Category: Statistics

BMJ Open. 2021 Nov 12;11(11):e049740. doi: 10.1136/bmjopen-2021-049740.

ABSTRACT

OBJECTIVES: Develop an individualised prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD).

DESIGN AND SETTING: This study developed and validated prognostic penalised logistic regression models using reports to the international Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease voluntary registry from March to October 2020. Model development was done using a training data set (85% of cases reported 13 March-15 September 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported 16 September-20 October 2020).

PARTICIPANTS: We included 2709 cases from 59 countries (mean age 41.2 years (SD 18), 50.2% male). All submitted cases after removing duplicates were included.

PRIMARY AND SECONDARY OUTCOME MEASURES: COVID-19 related: (1) Hospitalisation+: composite outcome of hospitalisation, ICU admission, mechanical ventilation or death; (2) Intensive Care Unit+ (ICU+): composite outcome of ICU admission, mechanical ventilation or death; (3) Death. We assessed the resulting models’ discrimination using the area under the curve of the receiver operator characteristic curves and reported the corresponding 95% CIs.

RESULTS: Of the submitted cases, a total of 633 (24%) were hospitalised, 137 (5%) were admitted to the ICU or intubated and 69 (3%) died. 2009 patients comprised the training set and 700 the test set. The models demonstrated excellent discrimination, with a test set area under the curve (95% CI) of 0.79 (0.75 to 0.83) for Hospitalisation+, 0.88 (0.82 to 0.95) for ICU+ and 0.94 (0.89 to 0.99) for Death. Age, comorbidities, corticosteroid use and male gender were associated with a higher risk of death, while the use of biological therapies was associated with a lower risk.

CONCLUSIONS: Prognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of patients with IBD. A free online risk calculator (https://covidibd.org/covid-19-risk-calculator/) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with patients with IBD.

PMID:34772750 | DOI:10.1136/bmjopen-2021-049740

BMJ Open. 2021 Nov 12;11(11):e052969. doi: 10.1136/bmjopen-2021-052969.

ABSTRACT

INTRODUCTION: Causal methods have been adopted and adapted across health disciplines, particularly for the analysis of single studies. However, the sample sizes necessary to best inform decision-making are often not attainable with single studies, making pooled individual-level data analysis invaluable for public health efforts. Researchers commonly implement causal methods prevailing in their home disciplines, and how these are selected, evaluated, implemented and reported may vary widely. To our knowledge, no article has yet evaluated trends in the implementation and reporting of causal methods in studies leveraging individual-level data pooled from several studies. We undertake this review to uncover patterns in the implementation and reporting of causal methods used across disciplines in research focused on health outcomes. We will investigate variations in methods to infer causality used across disciplines, time and geography and identify gaps in reporting of methods to inform the development of reporting standards and the conversation required to effect change.

METHODS AND ANALYSIS: We will search four databases (EBSCO, Embase, PubMed, Web of Science) using a search strategy developed with librarians from three universities (Heidelberg University, Harvard University, and University of California, San Francisco). The search strategy includes terms such as ‘pool*’, ‘harmoniz*’, ‘cohort*’, ‘observational’, variations on ‘individual-level data’. Four reviewers will independently screen articles using Covidence and extract data from included articles. The extracted data will be analysed descriptively in tables and graphically to reveal the pattern in methods implementation and reporting. This protocol has been registered with PROSPERO (CRD42020143148).

ETHICS AND DISSEMINATION: No ethical approval was required as only publicly available data were used. The results will be submitted as a manuscript to a peer-reviewed journal, disseminated in conferences if relevant, and published as part of doctoral dissertations in Global Health at the Heidelberg University Hospital.

PMID:34772754 | DOI:10.1136/bmjopen-2021-052969

BMJ Open. 2021 Nov 12;11(11):e048327. doi: 10.1136/bmjopen-2020-048327.

ABSTRACT

INTRODUCTION: Intimate partners of patients with cancer often experience significant distress, but there is a lack of psychological interventions that specifically target this population. ‘Resilient Caregivers’ is a novel resilience-based intervention for distressed partner cancer caregivers. The intervention was developed according to a resilience framework focusing on meta-reflective skills, coping strategies and value clarification. The aim of this study is to evaluate the effectiveness of this intervention in a randomised trial.

METHODS AND ANALYSIS: Eighty participants will be invited through the Oncology Department at Herlev Hospital, Denmark and randomised to either the intervention or usual care. Participants are eligible if they are partners (married or unmarried) of patients diagnosed with cancer and experience distress (>4 on the distress thermometer). ‘Resilient Caregivers’ consists of seven manualised group sessions (2.5 hours each), focusing on resilience in relation to being a partner caregiver of a patient with cancer. The primary outcome is symptoms of anxiety, while secondary outcomes include distress, depression, quality of life, sleep quality and resilience. Data will be collected at baseline, 3, 6 and 12 months follow-up using validated scales, and analysed using mixed models for repeated measures.

ETHICS AND DISSEMINATION: This study will follow the ethical principles in the Declaration of Helsinki and has been reviewed by the Ethics Committee of the Capital Region of Denmark (Journal no. 18055373). Written informed consent will be obtained from all participants. Results will be reported through scientific peer-reviewed journals and relevant conferences.

TRIAL REGISTRATION NUMBER: NCT04610034.

PMID:34772747 | DOI:10.1136/bmjopen-2020-048327

BMJ Open. 2021 Nov 12;11(11):e049245. doi: 10.1136/bmjopen-2021-049245.

ABSTRACT

INTRODUCTION: Primary retinitis pigmentosa (RP) is a common hereditary retinal disease in ophthalmology that has a considerable impact on quality of life, but there are few effective therapeutic strategies. This trial aims to determine the efficacy and safety of acupuncture versus sham acupuncture (SA) for RP.

METHODS AND ANALYSIS: This is a study protocol for a randomised, participant-blind, sham-controlled trial. 64 eligible patients with RP will randomly be divided into acupuncture group and SA group. All groups will receive 48 sessions over 3 months. Participants will complete the trial by visiting the research centre in month 6/9 for a follow-up assessment. The primary outcome is visual field mean sensitivity and visual field mean deviation at month 3/6/9 compared with baseline. Secondary outcomes include the best-corrected visual acuity, central macular thickness, subfoveal choroidal thicknes, traditional Chinese medicine syndrome score and the scale of life quality for diseases with visual impairment at month 3/6/9 compared with baseline. Adverse events and safety indexes will be recorded throughout the study. SPSS V.25.0 statistical software was used for analysis, and measurement data were expressed as mean±SD.

ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Chinese Clinical Trial Registry (approval no: ChiECRCT20200460). The results of this study will be published in a peer-reviewed journal, and trial participants will be informed via email and/or phone calls.

TRIAL REGISTRATION NUMBER: ChiCTR2000041090.

PMID:34772749 | DOI:10.1136/bmjopen-2021-049245

Clin J Am Soc Nephrol. 2021 Nov 12:CJN.09810721. doi: 10.2215/CJN.09810721. Online ahead of print.

ABSTRACT

Background and objectives: The physiological nocturnal blood pressure decline is often blunted in patients with chronic kidney disease (CKD); however, the consequences of blood pressure non-dipping in children are largely unknown. Our objective was to determine risk factors for non-dipping and to investigate if non-dipping is associated with higher left ventricular mass index (LVMI) in children with CKD. Design, setting, participants, and measurements: We conducted a cross-sectional analysis of ambulatory blood pressure monitoring and echocardiographic data in participants of the Chronic Kidney Disease in Children study. Multivariable linear and spline regression analyses were used to evaluate the relationship of risk factors with dipping, and of dipping with LVMI. Results: Within 552 participants, mean age was 11 (± 4) years, mean eGFR was 53 (± 20) ml/min/1.73m², and 41% were classified as non-dippers. In subjects with non-glomerular CKD, female sex and higher sodium intake were significantly associated with less systolic and diastolic dipping (p≤ 0.05). In those with glomerular CKD, African American race and greater proteinuria were significantly associated with less systolic and diastolic dipping (p≤ 0.05). Systolic and diastolic dipping were not significantly associated with LVMI; however, in spline regression plots, diastolic dipping appeared to have a non-linear relationship with LVMI. As compared to diastolic dipping of 20-25%, dipping of < 20% was associated with 1.41 g/m^2.7 higher LVMI (95% CI -0.47, 3.29), and dipping of > 25% was associated with 1.98 g/m^2.7 higher LVMI (95% CI -0.77, 4.73), though these relationships did not achieve statistical significance. Conclusion: African American race, female sex, and greater proteinuria and sodium intake were significantly associated with blunted dipping in children with CKD. We did not find a statistically significant association between dipping and LVMI.

PMID:34772729 | DOI:10.2215/CJN.09810721

J Magn Reson Imaging. 2021 Nov 12. doi: 10.1002/jmri.27983. Online ahead of print.

ABSTRACT

BACKGROUND: Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease.

PURPOSE: To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms.

STUDY TYPE: Prospective.

POPULATION: Thirty-three patients prospectively imaged prior to prostatectomy.

FIELD STRENGTH/SEQUENCE: 3 T, field-of-view optimized and constrained undistorted single-shot DWI sequence.

ASSESSMENT: Datasets, including a noise-free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono-exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi-exponential diffusion (BID), pseudo-diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC).

STATISTICAL TEST: Levene’s test, P < 0.05 corrected for multiple comparisons was considered statistically significant.

RESULTS: The DRO results indicated minimal discordance between sites. Comparison across sites indicated that K, DK, and MEADC had significantly higher prostate cancer detection capability (AUC range = 0.72-0.76, 0.76-0.81, and 0.76-0.80 respectively) as compared to bi-exponential parameters (BID, BID*, F) which had lower AUC and greater between site variation (AUC range = 0.53-0.80, 0.51-0.81, and 0.52-0.80 respectively). Post-processing parameters also affected the resulting AUC, moving from, for example, 0.75 to 0.87 for MEADC varying cluster size.

DATA CONCLUSION: We found that conventional diffusion models had consistent performance at differentiating prostate cancer from benign tissue. Our results also indicated that post-processing decisions on DWI data can affect sensitivity and specificity when applied to radiological-pathological studies in prostate cancer.

LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

PMID:34767682 | DOI:10.1002/jmri.27983

Scand J Med Sci Sports. 2021 Nov 12. doi: 10.1111/sms.14092. Online ahead of print.

ABSTRACT

This parallel-groups randomised controlled trial investigated the effect of concurrent strength and endurance (CSE) training on running performance, biomechanics, and muscle activity during overground running. Thirty moderately-trained distance runners were randomly assigned to 10-weeks CSE training (n = 15; 33.1 ± 7.5 years) or a control group (n = 15; 34.2 ± 8.2 years). Participants ran ≥ 30 km per week and had no experience with strength training. The primary outcome measure was two-kilometre run time. Secondary outcome measures included lower limb sagittal plane biomechanics and muscle activity during running (3.89 m·s^-1 and maximal sprinting); maximal aerobic capacity (V̇O₂ max); running economy; and, body composition. CSE training improved two-kilometre run time (mean difference (MD): -11.3 s [95% CI -3.7, -19.0]; p = 0.006) and time to exhaustion during the V̇O₂ max running test (MD 59.1 s [95% CI 8.58, 109.62]; p = 0.024). The CSE training group also reduced total body fat (MD: -1.05 kg [95% CI -0.21, -1.88]; p = 0.016) while total body mass and lean body mass were unchanged. Hip joint angular velocity during the early swing phase of running at 3.89 m·s^-1 was the only biomechanical or muscle activity variable that significantly changed following CSE training. CSE training is beneficial for running performance, but changes in running biomechanics and muscle activity may not be contributing factors to the performance improvement. Future research should consider other possible mechanisms and the effect of CSE training on biomechanics and muscle activity during prolonged running under fatigued conditions.

PMID:34767655 | DOI:10.1111/sms.14092

Int J Gynaecol Obstet. 2021 Nov 12. doi: 10.1002/ijgo.14022. Online ahead of print.

ABSTRACT

OBJECTIVE: Recurrent implantation failure (RIF) is defined as failure to achieve implantation after at least three cycles of assisted reproductive treatments (ART) with minimum of four high-quality transferred embryos. Deviations in normal expression profile of endometrial tissue can lead to unsuccessful implantation. Apolipoprotein E (APOE) gene up-regulation has been reported in the endometrium during the window of implantation. The present study aimed to examine the association between APOE polymorphisms and incidence of RIF.

METHODS: In a case-control study, 100 RIF patients were compared to 100 women with at least one live child. DNA was extracted from the peripheral blood and APOE genotyping was performed through PCR, followed by RFLP method. Statistical analysis was done by Pearson chi-square test.

RESULTS: Our data revealed a significantly higher frequency for the E3/E4 genotype and E4 allele in the RIF group compared to controls. Significant differences in frequencies of the E4 allele (P=0.026; OR=2.176; 95% CI: 1.131 to 4.185) and E3/E4 genotype (P=0.038; OR=2.203; 95% CI: 1.092 to 4.443) were observed between the groups.

CONCLUSION: The E4 polymorphism is correlated with RIF occurrence in ART patients and potentially can be considered as a risk factor to the human implantation process.

PMID:34767643 | DOI:10.1002/ijgo.14022

Pharmacotherapy. 2021 Nov 12. doi: 10.1002/phar.2646. Online ahead of print.

ABSTRACT

INTRODUCTION: Filgrastim is a human granulocyte colony-stimulating factor (G-CSF). There is limited data on dosing filgrastim in obesity. The objective of this study was to compare filgrastim pharmacokinetic parameters for morbidly obese and non-obese patients after a single subcutaneous dose of filgrastim dosed per actual body weight.

METHODS: This prospective, matched-pair study (NCT01719432) included patients ≥18 years of age, receiving filgrastim at 5 mcg/kg with a weight >190% of their ideal body weight (IBW) for “morbidly obese” patients or within 80-124% of IBW for matched control patients. The control group was prospectively matched for age (within 10 years), degree of neutropenia, and gender. Filgrastim doses were not rounded to vial size, to allow more accurate assessment of exposure. Blood samples were collected at 0 (prior to dose), 2, 4, 6, 8, 12, and 24 hours after the first subcutaneous administration of filgrastim.

RESULTS: A total of 30 patients were enrolled in this prospective pharmacokinetic study, with 15 patients assigned to each arm. Non-compartmental analysis showed that the systemic clearance (Cl) was 0.111 ± 0.041 mL/min in the morbidly obese group versus 0.124 ± 0.045 mL/min in the non-obese group (p=0.44). Additionally, the mean area under the curve (AUC_0-24h ) was 49.3 ± 13.9 ng/mL x min in the morbidly obese group versus 46.3 ± 16.8 ng/mL x min in the non-obese group (p=0.6). No differences were seen in maximum concentrations (C_max ) between the two groups (morbidly obese: 48.1 ± 14.7 ng/mL vs. non-obese: 49.2 ± 20.7 ng/mL (p=0.87)). The morbidly obese group had a numerically higher, but not statistically significant, increase in time to maximum concentration (T_max ) compared to the non-obese group (544 ± 145 min vs 436 ± 156 min (p=0.06), respectively).

CONCLUSION: Calculating subcutaneous filgrastim doses using actual body weight appears to produce similar systemic exposure in morbidly obese and non-obese patients with severe neutropenia.

PMID:34767652 | DOI:10.1002/phar.2646

PLoS One. 2021 Nov 12;16(11):e0260033. doi: 10.1371/journal.pone.0260033. eCollection 2021.

ABSTRACT

Medical leaders have warned of the potential public health burden of a “parallel pandemic” faced by healthcare workers during the COVID-19 pandemic. These individuals may have experienced scenarios in which their moral code was violated resulting in potentially morally injurious events (PMIEs). In the present study, hierarchical linear modeling was utilized to examine the role of PMIEs on COVID-19 pandemic-related difficulties in psychosocial functioning among 211 healthcare providers (83% female, 89% White, and an average of 11.30 years in their healthcare profession [9.31]) over a 10-month span (May 2020 -March 2021). Reported exposure to PMIEs was associated with statistically significant poorer self-reported psychosocial functioning at baseline and over the course of 10-months of data collection. Within exploratory examinations of PMIE type, perceptions of transgressions by self or others (e.g., “I acted in ways that violated my own moral code or values”), but not perceived betrayal (e.g., “I feel betrayed by leaders who I once trusted”), was associated with poorer COVID-19 related psychosocial functioning (e.g., feeling connected to others, relationship with spouse or partner). Findings from this study speak to the importance of investing in intervention and prevention efforts to mitigate the consequences of exposure to PMIEs among healthcare providers. Interventions for healthcare providers targeting psychosocial functioning in the context of moral injury is an important area for future research.

PMID:34767617 | DOI:10.1371/journal.pone.0260033