Category: Nevin Manimala

Infect Chemother. 2021 Jun;53(2):271-283. doi: 10.3947/ic.2021.0051.

ABSTRACT

BACKGROUND: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for Gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP).

MATERIALS AND METHODS: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. We included randomized clinical trials-with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A P-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I² statistic.

RESULTS: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups.

CONCLUSION: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, HABP, VABP).

PMID:34216121 | DOI:10.3947/ic.2021.0051

Infect Chemother. 2021 Jun;53(2):284-299. doi: 10.3947/ic.2020.0142.

ABSTRACT

BACKROUND: Data on Dengue virus (DENV) infection prevalence, geographic distribution and risk factors are necessary to direct appropriate utilization of existing and emerging control strategies. This study aimed to determine the pooled prevalence, risk factors of DENV infection and the circulating serotypes within Nigeria from January 1, 2009 to December 31, 2020.

MATERIALS AND METHODS: Twenty-one studies out of 2,215 available articles were eligible and included for this systematic review. Relevant articles were searched, screened and included in this study according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria. The risk of bias in primary studies was assessed by Cochrane’s method. Heterogeneity of pooled prevalence was calculated using the chi-square test on Cochrane’s Q statistic, which was quantified by I-square values. The random-effects analyses of proportions were used to determine the pooled prevalence of DENV antibodies, antigen and RNA from eligible studies.

RESULTS: Of these, 3 studies reported co-circulation of all the 4 serotypes, while 2 separately reported co-circulation of DENV-1 &2 and DENV-1 to -3. All the antibody-based studies had significantly high heterogeneity (I² >90%, P <0.05), while the NS1 and PCR-based studies had low heterogeneity (I² <25%, P >0.05). The pooled prevalence of DENV IgM, IgG, RNA, NS1 and neutralizing antibodies were 16.8%, 34.7%, 7.7%, 7.7% and 0.7%, respectively. South-east Nigeria had the highest pooled DENV-IgG seropositivity, 77.1%. Marital status, gender, educational level and occupation status, the proximity of residence to refuse dumpsite, frequent use of trousers and long sleeve shirts were significantly associated with DENV IgG seropositivity (P <0.05).

CONCLUSION: Based on these findings, it can be inferred that Nigeria is hyperendemic for Dengue fever and needs concerted efforts to control its spread within and outside the country.

PMID:34216122 | DOI:10.3947/ic.2020.0142

Vet Med Sci. 2021 Jul 3. doi: 10.1002/vms3.567. Online ahead of print.

ABSTRACT

Clostridioides difficile is an important enteric pathogen that causes significant morbidity and mortality in humans. With community-acquired infections on the rise, it is important to identify reservoirs of the pathogen. Companion animals can be asymptomatic carriers of C. difficile and may therefore represent a reservoir, but epidemiological studies of C. difficile within the pet-owner unit are needed, along with validated methods to detect C. difficile in both people and animals. The goal of this study was to assess the performance of commercial qPCR assays and a multiplex PCR for C. difficile compared to toxigenic culture. These assays were tested on up to 103 fecal samples from puppies, a population in which the prevalence of C. difficile is the highest. The sensitivities, specificities, positive predictive values and negative predictive values were respectively 84.2%, 87.7%, 61.5%, and 95.9% for the Cepheid GeneXpert; 66.7%, 66.7%, 29.6%, and 90.9% for the DiaSorin Simplexa; and 94.4%, 85.0%, 65.4%, and 98.1%, for the multiplex qPCR. The agreement was highest between the GeneXpert and the multiplex PCR (90.1% agreement, with a kappa statistic of 0.77). For diagnostic purposes, the positive predictive values of the assays were low. However, the high sensitivities of the assays could render them useful for epidemiologic purposes.

PMID:34216115 | DOI:10.1002/vms3.567

Infect Chemother. 2021 Jun;53(2):221-237. doi: 10.3947/ic.2021.0016.

ABSTRACT

This study aims to assess anakinra’s safety and efficacy for treating severe coronavirus disease 2019 (COVID-19). Numerous electronic databases were searched and finally 15 studies with a total of 3,530 patients, 757 in the anakinra arm, 1,685 in the control arm were included. The pooled adjusted odds ratio (OR) for mortality in the treatment arm was 0.34 (95% confidence interval [CI], 0.21 – 0.54, I² = 48%), indicating a significant association between anakinra and mortality. A significant association was found regarding mechanical ventilation requirements in anakinra group compared to the control group OR, 0.68 (95% CI, 0.49 – 0.95, I² = 50%). For the safety of anakinra, we evaluated thromboembolism risk and liver transaminases elevation. Thromboembolism risk was OR, 1.59 (95% CI, 0.65 – 3.91, I² = 0%) and elevation in liver transaminases with OR was 1.35 (95% CI, 0.61 – 3.03, I² = 76%). Both were not statistically significant over the control group. Anakinra is beneficial in lowering mortality in COVID-19 patients. However, these non-significant differences in the safety profile between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra’s safety profile.

PMID:34216117 | DOI:10.3947/ic.2021.0016

Diabetes Metab Res Rev. 2021 Jul 3:e3482. doi: 10.1002/dmrr.3482. Online ahead of print.

ABSTRACT

AIMS: The study aimed to elucidate the effects of rare genetic variants on the risk of type 2 diabetes (T2D).

MATERIALS AND METHODS: Weighted burden analysis of rare variants was applied to a sample of 200,000 exome-sequenced participants in the UK Biobank project, of whom over 13,000 were identified as having T2D. Variant weights were allocated based on allele frequency and predicted effect, as informed by a previous analysis of hyperlipidaemia.

RESULTS: There was an exome-wide significant increased burden of rare, functional variants in three genes, GCK, HNF4A and GIGYF1. GIGYF1 has not previously been identified as a diabetes risk gene and its product appears to be involved in the modification of insulin signalling. A number of other genes did not attain exome-wide significance but were highly ranked and potentially of interest, including ALAD, PPARG, GYG1 and GHRL. Loss of function (LOF) variants were associated with T2D in GCK and GIGYF1 whereas nonsynonymous variants annotated as probably damaging were associated in GCK and HNF4A. Overall, fewer than 1% of T2D cases carried one of these variants. In HNF1A and HNF1B there was an excess of LOF variants among cases but the small numbers of these fell short of statistical significance.

CONCLUSIONS: Rare genetic variants make an identifiable contribution to T2D in a small number of cases but these may provide valuable insights into disease mechanisms. As larger samples become available it is likely that additional genetic factors will be identified. This research has been conducted using the UK Biobank Resource. This article is protected by copyright. All rights reserved.

PMID:34216101 | DOI:10.1002/dmrr.3482

Pain Pract. 2021 Jul 3. doi: 10.1111/papr.13055. Online ahead of print.

ABSTRACT

The objective of this prospective, multicenter study is to characterize responses to percutaneous medial branch peripheral nerve stimulation (PNS) to determine if results from earlier, smaller single-center studies and reports were generalizable when performed at a larger number and wider variety of centers in patients recalcitrant to non-surgical treatments. Participants with chronic axial low back pain were implanted with percutaneous PNS leads targeting the lumbar medial branch nerves for up to 60 days, after which the leads were removed. Participants were followed long-term for 12 months after the 2-month PNS treatment. Data collection is complete for visits through end of treatment with PNS (Primary Endpoint) and 6 months after lead removal (8 months after start of treatment), with some participant follow-up visits thereafter in progress. Clinically and statistically significant reductions in pain intensity, disability, and pain interference were reported by a majority of participants. Seventy-three percent of participants were successes for the Primary Endpoint, reporting clinically significant (≥30%) reductions in back pain intensity after the 2-month percutaneous PNS treatment (n=54/74). While prospective follow up is ongoing, among those who had already completed the long-term follow up visits (n=51), reductions in pain intensity, disability, and pain interference were sustained in a majority of participants through 14 months after the start of treatment. Given the minimally invasive, non-destructive nature of percutaneous PNS and the significant benefits experienced by participants who were recalcitrant to non-surgical treatments, percutaneous PNS may provide a promising first-line neurostimulation treatment option for patients with chronic axial back pain.

PMID:34216103 | DOI:10.1111/papr.13055

Clin Transl Sci. 2021 Jul 3. doi: 10.1111/cts.13088. Online ahead of print.

ABSTRACT

Sepsis-induced metabolic dysfunction contributes to organ failure and death. L-carnitine has shown promise for septic shock, but a recent phase II study of patients with vasopressor-dependent septic shock demonstrated a non-significant reduction in mortality. We undertook a pharmacometabolomics study of these patients (n = 250) to identify metabolic profiles predictive of a 90-day mortality benefit from L-carnitine. The independent predictive value of each pretreatment metabolite concentration, adjusted for L-carnitine dose, on 90-day mortality was determined by logistic regression. A grid-search analysis maximizing the Z-statistic from a binomial proportion test identified specific metabolite threshold levels that discriminated L-carnitine responsive patients. Threshold concentrations were further assessed by hazard ratio and Kaplan-Meier estimate. Accounting for L-carnitine treatment and dose, 11 ¹ H-NMR metabolites and 12 acylcarnitines were independent predictors of 90-day mortality. Based on the grid-search analysis numerous acylcarnitines and valine were identified as candidate metabolites of drug response. Acetylcarnitine emerged as highly viable for the prediction of an L-carnitine mortality benefit due to its abundance and biological relevance. Using its most statistically significant threshold concentration, patients with pretreatment acetylcarnitine greater than or equal to 35 µM were less likely to die at 90 days if treated with L-carnitine (18 g) versus placebo (p = 0.01 by log rank test). Metabolomics also identified independent predictors of 90-day sepsis mortality. Our proof-of-concept approach shows how pharmacometabolomics could be useful for tackling the heterogeneity of sepsis and informing clinical trial design. In addition, metabolomics can help understand mechanisms of sepsis heterogeneity and variable drug response, because sepsis induces alterations in numerous metabolite concentrations.

PMID:34216108 | DOI:10.1111/cts.13088

J Aquat Anim Health. 2021 Jul 2. doi: 10.1002/aah.10130. Online ahead of print.

ABSTRACT

In this case study, phage therapy was applied to treat a multidrug-resistant case of septicemic cutaneous ulcerative disease (SCUD) caused by Citrobacter freundii in a loggerhead sea turtle Caretta caretta. Phages were applied topically, intravenously, into the carapace, and into the exhibit water using various phage cocktails specific to the causative agent over an 8-month period. This was performed in conjunction with antimicrobial therapy. The animal was monitored through weekly cultures, photographs, and complete blood cell counts, as well as immune assays (phagocytosis, plasma lysozyme and superoxide dismutase activity, and plasma electrophoresis profiles). The animal, in comparison to an untreated, unaffected control, had elevated antibody titers to the administered phages, which persisted for at least 35 weeks. Although cultures were clear of C. freundii after phage treatment, the infection did return over time and immune assays confirmed deficiencies when compared to a healthy loggerhead sea turtle. Immune parameters with statistically significant changes over the study period included the following: decreased phagocytosis, increased alpha- and gamma-globulin protein components, and an increased albumin : globulin ratio. When C. freundii appeared again, the multidrug-resistant status had reverted back to normal susceptibility patterns. Although not completely known whether it was another subspecies of bacteria, the therapy did resolve the multidrug-resistant challenge. Phage therapy in combination with antimicrobial agents may be an effective treatment for sea turtles with normally functioning immune systems or less-severe infections. Additional research is needed to better understand and quantify sea turtle immunology.

PMID:34216060 | DOI:10.1002/aah.10130

Health Econ. 2021 Jul 2. doi: 10.1002/hec.4372. Online ahead of print.

ABSTRACT

Prior to the Affordable Care Act (ACA), insurance companies could charge higher premiums, or outright deny coverage, to people with preexisting health problems. But the ACA’s “guaranteed issue” provision forbids such price discrimination and denials of coverage. This paper seeks to determine whether, after implementation of the ACA, nongroup private insurance plans have experienced adverse selection. Our empirical approach employs a copula-based hurdle regression model, with dependence modeled as a function of dimensions along which adverse selection might occur. Our main finding is that, after implementation of the ACA, nongroup insurance enrollees with preexisting health problems do not appear to exhibit adverse selection. This finding suggests that the ACA’s mandate that everyone acquire coverage might have attracted enough healthy enrollees to offset any adverse selection.

PMID:34216065 | DOI:10.1002/hec.4372

Perspect Psychiatr Care. 2021 Jul 2. doi: 10.1111/ppc.12898. Online ahead of print.

ABSTRACT

PURPOSE: This study was carried out to determine the effect of mindfulness levels on the life satisfaction of nursing students.

DESIGN AND METHODS: A descriptive correlational study was conducted on 333 nursing students enrolled at a state university in Turkey.

FINDINGS: The statistical analysis of the data indicated that students’ mindfulness levels had a significantly positive impact on their satisfaction with life.

IMPLICATIONS FOR PRACTICE: Activities that include exercises, meditation and training geared to raise the level of mindfulness can also be beneficial in terms of increasing satisfaction with life.

PMID:34216042 | DOI:10.1111/ppc.12898