Category: Statistics

Intensive Care Med. 2024 Oct 17. doi: 10.1007/s00134-024-07667-2. Online ahead of print.

ABSTRACT

PURPOSE: Antiseptic bathing has garnered attention in an effort to reduce hospital-acquired infections. Previous studies have shown the efficacy of antiseptic bathing in high-risk environments, such as intensive care units (ICUs), using chlorhexidine. In this study we aimed to evaluate the effectiveness of octenidine as a potential alternative due to its established popularity and widespread use in Europe.

METHODS: We compared the rates of ICU-acquired primary bacteremia and ICU-acquired multidrug-resistant organisms (MDROs) in a multicenter, cluster-randomized, double-blind, placebo-controlled, cross-over study using octenidine-impregnated and placebo washcloths. On 44 ICUs in 23 hospitals throughout Germany, we compared individual ICUs with themselves over two 12-month time periods. All data were obtained digitally via hospital information systems as individual ward-movement data and microbiological test results; both endpoints were algorithmically derived.

RESULTS: 104,039 ICU episodes from 93,438 patients with 712,784 microbiological test results were analyzed, thereby detecting 1508 cases of ICU-acquired primary bacteremia and 1871 cases of ICU-acquired MDRO. Bathing with octenidine-impregnated washcloths prevented ICU-acquired primary bacteremia; a risk reduction of 17% was seen homogeneously across all participating ICUs (adjusted hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.75; 0.92], p = 0.0003). This reduction affected predominantly coagulase-negative staphylococci (53%) and enterococci (17%). However, no intervention effect was seen for ICU-acquired MDROs (adjusted HR 0.98, 95% CI [0.83; 1.15]). Heterogeneity among intra-ICU intervention effects on MDRO acquisition was substantial.

CONCLUSIONS: Antiseptic bathing with octenidine may be effective in preventing ICU-acquired primary bacteremia, particularly due to Gram-positive bacteria and common skin commensals.

PMID:39417875 | DOI:10.1007/s00134-024-07667-2

Intensive Care Med. 2024 Oct 17. doi: 10.1007/s00134-024-07676-1. Online ahead of print.

ABSTRACT

PURPOSE: Net ultrafiltration (UF_NET) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0 ml·h^-1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UF_NET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care.

METHODS: In this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24 h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72 h a UF_NET ≥ 100 ml·h^-1, adjusted using a functional hemodynamic protocol (intervention), or a UF_NET ≤ 25 ml·h^-1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population.

RESULTS: Between June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was -2650 [-4574; -309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736-6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms.

CONCLUSION: In patients with vasopressors, a UF_NET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care.

PMID:39417870 | DOI:10.1007/s00134-024-07676-1

Eur J Appl Physiol. 2024 Oct 17. doi: 10.1007/s00421-024-05629-6. Online ahead of print.

ABSTRACT

Gas exchange data acquired repeatedly under the same exercise conditions are assembled together to improve the kinetic parameters of breath-by-breath oxygen uptake. The latter are provided by the non-linear regression procedure, together with the corresponding estimators of the width of the Confidence Intervals (i.e., the Asymptotic Standard Errors; ASEs). We tested, for two different assembling procedures, whether the range of values identified by the ASE actually correspond to the 95% Confidence Interval. Ten O₂ uptake responses were acquired on 10 healthy volunteers performing a square-wave moderate-intensity exercise. Kinetic parameters were estimated running the non-linear regression with a mono-exponential model on an increasingly greater number of responses (Nr, from 1 to 10), assembled together using the “stacking” and the “1-s-bins” procedures. Kinetic values obtained assembling together the 10 repetitions were assumed as “true” values. The time constant was not affected by Nr or by the assembling procedure (ANOVA; p>0.54 and p>0.16, respectively). The corresponding ASE decreased according to Nr (ANOVA; p=0.000), being significantly smaller for the “1-s-bins” procedure compared to the “stacking” one (ANOVA; p<0.001). Excluding 20s at the start of the fitting window, the range of values identified with the ASE provided by the “1-s-bins” and the “stacking” procedures included the “true” value in 85% and in 95% of cases, respectively. The “stacking” procedure should be preferred since it yielded ASEs for the time constant that provided a range of values satisfying the statistical meaning of the width of the Confidence Intervals, at the given degree of probability.

PMID:39417864 | DOI:10.1007/s00421-024-05629-6

Graefes Arch Clin Exp Ophthalmol. 2024 Oct 17. doi: 10.1007/s00417-024-06598-4. Online ahead of print.

ABSTRACT

PURPOSE: To assess the efficacy of adding Ahmed’s sub-flap mattress suture to deep sclerectomy (DS).

METHODS: Forty eyes with open angle glaucoma were assigned randomly into two groups: Group A: underwent DS with Ahmed’s sub-flap mattress suture. Group B: underwent conventional DS. Patients were followed up closely for 6 months with serial IOP measurements and ultrasound biomicroscopy (UBM) was used to assess the surgical site functionally and anatomically at the first and sixth month.

RESULTS: Adding Ahmed’s sub-flap mattress suture improved the IOP lowering effect of DS significantly from 43% in group B to 53% in group A at 6-month (p = 0.027). IOP in group A was at 1 week, 1 month and 6-month visits (7.9 ± 1.3, 11.7 ± 2.2 and 13.3 ± 1.9 mmHg respectively) compared to group B (10.1 ± 4.6, 14.1 ± 5.2 and 16.8 ± 4.1 mmHg respectively) (p = 0.025, 0.041 and 0.001 respectively). UBM parameters were significantly larger in group A at 1 and 6 months. Strong statistically significant negative correlations were established between IOP and all the UBM parameters apart from intrascleral lake height at the first and sixth month (p < 0.01 in all of them). Finally, significant correlations were found between IOP at 6 months and whole bleb anteroposterior length and height at 1 month (p = 0.001).

CONCLUSION: Adding Ahmed’s sub-flap mattress suture to routine DS is an effective economical addition that will enhance the IOP lowering effect of DS. Also, assessment of the bleb by UBM is useful in predicting the success of deep sclerectomy surgery.

PMID:39417853 | DOI:10.1007/s00417-024-06598-4

Acta Diabetol. 2024 Oct 17. doi: 10.1007/s00592-024-02374-2. Online ahead of print.

ABSTRACT

BACKGROUND: Diabetic nephropathy (DN) is a grave complication and the most common renal dysfunction of diabetes mellitus. Genetic factors, including Apolipoprotein E (APOE) isoforms, have been implicated in the pathogenesis of DN.

METHODS: A total of 577 type 2 Diabetes mellitus subjects were categorized into diabetes non-nephropathic (Controls: n = 321), diabetes nephropathic (DN: n = 256) groups. Demographic, clinical, and biochemical parameters including age, BMI, lipid profiles (TC, LDL-C, HDL-C, TG), glucose metabolism (plasma glucose, HbA1c, serum insulin), renal function (UACR, PCR), and blood pressure (SBP, DBP) were assessed. APOE variant frequencies were determined using restriction fragment length polymorphism (RFLP) analysis, validated against Hardy-Weinberg equilibrium (HWE), and statistically correlated with each clinical and biochemical parameter.

RESULTS: The DN group had an increased prevalence of hypertension, fatty liver, and dyslipidemia compared to the Control group. Biochemical analyses revealed elevated levels of TC (213.41 mg/dL vs. 189.32 mg/dL), LDL-C (134.46 mg/dL vs. 107.56 mg/dL), and reduced HDL-C (58.13 mg/dL vs. 65.32 mg/dL) in DN cases compared to Controls (all p < 0.0001). The APOE variants distribution showed a significant increase in E2 allele frequency (69.1% vs. 15.3%) and corresponding homozygous genotype (E2/2: 42.2% vs. 5.6%) in DN cohorts.

CONCLUSION: The study found a higher frequency of E2 allele in the DN group compared to Controls, though no statistically significant risk of DN was linked to this allele. The results suggest a potential association for APOE polymorphisms, requiring broader studies to clarify the role of APOE polymorphisms in DN susceptibility.

PMID:39417844 | DOI:10.1007/s00592-024-02374-2

Addiction. 2024 Oct 17. doi: 10.1111/add.16688. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: In 2018, the country of Georgia legalized cannabis for recreational use and decriminalized limited possession. This study aimed to assess whether cannabis use increased among young adults (ages 18-29 years) in Georgia after national policy changes and to evaluate whether perceived access became easier after legalization and current risk factors of young adult cannabis use.

METHODS: We used data from the Georgian nationally representative survey administered in 2015 (n = 1308) and 2022 (n = 758), before and after decriminalization. We performed appropriate bivariate analyses and multivariable linear and logistic regressions to assess the following: legalization’s impact on cannabis use; perceived difficulty to obtain cannabis; age of first use; differences in use between females and males; and factors associated with current use.

FINDINGS: Among young adults lifetime prevalence of cannabis use was similar in 2015 (17.3%) and 2022 (18.1%) [Odds Ratio (95% confidence interval) = 1.1 [0.7, 1.6], P = 0.726). Annual prevalence (7% in 2015 vs 7.7% in 2022) was also similar (1.1 [0.7, 2.0], P = 0.650). In 2022 it was less difficult to obtain cannabis than in 2015 (0.5 [0.4, 0.8], P = 0.021). The age of first use increased statistically significantly (18.1 years in 2015 vs 19.1 in 2022, P = 0.003). In 2022, annual prevalence of use was lower among females (1.9% vs 13.1%; OR = 0.1 [0.0, 0.3], P < 0.0001) and higher among those who gambled (11.7% vs 4.4%; OR = 3.2 [1.5, 6.8], P < 0.003). Males initiated cannabis use at an earlier age (19.1 years vs 20.6 for females, P = 0.03), and could obtain cannabis easier than females (P < 0.0001).

CONCLUSION: There was a minimal shift of cannabis use in young adults following implementation of recreational cannabis use legalization in Georgia. Males and people who gambled were at higher risk of cannabis use.

PMID:39417804 | DOI:10.1111/add.16688

Knee. 2024 Oct 15;51:258-267. doi: 10.1016/j.knee.2024.09.013. Online ahead of print.

ABSTRACT

BACKGROUND: Knee osteoarthritis (KOA) is a globally prevalent condition leading to joint pain and disabilities. Surgical interventions such as opening-wedge high tibial osteotomy (OWHTO) and opening-wedge distal tuberosity osteotomy (OWDTO) aim to alleviate symptoms and delay disease progression. Quadriceps strength, crucial for knee function, may decline postoperatively, affecting patient outcomes. However, little is known about quadriceps strength variation after OWHTO and OWDTO. This study investigated changes in quadriceps strength before and after OWHTO and OWDTO.

METHODS: This retrospective study included patients who underwent OWHTO or OWDTO between 2016 and 2022. Quadriceps strength and demographic and surgical data were collected preoperatively and at 6 and 12 months postoperatively. Statistical analyses were performed to compare changes in quadriceps strength over time.

RESULTS: Of 120 knees, 52 (OWHTO, 27; OWDTO, 25) were included in this study. Quadriceps strength increased over 12 months post-OWHTO, significantly improving at 12 months compared to the preoperative and 6-month values. In OWDTO, the strength improved but not significantly.

CONCLUSIONS: Quadriceps strength improved following OWHTO and OWDTO, with OWHTO showing significant enhancements. Future studies should investigate the relationship between quadriceps strength and functional outcomes and guide rehabilitation strategies for improved postoperative recovery.

PMID:39413454 | DOI:10.1016/j.knee.2024.09.013

Semin Arthritis Rheum. 2024 Oct 11;69:152561. doi: 10.1016/j.semarthrit.2024.152561. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the association of disease-modifying antirheumatic drugs (DMARDs) and risk of incident interstitial lung disease (ILD) among patients with rheumatoid arthritis (RA) using a systematic literature review and meta-analysis.

METHODS: We performed a systematic literature review and meta-analysis of studies examining the association of DMARDs with incident RA-ILD. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to November 2023 for randomized controlled trials (RCTs), observational studies, and post-marketing surveillance studies that investigated adults with RA and compared DMARDs of interest with placebo, no DMARDs, or other DMARDs. The outcome was incident ILD. We summarized the literature on DMARDs and incident RA-ILD risk. Among studies with sufficient quality, we performed meta-analyses to obtain odds ratios (OR) and 95 % confidence intervals (95 %CI) using the Mantel-Haenszel method.

RESULTS: Among 3,612 studies, we identified a total of 40 papers that encompassed 486,465 patients with RA and 3,928 incident ILD outcomes that were included in the final systematic review and meta-analysis. Among the studies, 24 were RCTs, 4 were prospective cohort studies, 9 were retrospective cohort studies, 2 were case-control studies, and 1 was a post-marketing surveillance study. The pooled analysis from RCTs revealed no statistically significant difference in the odds of ILD development for any specific DMARD across all comparisons examined. The largest identified RCT (Oral Surveillance trial) of tofacitinib (n = 2,911) vs. tumor necrosis factor inhibitor (TNFi, n = 1,451) found no relationship with incident ILD (OR 0.94, 95 %CI 0.52 to 1.69, p = 0.828). In 7 observational studies, the use of methotrexate (MTX) yielded a pooled OR for ILD of 0.49 (95 %CI 0.32 to 0.76, p < 0.001) compared to those not using MTX. In a single observational study, tofacitinib users had an OR for ILD of 0.36 (95 %CI 0.15 to 0.87, p = 0.024) compared to TNFi users.

CONCLUSION: Observational data suggest no increased risk for any DMARD for incident RA-ILD risk, and perhaps a potential protective role of MTX and tofacitinib. However, these studies may be susceptible to bias, and no specific DMARD showed associations with incident RA-ILD in RCTs. Further well-designed prospective studies are warranted for definitive conclusions on the potential relationship between DMARDs and RA-ILD risk.

PMID:39413452 | DOI:10.1016/j.semarthrit.2024.152561

Eur J Public Health. 2024 Oct 16:ckae142. doi: 10.1093/eurpub/ckae142. Online ahead of print.

ABSTRACT

Seventeen percent of people living in the UK are migrants. In high-income countries, migrants have been shown to have better all-cause mortality but worse mortality for some specific causes such as infectious diseases. This observational study aims to quantify the extent to which mortality from coronavirus disease 2019 (COVID-19) differed between migrants and non-migrants for the population of England and Wales, 2020-2021. We use Official National Statistics data to compare mortality from COVID-19 in 2020 and 2021 by country/region of birth, expressed as the standardized mortality ratio with those born in England and Wales as the reference population. Migrants from 17 of 19 countries/regions examined had higher mortality from COVID-19 than non-migrants. The highest mortality was those born in Bangladesh (females SMR = 3.39, 95% CIs 3.09-3.71; males 4.41, 95% CIs 4.09-4.75); Pakistan (females 2.73, 95% CIs 2.59-2.89; males 3.02, 95% CIs 2.89-3.14); and the Caribbean (females 2.03, 95% CIs 1.87-2.20; males 2.48, 95% CIs 2.37-2.60). Migrants born in Antarctica and Oceania (females 0.54, 95% CI 0.42-0.40; males 0.71, 95% CI 0.51-0.88), and North and Central America (females 0.95, 95% CI 0.80-1.11; males 0.85, 95% CI 0.72-0.99) had lower mortality than non-migrants. Most migrant populations had higher mortality from COVID-19 than non-migrants in England and Wales. Policy-makers must work to integrate migration status into routine data collection to inform future research and understand the causes of the inequalities seen.

PMID:39413439 | DOI:10.1093/eurpub/ckae142

N Engl J Med. 2024 Oct 17;391(15):1379-1389. doi: 10.1056/NEJMoa2405888.

ABSTRACT

BACKGROUND: Incorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin’s lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin’s lymphoma, including in preliminary studies involving previously untreated patients.

METHODS: We conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin’s lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause.

RESULTS: Of 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P = 0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse events were infrequent with nivolumab; brentuximab vedotin was associated with more treatment discontinuation.

CONCLUSIONS: N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin’s lymphoma and had a better side-effect profile. (Funded by the National Cancer Institute of the National Institutes of Health and others; S1826 ClinicalTrials.gov number, NCT03907488.).

PMID:39413375 | DOI:10.1056/NEJMoa2405888