Tag: statistics

JMIR Res Protoc. 2022 Aug 10;11(8):e35442. doi: 10.2196/35442.

ABSTRACT

BACKGROUND: More sensitive and less burdensome efficacy end points are urgently needed to improve the effectiveness of clinical drug development for Alzheimer disease (AD). Although conventional end points lack sensitivity, digital technologies hold promise for amplifying the detection of treatment signals and capturing cognitive anomalies at earlier disease stages. Using digital technologies and combining several test modalities allow for the collection of richer information about cognitive and functional status, which is not ascertainable via conventional paper-and-pencil tests.

OBJECTIVE: This study aimed to assess the psychometric properties, operational feasibility, and patient acceptance of 10 promising technologies that are to be used as efficacy end points to measure cognition in future clinical drug trials.

METHODS: The Method for Evaluating Digital Endpoints in Alzheimer Disease study is an exploratory, cross-sectional, noninterventional study that will evaluate 10 digital technologies’ ability to accurately classify participants into 4 cohorts according to the severity of cognitive impairment and dementia. Moreover, this study will assess the psychometric properties of each of the tested digital technologies, including the acceptable range to assess ceiling and floor effects, concurrent validity to correlate digital outcome measures to traditional paper-and-pencil tests in AD, reliability to compare test and retest, and responsiveness to evaluate the sensitivity to change in a mild cognitive challenge model. This study included 50 eligible male and female participants (aged between 60 and 80 years), of whom 13 (26%) were amyloid-negative, cognitively healthy participants (controls); 12 (24%) were amyloid-positive, cognitively healthy participants (presymptomatic); 13 (26%) had mild cognitive impairment (predementia); and 12 (24%) had mild AD (mild dementia). This study involved 4 in-clinic visits. During the initial visit, all participants completed all conventional paper-and-pencil assessments. During the following 3 visits, the participants underwent a series of novel digital assessments.

RESULTS: Participant recruitment and data collection began in June 2020 and continued until June 2021. Hence, the data collection occurred during the COVID-19 pandemic (SARS-CoV-2 virus pandemic). Data were successfully collected from all digital technologies to evaluate statistical and operational performance and patient acceptance. This paper reports the baseline demographics and characteristics of the population studied as well as the study’s progress during the pandemic.

CONCLUSIONS: This study was designed to generate feasibility insights and validation data to help advance novel digital technologies in clinical drug development. The learnings from this study will help guide future methods for assessing novel digital technologies and inform clinical drug trials in early AD, aiming to enhance clinical end point strategies with digital technologies.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35442.

PMID:35947423 | DOI:10.2196/35442

JMIR Res Protoc. 2022 Aug 10;11(8):e35729. doi: 10.2196/35729.

ABSTRACT

BACKGROUND: The health, social, and economic costs of sexually transmitted infections (STIs) represent a major public health concern. Young people are considered one of the groups most at risk for acquiring and transmitting STIs. Correct and consistent condom use has been shown to be the most effective method for reducing STIs; however, condoms are often not used properly. Evidence shows that brief behavior change interventions that focus on skills, communication, and motivation to acquire safe sex practices should be adopted into routine care to reduce STIs. Funding for sexual health services in England has declined dramatically, so novel ways of reducing clinic attendance are being sought. The home-based intervention strategy (HIS-UK) to promote condom use among young men has shown promise in feasibility and pilot studies by demonstrating high acceptability of the intervention in participant and health professional feedback, including aiding men to find condoms they like and feel more confident when using condoms.

OBJECTIVE: The aim of this study is to determine the effectiveness and cost-effectiveness of HIS-UK when compared to usual condom distribution care among young men.

METHODS: The 3 trial arms consisting of “e-HIS” (HIS-UK delivered digitally), “ProHIS” (HIS-UK delivered face-to-face), and control condition (usual National Health Service [NHS] care) will be compared against the following 3 primary outcomes: the extent to which correct and consistent condom use is increased; improvement of condom use experiences (pleasure as well as fit and feel); and decrease in chlamydia test positivity. Eligibility criteria include men aged 16-25 years at risk of STIs through reporting of condom use errors (ie, breakage or slippage) or condomless penile-vaginal or penile-anal intercourse with casual or new sexual partners during the previous 3 months. Prospective participants will be recruited through targeted advertisements and an opportunistic direct approach at selected sexual health and genitourinary medicine services and university-associated health centers and general practitioner practices. Community and educational establishments will be used to further advertise the study and signpost men to recruitment sites. Participants will be randomly allocated to 1 of 3 trial arms. A repeated measures design will assess the parallel arms with baseline and 12 monthly follow-up questionnaires after intervention and 3 chlamydia screening points (baseline, 6, and 12 months).

RESULTS: Recruitment commenced in March 2020. Due to the COVID-19 pandemic, the study was halted and has since reopened for recruitment in Summer 2021. A 30-month recruitment period is planned.

CONCLUSIONS: If effective and cost-effective, HIS-UK can be scaled up into routine NHS usual care to reduce both STI transmission in young people and pressure on NHS resources. This intervention may further encourage sexual health services to adopt digital technologies, allowing for them to become more widely available to young people while decreasing health inequalities and fear of stigmatization.

TRIAL REGISTRATION: ISRCTN Registry ISRCTN11400820; https://www.isrctn.com/ISRCTN11400820.

PMID:35947422 | DOI:10.2196/35729

Clin Neuropharmacol. 2022 Aug 9. doi: 10.1097/WNF.0000000000000515. Online ahead of print.

ABSTRACT

OBJECTIVE: Trichotillomania (TTM) is a clinical psychiatric manifestation involving significant hair loss in association with recurrent hair-pulling behavior, the etiology of which is still unknown. Insufficiency or disorder in the synthesis of brain-derived neurotrophic factor (BDNF) is reported to be potentially associated with neurological, neurodegenerative, and psychiatric diseases in humans and animals. This study examines the relationship between serum BDNF levels and TTM.

METHODS: Ninety-four children and adolescents, 47 patients with TTM and a 47-member control group, were included in the study. Participants were administered the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (6-18 Years) Present and Lifetime Version, and the members of the case group completed the Clinical Global Impression scale. Serum BDNF levels were determined from blood specimens collected from the study and control groups, and the results were subjected to statistical analysis.

RESULTS: Serum BDNF levels were 11.06 ± 1.9 ng/mL in the TTM group and 13.78 ± 2.2 ng/mL in the control group. Serum BDNF was significantly lower in the case group than in the control group. Moderate negative correlation was also determined between Clinical Global Impression scores and serum BDNF levels in the case group.

CONCLUSIONS: Low serum BDNF was associated with TTM and the severity thereof. Furthermore, more extensive studies are needed to elucidate this association.

PMID:35947418 | DOI:10.1097/WNF.0000000000000515

Sud Med Ekspert. 2022;65(4):18-23. doi: 10.17116/sudmed20226504118.

ABSTRACT

The objective of the study is to establish a set of possible causes and patterns that influence the frequency and severity of road traffic accidents with fatalities. The results of the 5-year monitoring analysis of fatal road traffic injuries in Kazan are presented. We analyzed 662 cases. It was established that the main risk group for fatal road accidents includes subjects aged 20-39. The risk group for drivers is 30-39 years old, passengers 20-29 years old, and pedestrians 55-64 years old. Children account for 3% of all traffic fatalities; 80% of them are under 10 years old. Most children (70%) were in the vehicle at the time of the crash, and their parents may not have been using special equipment (car seats and seat belts). We identified the most traumatic months of the year, days of the week and times of the day for drivers, passengers and pedestrians. These patterns can be used for organizational measures to prevent road accidents.

PMID:35947404 | DOI:10.17116/sudmed20226504118

Sud Med Ekspert. 2022;65(4):5-8. doi: 10.17116/sudmed2022650415.

ABSTRACT

The study objective is to improve epidemic control measures in the bureau of forensic medicine by reviewing current local regulatory documents, formulating proposals for their modification, and updating issues related to infectious safety and diagnostic accuracy of infectious diseases. Specific proposals have been provided for modifications of statistical forms for infectious disease recording, regulatory documents, and internal instructions.

PMID:35947401 | DOI:10.17116/sudmed2022650415

JAMA Netw Open. 2022 Aug 1;5(8):e2225973. doi: 10.1001/jamanetworkopen.2022.25973.

ABSTRACT

IMPORTANCE: Of approximately 9 million patients with cancer in China in 2020, more than half were diagnosed with late-stage cancers. Recent regulatory reforms in China have focused on improving the availability of new cancer drugs. However, evidence on the clinical benefits of new cancer therapies authorized in China is not available.

OBJECTIVE: To characterize the clinical benefits of cancer drugs approved in China, as defined by the availability and magnitude of statistically significant overall survival (OS) results.

DESIGN, SETTING, AND PARTICIPANTS: This mixed-methods study comprising a systematic review and cross-sectional analysis identified antineoplastic agents approved in China between January 1, 2005, and December 31, 2020, using publicly available data and regulatory review documents issued by the National Medical Products Administration. The literature published up to June 30, 2021, was reviewed to collect results on end points used in pivotal trials supporting cancer drug approvals.

MAIN OUTCOMES AND MEASURES: The primary outcome measure was a documented statistically significant positive OS difference between a new cancer therapy and a comparator treatment. Secondary outcome measures were the magnitude of OS benefit and other primary efficacy measures in pivotal trials.

RESULTS: Between 2005 and 2020, 78 cancer drugs corresponding to 141 indications were authorized in China, including 20 drugs (25.6%) (for 30 indications) approved in China only. Of all indications, 26 (18.4%) were evaluated in single-arm or dose-optimization trials, most of which were authorized after 2017. By June 30, 2021, 34 drug indications (24.1%) had a documented lack of OS gain. For 68 indications (48.2%) that had documented evidence of OS benefit, the median magnitude of OS improvement was 4.1 (range, 1.0-35.0) months. After a median follow-up of 1.9 (range, 1.0-11.1) years from approval, OS data for 13 indications (9.2%) were either not reported or were still not mature. Fewer than one-third of cancer drug indications approved in China only had documented evidence of OS benefits (9 of 30 [30.0%]), whereas more than one-half of the cancer drug indications also available in the US or Europe had OS benefits (59 of 111 [53.1%]).

CONCLUSIONS AND RELEVANCE: In this study, almost half of cancer drug indications approved in China had demonstrated OS gain. With the increase of cancer drug approvals based on single-arm trials or immature survival data in recent years, these findings highlight the need to routinely monitor the clinical benefits of new cancer therapies in China.

PMID:35947385 | DOI:10.1001/jamanetworkopen.2022.25973

JAMA Surg. 2022 Aug 10. doi: 10.1001/jamasurg.2022.3113. Online ahead of print.

NO ABSTRACT

PMID:35947378 | DOI:10.1001/jamasurg.2022.3113

JAMA Surg. 2022 Aug 10. doi: 10.1001/jamasurg.2022.3110. Online ahead of print.

NO ABSTRACT

PMID:35947376 | DOI:10.1001/jamasurg.2022.3110

JAMA Surg. 2022 Aug 10:e222935. doi: 10.1001/jamasurg.2022.2935. Online ahead of print.

ABSTRACT

IMPORTANCE: Patients with abdominal aortic aneurysm (AAA) can choose open repair or endovascular repair (EVAR). While EVAR is less invasive, it requires lifelong surveillance and more frequent aneurysm-related reinterventions than open repair. A decision aid may help patients receive their preferred type of AAA repair.

OBJECTIVE: To determine the effect of a decision aid on agreement between patient preference for AAA repair type and the repair type they receive.

DESIGN, SETTING, AND PARTICIPANTS: In this cluster randomized trial, 235 patients were randomized at 22 VA vascular surgery clinics. All patients had AAAs greater than 5.0 cm in diameter and were candidates for both open repair and EVAR. Data were collected from August 2017 to December 2020, and data were analyzed from December 2020 to June 2021.

INTERVENTIONS: Presurgical consultation using a decision aid vs usual care.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who had agreement between their preference and their repair type, measured using χ2 analyses, κ statistics, and adjusted odds ratios.

RESULTS: Of 235 included patients, 234 (99.6%) were male, and the mean (SD) age was 73 (5.9) years. A total of 126 patients were enrolled in the decision aid group, and 109 were enrolled in the control group. Within 2 years after enrollment, 192 (81.7%) underwent repair. Patients were similar between the decision aid and control groups by age, sex, aneurysm size, iliac artery involvement, and Charlson Comorbidity Index score. Patients preferred EVAR over open repair in both groups (96 of 122 [79%] in the decision aid group; 81 of 106 [76%] in the control group; P = .60). Patients in the decision aid group were more likely to receive their preferred repair type than patients in the control group (95% agreement [93 of 98] vs 86% agreement [81 of 94]; P = .03), and κ statistics were higher in the decision aid group (κ = 0.78; 95% CI, 0.60-0.95) compared with the control group (κ = 0.53; 95% CI, 0.32-0.74). Adjusted models confirmed this association (odds ratio of agreement in the decision aid group relative to control group, 2.93; 95% CI, 1.10-7.70).

CONCLUSIONS AND RELEVANCE: Patients exposed to a decision aid were more likely to receive their preferred AAA repair type, suggesting that decision aids can help better align patient preferences and treatments in major cardiovascular procedures.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03115346.

PMID:35947375 | DOI:10.1001/jamasurg.2022.2935

JAMA Psychiatry. 2022 Aug 10. doi: 10.1001/jamapsychiatry.2022.2196. Online ahead of print.

ABSTRACT

IMPORTANCE: Past studies have identified associations between brain macrostructure and alcohol use behaviors. However, identifying directional associations between these phenotypes is difficult due to the limitations of observational studies.

OBJECTIVE: To use mendelian randomization (MR) to identify directional associations between brain structure and alcohol use and elucidate the transcriptomic and cellular underpinnings of identified associations.

DESIGN, SETTING, AND PARTICIPANTS: The main source data comprised summary statistics from population-based and case-control genome-wide association studies (GWAS) of neuroimaging, behavioral, and clinical phenotypes (N = 763 874). Using these data, bidirectional and multivariable MR was performed analyzing associations between brain macrostructure and alcohol use. Downstream transcriptome-wide association studies (TWAS) and cell-type enrichment analyses investigated the biology underlying identified associations. The study approach was data driven and did not test any a priori hypotheses. Data were analyzed August 2021 to May 2022.

MAIN OUTCOMES AND MEASURES: Brain structure phenotypes (global cortical thickness [GCT] and global cortical surface area [GCSA] in 33 709 individuals and left-right subcortical volumes in 19 629 individuals) and alcohol use behaviors (alcoholic drinks per week [DPW] in 537 349 individuals, binge drinking frequency in 143 685 individuals, and alcohol use disorder in 8845 individuals vs 20 657 control individuals [total of 29 502]).

RESULTS: The main bidirectional MR analyses were performed in samples totaling 763 874 individuals, among whom more than 94% were of European ancestry, 52% to 54% were female, and the mean cohort ages were 40 to 63 years. Negative associations were identified between genetically predicted GCT and binge drinking (β, -2.52; 95% CI, -4.13 to -0.91) and DPW (β, -0.88; 95% CI, -1.37 to -0.40) at a false discovery rate (FDR) of 0.05. These associations remained significant in multivariable MR models that accounted for neuropsychiatric phenotypes, substance use, trauma, and neurodegeneration. TWAS of GCT and alcohol use behaviors identified 5 genes at the 17q21.31 locus oppositely associated with GCT and binge drinking or DPW (FDR = 0.05). Cell-type enrichment analyses implicated glutamatergic cortical neurons in alcohol use behaviors.

CONCLUSIONS AND RELEVANCE: The findings in this study show that the associations between GCT and alcohol use may reflect a predispositional influence of GCT and that 17q21.31 genes and glutamatergic cortical neurons may play a role in this association. While replication studies are needed, these findings should enhance the understanding of associations between brain structure and alcohol use.

PMID:35947372 | DOI:10.1001/jamapsychiatry.2022.2196