Tag: statistics

Arch Pharm Res. 2025 May 19. doi: 10.1007/s12272-025-01549-x. Online ahead of print.

ABSTRACT

The use of tacrolimus (TAC), a critical immunosuppressant post transplantation, is complicated by its high pharmacokinetic variability. While the gut microbiota has gained attention as a potential contributor, few studies have assessed its role in TAC metabolism variability. This study investigated the associations between the gut microbiota and TAC metabolism rates in kidney transplant recipients during the first month post transplantation-a crucial period for adjusting TAC to achieve therapeutic levels. We recruited 20 kidney transplant recipients and profiled their gut microbiota diversity and composition from stool samples collected before transplantation and at weeks 1 and 4 post transplantation via 16S rRNA sequencing. The TAC pharmacokinetic parameters were also collected. Associations between TAC metabolism status or pharmacokinetic parameters and gut microbiota diversity and composition were evaluated. Recipients with a fast TAC metabolism rate (C₀/D ratio < 1.05 ng/mL × 1/mg) presented significantly greater changes in both bacterial alpha and beta diversity metrics at 1 week post transplantation than did those with a slow metabolism rate (C₀/D ratio ≥ 1.05 ng/mL × 1/mg). Compared with slow metabolizers, fast metabolizers were associated with a significant increase in the abundance of three bacterial genera (Faecalibacterium, Clostridia vadinBB60, and Ruminococcus) and a significant decrease in the abundance of two bacterial species (Bacteroides plebeius and Parabacteroides goldsteinii). This study revealed links between gut microbiota diversity and composition and TAC metabolism rates in kidney transplant recipients during the early posttransplant period, underscoring the importance of investigating the gut microbiota as a contributor to TAC pharmacokinetic variability. Clarifying this causal relationship could better predict inter- and intraindividual TAC pharmacokinetic variability.

PMID:40388103 | DOI:10.1007/s12272-025-01549-x

J Epidemiol Glob Health. 2025 May 19;15(1):72. doi: 10.1007/s44197-025-00415-9.

ABSTRACT

OBJECTIVE: The COVID-19 lockdown impacted interactions with the health care system and societal stress levels. Previous US-based studies suggest that pandemic lockdowns may have lowered preterm birth rates although there are mixed findings from different settings. We evaluated the impact of COVID-19 on preterm birth and low birthweight rates at two San Francisco hospitals.

METHODS: We compared rates of preterm birth (< 37 weeks) and low birthweight (< 2500 g) in San Francisco at a safety net hospital and an academic medical center during two time periods early in the COVID-19 pandemic compared with the same months from the prior year: from March to May 2019 and 2020 and August to December 2019 and 2020. We calculated crude rates for preterm birth and low birth weight as well as compared maternal and infant birth demographics and health characteristics during these same time periods using descriptive statistics. Secondly using a cross-sectional study design, we used logistic and linear regression models to evaluate risk for preterm birth, gestational age at birth, and low birthweight adjusting for confounders comparing the lockdown period with the pre-COVID year. All analyses were conducted using Stata 15.0.

RESULTS: From August to December 2019 to 2020, the preterm birth rate decreased from 13.20 to 7.96% in the combined hospital data (p < 0.01), and the low birthweight rate decreased from 11.33 to 9.70% during the same time period (p = 0.13). We did not find a comparable reduction from March to May 2019 to 2020. Maternal age at delivery was significantly younger during the lockdown period, August to December, than in the prior year (36.29 ± 5.69 versus 37.15 ± 5.68 years p < 0.01) and parity was greater (0.83 ± 1.15 versus 0.74 ± 1.04, p = 0.03) but there were no other significant differences in race or ethnicity, infant sex or type of delivery (vaginal versus Cesarean section) from 2019 to 2020. In a logistic and linear regression model adjusting for maternal age and infant sex and other confounders, the lockdown period from August to December was protective against preterm birth (OR 0.65, 95%CI 0.51-0.82) and associated with overall longer gestational duration (Coeff 0.23, 95%CI 0.07-0.39). The August to December lockdown period was also associated with greater birthweight (Coeff 43.76, 95%CI 2.19-85.34).

CONCLUSIONS: In San Francisco, COVID-19 lockdowns lowered the preterm birth and increased gestational duration in infants comparing 2019 with 2020 for August to December. The reduced in preterm birth rates may be related to the overall strict lockdown measures that San Francisco implemented compared with other US cities. WHAT THIS STUDY ADDS TO THE CLINICAL WORK?: This study suggests that COVID-19 lockdowns lowered the preterm birth rate in August -December 2020 compared with the same months in 2019 in two hospitals in San Francisco. San Francisco had strict lockdowns compared with other areas of the country and fewer deaths. The stay-at-home measures could possibly have reduced stress for pregnant women or had other positive benefits that reduced the preterm birth rate.

PMID:40388095 | DOI:10.1007/s44197-025-00415-9

Adv Ther. 2025 May 19. doi: 10.1007/s12325-025-03230-7. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of this study was to determine the number of people within glycated haemoglobin (HbA1c) targets and achieving weight-loss goals during the first 5 years after type 2 diabetes (T2D) diagnosis and to explore the relationship between early weight loss and glycaemic control in routine care in Spain.

METHODS: This was an observational retrospective study using IQVIA’s electronic medical record database, including adults aged ≤ 65 years newly diagnosed with T2D. Variables included baseline sociodemographic/clinical characteristics, yearly HbA1c and weight data, and treatment patterns. Descriptive statistics and regression analyses were used.

RESULTS: A total of 8973 people with T2D were included (mean age 53 years; mean baseline HbA1c 7.7%; obesity at diagnosis: 64%). During the first 5 years post-T2D diagnosis, 46-63% of the population did not have HbA1c < 6.5%, and > 60%, and > 80% of subjects did not achieve ≥ 5% and ≥ 10% weight loss, respectively. Early weight loss goal achievement (1st year after diagnosis) and weight loss magnitude were associated with a higher percentage of people with HbA1c < 6.5%.

CONCLUSIONS: Many individuals with T2D did not have HbA1c < 6.5% in the first 5 years after diagnosis and did not achieve ≥ 5% or ≥ 10% weight loss. Early weight loss after T2D diagnosis was associated with higher likelihood of achieving early glycaemic control.

PMID:40388088 | DOI:10.1007/s12325-025-03230-7

Adv Ther. 2025 May 19. doi: 10.1007/s12325-025-03180-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Patients diagnosed with pulmonary arterial hypertension (PAH) often present with risk factors associated with cardiovascular disease, including diabetes mellitus (DM), hypertension (HTN), and obesity. The 2022 ESC/ERS pulmonary hypertension treatment guidelines recommend initial monotherapy with an endothelin receptor antagonist (ERA) or phosphodiesterase-5 inhibitor (PDE5i) for patients with PAH and cardiopulmonary comorbidities, with treatment escalation to be considered on an individual basis. Data on safety, tolerability, and effectiveness of combination therapy in these patients are lacking.

METHODS: OPUS (prospective, observational drug registry) and OrPHeUS (retrospective, medical chart review) were multicenter US studies of patients newly initiating the ERA macitentan (2013-2020). Patients in the combined OPUS/OrPHeUS dataset with PAH receiving combination therapy with macitentan and the PDE5i tadalafil were identified. Descriptive analyses were performed for patients with ≥ 1 of DM/HTN/obesity and those without these comorbidities.

RESULTS: In OPUS/OrPHeUS, 1336 patients with PAH received macitentan plus tadalafil during the observation period. Of these, 820 (61.4%) had ≥ 1 of DM/HTN/obesity and 516 (38.6%) had none of these comorbidities at or before enrollment. Median (Q1, Q3) exposure to macitentan and tadalafil combination therapy was similar at 13.7 (3.5, 28.0) and 14.8 (5.4, 27.4) months, respectively. For patients with ≥ 1 of DM/HTN/obesity versus those without, 1-year Kaplan-Meier estimates (95% confidence limits) for survival were 92.3% (89.9, 94.1) and 91.9% (88.8, 94.1), for patients free from hospitalization were 63.6% (59.6, 67.2) and 60.0% (55.1, 64.5), and for patients persisting on combination therapy were 66.5% (63.1, 69.8) and 68.5% (64.1, 72.4). Adverse events (AE; OPUS only) were reported in 78.4% and 80.0%, respectively, with no unexpected AEs observed. There was a trend towards higher AE incidence with increasing comorbidity number and in patients with cardiovascular comorbidities who were treatment-naïve.

CONCLUSION: Patients with PAH and ≥ 1 of diabetes mellitus, hypertension, or obesity treated with macitentan and tadalafil combination therapy had similar hospitalization, survival, and safety profiles as those without these comorbidities, though patients with comorbidities initiated on combination therapy and those with multiple comorbidities may require closer monitoring. These real-world data suggest that combination therapy may be considered for patients with PAH and cardiovascular comorbidities.

TRIAL REGISTRATION: OPsumit^® Users Registry (OPUS): NCT02126943; Opsumit^® Historical Users cohort (OrPHeUS): NCT03197688; URL https://www.

CLINICALTRIALS: gov/.

PMID:40388087 | DOI:10.1007/s12325-025-03180-0

Curr Rev Musculoskelet Med. 2025 May 19. doi: 10.1007/s12178-025-09980-9. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: The discoid lateral meniscus is an abnormal variant that can lead to pain and mechanical symptoms. This review aims to summarize the clinical outcomes after surgical management of the discoid lateral meniscus. Procedures included saucerization/meniscectomies, repair, or meniscus allograft transplantation.

RECENT FINDINGS: A total of 52 articles were included, consisting of 4,503 patients (4,784 knees). Weighted preoperative and postoperative Lysholm scores were 57.8 and 88.6, respectively, with 100% of studies (27/27) finding a significant improvement in scores postoperatively. Weighted preoperative and postoperative IKDC scores were 59.6 and 87.3, respectively, with 88.9% of studies (8/9) finding a statistically significant improvement in scores. Weighted preoperative and postoperative Tegner scores were 4.8 and 7.3, respectively, with 100% of studies (5/5) finding a statistically significant improvement in scores postoperatively. Weighted preoperative and postoperative VAS scores were 5.3 and 3.2, respectively, with 100% of studies (5/5) finding a statistically improvement in scores postoperatively. Amongst patients with reported values, 209 (6.6%; range 0-23.7%) suffered retears, while there were 290 reoperations (6.0%; range: 0-36.7%). Complications included persistent pain, mechanical symptoms, or swelling (n = 115; 2-4%). Studies to date have reported good outcomes overall following surgical management of the discoid lateral meniscus, with significant improvements in PROMs. However, retear and reoperation rates within the literature have been reported to be as high as 23.7% and 36.7%, respectively.

PMID:40388072 | DOI:10.1007/s12178-025-09980-9

J Patient Rep Outcomes. 2025 May 19;9(1):55. doi: 10.1186/s41687-025-00889-y.

ABSTRACT

BACKGROUND: Patient-reported outcomes measures (PROMs) profile patient health status, have been found to be helpful in identifying high health care utilizers, and may be useful in providing targeted interventions to decrease health care costs. In 2013 the University of Utah Health (UU Health) began collecting mental and physical health PROMs using Patient Reported Outcomes Measurement Information System (PROMIS) instruments through a tool called My Evaluation (mEVAL). In 2012 UU Health began cataloguing inpatient and outpatient healthcare-associated costs. The objective of this study was to identify association of poor PROMIS physical function and depression scores with (1) likelihood of inpatient hospitalization and (2) overall inpatient healthcare costs.

METHODOLOGY: This study was a retrospective observational cohort study including patients seen at UU Health between 1/2013 and 12/2017 who completed PROMIS instruments at an outpatient visit using the mEVAL platform. PROMIS instruments were completed prior to outpatient visits. The primary outcome was time to incident hospitalization modeled by using the Cox proportional hazards approach. For cost analysis, raw inpatient healthcare costs were fitted using a median regression model. Both results were adjusted.

RESULTS: Of 92,383 people, the average age was 48 (SD 18.6); 57% were female; and 87% identified as non-Hispanic white. A total of 11,909 patients who completed one or both of the mEVAL PROMIS instruments were admitted. The average PROMIS physical function and depression scores were 44.9 and 51.1, respectively. Those with worse physical function scores and worse depression scores were more likely to be hospitalized [HR = 1.77, 95% confidence interval (CI) (1.678, 1.872); HR (95% CI) = 1.149 (1.059, 1.246), respectively]. A physical function score 1.5 SD below the mean was associated with an increased median hospitalization cost of $2496; there was no statistically significant association between depression score 1.5 SD above mean and hospitalization costs.

CONCLUSIONS: Poor physical function scores were associated with an increased risk of hospitalization and higher inpatient health costs, while poor depression scores were only associated with increased risk of hospitalization. Future work should examine if improvement in these PROMs alters these metrics.

PMID:40388054 | DOI:10.1186/s41687-025-00889-y

Laryngoscope. 2025 May 19. doi: 10.1002/lary.32271. Online ahead of print.

ABSTRACT

OBJECTIVE: Cochlear implantation in otosclerosis patients presents unique surgical and programming challenges. The success and satisfaction of these patients heavily depend on precise speech processor fitting. Increased bone growth and tissue mass associated with otosclerosis can hinder electrical current flow, adding resistance to stimuli transmission to ganglion cells. This study aimed to evaluate mid- and long-term cochlear implant fitting in otosclerosis patients compared to a control group.

METHODS: This was a monocentric retrospective case-control study conducted at a tertiary referral center comparing patients with far advanced otosclerosis and a control group of post-lingually deafened individuals from the same database. Data collected included: age, sex, etiology, hearing deprivation duration, implantation age and side, surgical details, postoperative complications (e.g., tinnitus, dizziness, or facial nerve stimulation), hearing tests, and cochlear implant fitting details.

RESULTS: The study analyzed 80 patients: 29 with otosclerosis and 51 controls. Higher impedances were seen in the otosclerosis group at 2 and 5 years, statistically significant for basal, middle, and overall electrodes at 2 years. Higher C- and T-levels for apical electrodes at 2 years were identified, and neural response telemetry thresholds were significantly higher for medial and apical electrodes in otosclerosis patients at 2 years. Despite these differences, auditory outcomes at 5 years were comparable between groups.

CONCLUSION: These findings suggest significant tissue remodeling at the cochlear apex in otosclerosis patients, likely increasing resistance to electrical currents delivered by the implant. This highlights the importance of tailored programming and long-term monitoring for otosclerosis patients.

LEVEL OF EVIDENCE: Level 3.

PMID:40384602 | DOI:10.1002/lary.32271

Spine (Phila Pa 1976). 2025 May 19. doi: 10.1097/BRS.0000000000005392. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective Cohort Study.

OBJECTIVE: This study aimed to compared radiographic and clinical outcomes in Adolescent Idiopathic Scoliosis (AIS) patients undergoing posterior spinal fusion (PSF) with and without thoracoplasty.

SUMMARY OF BACKGROUND DATA: Scoliosis is a three-dimensional deformity. As a result, patients often have an associated rib cage deformity, with clinical and aesthetic implications. Direct vertebral rotation (DVR) allows for some reduction of the rib hump; however, the deformed ribs remain deformed. Rib resection has been utilized to further reduce the rib hump, however there are concerns of increased pain, operative time, and blood loss.

METHODS: Retrospective review of 400 AIS patients undergoing PSF between 2018-2023. Patients were stratified based on those who underwent rib resectioning (RR) and those who did not (Non-Rib Resection, N-RR). Radiographic, surgical, and clinical outcomes were compared. Clinical outcomes were collected utilizing SRS-22 and our institution’s activity questionnaire, validated via “test-retest” method. All data is presented as medians, IQR, frequencies, and percents. Fisher’s Exact, Chi-squared, and Wilcoxon rank-sum tests were used.

RESULTS: 153 patients were in the RR group, 247 were in the N-RR. Preoperative rib hump was not statistically significant between the two groups (P=0.49). Final rib hump was 16.3 mm in RR patients and 29.8 mm in N-RR (P<0.001). RR had 60.5% rib hump correction; N-RR had 30.4% correction (P<0.001). Patient reported self-image (P=0.02) and mental health (P=0.01) scores had significantly improved in RR. No differences in 90-day complication rates (P=0.19) or self-reported return to activities (P>0.05).

CONCLUSION: Rib resectioned patients had approximately double the amount of rib hump correction at 60.5%, compared to those who did not undergo rib resectioning at 30.4%, with no increase in the rate of complications. RR patients had improved self-reported self-image and mental health scores, with no difference in timing for return to activities.

PMID:40384585 | DOI:10.1097/BRS.0000000000005392

Nurs Crit Care. 2025 May;30(3):e70055. doi: 10.1111/nicc.70055.

ABSTRACT

BACKGROUND: Increased workload is associated with a higher prevalence of missed nursing care.

AIM: Describe the prevalence of missed care in intensive care units (ICUs) and identify the workload scale most strongly associated with this prevalence.

STUDY DESIGN: A cross-sectional survey was combined with a longitudinal study conducted in 2024, between 15 January and 15 April, in France to assess the workload. A total of 1271 nurses working in 61 ICUs completed the questionnaire one time per shift.

RESULTS: A total of 72.3% of nurses reported at least one missed care. The Nursing Activities Score provided the strongest association with the prevalence of missed care compared to patient-to-nurse ratio and the Practice Environment Scale of the Nursing Work Index.

CONCLUSION: The prevalence of missed care and nursing workload was high. Nurses tended to focus on direct patient care.

RELEVANCE TO CLINICAL PRACTICE: Continuously assessing the prevalence of missed care can be a valuable tool for managing workload in ICUs.

PMID:40384582 | DOI:10.1111/nicc.70055

Stat Med. 2025 May;44(10-12):e70124. doi: 10.1002/sim.70124.

ABSTRACT

The MCP-Mod approach by Bretz et al. is commonly applied for dose-response testing and estimation in clinical trials. The MCP part of MCP-Mod was originally developed to detect a dose-response signal using a multiple contrast test, but it is not appropriate to make a specific claim that the drug has a positive effect at an individual dose. In this paper, we extend the MCP-Mod approach to obtain confirmatory p-values for detecting a dose-response signal as well as for the pairwise comparisons of the individual doses against placebo. We apply the closed test principle from Marcus et al. to the optimal contrast tests based on a candidate set of plausible dose-response shapes available at the planning stage of a clinical trial. We show that the contrast coefficients have to be optimized under suitable constraints to guarantee strong Type 1 error rate control at a pre-specified significance level. Motivated by a recent clinical trial, we evaluate the operating characteristics of the proposed methods in a comprehensive simulation study.

PMID:40384574 | DOI:10.1002/sim.70124