Tag: statistics

Am J Hypertens. 2024 Mar 19:hpae033. doi: 10.1093/ajh/hpae033. Online ahead of print.

ABSTRACT

BACKGROUND: While Renin-Angiotensin System (RAS) inhibitors have a longstanding history in blood pressure control, their suitability as first-line in-patient treatment may be limited due to prolonged half-life and kidney failure concerns.

METHODS: Using a cohort design, we assessed the impact of RAS inhibitors, either alone or in combination with beta-blockers, on mortality, while exploring interactions, including those related to end-stage renal disease and serum creatinine levels. Eligible subjects were AIS patients aged 18 or older with specific subtypes who received in-patient antihypertensive treatment. The primary outcome was mortality rates. Statistical analyses included cross-sectional and longitudinal approaches, employing generalized linear models, G-computation, and discrete time survival analysis over a 20-day follow-up period.

RESULTS: In our study of 3058 AIS patients, those using RAS inhibitors had significantly lower in-hospital mortality (2.2%) compared to non-users (12.1%), resulting in a relative risk (RR) of 0.18 (95% CI 0.12-0.26). Further analysis using G-computation revealed a marked reduction in mortality risk associated with RAS inhibitors (0.0281 vs. 0.0913, Risk Difference (RD) of 6.31% or 0.0631, 95% CI 0.046-0.079). Subgroup analysis demonstrated notable benefits, with individuals having creatinine levels below and above 1.3 mg/dL exhibiting statistically significant RD (RD -0.0510 vs. -0.0895), and a significant difference in paired comparison (-0.0385 or 3.85%, CI 0.023-0.054). Additionally, longitudinal analysis confirmed a consistent daily reduction of 0.93% in mortality risk associated with the intake of RAS inhibitors.

CONCLUSION: RAS inhibitors are associated with a significant reduction in in-hospital mortality in AIS patients, suggesting potential clinical benefits in improving patient outcomes.

PMID:38501167 | DOI:10.1093/ajh/hpae033

J Biopharm Stat. 2024 Mar 19:1-28. doi: 10.1080/10543406.2024.2330213. Online ahead of print.

ABSTRACT

For the approval of a drug product, the United States Food and Drug Administration requires substantial evidence (SE) regarding effectiveness and safety of the test drug to be provided. In recent years, the use of real-world data in support of regulatory submission of pharmaceutical development has received much attention, and real-world evidence (RWE) is treated as complementary to SE by evaluating the real-world performance of the test treatment. In this article, we start by summarizing current regulatory perspectives on drug evaluation and some potential challenges in using RWE. To test for superiority in co-primary endpoints, a two-stage hybrid RCT/RWS adaptive design that combines randomized control trial for providing SE and real-world study for generating RWE is proposed. We use superiority in effectiveness and non-inferiority in safety as an example to illustrate how to implement this design. Numerical studies have shown that the proposed design has merits in reducing the required sample size compared with traditional co-primary endpoint tests while maintaining statistical power and controlling type I error inflation. The proposed design can be implemented in drug development considering co-primary endpoints, especially for oncology and rare disease drug development.

PMID:38501166 | DOI:10.1080/10543406.2024.2330213

Trauma Surg Acute Care Open. 2024 Mar 15;9(1):e001412. doi: 10.1136/tsaco-2024-001412. eCollection 2024.

NO ABSTRACT

PMID:38501133 | PMC:PMC10946341 | DOI:10.1136/tsaco-2024-001412

BMJ Neurol Open. 2024 Mar 13;6(1):e000544. doi: 10.1136/bmjno-2023-000544. eCollection 2024.

ABSTRACT

Background There are increasing reports of cases of Guillain-Barré syndrome (GBS), as an adverse event of an immune checkpoint inhibitor (ICI) but postmarket data on the incidence of this remains scarce. This study sought to conduct a comprehensive review of GBS events arising as a secondary outcome of ICI treatments in real-world patients, using the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods Data covering the period from the third quarter of 2003 to the second quarter of 2023 were extracted from the FAERS database. GBS cases (associated with the usage of avelumab, atezolizumab, ipilimumab, nivolumab and pembrolizumab) were subjected to disproportionality analysis to detect potential signals. Results A total of 2208 reports of GBS were identified within the FAERS database, with 242 of these cases (10.9%) being associated with ICIs. All five drugs exhibited a disproportionality in the reporting of adverse events, with the highest observed for avelumab (reporting OR, ROR: 29.8), followed by atezolizumab (ROR: 17.0), ipilimumab (ROR: 16.0), pembrolizumab (ROR: 11.9) and nivolumab (ROR: 8.2). Conclusion These checkpoint inhibitors are associated with a statistically significant disproportionate number of reports of GBS as an adverse event, with avelumab being the ICI with the highest association. The present pharmacovigilance study serves as a valuable tool, offering a more comprehensive and nuanced perspective on GBS associated with ICIs. This study contributes to a deeper comprehension of this rare adverse drug effect.

PMID:38501128 | PMC:PMC10946360 | DOI:10.1136/bmjno-2023-000544

Front Endocrinol (Lausanne). 2024 Mar 4;15:1334418. doi: 10.3389/fendo.2024.1334418. eCollection 2024.

ABSTRACT

BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) is a multifunctional protein involved in the chronic inflammatory process, implicated in the pathogenesis of diabetic kidney disease (DKD). However, its potential as a diagnostic and prognostic biomarker of DKD has yet to be evaluated. This study explored the clinical utility of SLPI in the diagnosis and prognosis of renal endpoint events in patients with DKD.

METHODS: A multi-center cross-sectional study comprised of 266 patients with DKD and a predictive cohort study comprised of 120 patients with stage IV DKD conducted between December 2016 and January 2022. The clinical parameters were collected for statistical analysis, a multivariate Cox proportional hazards model was used to evaluate the independent risk factors for renal endpoints.

RESULTS: Serum SLPI levels gradually increased with DKD progression (p<0.01). A significant correlation was observed between serum SLPI levels and renal function in patients with DKD. The mean follow-up duration in this cohort study was 2.32 ± 1.30 years. Multivariate Cox regression analysis showed SLPI levels≥51.61ng/mL (HR=2.95, 95% CI[1.55, 5.60], p<0.01), 24h urinary protein levels≥3500 mg/24h (HR=3.02, 95% CI[1.66, 5.52], p<0.01), Alb levels<30g/l (HR=2.19, 95% CI[1.12, 4.28], p<0.05), HGB levels<13g/dl (HR=3.18, 95% CI[1.49, 6.80], p<0.01), and urea levels≥7.1 mmol/L (HR=8.27, 95% CI[1.96, 34.93], p<0.01) were the independent risk factors for renal endpoint events in DKD patients.

CONCLUSIONS: Serum SLPI levels increased with DKD progression and were associated with clinical parameters of DKD. Moreover, elevated SLPI levels showed potential prognostic value for renal endpoint events in individuals with DKD. These findings validate the results of previous studies on SLPI in patients with DKD and provide new insights into the role of SLPI as a biomarker for the diagnosis and prognosis of DKD that require validation.

PMID:38501106 | PMC:PMC10944902 | DOI:10.3389/fendo.2024.1334418

Front Endocrinol (Lausanne). 2024 Mar 4;15:1323026. doi: 10.3389/fendo.2024.1323026. eCollection 2024.

ABSTRACT

OBJECTIVE: Although several studies have examined the relationship between thyroid function and muscle strength, their population primarily derived from Asian areas, and their results were controversial. Thus, this study aimed to explore the association between thyroid function and handgrip strength (HGS) in the U.S. population.

METHODS: A total of 1,067 participants from NHANES were categorized into three different age groups including young (<45 years), middle (45~64 years), and old (≥65 years) age groups. Thyroid function was measured by the competitive binding immune-enzymatic assays, while HGS was examined by a trained evaluator using a dynamometer. The weighted multiple linear regression models were used to examine the association between thyroid function and handgrip strength. The restricted cubic splines were employed to explore the non-linear relationship between these two variables. All statistical analyses were performed using the SPSS version 20.0 and R software.

RESULTS: After adjustment for potential covariates, FT3/FT4, but not TSH was positively associated with HGS in middle age group (β=0.091, t=2.428, P=0.016). The subgroup analysis by sex revealed that the positive association between FT3/FT4 and HGS was observed in the middle age group for both male and female participants (β=0.163, t=2.121, P=0.035; β=0.157, t=2.180, P=0.031). The RCS analysis showed a statistically significant non-linear association between FT3/FT4 and HGS in overall population (P for non-linear=0.026). After adjustment for covariates, men with low HGS had a significant lower FT3/FT4 than those without low HGS in old age group (P=0.013). There was a significant increase in TSH level for female participants with low HGS in old age group compared to those with normal HGS (P=0.048).

CONCLUSIONS: This study demonstrated FT3/FT4, but not TSH, was positively associated with HGS in middle age group, and the different association was observed in men in middle age group when participants were stratified by sex. Future longitudinal cohort study should be conducted to reveal the causal relationship between thyroid function and muscle strength.

PMID:38501102 | PMC:PMC10947195 | DOI:10.3389/fendo.2024.1323026

Front Endocrinol (Lausanne). 2024 Mar 4;15:1342240. doi: 10.3389/fendo.2024.1342240. eCollection 2024.

ABSTRACT

OBJECTIVES: The modified three-level technique for retroperitoneal laparoscopic adrenalectomy (RLA) has proven beneficial in the treatment of adrenal lesions in patients with BMI≥25 Kg/m². This paper aims to summarize our institution’s seven-year experience using this technique for all patients with Adrenal Lesions ≤ 6cm.

PATIENTS AND METHODS: Between January 2016 and December 2022. The patients underwent laparoscopic adrenal surgery were categorized into Zhang’s technique (ZT) (Three-level Technique) group and modified technique (MT) group. The fundamental characteristics and perioperative data were analyzed, with statistical significance set at p<0.05.

RESULTS: In total, 731 patients were stratified into two groups: ZT (n=448) and MT (n=283). Statistically significant distinctions were not detected between the two groups regarding sex, BMI, tumor location, tumor size, tumor type, or American Society of Anesthesiologists (ASA) score (p>0.05). The MT group demonstrated superior outcomes compared to the ZT group in terms of operative time, estimated blood loss, drainage volume, diet recovery time, complication rates, and postoperative hospitalization duration (p<0.05). 17 (4.34%) in the ZT group required unplanned adrenalectomy, while there was none in MT group (P<0.05).

CONCLUSION: MT retroperitoneal laparoscopic adrenalectomy has demonstrated its benefits in the treatment of adrenal lesions across all patients with adrenal lesions ≤ 6cm, serving as a valuable point of reference for the surgical management of adrenal diseases.

PATIENT SUMMARY: We have made modifications to the classic retroperitoneal laparoscopic adrenalectomy and achieved superior surgical outcomes, resulting in a procedure known as modified retroperitoneal laparoscopic adrenalectomy. This technique is suitable for both obese individuals and the general population with adrenal lesions ≤ 6cm.

PMID:38501101 | PMC:PMC10944954 | DOI:10.3389/fendo.2024.1342240

Front Psychiatry. 2024 Mar 4;15:1270543. doi: 10.3389/fpsyt.2024.1270543. eCollection 2024.

ABSTRACT

INTRODUCTION: Depression and anxiety are the most common mental health disorders worldwide. Internet-Delivered Cognitive Behaviour Therapy (ICBT) can reduce barriers to care to broad cross sections of the population. However, People of Diverse Ethnocultural Backgrounds (PDEGs) other than White/Caucasian underutilize mental health services and are under represented in clinical trials of psychological interventions.

METHODS: To address this research gap we adapted an evidence-based ICBT program for PDEGs. The current pilot study explores the engagement, satisfaction, and effectiveness in the adapted ICBT program by PDEGs (N=41) when benchmarked against a sample of PDEGs (N=134) who previously completed a non-adapted version of the ICBT program.

RESULTS: An intent-to-treat analyses showed that the adapted ICBT program is effective in reducing anxiety and depression symptoms among PDEGs. Large within-group pre-to post-treatment Cohen’s effect sizes of d = 1.23, 95% CI [0.68, 1.77] and d = 1.24, 95% CI [0.69, 1.79] were found for depression and anxiety, respectively. Further, 81.8% of the PDEGs who received the adapted ICBT reported overall satisfaction, 90.9% reported increased confidence in managing symptoms, and 70.7% completed majority of the psychoeducational lessons in the ICBT program.

CONCLUSION: No statistically significant differences in the clinical outcomes, engagement, and satisfaction were found between the pilot study and benchmark sample. Future directions for ICBT research with PDEGs are described.

CLINICAL TRIAL REGISTRATION: https://beta.clinicaltrials.gov/study/NCT05523492, identifier NCT05523492.

PMID:38501087 | PMC:PMC10944864 | DOI:10.3389/fpsyt.2024.1270543

Front Psychiatry. 2024 Feb 29;15:1301976. doi: 10.3389/fpsyt.2024.1301976. eCollection 2024.

ABSTRACT

BACKGROUND: Substance use is prevalent among people with mental health issues, and patients with psychosis are more likely to use and misuse substances than the general population. Despite extensive research on substance abuse among the general public in Kenya, there is a scarcity of data comparing substance use among people with and without psychosis. This study investigates the association between psychosis and various substances in Kenya.

METHODS: This study utilized data from the Neuro-GAP Psychosis Case-Control Study between April 2018 and December 2022. The KEMRI-Wellcome Trust Research Programme recruited participants from various sites in Kenya, including Kilifi County, Malindi Sub-County, Port Reitz and Coast General Provincial Hospitals, and Moi Teaching and Referral Hospital, as well as affiliated sites in Webuye, Kapenguria, Kitale, Kapsabet, and Iten Kakamega. The collected data included sociodemographic information, substance use, and clinical diagnosis. We used the summary measures of frequency (percentages) and median (interquartile range) to describe the categorical and continuous data, respectively. We examined the association between categorical variables related to psychosis using the chi-square test. Logistic regression models were used to assess the factors associated with the odds of substance use, considering all relevant sociodemographic variables.

RESULTS: We assessed a total of 4,415 cases and 3,940 controls. Except for alcohol consumption (p-value=0.41), all forms of substance use showed statistically significant differences between the case and control groups. Cases had 16% higher odds of using any substance than controls (aOR: 1.16, 95%CI: 1.05-1.28, p=0.005). Moreover, males were 3.95 times more likely to use any substance than females (aOR:3.95; 95%CI: 3.43-4.56). All the categories of living arrangements were protective against substance use.

CONCLUSION: The findings of this study suggest that psychotic illnesses are associated with an increased likelihood of using various substances. These findings are consistent with those of previous studies; however, it is crucial to investigate further the potential for reverse causality between psychosis and substance abuse using genetically informed methods.

PMID:38501084 | PMC:PMC10945606 | DOI:10.3389/fpsyt.2024.1301976

Lancet Reg Health West Pac. 2024 Mar 11;44:101043. doi: 10.1016/j.lanwpc.2024.101043. eCollection 2024 Mar.

NO ABSTRACT

PMID:38501078 | PMC:PMC10945237 | DOI:10.1016/j.lanwpc.2024.101043