Tag: statistics

BMJ Open. 2023 Sep 12;13(9):e069499. doi: 10.1136/bmjopen-2022-069499.

ABSTRACT

INTRODUCTION: Recent preclinical studies have discovered unique synergism between radiotherapy and immune checkpoint inhibitors, which has already brought significant survival benefit in lung cancer. In locally advanced rectal cancer (LARC), neoadjuvant radiotherapy plus immune checkpoint inhibitors have also achieved surprisingly high pathological complete response (pCR) rates even in proficient mismatch-repair patients. As existing researches are all phase 2, single-cohort trials, we aim to conduct a randomised, controlled trial to further clarify the efficacy and safety of this novel combination therapy.

METHODS AND ANALYSIS: Eligible patients with LARC are randomised to three arms (two experiment arms, one control arm). Patients in all arms receive long-course radiotherapy plus concurrent capecitabine as neoadjuvant therapy, as well as radical surgery. Distinguishingly, patients in arm 1 also receive anti-PD-1 (Programmed Death 1) treatment starting at Day 8 of radiation (concurrent plan), and patients in arm 2 receive anti-PD-1 treatment starting 2 weeks after completion of radiation (sequential plan). Tislelizumab (anti-PD-1) is scheduled to be administered at 200 mg each time for three consecutive times, with 3-week intervals. Randomisation is stratified by different participating centres, with a block size of 6. The primary endpoint is pCR rate, and secondary endpoints include neoadjuvant-treatment-related adverse event rate, as well as disease-free and overall survival rates at 2, 3 and 5 years postoperation. Data will be analysed with an intention-to-treat approach.

ETHICS AND DISSEMINATION: This protocol has been approved by the institutional ethical committee of Beijing Friendship Hospital (the primary centre) with an identifying serial number of 2022-P2-050-01. Before publication to peer-reviewed journals, data of this research will be stored in a specially developed clinical trial database.

TRIAL REGISTRATION NUMBER: NCT05245474.

PMID:37699634 | DOI:10.1136/bmjopen-2022-069499

BMJ Open. 2023 Sep 12;13(9):e075007. doi: 10.1136/bmjopen-2023-075007.

ABSTRACT

INTRODUCTION: Following the discovery of various effects on skin function by modifying endocannabinoid systems, multiple preclinical studies have revealed the promise of cannabis and cannabinoids in the treatment of a variety of skin diseases. However, its clinical efficacy is still debated.

METHODS AND ANALYSIS: The protocol has been prepared using the Preferred Items for Systematic Review and Meta-analysis Protocols guidelines. A systematic search will be conducted using PubMed, EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials and Web of Science. We will include randomised controlled trials and observational studies investigating alterations to dermatological characteristics following administration of cannabis and cannabinoids for dermatological diseases and disorders. The two reviewers will perform both the title and abstract and full-text screenings. The Cochrane Risk-of-Bias 2 and ROBINS-1 tools will be used to evaluate the risk of bias. If a group of comparable studies for each quantitative outcome can be discovered, we will conduct a random effects meta-analysis. We will investigate heterogeneity using a combination of visual inspection of the forest plot, the Cochran’s Q test and Higgins’ test [I2]. Sensitivity analyses will be performed to assess the statistical robustness of the primary outcome. To evaluate a publication bias, the Egger’s regression asymmetry test and funnel plots will be considered.

ETHICS AND DISSEMINATION: This study does not require ethical approval because no original data will be collected. The findings will be presented at conferences and published in peer-reviewed journals.

PROSPERO REGISTRATION NUMBER: CRD42023397189.

PMID:37699631 | DOI:10.1136/bmjopen-2023-075007

BMJ Open. 2023 Sep 12;13(9):e073735. doi: 10.1136/bmjopen-2023-073735.

ABSTRACT

OBJECTIVES: Patient experiences are critical when determining the acceptability of novel interventional pharmaceuticals. Here, we report the development and validation of a product acceptability questionnaire (SPRAY PAL) assessing feasibility, acceptability and tolerability of an intranasal Q-Griffithsin (Q-GRFT) drug product designed for COVID-19 prophylaxis.

DESIGN: SPRAY PAL validation was undertaken as part of an ongoing phase 1 clinical trial designed to test the safety, pharmacokinetics and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection.

SETTING: The phase 1 clinical trial took place at a University Outpatient Clinical Trials Unit from November 2021 to September 2023.

PARTICIPANTS: The initial SPRAY PAL questionnaire was piloted among healthy volunteers ages 25 to 55 in phase 1a of the clinical trial (N=18) and revised for administration in phase 1b for participants ages 24-59 (N=22).

RESULTS: Spearman correlations tested convergent and discriminant validity. Internal consistency was assessed using Cronbach’s alpha, and test-retest reliability was assessed using intraclass correlation coefficients of responses collected from three repeated questionnaire administrations. The initial version demonstrated excellent internal consistency. The revised version demonstrated very good internal consistency after removal of one item (alpha=0.739). Excellent test-retest reliability (intraclass coefficient=0.927) and adequate convergent (r’s=0.208-0.774) and discriminant (r’s=0.123-0.392) validity were achieved. Subscales adequately distinguished between the constructs of acceptability, feasibility and tolerability.

CONCLUSIONS: The SPRAY PAL product acceptability questionnaire is a valid and reliable patient-reported outcomes measure that can be considered a credible tool for assessing patient-reported information about product acceptability, feasibility of use, tolerability of product and side effects and cost of product for novel intranasal drug formulations. The SPRAY PAL is generalisable, and items may be readily adapted to assess other intranasal formulations.

TRIAL REGISTRATION NUMBERS: NCT05122260 and NCT05437029.

PMID:37699630 | DOI:10.1136/bmjopen-2023-073735

BMJ Open. 2023 Sep 12;13(9):e071032. doi: 10.1136/bmjopen-2022-071032.

ABSTRACT

OBJECTIVES: To illustrate the utility of unsupervised machine learning compared with traditional methods of analysis by identifying archetypes within the population that may be more or less likely to get the COVID-19 vaccine.

DESIGN: A longitudinal prospective cohort study (n=2009 households) with recurring phone surveys from 2020 to 2022 to assess COVID-19 knowledge, attitudes and practices. Vaccine questions were added in 2021 (n=1117) and 2022 (n=1121) rounds.

SETTING: Five informal settlements in Nairobi, Kenya.

PARTICIPANTS: Individuals from 2009 households included.

OUTCOME MEASURES AND ANALYSIS: Respondents were asked about COVID-19 vaccine acceptance (February 2021) and vaccine uptake (March 2022). Three distinct clusters were estimated using K-Means clustering and analysed against vaccine acceptance and vaccine uptake outcomes using regression forest analysis.

RESULTS: Despite higher educational attainment and fewer concerns regarding the pandemic, young adults (cluster 3) were less likely to intend to get the vaccine compared with cluster 1 (41.5% vs 55.3%, respectively; p<0.01). Despite believing certain COVID-19 myths, older adults with larger households and more fears regarding economic impacts of the pandemic (cluster 1) were more likely to ultimately to get vaccinated than cluster 3 (78% vs 66.4%; p<0.01), potentially due to employment requirements. Middle-aged women who are married or divorced and reported higher risk of gender-based violence in the home (cluster 2) were more likely than young adults (cluster 3) to report wanting to get the vaccine (50.5% vs 41.5%; p=0.014) but not more likely to have gotten it (69.3% vs 66.4%; p=0.41), indicating potential gaps in access and broader need for social support for this group.

CONCLUSIONS: Findings suggest this methodology can be a useful tool to characterise populations, with utility for improving targeted policy, programmes and behavioural messaging to promote uptake of healthy behaviours and ensure equitable distribution of prevention measures.

PMID:37699627 | DOI:10.1136/bmjopen-2022-071032

BMJ Open. 2023 Sep 12;13(9):e070645. doi: 10.1136/bmjopen-2022-070645.

ABSTRACT

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects of chemotherapeutic drugs. Numerous clinical trials of various targeted drugs for the prevention or treatment of CIPN have been conducted; however, previous systematic reviews with direct comparisons have failed to demonstrate the efficacy of these drugs in the prevention or treatment of CIPN. In addition, no systematic reviews have indirectly compared CIPN prevention and treatment. This article describes a protocol for evaluating the efficacy and safety of drug therapy for the prevention and treatment of CIPN. The results of the proposed systematic review with network meta-analysis (NMA) will provide new insights into the prevention and treatment of CIPN.

METHODS AND ANALYSIS: We will conduct a literature search in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov to find relevant articles published through January 2023. We will include studies that investigated the efficacy and safety of vitamin B₁₂, goshajinkigan, non-steroidal anti-inflammatory analgesics, opioids, calcium and magnesium, antidepressants and anticonvulsants on CIPN. Two authors will individually screen the retrieved reports and review the full text based on the selection criteria. The primary outcome is the incidence and severity of CIPN. The risk of bias will be assessed using V.2.0 of the Cochrane risk-of-bias tool. We will apply a frequentist random-effects NMA model to pool effect sizes across trials using risk ratios and mean differences with their 95% CIs. Competing interventions will be ranked using the surface under cumulative ranking probabilities. Heterogeneity will be assessed using the heterogeneity variance τ², Cochran’s Q test and I² statistic.

ETHICS AND DISSEMINATION: This review does not require ethical approval. The research will be published in a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER: CRD42022371829.

PMID:37699621 | DOI:10.1136/bmjopen-2022-070645

BMJ Open. 2023 Sep 12;13(9):e074626. doi: 10.1136/bmjopen-2023-074626.

ABSTRACT

BACKGROUND: Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.

METHODS/DESIGN: The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.

ETHICS AND DISSEMINATION: Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.

PMID:37699620 | DOI:10.1136/bmjopen-2023-074626

BMJ Open. 2023 Sep 12;13(8):e070016. doi: 10.1136/bmjopen-2022-070016.

ABSTRACT

OBJECTIVE: The primary and secondary impacts from the COVID-19 pandemic are claimed to have had a detrimental impact on health professional retention within the UK National Health Service (NHS). This study set out to identify priorities for intervention by scaling the relative importance of widely cited push (leave) influences.

DESIGN: During Summer/Autumn 2021, a UK-wide opportunity sample (n=1958) of NHS health professionals completed an online paired-comparisons exercise to determine the relative salience of work-related stress, workload intensity, time pressure, staffing levels, working hours, work-homelife balance, recognition of effort and pay as reasons why health professionals leave NHS employment.

SETTING: The study is believed to be the first large-scale systematic assessment of factors driving staff exits from the NHS since the COVID-19 pandemic.

RESULTS: All professions gave primacy to work-related stress, workload intensity and staffing levels. Pay was typically located around the midpoint of the respective scales; recognition of effort and working hours were ranked lowest. However, differences were apparent in the rank order and relative weighting of push variables between health professions and care delivery functions. Ambulance paramedics present as an outlier, notably with respect to staffing level (F-stat 4.47, p=0.004) and the primacy of work-homelife balance. Relative to staffing level, other push variables exert a stronger influence on paramedics than nurses or doctors (f 4.29, p=0.006).

CONCLUSION: Findings are relevant to future NHS health professional retention intervention strategy. Excepting paramedics/ambulance services, rankings of leave variables across the different health professional families and organisation types exhibit strong alignment at the ordinal level. However, demographic differences in the weightings and rankings, ascribed to push factors by professional family and organisation type, suggests that, in addition to signposting universal (all-staff) priorities for intervention, bespoke solutions for different professions and functions may be needed.

PMID:37699606 | DOI:10.1136/bmjopen-2022-070016

Chin Clin Oncol. 2023 Aug;12(4):35. doi: 10.21037/cco-23-54.

ABSTRACT

BACKGROUND: Psychological distress has been associated with greater physical symptom severity, suffering, and mortality in cancer patients. For this reason, today, psychological care represents a fundamental tool for improving the quality of life of cancer patients.

METHODS: From September 2021 to May 2022, 170 newly diagnosed cancer patients, were enrolled in the observational study at Medical Oncology Unit, “San Giovanni di Dio” Hospital. Before the start of oncological treatment, they were subjected to the Kessler 10 (K10) test, a validated measure of non-specific symptoms of psychological distress of the past 4 weeks. On the basis of the score, they were divided into three groups: low [10-19], moderate [20-29] and high [30-50] distress. After 3 months of psychological therapy, they repeated the test.

RESULTS: Majority of patients were female (74.1%), aged <70 years (78.2%). The most represented tumours were breast (47.6%), colon (15.3%), urothelial (10.6%) and lung (7.6%) cancer and most patients started intravenous chemotherapy treatment (74.7%) rather than oral therapy. The previous remote pathological history and the family cancer history of the patients were also evaluated. Finally, marital status, schooling and employment status were recorded. At baseline we found 55, 72, and 43 patients with a low, moderate and high psychological distress, respectively. After the 3 months of psychotherapy, we re-administered the K10 test and we found a radical improvement in the degree of psychological distress (96 patients had a low score, 62 with a moderate score and just 12 patients with a high score). The great reduction in the score in K10 was statistically significant with a P value of <0.0001. The reduction of the K10 score was observed indiscriminately in all subgroups analysed. A statistically significant difference was observed between patients with different education levels (low 56% vs. high 32% of reduction in K10 score). Furthermore, the improvement in psychological health was greater in unemployed patients than in workers.

CONCLUSIONS: The use of the K10 test is helpful in monitoring the degree of psychological distress of patients facing the diagnosis of cancer and who are about to start oncological treatment. Psychotherapy is effective in reducing the distress of these patients just a few months after starting treatment.

PMID:37699600 | DOI:10.21037/cco-23-54

Clin Psychol Psychother. 2023 Sep 12. doi: 10.1002/cpp.2907. Online ahead of print.

ABSTRACT

Studies of anger treatment have often reported on reappraisal and relaxation techniques delivered in person to forensic and psychiatric samples. The present study evaluated an integrative programme of cognitive-behavioural affective therapy (CBAT) delivered remotely to chronic pain sufferers with comorbid anger. Volunteers (N = 54) were randomly assigned to either CBAT or an Emotional Education (EE) group, both receiving hour-long videorecorded sessions twice a week for 4 weeks plus weekly calls by telephone. At 1-month post-treatment, follow-up was conducted. Outcomes were measured using the Anger Parameters Scale (APS) and its five subscales (frequency, duration, intensity, latency and threshold) as well as daily self-monitored anger logs. As hypothesized, pre- to post-treatment decline in APS total scores was significant for CBAT, Hedges’ g = 0.65, 95% CI [0.14, 1.16] but nonsignificant and small for EE, g = 0.17, CI [-0.41, 0.75]. At the primary endpoint (post-treatment), APS total scores were significantly lower for CBAT than for EE. Treatment gains were maintained till follow-up. On all five APS subscales, pre-post effect sizes were medium-sized for CBAT and generally small for EE. This picture was mirrored in the self-monitored frequency, duration and intensity of anger. Findings support the efficacy of CBAT over time, its comparative efficacy over EE and its ecological generalizability. Future research could expand sample size, reduce sample imbalance, extend follow-up and strengthen treatment potency with more sessions. The present study renews enthusiasm for teletherapy and is the first to demonstrate CBAT efficacy in treating maladaptive anger in the chronic pain population.

PMID:37699599 | DOI:10.1002/cpp.2907

J Parasitol. 2023 Oct 1;109(5):450-463. doi: 10.1645/23-4.

ABSTRACT

Recent studies of louse ectoparasites from mummies have developed robust data sets that allow a true epidemiological approach to the prehistory of louse parasitism. One epidemiological principle is that the binomial of overdispersion is normally negative, meaning that in a host population, parasites are aggregated in a few individuals. We demonstrate the overdispersion of lice in 3 different prehistoric communities that differ along 3 axes or variables: environmental setting, socioeconomic status, and cultural affiliation. Distinct cultural practices could have been involved in different patterns of louse infestation. Prevalence, intensity, and abundance of infestations exhibit statistically significant differences between the communities. We also find differences in prevalence between subadults and adults that contrasted by cultural affiliation and suggest conditions different from those seen today. We show that overall prevalence was affected primarily by ecological setting, not socioeconomic status nor cultural affiliation. These findings demonstrate that statistical analysis of archaeological data can reveal the states of infestation in past populations with lifestyles not seen in modern people. Our approach paves the way for future comparisons of subpopulations within archaeological communities.

PMID:37699596 | DOI:10.1645/23-4