Tag: nevin manimala

Clin Trials. 2025 Jan 2:17407745241304059. doi: 10.1177/17407745241304059. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical trials handle a huge amount of data which can be used during the trial to improve the ongoing study conduct. It is suggested by regulators to implement the remote approach to evaluate clinical trials by analysing collected data. Central statistical monitoring helps to achieve that by employing quantitative methods, the results of which are a basis for decision-making on quality issues.

METHODS: This article presents a scoping review which is based on a systematic and iterative approach to identify and synthesise literature on central statistical monitoring methodology. In particular, we investigated the decision-making processes (with emphasis on quality issues) of central statistical monitoring methodology and its place in the clinical trial workflow. We reviewed papers published over the last 10 years in two databases (Scopus and Web of Science) with a focus on data mining algorithms of central statistical monitoring and its benefit to the quality of trials.

RESULTS: As a result, 24 scientific papers were selected for this review, and they consider central statistical monitoring at two levels. First, the perspective of the central statistical monitoring process and its location in the study conduct in terms of quality issues. Second, central statistical monitoring methods categorised into practices applied in the industry, and innovative methods in development. The established methods are discussed through the prism of categories of their usage. In turn, the innovations refer to either research on new methods or extensions to existing ones.

DISCUSSION: Our review suggests directions for further research into central statistical monitoring methodology – including increased application of multivariate analysis and using advanced distance metrics – and guidance on how central statistical monitoring operates in response to regulators’ requirements.

PMID:39744904 | DOI:10.1177/17407745241304059

Environ Sci Process Impacts. 2025 Jan 2. doi: 10.1039/d4em00376d. Online ahead of print.

ABSTRACT

Background: Exposure to particulate matter <2.5 μm (PM_2.5) is linked to chronic obstructive pulmonary disease (COPD), but most studies lack individual PM_2.5 measurements. Seasonal variation and their impact on clinical outcomes remain understudied. Objective: This study investigated the impact of PM_2.5 concentrations on COPD-related clinical outcomes and their seasonal changes. Methods: A multicentre panel study enrolled 105 COPD patients (age range: 46-82) from July 2019 to August 2020. Their mean forced expiratory volume in 1 second after bronchodilation was 53.9%. Individual PM_2.5 levels were monitored continuously with indoor measurements at residences and outdoor data from the National Ambient Air Quality Monitoring Information System. Clinical parameters, including pulmonary function tests, symptom questionnaires (CAT and SGRQ-C), and impulse oscillometry (IOS), were assessed every three months over the course of one year. Statistical analysis was conducted using a linear mixed-effect model to account for repeated measurements and control for confounding variables, including age, sex, smoking status and socioeconomic status. Results: The mean indoor and outdoor PM_2.5 concentrations were 16.2 ± 8.4 μg m^-3 and 17.2 ± 5.0 μg m^-3, respectively. Winter had the highest PM_2.5 concentrations (indoor, 18.8 ± 11.7 μg m³; outdoor, 22.5 ± 5.0 μg m^-3). Higher PM_2.5 concentrations significantly correlated with poorer St. George’s Respiratory Questionnaire for COPD (SGRQ-C) scores and increased acute exacerbations, particularly in winter. Patients of lower socioeconomic status were more vulnerable. Increased PM_2.5 concentrations were also associated with amplified small airway resistance (R5-R20). Conclusions: PM_2.5 concentration changes are positively correlated with poorer SGRQ-C scores and increased acute exacerbations in COPD patients with significant seasonal variations, especially in winter.

PMID:39744880 | DOI:10.1039/d4em00376d

Eur J Breast Health. 2025 Jan 1;21(1):1-8. doi: 10.4274/ejbh.galenos.2024.2024-8-1.

ABSTRACT

We investigate the evidence for adverse effects of intraparenchymal and peritumoral application of isosulfan blue dye in sentinel lymph node (SLN) mapping in breast cancer patients. A meta-analysis on the adverse effects of intraparenchymal and peritumoral application of isosulfan application in SLN mapping was conducted using Medline and Embase databases up to 2023. Procedure-based adverse reactions were divided into three grades: Grade I (allergic skin reactions), Grade II (hypotension) and Grade III (requiring vasopressor support). Heterogeneity was expressed with I-squared and tau statistics. Subgroup analysis was conducted for administrative route. Univariable meta-regression was performed to assess dose-response effect on adverse reactions. Sensitivity analysis was conducted using fixed effect modelling. A total of 19,183 patients were identified from eight studies. The pooled total adverse event rate after isosulfan administration was 11.65 events per 1,000 patients [95% confidence interval (CI) 7.44-18.19]. The rate of Grade I reactions was 7.96 per 1,000 (95% CI 4.08-15.46); Grade II 0.08 per 1,000 (95% CI 0.00-1.31), Grade III 1.86 per 1,000 (95% CI 0.94-3.66), with no reported mortalities. Intraparenchymal administration was associated with 15.16 events per 1,000 (95% 8.64-26.45), versus 7.04 events per 1,000 (95% CI 5.24-9.45) in peritumoral administration (p=0.02). Univariable meta-regression did not show a significant association between volume of dye infused and total adverse events (-0.164 events per mL, 95% CI -0.864 to 0.534, p=0.645). Isosulfan has low adverse event rates regardless of injection technique or volume administered. Clinicians should have a high level of confidence in its use as an agent for SLN mapping, especially when administering it peritumorally.

PMID:39744877 | DOI:10.4274/ejbh.galenos.2024.2024-8-1

Urogynecology (Phila). 2024 Dec 31. doi: 10.1097/SPV.0000000000001642. Online ahead of print.

ABSTRACT

IMPORTANCE: Wound complications after obstetric anal sphincter injury (OASI) can amplify morbidity and affect quality of life.

OBJECTIVE: The objective of this study was to evaluate for characteristics associated with wound complications after OASI.

STUDY DESIGN: This was a retrospective cohort study of patients with an OASI who were evaluated in a postpartum pelvic floor healing clinic between November 1, 2020, and May 16, 2023. Our primary outcome was to identify factors associated with wound complications (wound infection or breakdown, antibiotic treatment, or surgical intervention). We hypothesized that operative vaginal delivery would be associated with wound complications and that peripartum antibiotics would be protective. Statistical analyses included t tests, chi-square test, Fisher exact test, and multivariable logistic regression.

RESULTS: Of 332 patients with an OASI, 74 (22.3%) experienced a wound complication. There were 31 (9.3%) wound infections and 62 (18.7%) wound breakdowns; 50 (15.1%) patients received additional antibiotics, and 20 (6.0%) underwent additional surgical intervention. On univariate analysis, those with wound complications were older (31.9 vs 30.6 years, P = 0.01) and more likely to have had an episiotomy (23.0% vs 12.5%, P = 0.03). On multivariable logistic regression, older maternal age was associated with wound complication (odds ratio, 1.1, 95% CI, 1.01-1.13, P = 0.03), and peripartum antibiotics were associated with decreased odds of wound complication (odds ratio, 0.57, 95% CI, 0.33-0.97, P = 0.04). Patients with wound complications were more likely to undergo in-office procedures (P < 0.001) and report postpartum pain (P < 0.001), urinary incontinence (P = 0.02), fecal urgency (P = 0.02), and other symptoms (P = 0.04).

CONCLUSIONS: Older maternal age was associated with wound complications after OASI, while peripartum antibiotics were protective. Patients with wound complications were more likely to report symptoms of pelvic floor disorders.

PMID:39744876 | DOI:10.1097/SPV.0000000000001642

Stroke. 2025 Jan 2. doi: 10.1161/STROKEAHA.124.048024. Online ahead of print.

ABSTRACT

Noninferiority trials aim to prove that the efficacy, defined in terms of a key clinical outcome, of a new treatment is not meaningfully worse than that of an established active control. Noninferiority trials are important when other aspects of care can be improved, such as convenience, toxicity, costs, and safety (nonefficacy benefits). While the motivation for a noninferiority trial is straightforward, the design, execution, and interpretation of these trials is not a trivial task. Several safeguards that protect superiority trials from incorrect conclusions do not apply or even work in reverse for noninferiority trials. This review aims to provide stroke clinicians and researchers with a general overview of noninferiority trials and a deeper understanding of 10 pitfalls they should consider when designing and interpreting such trials.

PMID:39744847 | DOI:10.1161/STROKEAHA.124.048024

Am J Med Genet B Neuropsychiatr Genet. 2025 Jan 2:e33020. doi: 10.1002/ajmg.b.33020. Online ahead of print.

ABSTRACT

Externalizing traits and behaviors are broadly defined by impairments in self-regulation and impulse control that typically begin in childhood and adolescence. Externalizing behaviors, traits, and symptoms span a range of traditional psychiatric diagnostic categories. In this study, we sought to generate an algorithm that could reliably identify transdiagnostic childhood-onset externalizing cases and controls within a university hospital electronic health record (EHR) database. Within the Vanderbilt University Medical Center (VUMC) EHR, our algorithm identified cases with a clinician-validated positive predictive value of 90% and controls with a negative predictive value of 88%. In individuals of genetically defined European ancestry (CEU-clustered; N_case = 487, N_control = 5638), case status was significantly associated with psychiatric comorbidity and with elevated externalizing polygenic scores (OR: 1.20; 95% CI: 1.09-1.33; p = 1.14 × 10^-3; based on published genome-wide association data). To test whether our cohort definitions could be applied to generate novel genetic insights, we examined rare (allele frequency < 0.5%) copy number variation. An association (OR: 9.70; CI: 3.24-29.0) was identified in the CEU-clustered cohort on chromosome 2 (chr2: 45,408,678-45,551,530; duplication), although the statistical strength of this association was modest (p = 0.052). We also examined the role of an externalizing burden score based on the number of externalizing diagnoses present in cases and found similar results to our case-control analysis. This analysis identified several other statistically significant CNV region associations. This study provides a framework for identifying childhood externalizing case-control cohorts within an EHR. Future work should validate this framework within other health systems. A broadly applicable algorithm, like this one, may allow for detection of rare outcomes or outcomes in populations historically excluded from genomic research through meta-analysis of data across health care systems.

PMID:39744833 | DOI:10.1002/ajmg.b.33020

Acta Obstet Gynecol Scand. 2025 Jan 2. doi: 10.1111/aogs.15022. Online ahead of print.

ABSTRACT

INTRODUCTION: Evidence suggests that gestational diabetes mellitus (GDM) is associated with subsequent cardiovascular disease; however, it is unclear what impact changes in screening and diagnostic criteria have had on the association of GDM with long-term outcomes such as cardiovascular disease. The purpose of this study was to determine the association between GDM and subsequent cardiovascular disease during a period of rising gestational diabetes diagnosis in England. Specifically, associations were compared before and after 2008, when national guidelines supporting risk factor-based screening were introduced.

MATERIAL AND METHODS: We conducted a cohort study using routinely collected data from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. The study consisted of persons aged 15-45 years with a livebirth or stillbirth between 1998 and 2017 and without a history of cardiovascular disease or pre-pregnancy diabetes mellitus. Cox proportional hazards models, with propensity score weighting using matching weights, were used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the association of GDM diagnosis in the first recorded pregnancy with subsequent cardiovascular disease.

RESULTS: Among 232 315 individuals, the incidence of cardiovascular disease was 6.6 per 1000 person-years among those with GDM and 2.2 per 1000 person-years among those without GDM over a mean follow-up duration of 5.8 years. The overall aHR, 95% CI was 1.91 (1.41, 2.60). Diagnosis of GDM increased over the study period, from 0.7% in 1998-99 to 5.3% in 2017. The effect size was not markedly different in the years before (1998-2007: adjusted HR 2.05, 95% CI 2.05 1.35, 3.12) and after 2008 (2008-2017: adjusted HR 1.79, 95% CI 1.15, 2.80).

CONCLUSIONS: There was a strong association of GDM with cardiovascular disease after accounting for social and demographic factors and multiple comorbidities, and this association was present both before and after 2008, when national gestational diabetes screening criteria were established.

PMID:39744821 | DOI:10.1111/aogs.15022

Int J Clin Pharmacol Ther. 2024 Dec 31. doi: 10.5414/CP204652. Online ahead of print.

ABSTRACT

BACKGROUND: Serratia marcescens has recently been categorized as low-risk for AmpC β-lactamase inducible production, but research on outcomes in Serratia bacteremia by antibiotic choice is limited.

OBJECTIVES: This study examined the clinical characteristics and outcomes of patients with ceftriaxone-susceptible Serratia bacteremia who received AmpC-directed β-lactam therapy vs. narrower spectrum therapies.

MATERIALS AND METHODS: Records of hospitalized adults with at least one positive blood culture for Serratia, over an 8-year period, across seven hospitals in an integrated health care system, were reviewed.

RESULTS: Of the 73 identified patients, 17 (23.3%) received carbapenem-based therapy. More than half of cases were community-acquired, with urological and intravenous drug use being the most common sources. While there was a trend toward lower mortality in carbapenem-treated patients (14.8 vs. 0%; p = 0.10), this was not statistically significant. The composite outcome of clinical failure was also not significant. However, compared to non-carbapenem-treated patients, carbapenem-treated patients had longer treatment duration (13 vs. 15 days; p = 0.02), prolonged hospital stays (5 vs. 11 days; p < 0.001), and higher infection-related readmission rates (17.6 vs. 3.6%; p = 0.04). A subset analysis of the 56 non-carbapenem treated patients found no significant difference in 30-day mortality or clinical failure between cefepime and non-cefepime-containing subgroups.

CONCLUSION: Our study found that cefepime- or carbapenem-based therapy may have limited clinical relevance in the treatment of Serratia bacteremia when the strains are initially susceptible to ceftriaxone, highlighting the importance of antibiotic stewardship to prevent emergence of multidrug resistant organisms.

PMID:39744800 | DOI:10.5414/CP204652

Emerg Med Australas. 2025 Feb;37(1):e14559. doi: 10.1111/1742-6723.14559.

ABSTRACT

OBJECTIVES: Somatic symptom and related disorders (SSRDs) are complex disorders that are commonly encountered in tertiary paediatric settings. Despite this, little is known about ED use prior to hospital admission. We aimed to describe the pattern of ED use in a cohort of children and adolescents who were subsequently admitted to hospital with SSRD and to identify factors associated with ED presentations.

METHOD: We conducted a retrospective review of the electronic medical records of 123 patients admitted with SSRD to ascertain their ED contact in the 12 months preceding their initial admission. Documentation about patient and presentation characteristics, ED management and discharge recommendations were recorded. Descriptive statistics, including Fisher’s Exact Test, were used.

RESULTS: Our patient group (65.9% female) had a median age of 14.3 years (range 7.3-18.3 years). Patient and presentation characteristics differed little by frequency of presentation to the ED; the symptom of pain was the only significant factor associated with the multiple ED presentations (P = 0.015). Documentation of a possible SSRD presentation in ED was significantly associated with the recommendation for mental health follow-up (P = 0.005), however engagement with mental healthcare at the time of a patient’s initial admission was uncommon.

CONCLUSIONS: Children and adolescents with SSRD who go on to have a hospital admission present frequently to EDs, especially in the setting of pain symptoms. Training of ED clinicians in diagnosing SSRD appears indicated, as is the development of local care pathways that may obviate the need for hospital admission in at least some patients.

PMID:39744779 | DOI:10.1111/1742-6723.14559

Emerg Med Australas. 2025 Feb;37(1):e14552. doi: 10.1111/1742-6723.14552.

ABSTRACT

OBJECTIVE: To compare the frequency of clinically significant missed injuries in clinically stable trauma patients undergoing initial whole-body computed tomography (WBCT) versus selective imaging. Secondary objectives include comparisons of radiation exposure, incidental findings, ED length of stay (LOS), hospital LOS and mortality.

METHODS: We performed a retrospective cohort study of trauma activations at a tertiary trauma centre in patients with normal vital signs from 1st January 2022 to 31st December 2022. Data were collected from the trauma registry and chart review of medical records.

RESULTS: A total of 665 patients were included with 42% (n = 277) receiving a WBCT, compared to 58% (n = 388) undergoing selective imaging. Most patients (52%) did not have any traumatic axial injuries identified. Missed injuries were identified in 0.8% (n = 3/388) of patients in the selective imaging cohort, with no adverse patient outcomes or major alteration to inpatient management. No missed injuries were identified in the WBCT group. Mortality was rare (0.9%, n = 6/665), occurring exclusively in elderly patients and mostly attributed to non-traumatic pathologies. Patients undergoing WBCT had a significantly increased likelihood of incidental findings (75% vs 35%, P < 0.001), increased radiation exposure (mean 24.67 vs 8.19 millisieverts [mSv], P < 0.001), longer ED LOS (9.86 vs 8.43 h, P = 0.012) and a higher likelihood of admission (65.3% vs 55.7%, P = 0.012).

CONCLUSIONS: Missed injuries were rare and without major complications in this clinically stable cohort. The liberal use of WBCT, despite low rates of missed injuries, morbidity and mortality, suggests over-utilisation of WBCT for ‘mechanism only’ traumas.

PMID:39744774 | DOI:10.1111/1742-6723.14552