Nevin Manimala

Clin Microbiol Infect. 2022 Jul 1:S1198-743X(22)00330-5. doi: 10.1016/j.cmi.2022.06.017. Online ahead of print.

ABSTRACT

BACKGROUND: Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI).

OBJECTIVES: To estimate the effect of these strategies and to identify symptoms, signs or other factors that indicate a benefit from these strategies.

DATA SOURCES: MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials.

STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: RCTs investigating any strategies to reduce antibiotics versus immediate antibiotics in adult women with uUTI in primary care.

DATA SYNTHESIS: We extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD.

RESULTS: We analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (odds ratio [OR] 3.0; 95% credible interval [CI] 1.7-5.5; Bayesian p-value p_B=0.0017; τ=0.6), subsequent antibiotic treatment (OR 3.5 [95% CI 2.1, 5.8; p_B=0.0003) and pyelonephritis (OR 5.6; 95% CI 2.3, 13.9; p_B=0.0003). Conversely, they decreased overall antibiotic use by 63%. In patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CI 2.1-10.8; p_B =0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CI 0.3-2.0; p_B =0.667). In patients treated with using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis.

CONCLUSIONS AND RELEVANCE: Compared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing.

PMID:35788049 | DOI:10.1016/j.cmi.2022.06.017

BMJ. 2022 Jul 4;378:e070022. doi: 10.1136/bmj-2022-070022.

ABSTRACT

OBJECTIVE: To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital.

DESIGN: Systematic review and network meta-analysis.

DATA SOURCES: Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital.

MAIN OUTCOME MEASURES: Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework.

RESULTS: 44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses.

CONCLUSIONS: Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020173088.

PMID:35788047 | DOI:10.1136/bmj-2022-070022

Neuroimage. 2022 Jul 1:119439. doi: 10.1016/j.neuroimage.2022.119439. Online ahead of print.

ABSTRACT

Quantification methods based on the acquisition of diffusion magnetic resonance imaging (dMRI) with multiple diffusion weightings (e.g., multi-shell) are becoming increasingly applied to study the in-vivo brain. Compared to single-shell data for diffusion tensor imaging (DTI), multi-shell data allows to apply more complex models such as diffusion kurtosis imaging (DKI), which attempts to capture both diffusion hindrance and restriction effects, or biophysical models such as NODDI, which attempt to increase specificity by separating biophysical components. Because of the strong dependence of the dMRI signal on the measurement hardware, DKI and NODDI metrics show scanner and site differences, much like other dMRI metrics. These effects limit the implementation of multi-shell approaches in multicenter studies, which are needed to collect large sample sizes for robust analyses. Recently, a post-processing technique based on rotation invariant spherical harmonics (RISH) features was introduced to mitigate cross-scanner differences in DTI metrics. Unlike statistical harmonization methods, which require repeated application to every dMRI metric of choice, RISH harmonization is applied once on the raw data, and can be followed by any analysis. RISH features harmonization has been tested on DTI features but not its generalizability to harmonize multi-shell dMRI. In this work, we investigated whether performing the RISH features harmonization of multi-shell dMRI data removes cross-site differences in DKI and NODDI metrics while retaining longitudinal effects. To this end, 46 subjects underwent a longitudinal (up to 3 time points) two-shell dMRI protocol at 3 imaging sites. DKI and NODDI metrics were derived before and after harmonization and compared both at the whole brain level and at the voxel level. Then, the harmonization effects on cross-sectional and on longitudinal group differences were evaluated. RISH features averaged for each of the 3 sites exhibited prominent between-site differences in the frontal and posterior part of the brain. Statistically significant differences in fractional anisotropy, mean diffusivity and mean kurtosis were observed both at the whole brain and voxel level between all the acquisition sites before harmonization, but not after. The RISH method also proved effective to harmonize NODDI metrics, particularly in white matter. The RISH based harmonization maintained the magnitude and variance of longitudinal changes as compared to the non-harmonized data of all considered metrics. In conclusion, the application of RISH feature based harmonization to multi-shell dMRI data can be used to remove cross-site differences in DKI metrics and NODDI analyses, while retaining inherent relations between longitudinal acquisitions.

PMID:35788044 | DOI:10.1016/j.neuroimage.2022.119439

BJGP Open. 2022 Jul 4:BJGPO.2022.0060. doi: 10.3399/BJGPO.2022.0060. Online ahead of print.

ABSTRACT

BACKGROUND: The British Lung Foundation previously estimated that 2.2 million symptomatic but undiagnosed people with COPD live in the UK.

AIM: This study investigates the proportion of patients with a missed COPD diagnosis among those with COPD as the cause of death on their death certificate and how this has changed over the past 17 years.

DESIGN & SETTING: We linked Clinical Practice Research Datalink Aurum and GOLD primary care data with Office for National Statistics mortality data and Hospital Episode Statistics data. We included adults who died between 2000 and 2017 with COPD as their main cause of death.

METHOD: Using a range of diagnostic COPD criteria, we estimated the proportion of patients with a missed COPD diagnosis, and described the demographic and clinical characteristics of patients with and without prior COPD diagnosis using a mixed effect logistic regression model.

RESULTS: Depending on the COPD definition used, between 96% and 27% of the 78,621 patients included received a diagnosis of COPD prior to death. Using presence of a COPD Read or SNOMED CT code and performed spirometry as a main definition, just over half of the patients (52%) had received a COPD diagnosis overall, with a proportion of those who did not decreasing from 91% in 2000 to 31% in 2017 (p-trend <0.001).

CONCLUSION: The proportion of people with COPD-recorded death who had received a diagnosis of COPD has improved over time and currently represents the majority of them, suggesting that few patients are being missed.

PMID:35788026 | DOI:10.3399/BJGPO.2022.0060

Exp Gerontol. 2022 Jul 1:111884. doi: 10.1016/j.exger.2022.111884. Online ahead of print.

ABSTRACT

INTRODUCTION: Sarcopenia, the age-related loss of skeletal muscle strength and mass, carries a significant burden for affected individuals. There has been little investigation of sarcopenia using experimental medicine techniques to study human muscle tissue in detail. The aim of the Muscle Ageing Sarcopenia Studies Lifecourse (MASS_Lifecourse) study is to recruit up to 160 participants, equally divided between females and males between ages 45 and 85 years for detailed phenotyping of skeletal muscle health. Here we describe the protocol for the study and the characteristics of the first 80 participants.

METHODS: We are recruiting participants from three sources in the north-east of England. Study fieldwork comprises a home visit (or videocall) for consent and assessment of health, cognition, lifestyle, and wellbeing. This is followed by a visit to a clinical research facility for assessment of sarcopenia status and collection of samples including a vastus lateralis muscle biopsy. We produced descriptive statistics for the first 80 participants, including expressing their grip strength relative to normative data in the form of Z-scores.

RESULTS: The first 80 participants (53.8 % female) covered the target ages, ranging from 48 to 84 years. They were regularly physically active, reported good physical function and had a prevalence of sarcopenia (including probable sarcopenia) of 11.3 % based on the revised European consensus. Their grip strength was similar to that in the general population, with a mean Z-score of 0.09 standard deviations (95 % CI: -1.64, 1.83) above that expected.

CONCLUSIONS: The MASS_Lifecourse study combines comprehensive health and lifestyle data with a range of biological samples including skeletal muscle. The findings from planned analyses should contribute to improvements in the diagnosis, treatment, and prevention of sarcopenia.

PMID:35788023 | DOI:10.1016/j.exger.2022.111884

Urology. 2022 Jul 1:S0090-4295(22)00517-9. doi: 10.1016/j.urology.2022.05.038. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine whether the omission of pre-procedure genitourinary exam for vasectomy inherent to a virtual consultation reduces the likelihood of successfully completing in-office vasectomy. Currently, the AUA Vasectomy guidelines encourage in-person examination when possible, though COVID-19 has catalyzed the uptake of virtual consultations at many institutions. We hypothesized that rates of completed in-office vasectomy do not significantly differ between patients examined during consultation in the office and those seen virtually with no exam.

METHODS: Virtual vasectomy consults from April to December 2020 were retrospectively reviewed and compared to a size-matched, randomly-selected control group who underwent in-office vasectomy consultation. The primary outcome was completion of in-office bilateral vasectomy. Baseline demographic characteristics were compared. Fisher’s exact test and Student’s t-test were performed on categorical and continuous variables, respectively.

RESULTS: Of 211 patients who underwent virtual vasectomy consultation during the study period, 153 presented for in-office vasectomy. They were compared to 153 vasectomies from the in-person consult cohort. No demographic differences were observed between virtual and in-office consult groups. No statistical difference was observed in completion rates of in-office vasectomy, which was 97.4% (149/153) in the virtual consult cohort and 98.7% (151/153) in the in-office consultation cohort (p = 0.68).

CONCLUSIONS: Rates of completed in-office vasectomy did not significantly differ based on consult platform, suggesting that a pre-vasectomy physical exam is not required to predict successful completion of the procedure. Telehealth should be utilized as an additional platform to improve access for male contraceptive procedures in a young and busy population.

PMID:35788017 | DOI:10.1016/j.urology.2022.05.038

Int J Biol Macromol. 2022 Jul 1:S0141-8130(22)01363-0. doi: 10.1016/j.ijbiomac.2022.06.150. Online ahead of print.

ABSTRACT

This study presents the preparation of cellulose micro-nanofibrils (CMNFs) from Enteromorpha (EP) and the application in PVA/acetylated distarch phosphate (ADSP)/CMNFs composite films. The Micro-nano scale, hydrophilicity, and strong hydrogen bond characteristics of CMNFs prepared form EP by acid hydrolysis were confirmed through the granular statistics, XRD analysis and chemical structure analysis. With the addition of CMNFs, the ultimate tensile strength and elongation at break of composite films are increased by 42.4 % and 90.3 %. An original Weibull statistical analysis shows the impact of CMNFs’ added amount on strength distribution and ultimate stress. SEM and polarizing microscope images show the CMNFs’ dispersion state in that films is optimal, when their addition was to be 2 %-3 % of total dry weight of PVA/ADSP matrix， which is consistent with the results of Weibull modulus analysis. The main thermal weight-loss process of the composite film is divided into four stages, CMNFs can significantly increase the thermostability at 280 °C to 400 °C. The experiment of water contact angle and water vapor transmission rate of the composite films confirmed that CMNFs can improve films’ hydrophilicity. This study provides basis for the preparation of hydrophilic CMNFs and mechanism of modification study PVA-based composites.

PMID:35788004 | DOI:10.1016/j.ijbiomac.2022.06.150

Burns. 2022 Jun 10:S0305-4179(22)00144-9. doi: 10.1016/j.burns.2022.06.003. Online ahead of print.

ABSTRACT

Low- and middle-income countries (LMICs) remain drastically underrepresented in health research, with African countries producing less than 1% of the global output. This work investigates authorship patterns of publications on burns in LMICs. Original research studies addressing burn injuries in LMICs and published between 1st January 2015 and 31st December 2020 were included in the review. Descriptive statistics were performed for country affiliations of authors, World Bank Country Income Groups, WHO group, study-focus and country studied. Of the 458 results, 426 studies met the inclusion criteria. Nearly a quarter of papers on burns in LMICs had both first and senior authors from high-income countries (HICs, n = 95, 24.4%), more than half of the papers had both first and senior authors from upper middle- income countries (upper MICs, n = 222, 57.2%), while less than 1% (n = 3) had first and senior authors exclusively from lower-income countries (LICs). Eleven percent (n = 41/388) of all papers were written without either first nor senior author being from the country studied, and 17 of them (41%) had both first and senior authors from the USA. Twenty-five (6%) of the papers had the first author and not the senior author from the country of focus, while six (2%) had the senior and not the first author from the country of interest. To overcome global health challenges such as burns, locally led research is imperative. The maximum benefit of HIC-LMIC collaborations is achieved when LMICs play an active role in leading the research. When LMICs direct the research being conducted in their country, the harm of inherently inequitable relationships is minimized.

PMID:35787966 | DOI:10.1016/j.burns.2022.06.003

Burns. 2022 Jun 22:S0305-4179(22)00160-7. doi: 10.1016/j.burns.2022.06.010. Online ahead of print.

ABSTRACT

BACKGROUND: Intermittent Fasting (IF) has proved to have various positive effects on life span, diseases, and healing of tissues in rodents. We evaluated the protective effect of fasting in maintaining the ischemic zones in burn wounds.

METHODS: In this study, 20 rats were divided into two groups where the IF rats were deprived of food for three months. Burn wounds were created by burn comb model on the back of all rats. On days 3 and 21 after injury, five rats in each group were euthanized whereby samples were collected for histopathological, immunohistochemical (Bcl2, P53 and VEGF), and biochemical (MDA, TAC, HP) evaluations.

RESULTS: Histopathological analysis revealed epithelial layer and zone of ischemia remained viable in the intermittent fasting group on day 3. On the 21st day, epithelialization, angiogenesis, inflammation, fibrocyte-fibroblast, and collagen density were different in the ischemic and necrotic zones between the control and intermittent fasting groups (p<0.05). We found no statistical differences in Bcl2, P53, VEGF, MDA, TAC, and HP on day 3 between the intermittent fasting and control groups.

CONCLUSIONS: Intermittent fasting before burn wounds reduces tissue damage caused by ischemia and enhanced the viability of cells in zone of stasis. It also accelerated wound healing by increasing epithelialization and collagen production in the skin and regulating inflammatory responses. This intervention appears to be related to better collagen arrangement and angiogenesis.

PMID:35787965 | DOI:10.1016/j.burns.2022.06.010

World Neurosurg. 2022 Jul 1:S1878-8750(22)00914-7. doi: 10.1016/j.wneu.2022.06.129. Online ahead of print.

ABSTRACT

OBJECTIVE: Angiographic treatment of asymptomatic cerebral vasospasm in aneurysmal subarachnoid hemorrhage remains controversial. We sought to investigate its relationship with the development of delayed cerebral ischemia.

METHODS: Consecutive patients admitted between July 2017 and June 2019, with a diagnosis of aneurysmal subarachnoid hemorrhage, were retrospectively analyzed. The rate of development of delayed cerebral ischemia was compared between a group of patients who underwent cerebral angiography for asymptomatic cerebral vasospasm and those who did not. The Mann-Whitney U test or chi-square test was used to compare the two groups.

RESULTS: 37 of the 94 patients with aneurysmal subarachnoid hemorrhage were screened for cerebral vasospasm, of whom 16 (43%) had moderate-severe vasospasm. When patients who underwent therapeutic cerebral angiography were compared with those who did not, and after adjusting for sex, age, and grade of subarachnoid hemorrhage, treatment was not found to be significantly associated with delayed cerebral ischemia (HR=0.82, 95% CI: 0.19-3.52, p=0.79). We found that the median length of stay in the intensive care unit and hospital increased significantly with the severity of cerebral vasospasm (p<0.001).

CONCLUSIONS: Cerebral angiography has a low rate of detecting moderate-severe cerebral vasospasm in asymptomatic patients. Moreover, there was no statistically significant difference in the rate of delayed cerebral ischemia between asymptomatic patients treated versus those not treated for cerebral vasospasm.There was significant association between the severity of CVS and the ICU and hospital length of stay. More studies are needed to evaluate the utility of treating asymptomatic cerebral vasospasm in high-grade aneurysmal subarachnoid hemorrhage.

PMID:35787959 | DOI:10.1016/j.wneu.2022.06.129