Category: Statistics

Vaccine. 2022 Dec 22:S0264-410X(22)01531-6. doi: 10.1016/j.vaccine.2022.12.017. Online ahead of print.

ABSTRACT

Despite the widespread effectiveness of pneumococcal conjugate vaccines on the overall incidence of invasive pneumococcal disease, the global epidemiological landscape continues to be transformed by residual disease from non-vaccine serotypes, thus highlighting the need for vaccines with expanded disease coverage. To address these needs, we have developed V116,an investigational 21-valent non-adjuvanted pneumococcal conjugate vaccine (PCV),containingpneumococcal polysaccharides (PnPs) 3, 6A, 7F, 8, 9N, 10A, 11A,12F, 15A, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B, anda de-O-acetylated 15B(deOAc15B) individually conjugated to the nontoxic diphtheria toxoid CRM197 carrier protein. Preclinical studies evaluated the immunogenicity of V116 inadult monkeys, rabbits, and mice. Following one dose, V116 was found to be immunogenic in preclinical animal species and induced functional antibodies for all serotypes included in the vaccine, in addition to cross-reactive functional antibodies to serotypes 6C and 15B. In these preclinical animal studies, the increased valency of V116 did not result in serotype-specific antibody suppression when compared to lower valent vaccines V114 or PCV13. In addition, when compared with naïve controls, splenocytes from V116 to immunized animals demonstrated significant induction of CRM197-specific T cells in both IFN-γ and IL-4 ELISPOT assays, as well as Th1 and Th2 cytokine induction through in vitro stimulation assays, thus suggesting the ability of V116 to engage T cell dependent immune response pathways to aid in development of memory B cells. V116 also demonstrated significant protection in mice from intratracheal challenge with serotype 24F, a novel serotype not contained in any currently licensed vaccine.

PMID:36566163 | DOI:10.1016/j.vaccine.2022.12.017

J Am Pharm Assoc (2003). 2022 Nov 12:S1544-3191(22)00367-3. doi: 10.1016/j.japh.2022.10.022. Online ahead of print.

ABSTRACT

PURPOSE: Accurately describing pharmacy productivity in the ambulatory oncology infusion setting is important to ensure appropriate labor utilization. The purpose of this study was to develop a productivity model utilizing weighted medication complexity and prospective schedule data to determine if predicted productivity corresponds to actual productivity across 6 ambulatory oncology infusion sites.

METHODS: This study was a 2-part analysis. Part 1 was to modify the historic productivity model from dispense code weighting to individual medication complexity weighting. Medication-specific relative value units were determined by analyzing 12 months of historic timestamp data from the electronic health record and gravimetric technology software. The productivity model containing updated relative value units was compared to the historic model to determine if the difference in total calculated full-time equivalents (FTEs) was within 2.0 FTEs. Part 2 applied prospective infusion schedule data to the updated model to determine if predicted productivity corresponded to actual productivity (within 2.0 FTEs) for pharmacy infusion services.

RESULTS: The mean difference in total calculated FTEs for infusion during the study period was 2.46 (standard deviation = 1.87) and was within the range of 2.0 FTEs (P = 0.54), indicating that the updated model was not statistically different from the historic model. The mean difference in total calculated FTEs between the predictive and actual productivity model for infusion was 18.28 (standard deviation = 1.00) and was out of the range of 2.0 FTEs (P < 0.001), indicating that predicted productivity was statistically different from the actual productivity.

CONCLUSION: Medication complexity weighting can be used to provide a comprehensive assessment of workload and productivity across pharmacy infusion services. The methodology used to assess predictive productivity should be explored further.

PMID:36566159 | DOI:10.1016/j.japh.2022.10.022

J Am Heart Assoc. 2022 Dec 24:e027652. doi: 10.1161/JAHA.122.027652. Online ahead of print.

ABSTRACT

Background Outcomes and treatment effects of therapy may vary according to the cause of heart failure (HF). Methods and Results In this post hoc analysis of the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial, the effect of empagliflozin on cardiovascular and renal outcomes was assessed according to the cause of HF. The cause of HF was investigator reported and stratified as ischemic or nonischemic. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs. Of the 3730 patients enrolled, 1929 (51.7%) had ischemic cause. In the placebo arm, patients with ischemic cause of HF did not have a significantly higher risk of cardiovascular mortality (HR, 1.21 [95% CI, 0.90-1.63]) and hospitalization for HF (HR, 0.90 [95% CI, 0.72-1.12]) compared with nonischemic cause. Empagliflozin compared with placebo significantly reduced the risk of cardiovascular death or hospitalization for HF in patients with ischemic and nonischemic cause (HR, 0.82 [95% CI, 0.68-0.99] for ischemic and HR, 0.67 [95% CI, 0.55-0.82] for nonischemic cause; P interaction=0.15). The benefit of empagliflozin on HF hospitalization, the renal composite end point, estimated glomerular filtration slope changes, and health status scores were also consistent in both groups without treatment by cause modification. Conclusions Empagliflozin offers cardiovascular and renal benefits in patients with heart failure with reduced ejection fraction regardless of the cause of HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.

PMID:36565199 | DOI:10.1161/JAHA.122.027652

J Am Heart Assoc. 2022 Dec 24:e028144. doi: 10.1161/JAHA.122.028144. Online ahead of print.

ABSTRACT

Background Transcatheter aortic valve replacement (TAVR)/intervention has become the standard of care for treatment of severe aortic stenosis across the spectrum of risk. There are socioeconomic disparities in access to TAVR. The impact of these disparities on postprocedural outcomes remains unknown. Our objective was to examine the association between neighborhood-level social deprivation and post-TAVR mortality and hospital readmission. Methods and Results We conducted a population-based retrospective cohort study of all 4145 patients in Ontario, Canada, who received TAVR from April 1, 2017, to March 31, 2020. Our co-primary outcomes were 1-year postprocedure mortality and 1-year postprocedure readmission. Using Cox proportional hazards models for mortality and cause-specific competing risk hazard models for readmission, we evaluated the relationship between neighborhood-level measures of residential instability, material deprivation, and concentration of racial and ethnic groups with post-TAVR outcomes. After multivariable adjustment, we found a statistically significant relationship between residential instability and postprocedural 1-year mortality, ranging from a hazard ratio of 1.64 to a hazard ratio of 2.05. There was a significant association between the highest degree of residential instability and 1-year readmission (hazard ratio, 1.23 [95% CI, 1.01-1.49]). There was no association between material deprivation and concentration of racial and ethnic groups with post-TAVR outcomes. Conclusions Residential instability was associated with increased risk for post-TAVR mortality, and the highest quintile of residential instability was associated with increased post-TAVR readmission. To reduce health disparities and promote an equitable health care system, further research and policy interventions will be required to identify and support economically and socially minoritized patients undergoing TAVR.

PMID:36565194 | DOI:10.1161/JAHA.122.028144

J Am Heart Assoc. 2022 Dec 24:e027790. doi: 10.1161/JAHA.122.027790. Online ahead of print.

ABSTRACT

Background Peripheral artery disease is endemic in our globally aging population, with >200 million affected worldwide. Graft/stent thrombosis after revascularization is common and frequently results in amputation, major adverse cardiovascular events, and cardiovascular mortality. Optimizing medications to decrease thrombosis is of paramount importance; however, limited guidance exists on how to use and monitor antithrombotic therapy in this heterogeneous population. Thromboelastography with platelet mapping (TEG-PM) provides comprehensive coagulation metrics and may be integral to the next stage of patient-centered thrombophrophylaxis. This prospective study aimed to determine if TEG-PM could predict subacute graft/stent thrombosis following lower extremity revascularization, and if objective cut point values could be established to identify those high-risk patients. Methods and Results We conducted a single-center prospective observational study of patients undergoing lower extremity revascularization. Patients were followed up for the composite end point postoperative graft/stent thrombosis at 1 year. TEG-PM analysis of the time point before thrombosis in the event group was compared with the last postoperative visit in the nonevent group. Cox proportional hazards analysis examined the association of TEG-PM metrics to thrombosis. Cut point analysis explored the predictive capacity of TEG-PM metrics for those at high risk. A total of 162 patients were analyzed, of whom 30 (18.5%) experienced graft/stent thrombosis. Patients with thrombosis had significantly greater platelet aggregation (79.7±15.7 versus 58.5±26.4) and lower platelet inhibition (20.7±15.6% versus 41.1±26.6%) (all P<0.01). Cox proportional hazards analysis revealed that for every 1% increase in platelet aggregation, the hazard of experiencing an event during the study period increased by 5% (hazard ratio, 1.05 [95% CI, 1.02-1.07]; P<0.01). An optimal cut point of >70.8% platelet aggregation and/or <29.2% platelet inhibition identifies those at high risk of thrombosis with 87% sensitivity and 70% to 71% specificity. Conclusions Among patients undergoing lower extremity revascularization, increased platelet reactivity was predictive of subacute postoperative graft/stent thrombosis. On the basis of the cut points of >70.8% platelet aggregation and <29.2% platelet inhibition, consideration of an alternative or augmented antithrombotic regimen for high-risk patients may decrease the risk of postoperative thrombotic events.

PMID:36565191 | DOI:10.1161/JAHA.122.027790

J Am Heart Assoc. 2022 Dec 24:e026578. doi: 10.1161/JAHA.122.026578. Online ahead of print.

ABSTRACT

Background Salt restriction may lower blood pressure variability (BPV), but previous studies have shown inconsistent results. Therefore, we investigated in an observational study and intervention trial whether urinary sodium excretion and salt intake are associated with 24-hour BPV. Methods and Results We used data from the cross-sectional population-based Maastricht Study (n=2652; 60±8 years; 52% men) and from a randomized crossover trial (n=40; 49±11 years; 33% men). In the observational study, we measured 24-hour urinary sodium excretion and 24-hour BPV and performed linear regression adjusted for age, sex, mean blood pressure, lifestyle, and cardiovascular risk factors. In the intervention study, participants adhered to a 7-day low- and high-salt diet (50 and 250 mmol NaCl/24 h) with a washout period of 14 days, 24-hour BPV was measured during each diet. We used linear mixed models adjusted for order of diet, mean blood pressure, and body mass index. In the observational study, 24-hour urinary sodium excretion was not associated with 24-hour systolic or diastolic BPV (β, per 1 g/24 h urinary sodium excretion: 0.05 mm Hg [95% CI, -0.02 to 0.11] and 0.04 mm Hg [95% CI, -0.01 to 0.09], respectively). In the intervention trial, mean difference in 24-hour systolic and diastolic BPV between the low- and high-salt diet was not statistically significantly different (0.62 mm Hg [95% CI, -0.10 to 1.35] and 0.04 mm Hg [95% CI, -0.54 to 0.63], respectively). Conclusions Urinary sodium excretion and salt intake are not independently associated with 24-hour BPV. These findings suggest that salt restriction is not an effective strategy to lower BPV in the White general population. Registration URL: https://clinicaltrials.gov/ct2/show/NCT02068781.

PMID:36565181 | DOI:10.1161/JAHA.122.026578

Ann Work Expo Health. 2022 Dec 24:wxac085. doi: 10.1093/annweh/wxac085. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to characterize polycyclic aromatic hydrocarbons (PAHs) in the breathing zone and on the skin of wildland firefighters and to assess their contribution to urinary 1-hydroxypyrene (1-HP) over repeated firefighting rotations. We asked if improved skin hygiene or discretionary use of an N95 mask would reduce absorption.

METHODS: In collaboration with wildfire services of two Canadian provinces, Alberta and British Columbia (BC), we recruited wildland firefighters from crews willing to be followed up over successive rotations and to be randomly assigned to normal practice, enhanced skin hygiene (ESH), or ESH plus discretionary use of an N95 mask. We collected spot urine samples at the beginning and end of up to four rotations/firefighter. On designated fire days, as close as possible to the end of rotation, we collected skin wipes from the hands, throat, and chest at the beginning and end of the fire day and, in BC, start of fire-day urine samples. Volunteers carried air monitoring pumps. Participants completed questionnaires at the beginning and end of rotations. Exposure since the start of the fire season was estimated from fire service records. Urinary 1-HP was analyzed by LC-MS-MS. Analysis of 21 PAHs on skin wipes and 27 PAHs from air sampling was done by GC-MS-MS. Statistical analysis used a linear mixed effects model.

RESULTS: Firefighters in Alberta were recruited from five helitack crews and two unit crews, and in BC from two unit crews with 80 firefighters providing data overall. The fire season in BC was very active with five monitored fire days. In Alberta, with more crews, there were only seven fire days. Overall, log 1-HP/creatinine (ng/g) increased significantly from the start (N = 145) to end of rotation (N = 136). Only three PAHs (naphthalene, phenanthrene, and pyrene) were found on >20% of skin wipes. PAHs from 40 air monitoring pumps included 10 PAHs detected on cassette filters (particles) and 5 on sorbent tubes (vapor phase). A principal component extracted from air monitoring data represented respiratory exposure and total PAH from skin wipes summarized skin exposure. Both routes contributed to the end of rotation urinary 1-HP. The ESH intervention was not demonstrated to effect absorption. Allocation of an N95 mask was associated with lower 1-HP when modeling respiratory exposure (β = -0.62, 95% CI -1.15 to -0.10: P = 0.021). End of rotation 1-HP was related to 1-HP at the start of the next rotation (β = 0.25, 95% CI 0.12 to 0.39: P < 0.001).

CONCLUSIONS: Exposures to PAHs during firefighting were significant, with samples exceeding the American Conference of Governmental Industrial Hygienists Biological Exposure Index for 1-HP suggesting a need for control of exposure. PAH exposure accumulated during the rotation and was not fully eliminated during the break between rotations. Both respiratory and skin exposures contributed to 1-HP. While improved skin hygiene may potentially reduce dermal absorption, that was not demonstrated here. In contrast, those allocated to discretionary use of an N95 mask had reduced 1-HP excretion. Wildland firefighters in North America do not use respiratory protection, but the results of this study support more effective interventions to reduce respiratory exposure.

PMID:36565164 | DOI:10.1093/annweh/wxac085

Pharmacol Res Perspect. 2023 Feb;11(1):e01017. doi: 10.1002/prp2.1017.

ABSTRACT

Population-based drug utilization studies are scanty in Nigeria. The aim was to determine the pattern and predictors of medication use among adults in the communities of Southwestern Nigeria. A cross-sectional study was conducted among adults selected by multi-stage sampling from Oyo State communities. The questionnaires, adapted from the WHO Students’ Drug Use Questionnaire and previous studies, were pretested and interviewer administered. The respondents’ socio-demographic characteristics, the pattern of medication use, prescribers, and sources of drug acquisition were obtained. Binary logistic regression was used to determine the predictor of medications used. Of the 999 respondents, 501 resided in rural communities while 498 dwelled in urban areas. The mean (±SD) age of the respondents was 38 ± 15 years. The median (range)% prevalence of medication use were as follows: lifetime use, 58.2 (17.7-81.0); current use, 31.2 (8.9-65.9); and past use, 20.3 (9.2-28.9). Medications were mainly obtained from patent medicine stores, median (range%), 71 (65-80). The commonly used drugs were paracetamol, 626 (67.6); nonsteroidal anti-inflammatory drugs, 174 (18.8); artemether/lumefantrine, 422 (68.2); ampicillin/cloxacillin, 220 (48.6); and chlorpheniramine, 59 (39.9). Factors predictive of current medication use, adjusted odd ratio (95% confidence interval) were as follows: antimalarial [male, 0.7 (0.5, 0.9)]; antibacterial [male, 0.6 (0.4-0.9)]; analgesics [married, 1.5 (1.1-2.2); presence of health facilities, 0.5 (0.3-0.7); and shorter distance to health facility, 1.5 (1.1-2.1)]. Antimalarials, antibacterial, and analgesics were commonly used and inappropriately obtained by adults in Southwestern Nigeria. Factors predictive of current medication use were gender, marital status, the presence of health facilities, and distance to health facilities. There is a need for more extensive countrywide medication use studies and enlightenment programs to ensure the appropriate use of medications.

PMID:36565158 | DOI:10.1002/prp2.1017

Am Surg. 2022 Dec 24:31348221146945. doi: 10.1177/00031348221146945. Online ahead of print.

ABSTRACT

INTRODUCTION: The gender and minority gap in general surgery residency is narrowing; however, literature lacks comprehensive data regarding the demographics of fellowship programs following general surgery training.

METHODS: Data from 2017 to 2021 for gender, ethnicity, and surgical subspecialty are publicly available from the ERAS database and ACGME yearly data reports. Cochran-Armitage trend tests were used to determine statistical significance in trends for female and minority applicants and trainees.

RESULTS: The overall trend of female applicants to surgical specialties remained stagnant. However, female applicants to vascular surgery increased significantly from 25% to 35% (P = .045). There was no significant increase in female trainees in any surgical specialties evaluated. Furthermore, the overall trend of minority applicants to surgical specialties also remained stagnant, except for pediatric surgery, which showed significantly fewer minority applicants. Despite pediatric surgery having fewer applicants, minority trainees in this specialty increased significantly from 8% to 19% (P = .008).

CONCLUSION: Several current initiatives, such as intentional mentorship, are being reported to promote diverse and equal representation among female and minority applicants and trainees. However, the current overall margin of increase in diversity among surgical specialty applicants and trainees is minimal, indicating that continued efforts are needed to diversify surgical specialty training programs.

PMID:36565153 | DOI:10.1177/00031348221146945

J Neuromuscul Dis. 2022 Dec 16. doi: 10.3233/JND-221600. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Disease progression in patients with spinal muscular atrophy (SMA) has changed dramatically within the past years due to the approval of three different disease-modifying treatments. Nusinersen was the first drug to be approved for the treatment of SMA patients. Clinical trials provided data from infants with SMA type 1 and children with SMA type 2, but there is still insufficient evidence and only scarcely reported long-term experience for nusinersen treatment in ambulant patients. Here, we report data from the SMArtCARE registry of ambulant patients under nusinersen treatment with a follow-up period of up to 38 months.

METHODS: SMArtCARE is a disease-specific registry in Germany, Austria and Switzerland. Data are collected as real-world data during routine patient visits. Our analysis included all patients under treatment with nusinersen able to walk independently before start of treatment with focus on changes in motor function.

RESULTS: Data from 231 ambulant patients were included in the analysis. During the observation period, 31 pediatric walkers (27.2%) and 31 adult walkers (26.5%) experienced a clinically meaningful improvement of≥30 m in the 6-Minute-Walk-Test. In contrast, only five adult walkers (7.7%) showed a decline in walking distance≥30 m, and two pediatric walkers (1.8%) lost the ability to walk unassisted under treatment with nusinersen. HFMSE and RULM scores improvemd in pediatric and remaind stable in adult patients.

CONCLUSION: Our data demonstrate a positive effect of nusinersen treatment in most ambulant pediatric and adult SMA patients. We not only observed a stabilization of disease progression or lack of deterioration, but clinically meaningful improvements in walking distance.

PMID:36565133 | DOI:10.3233/JND-221600