Nevin Manimala

J Am Med Dir Assoc. 2021 Jul 21:S1525-8610(21)00644-7. doi: 10.1016/j.jamda.2021.07.006. Online ahead of print.

ABSTRACT

Vaccines are critical to protect both nursing home residents and staff from COVID-19, but some staff have expressed reservations about being vaccinated. In this brief report, we describe interventions that Genesis HealthCare-one of the largest US long-term care providers-implemented after recognizing midway through vaccinations that racial and ethnic disparities existed in vaccine uptake among employees, with black and Hispanic employees having significantly lower rates of vaccination than their peers. Specifically, Genesis engaged its Diversity, Equity, and Inclusion (DEI) Committee to identify ways to augment its already comprehensive vaccine education campaign in order to build confidence among employees from minority communities. Interventions implemented beginning in late January 2021 included adding DEI representatives to information sessions to facilitate culturally sensitive discussions; holding information sessions at all times of day and night, and inviting employees’ family members to join; increasing availability of multilingual educational materials; and featuring DEI representatives in social media campaigns. Between the end of January and beginning of March 2021, we observed statistically significant improvements in the likelihood of black and Hispanic employees being vaccinated relative to white employees, calculated as the relative risk of vaccination, suggesting a reduction in vaccination disparity. Whether these trends are directly related to the organization’s efforts, or rather reflect individuals needing longer to become comfortable with the vaccines, is difficult to discern in the absence of a formal pragmatic trial. Still, these findings support the continuation of targeted educational and engagement efforts to improve vaccine uptake among staff, and the critical need to ensure that nursing homes have ongoing access to vaccine supply to continue their vaccination programs.

PMID:34375655 | DOI:10.1016/j.jamda.2021.07.006

Physiol Behav. 2021 Aug 7:113554. doi: 10.1016/j.physbeh.2021.113554. Online ahead of print.

ABSTRACT

We identified associations between cigarette-smoking and taste function in the U.S. NHANES 2013-2014. Adults ≥40 years (n=2849, nearly half former or current smokers) rated whole-mouth and tongue-tip bitter (1mM quinine) and salt (1M NaCl, 0.32 M NaCl) intensities and reported smoking history (pack years, PY), dependence (time to first cigarette, TTFC) and menthol/non-menthol use. Perceived intensity on the tongue-tip averaged just below moderate for quinine and moderate to strong for 1M NaCl. Current chronic smokers (≥20 PY) reported lower bitter and salty intensities on the tongue-tip (β: -2.0, 95% CI: -3.7 to -0.4 and β: -3.6, 95% CI: -6.9 to -0.3, respectively) than never smokers. Similarly, compared to never smokers, dependent current smokers (TTFC≤30 minutes) and dependent chronic smokers (≥20 PY, TTFC≤30 minutes) rated less bitter (β: -2.0, 95% CI: -4.0 to 0.1 and β: -2.9, 95% CI: -4.5 to -1.3, respectively) and salty (β: -5.3, 95% CI: -9.3 to -1.4 and β: -4.7, 95% CI: -8.6 to -0.7, respectively) intensities on the tongue-tip. Depressed tongue-tip intensity in dependent smokers (with/without chronicity) versus never smokers was significant in younger (40-65 years), but not older (>65 years) adults. Former smokers, non-chronic/less dependent smokers, and menthol smokers were more likely to report elevated whole-mouth quinine and 1 M NaCl intensities. Tongue-tip and whole-mouth taste intensity concordance varied between smokers and never smokers-current dependent smokers were more likely to rate tongue-tip quinine and NaCl lower than their respective whole-mouth tastants (OR: 1.8, 95% CI: 1.0 to 3.1 and OR: 1.8, 95% CI: 1.1 to 2.8, respectively). In summary, these U.S. nationally-representative data show that current smoking with chronicity and/or dependence associates with lower tongue-tip intensity for bitter and salty stimuli. Smokers with greater exposure to nicotine and/or dependence showed greater risk of taste alterations, with implications for diet- and smoking-related health outcomes.

PMID:34375623 | DOI:10.1016/j.physbeh.2021.113554

Epidemiol Infect. 2021 Aug 10;149:e180. doi: 10.1017/S0950268821001825.

ABSTRACT

Several studies have demonstrated that higher levels of vitamin D are associated with better prognosis and outcomes in infectious diseases. We aimed to compare the vitamin D levels of paediatric patients with mild/moderate coronavirus disease 2019 (COVID-19) disease and a healthy control group. We retrospectively reviewed the medical records of patients who were hospitalised at our university hospital with the diagnosis of COVID-19 during the period between 25 May 2020 and 24 December 2020. The mean age of the COVID-19 patients was 10.7 ± 5.5 years (range 1-18 years); 43 (57.3%) COVID-19 patients were male. The mean serum vitamin D level was significantly lower in the COVID-19 group than the control group (21.5 ± 10.0 vs. 28.0 ± 11.0 IU, P < 0.001). The proportion of patients with vitamin D deficiency was significantly higher in the COVID-19 group than the control group (44% vs. 17.5%, P < 0.001). Patients with low vitamin D levels were older than the patients with normal vitamin D levels (11.6 ± 4.9 vs. 6.2 ± 1.8 years, P = 0.016). There was a significant male preponderance in the normal vitamin D group compared with the low vitamin D group (91.7% vs. 50.8%, P = 0.03). C-reactive protein level was higher in the low vitamin D group, although the difference did not reach statistical significance (9.6 ± 2.2 vs. 4.5 ± 1.6 mg/l, P = 0.074). Our study provides an insight into the relationship between vitamin D deficiency and COVID-19 for future studies. Empiric intervention with vitamin D can be justified by low serum vitamin D levels.

PMID:34375576 | DOI:10.1017/S0950268821001825

BJU Int. 2021 Aug 10. doi: 10.1111/bju.15567. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess whether bacillus Calmette-Guérin (BCG) responsiveness after initiation of an adequate BCG treatment (at least five of six instillations of induction and at least two of three instillations of maintenance) impacts oncological outcomes in patients with CIS of the bladder treated with BCG immunotherapy.

PATIENTS AND METHODS: Data were available for 193 patients with bladder CIS with or without associated cTa/cT1 disease who received an adequate BCG treatment between 2008 and 2015. Bladder biopsies were performed at 6 months and patients were then stratified as either BCG responsive (negative biopsies) or BCG unresponsive (positive biopsies). Inverse probability weighting (IPW)-adjusted Kaplan-Meier and IPW-adjusted Cox regression were performed to compare progression-free survival (PFS), radical cystectomy-free survival (RCFS), overall survival OS, and cancer-specific survival (CSS) in the two groups.

RESULTS AND LIMITATIONS: Comparing the BCG-responsive and BCG-unresponsive groups, IPW-adjusted Kaplan-Meier analysis revealed, respectively, a PFS of 9 months (IQR 5-15) vs 48.5 months (IQR 28-77) (p=0.001), an RCFS of 11 months (IQR 9-15) vs 49 months (IQR 24-76) (p<0.001), and a CSS of 25 months (IQR 13-60) vs 109 months (IQR 78-307) (p=0.004). On IPW-adjusted Cox regression analysis, BCG-unresponsive patients had a worse PFS (HR 3.40, 95% CI 1.59-7.27), RCFS (HR 3.52, 95% CI 1.77-7), and CSS (HR 4.42, 95% CI 1.95-10.01). We found no significant differences for OS.

CONCLUSION: Using an IPW method we found that lack of response after initiation of an adequate BCG treatment has prognostic implications beyond identification of complete response in patients with CIS. BCG-unresponsive patients, satisfying the novel definition of BCG unresponsive, showed a poor PFS, RCFS, and CSS. In this setting, the patients should be counseled regarding radical cystectomy as a first option or enrolled in a clinical trial if they refuse radical cystectomy or are unfit for surgery.

PMID:34375494 | DOI:10.1111/bju.15567

BJU Int. 2021 Aug 10. doi: 10.1111/bju.15566. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate gene alterations as diagnostic and prognostic markers in upper tract urothelial carcinoma (UTUC).

PATIENTS AND METHODS: Patients with UTUC who underwent nephroureterectomy in 2005-2012 were followed until November 2020. DNA was extracted from paraffin-embedded tumour tissue. Next-generation sequencing using a 388-gene panel was performed. First a blinded analysis using principal component analysis and hierarchical clustering was used to search for patterns of mutations. Then a comparative analysis using ANOVA was used to search for mutations enriched in groups of various grade, stage and survival. In addition, careful manual annotation was used to identify pathogenic mutations overrepresented in tumours of high grade/stage and/or poor survival.

RESULTS: 39 patients were included. All tumour stages and grades were represented in the cohort. The median follow-up was 10.6 years. Eleven patients died from UTUC during the follow-up time. Tumour mutational burden showed a statistically significant correlation with stage, grade and stage + grade. G1, G2 and G3 tumours had different mutational patterns. Patients who died from UTUC had pathogenic mutations in specific genes e.g. TP53 and HRAS. Patients with TaG1 tumours with a known pathogenic FGFR3 mutation did not die of UTUC.

CONCLUSION: The genetic analysis was highly concordant with histopathological features and added prognostic information in some cases. Thus, results from genomic profiling may contribute to the choice of treatment and follow-up regimens in the future.

PMID:34375486 | DOI:10.1111/bju.15566

Clin Exp Pharmacol Physiol. 2021 Aug 10. doi: 10.1111/1440-1681.13570. Online ahead of print.

ABSTRACT

This study investigated the impact of intra-renal angiotensin 1-7 (Ang (1-7)) infusion on renal excretory function in a rat model of hypertension. Eleven-week-old spontaneously hypertensive rats (SHRs, n=7) and Han Wistar controls (NCR, n=7) were anaesthetised with sodium pentobarbital (60mg/kg i.p.) and prepared for the measurement of mean arterial pressure (MAP) and left renal function during renal interstitial infusion of Ang (1-7) (50ng/min). The kidneys were harvested, the renal cortex and medulla separated, prepared for measurement of Ang II and Ang (1-7) and Western blot determination of AT1 and Mas receptor protein expression. MAP, glomerular filtration rate (GFR), urine flow (UF) and absolute sodium excretion (UNaV) were 109±16mmHg, 4.4±1.0ml/min/kg, 102±16µl/min/kg and 16±3µmol/min/kg, respectively in the NCR and 172±24mmHg, 3.4±0.7ml/min/kg, 58±30μl/min/kg and 8.6±4.8μmol/min/kg respectively in the SHR. Ang (1-7) increased UF (31%), U_Na V (50%) and FENa⁺ (22%) in the NCR group (all P<0.05) but had no effect on GFR in either group. The magnitudes of the Ang (1-7)-induced increases in UF and U_Na V were significantly blunted in the SHR group (model×drug P<0.05). Renal cortical AT1:Mas receptor expression ratio was significantly higher in the SHR group (P<0.05) but renal Ang II and Ang (1-7) levels were not statistically different between groups. The Ang (1-7) induced increases in sodium and water excretion were impaired in the SHR group in the context of an unstimulated RAS. The decrease in responsiveness of the SHR kidney to Ang (1-7) appears to be associated with higher levels of AT1 receptor expression in the renal cortex.

PMID:34375480 | DOI:10.1111/1440-1681.13570

Med Educ. 2021 Aug 10. doi: 10.1111/medu.14606. Online ahead of print.

ABSTRACT

CONTEXT: Although many medical schools seek to improve diversity, they grapple with the challenge of how to weight the scores of different admission methods to achieve a balance between obtaining high predictiveness and ensuring diversity in the selected student pool. Yet, in large-scale employment settings, substantial progress has been made on this front: Pareto-optimization has been introduced as an elegant statistical tool to assist decision makers in determining the weights assigned to selection methods in advance (before the selection has taken place) so that a selection system is designed to achieve an optimal balance as reflected by the trade-off that one outcome (e.g., predictiveness) cannot be improved without harm to the other outcome (e.g., diversity).

AIMS: This paper reviews the theory and research evidence about Pareto-optimization and explains how Pareto-optimization permits medical schools to better balance predictiveness and diversity in medical admission systems.

METHODS: After reviewing common weighting schemes (unit, regression-based, and ad hoc weighting) and their drawbacks, we introduce the theory and logic of Pareto-optimization for better balancing predictiveness and diversity. To this end, we also offer an illustrative example. Next, we review the mathematical basis and available research evidence regarding Pareto-optimization. Finally, we discuss potential criticisms (i.e., complexity, legal concerns).

CONCLUSIONS: Compared to traditional unit weighting, regression-based weighting, and ad hoc weighting, Pareto-optimization leads to substantial increases in diversity intake (up to three times more), while keeping the predictiveness of the selection methods at the same level. Moreover, the Pareto-optimization is robust to sampling variability and variability of the input selection parameters.

PMID:34375476 | DOI:10.1111/medu.14606

Pharmacoepidemiol Drug Saf. 2021 Aug 10. doi: 10.1002/pds.5338. Online ahead of print.

ABSTRACT

In the causal analysis of observational data, the positivity assumption requires that all treatments of interest be observed in every patient subgroup. Violations of this assumption are indicated by nonoverlap in the data in the sense that patients with certain covariate combinations are not observed to receive a treatment of interest, which may arise from contraindications to treatment or small sample size. In this paper, we emphasize the importance and implications of this often-overlooked assumption. Further, we elaborate on the challenges nonoverlap poses to estimation and inference and discuss previously proposed methods. We distinguish between structural and practical violations and provide insight into which methods are appropriate for each. To demonstrate alternative approaches and relevant considerations (including how overlap is defined and the target population to which results may be generalized) when addressing positivity violations, we employ an electronic health record-derived data set to assess the effects of metformin on colon cancer recurrence among diabetic patients. This article is protected by copyright. All rights reserved.

PMID:34375473 | DOI:10.1002/pds.5338

Int Endod J. 2021 Aug 10. doi: 10.1111/iej.13606. Online ahead of print.

ABSTRACT

AIM: To evaluate if treatment with resiniferatoxin (RTX) is capable of lowering the plasma levels of PGE₂ and TNF-α, as well as histopathological parameters in inflammation of pulp tissue in a mouse experimental model.

METHODOLOGY: Ten groups of six BALB/c mice were formed as follows: healthy group (H_C ), healthy group treated with RTX (H_RTX ), two groups with pulp inflammation at 14 and 18 hours (PI₁₄ /PI₁₈ ); six groups with pulpal inflammation plus treatment with Ibuprofen (IBU₁₄ /IBU₁₈ ), dexamethasone (DEX₁₄ /DEX₁₈ ) and resiniferatoxin (RTX₁₄ /RTX₁₈ ) at 14 and 18 hours, respectively. Pulpal inflammation was induced through occlusal exposure of the pulp of the maxillary first molar. The plasma levels of PGE₂ and TNF-α and the histological parameters of the pulp tissue of the H_C and H_RTX groups were evaluated at the time of acquiring the animals. In the other groups, the plasma levels of PGE₂ and TNF-α and the histopathological parameters were evaluated at 14 and 18 hours after pulp damage. Plasma levels of PGE₂ and TNF-α were quantified by ELISA assay and the histopathological parameters were evaluated by H/E staining. Statistical significance was determined by one-way analysis of variance (ANOVA) to test for overall differences between group means.

RESULTS: A significant increase (*p<0.05) in plasma levels of PGE₂ and TNF-α occurred 14 and 18 hours after pulp damage. In addition, treatment with RTX significantly decreased (*p<0.05) the plasma levels of PGE₂ and TNF-α at 14 and 18 hours after pulp damage, as well as the infiltrate of inflammatory cells at 18 hours after pulp damage, similarly to treatment with ibuprofen and dexamethasone.

CONCLUSION: It was possible to detect systemic levels of PGE₂ and TNF-α at 14 and 18 hours after pulp damage. Likewise, treatment with RTX was associated with an anti-inflammatory effect similar to treatment with ibuprofen and dexamethasone. These findings place resiniferatoxin as a therapeutic alternative in the treatment of inflammatory diseases in Dentistry.

PMID:34375451 | DOI:10.1111/iej.13606

Vet Rec. 2021 Aug 10:e775. doi: 10.1002/vetr.775. Online ahead of print.

ABSTRACT

BACKGROUND: Farm management practices have a major impact on nematode population dynamics. The presented study aimed to understand current nematode management practices on UK sheep farms; with a particular focus on Nematodirus battus because of the changing epidemiology, and emerging anthelmintic resistance observed in this species.

METHODS: A 42 question online survey covering grazing management, farm demographics and parasite control strategies was developed and distributed to the farming community in 2016. Analysis of the 187 completed questionnaires explored regional variations in practices.

RESULTS: Uptake of recommendations was variable, particularly quarantine practices and monitoring tools. Results also highlighted variation in the epidemiology of N. battus; respondents in the north (Scotland, north-west and north-east England) typically reported N. battus in spring with a perception of more severe clinical symptoms than those from the south (Midlands, Wales, south-east and south-west England; p = 0.03). Farms in the south observed greater changes in the timing of disease (p = 0.006) with N. battus being reported throughout the year on some holdings and more frequent use of faecal egg count monitoring (p = 0.006).

CONCLUSIONS: Control of N. battus infection is challenging and ‘one-size-fits-all’ advice is not applicable; however, the information gathered will enable the development of effective, adaptable control strategies.

PMID:34375447 | DOI:10.1002/vetr.775