of antibiotics to be prescribed) required further development. ePAMS+ uptake was low (28 antibiotic review records from 600 admissions; 0.047 records per admission), preventing full development of a Fidelity Index. Normal linear modelling of antibiotic DDD per admission showed a residual variance of 1.086 (log-transformed scale). Unavailability of indication data prevented measurement of some outcomes (e.g. number of antibiotic courses per indication).ConclusionsThis feasibility trial encountered unforeseen circumstances due to contextual factors and a global pandemic, highlighting the need for careful adaptation of complex intervention implementations to the local setting. We identified key refinements to ePAMS+ to support its wider adoption in clinical practice, requiring further piloting before a confirmatory effectiveness trial.Trial registrationISRCTN Registry ISRCTN13429325, 24 March 2022.

Power and sample size calculations for testing the ratio of reproductive values in phylogenetic samples.

The quality of the inferences we make from pathogen sequence data is determined by the number and composition of pathogen sequences that make up the sample used to drive that inference. However, there remains limited guidance on how to best structure and power studies when the end goal is phylogenetic inference. One question that we can attempt to answer with molecular data is whether some people are more likely to transmit a pathogen than others. Here we present an estimator to quantify differential transmission, as measured by the ratio of reproductive numbers between people with different characteristics, using transmission pairs linked by molecular data, along with a sample size calculation for this estimator. We also provide extensions to our method to correct for imperfect identification of transmission linked pairs, overdispersion in the transmission process, and group imbalance. We validate this method via simulation and provide tools to implement it in an R package, phylosamp.