Tag: nevin manimala

Liver Int. 2021 Jul 9. doi: 10.1111/liv.15009. Online ahead of print.

ABSTRACT

BACKGROUND&AIMS: Sustained virologic response (SVR) to direct-acting antivirals (DAA) ameliorates portal hypertension, improves hepatic function and may reverse the procoagulant state observed in patients with cirrhosis. However, an unexpected incidence of portal vein thrombosis (PVT) immediately after antiviral therapy has recently been reported. Therefore, we analyzed the long-term impact of SVR on the development of non-tumoral-PVT.

METHODS: Our study comprised two well-characterized prospective cohorts (‘HCV-Cured’:n=354/’HCV-Active’:n=179) of patients with HCV-cirrhosis who underwent standardized ultrasound surveillance. In the main analysis, the event of interest was de novo non-tumoral-PVT and events known to modify its natural history (OLT, TIPS, death, tumoral-PVT and anticoagulation) were considered as competing risk. Adjusted models were built using propensity scores for baseline covariates. Moreover, predictive factors were investigated by conventional multivariate analysis.

RESULTS: Ten (2.8%) patients in the ‘HCV-Cured’-cohort developed a non-tumoral-PVT during a median follow-up of 37.1 months, while 8 (4.5%) patients in the ‘HCV-Active’-cohort were diagnosed with non-tumoral-PVT during a median follow-up of 42.2 months. High Child-Pugh score was the only independent risk factor for non-tumoral-PVT-development and stage A patients were at low risk. Importantly, HCV-cure did not decrease the risk of non-tumoral-PVT in inverse probability of treatment-weighted (IPTW) analysis (subdistribution hazard ratio (sHR): 1.31(95% confidence interval (95%CI): 0.43-3.97); P=0.635). In contrast, SVR was associated with a substantial reduction in mortality (IPTW-adjusted sHR: 0.453 (95%CI: 0.287-0.715); P<0.001).

CONCLUSIONS: The risk of non-tumoral-PVT persists after HCV-cure in patients with cirrhosis, despite improving survival. Even after etiological cure, severity of liver disease remains the main determinant of non-tumoral-PVT-development.

PMID:34242479 | DOI:10.1111/liv.15009

Liver Int. 2021 Jul 9. doi: 10.1111/liv.15011. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Aspirin and statins have been suggested to prevent hepatocellular carcinoma (HCC). However, the combined effects of aspirin and statins on HCC risk in patients with chronic hepatitis B (CHB) is not clear.

METHODS: A nationwide nested case-control study was performed with data from the National Health Insurance Service gathered between 2005 and 2015 in Korea. In a cohort of 538,135 treatment-naïve, non-cirrhotic patients with CHB, 6,539 HCC cases were matched to 26,156 controls and were analyzed by conditional logistic regression. Separate historical cohort studies for each drug were analyzed by time-dependent Cox regression as a sensitivity analysis.

RESULTS: In the nested case-control study, statins (OR 0.34; 95% CI 0.32-0.37) and aspirin (OR 0.92; 95% CI 0.85-0.99) were significantly associated with a HCC risk reduction. However, dose-dependent risk reduction was observed only with statins. By sensitivity analysis in the historical cohorts, statin users (n = 244,455; HR 0.67; 95% CI 0.66-0.68) and aspirin users (n = 288,777; HR 0.81; 95% CI 0.80-0.82) had significantly lower HCC risk. In the drug-stratified analyses, statins were associated with significantly reduced risk of HCC regardless of aspirin, whereas aspirin did not show such associations.

CONCLUSIONS: In this nationwide population-based study of patients with CHB, statin use was consistently associated with a significant and dose-dependent reduction in HCC risk. In contrast, the association between aspirin use and HCC risk reduction was not dose-dependent and was suggested to be confounded by statins.

PMID:34242482 | DOI:10.1111/liv.15011

Curr Protoc. 2021 Jul;1(7):e194. doi: 10.1002/cpz1.194.

ABSTRACT

Candida albicans biofilm formation in the presence of drugs can be examined through time-lapse microscopy. In many cases, the images are used qualitatively, which limits their utility for hypothesis testing. We employed a machine-learning algorithm implemented in the Orbit Image Analysis program to detect the percent area covered by cells from each image. This is combined with custom R scripts to determine the growth rate, growth asymptote, and time to reach the asymptote as quantitative proxies for biofilm formation. We describe step-by-step protocols that go from sample preparation for time-lapse microscopy through image analysis parameterization and visualization of the model fit. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Sample preparation Basic Protocol 2: Time-lapse microscopy: Evos protocol Basic Protocol 3: Batch file renaming Basic Protocol 4: Machine learning analysis of Evos images with Orbit Basic Protocol 5: Parametrization of Orbit output in R Basic Protocol 6: Visualization of logistic fits in R.

PMID:34242490 | DOI:10.1002/cpz1.194

Eur J Pain. 2021 Jul 9. doi: 10.1002/ejp.1836. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic pain is a significant health problem worldwide and requires a biopsychosocial treatment approach. Access to traditional pain medicine specialist services is limited and innovative treatment models are required to support patients in tertiary care. The study evaluated the clinical effectiveness and safety of the Treatment Access Pathway (TAP), an allied health expanded scope model of care which included innovative group assessment and collaboration with patients to create individualised treatment plans.

METHODS: One hundred and eighty-one patients referred to a tertiary level chronic pain service were randomly allocated to either the TAP or the waitlist study groups. Primary (pain interference) and secondary outcome measures were collected at recruitment and again at 6 months. Per-protocol analyses were utilised due to high participant attrition (46% across groups).

RESULTS: The TAP group reported greater reductions in pain interference at 6-months than waitlist group (0.9, 95% CI: 0.2 to 1.6), with more than half of the TAP group (52%) reporting clinically significant improvement. In addition, statistically significant differences between the TAP and waitlist groups were observed for objective measurements of walking endurance (5.4 meters, 95% CI: 1.7 to 9.1); and global impressions of change (1.4 unit decrease, 95% CI: 1 to 1.9). Nil adverse events were recorded.

CONCLUSIONS: The study suggests that an expanded scope allied health model of care prioritising patient choice and group-based interventions, provides modest benefits for tertiary-referral chronic pain patients. TAP warrants further investigation as a potentially viable alternative for tertiary healthcare where traditional pain services are unavailable or have long waiting lists.

PMID:34242463 | DOI:10.1002/ejp.1836

Clin Pharmacol Drug Dev. 2021 Jul 9. doi: 10.1002/cpdd.989. Online ahead of print.

ABSTRACT

This single-center, randomized, 3-way crossover thorough QT study evaluated the effect of steady-state supratherapeutic venlafaxine (Effexor) on cardiac repolarization. Fifty-four healthy adults received double-blinded extended-release venlafaxine 450 mg/d and placebo and open-label positive-control moxifloxacin 400 mg. The postdose QT intervals corrected for heart rate using the Fridericia formula (QTcF) were assessed on day 14 with an analysis of covariance using a mixed-effects model. At each time, the upper bound of the 2-sided 90%CI for time-matched least-squares (LS) mean difference between venlafaxine and placebo did not exceed the predefined cutoff of 10 milliseconds; the highest 90%CI upper bound was 5.8 milliseconds 24 hours postdose, demonstrating the lack of effect of venlafaxine on the QTc interval (primary objective). Assay sensitivity was established because the lower bound of the 2-sided 90%CI for LS mean difference in QTcF between moxifloxacin and placebo was 7.413 milliseconds on day 14 (postdose 3 hours). The exposure-response analysis demonstrated no evidence of increase in QTcF with increase in venlafaxine and desvenlafaxine concentrations. Also, supratherapeutic venlafaxine was found to be safe and well tolerated. Overall, the results demonstrated the lack of significant prolongation of the QTc interval with supratherapeutic venlafaxine 450 mg/d.

PMID:34242472 | DOI:10.1002/cpdd.989

Clin Pharmacol Ther. 2021 Jul 9. doi: 10.1002/cpt.2362. Online ahead of print.

ABSTRACT

The association between the use of Vitamin K antagonists (VKA) and cancer risk reduction remains unclear. We aimed to assess the association between the use of VKA or DOAC and the incidence of cancer in a large cohort of AF patients by meaans of a population-based, propensity-weighted cohort study using population-wide databases including patients diagnosed with non-valvular AF (NVAF) followed for up of 5 years (median 2.94 years). We created two cohorts based on the initiation therapy (VKA or DOAC). Initiation with VKA or DOAC was defined as filling a prescription with no previous exposure in the preceding 12 months. Cancer diagnoses of any type and for specific tumours (lung, colon, prostate, bladder, breast). We included 39,989 patients, 31,200 (78.0%) in the VKA cohort. Incidence rate for any cancer was 12.45 per 1000 person-year in the DOAC cohort, vs. 14.55 in the VKA cohort (adjusted HR: 1.16, 95% CI: 1.02-1.32). In secondary outcomes, no differences were found for specific types of cancer such as lung (HR: 1.28, CI: 0.89-1.83), colon (HR: 0.84, CI: 0.62-1.13), prostate (HR: 1.40, CI: 0.94-2.10), bladder (HR: 1.07, CI: 0.76-1.52), breast (HR: 1.05, CI: 0.66-1.69). Sensitivity analyses yielded similar results. Subgroup analyses also produced consistent findings, except for men, for whom VKA was associated with a lower risk of colon cancer (HR: 0.68; 95%CI: 0.48-0.96). Our results do not confirm a chemoprotective effect of VKA when compared to DOAC in a large, real-world cohort of NVAF patients followed for up to 5 years.

PMID:34242404 | DOI:10.1002/cpt.2362

Hepatology. 2021 Jul 9. doi: 10.1002/hep.32052. Online ahead of print.

ABSTRACT

The research by Liao et al.⁽¹⁾ showed that postdiagnosis aspirin use improved the mortality of various subtypes of biliary tract cancer (BTC). The results were impressive, with the adjusted hazard ratios of mortality ranging from 0.51 to 0.58, and all subgroup analyses were statistically significant. However, we think that some other aspects should be discussed.

PMID:34242426 | DOI:10.1002/hep.32052

Neuromodulation. 2021 Jul 9. doi: 10.1111/ner.13477. Online ahead of print.

ABSTRACT

OBJECTIVES: The purpose of the ongoing follow-up of ReActiv8-A clinical trial is to document the longitudinal benefits of episodic stimulation of the dorsal ramus medial branch and consequent contraction of the lumbar multifidus in patients with refractory mechanical chronic low back pain (CLBP). We report the four-year outcomes of this trial.

MATERIALS AND METHODS: ReActiv8-A is a prospective, single-arm trial performed at nine sites in the United Kingdom, Belgium, and Australia. Eligible patients had disabling CLBP (low back pain Numeric Rating Scale [NRS] ≥6; Oswestry Disability Index [ODI] ≥25), no indications for spine surgery or spinal cord stimulation, and failed conventional management including at least physical therapy and medications for low back pain. Fourteen days postimplantation, stimulation parameters were programmed to elicit strong, smooth contractions of the multifidus, and participants were given instructions to activate the device for 30-min stimulation-sessions twice daily. Annual follow-up through four years included collection of NRS, ODI, and European Quality of Life Score on Five Dimensions (EQ-5D). Background on mechanisms, trial design, and one-year outcomes were previously described.

RESULTS: At baseline (N = 53) (mean ± SD) age was 44 ± 10 years; duration of back pain was 14 ± 11 years, NRS was 6.8 ± 0.8, ODI 44.9 ± 10.1, and EQ-5D 0.434 ± 0.185. Mean improvements from baseline were statistically significant (p < 0.001) and clinically meaningful for all follow-ups. Patients completing year 4 follow-up, reported mean (±standard error of the mean) NRS: 3.2 ± 0.4, ODI: 23.0 ± 3.2, and EQ-5D: 0.721 ± 0.035. Moreover, 73% of participants had a clinically meaningful improvement of ≥2 points on NRS, 76% of ≥10 points on ODI, and 62.5% had a clinically meaningful improvement in both NRS and ODI and 97% were (very) satisfied with treatment.

CONCLUSIONS: In participants with disabling intractable CLBP who receive long-term restorative neurostimulation, treatment satisfaction remains high and improvements in pain, disability, and quality-of-life are clinically meaningful and durable through four years.

PMID:34242440 | DOI:10.1111/ner.13477

PLoS One. 2021 Jul 9;16(7):e0254460. doi: 10.1371/journal.pone.0254460. eCollection 2021.

ABSTRACT

This study aimed to evaluate the link between health problems, demographic factors, and the indoor environment quality of residents in Indonesia. We conducted a cross-sectional design study through a questionnaire survey with 443 respondents aged between 12 and 81 years. The questionnaire was concerned with previous health problem occurrences associated with thermal discomfort experiences, indoor environments, economic conditions, and basic anthropometric factors. Logistic regression with the odds ratio (OR) was applied to evaluate the tendency of different respondent groups to suffer from certain health problems, when compared to reference groups. Furthermore, structural equation modelling (SEM) was used to incorporate certain factors (economic conditions, thermal discomfort experiences, and perceived indoor environments) into a single model to understand their direct and indirect effects on health conditions. The results indicate that economic conditions are the most significantly associated with health problems. Furthermore, we found that the low-income group was the most vulnerable to health problems, including coughing, puking, diarrhoea, odynophagia, headaches, fatigue, rheumatism, fidgeting, skin rashes, muscle cramps, and insomnia (OR: 1.94-6.04, p <0.05). Additionally, the SEM suggested that the respondents’ economic conditions and thermal discomfort experiences had significant direct effects on their health problems with standardized estimates of -0.29 and 0.55, respectively. Additionally, perceived indoor environment quality, which is possible to cause thermal discomfort experience, indirectly affect health problems. These findings contribute an insightful and intuitive knowledge base which can aid health assessments associated with demographic and physical environments in developing sustainable and healthy environment strategies for the future.

PMID:34242376 | DOI:10.1371/journal.pone.0254460

PLoS One. 2021 Jul 9;16(7):e0254446. doi: 10.1371/journal.pone.0254446. eCollection 2021.

ABSTRACT

INTRODUCTION: From the outset of the COVID-19 pandemic, guidance from WHO has promoted social distancing, wearing face masks, frequent hand washing, and staying-at-home as measures to prevent the spread of COVID-19. For many across Africa, compliance can be difficult. The aim of this study was to 1) understand the impact of student’s household’s ability to comply with COVID-19 mitigation strategies, 2) identify predictors of mitigation strategy compliance, and 3) describe the impact of COVID-19 on household economics, food-security, and mental well-being.

MATERIALS AND METHODS: We conducted an email-based survey among current medical and pharmacy students of the University of Liberia College of Health Sciences between July and October 2020. The questionnaire was designed to explore their household’s ability to comply with current mitigation strategies, as well as the pandemic´s impact on the student’s household’s finances and food security. Descriptive statistics were used to delineate demographic characteristics. Logistic regression was used to model factors associated with ability to comply with COVID-19 mitigation strategies, as well as participant’s food security.

RESULTS: 113 persons responded to the questionnaire. Seventy-six (67∙3%) reported income losses as a result of the pandemic, with 93 (82∙3%) reporting being “somewhat” or “very worried” about their households’ finances. Seventy-seven (68∙1%) participants reported food stocks that were sufficient for one-week or less. Forty (35%) participants reported eating less preferred foods or skipping meals in the past week. Overall, 20 participants (19∙4%) had a positive depression screen.

CONCLUSIONS: Study participants showed mixed results in being able to adhere to national COVID-19 mitigation strategies, with household level stressors experienced around finances and food security. Until Liberia has access to vaccinations for most of its citizens, COVID-19 response measures need to provide social protections that address basic needs (shelter, clothing and food), and which specifically targets food insecurity. Preventative interventions for mental health problems must be incorporated into Liberia’s response to the pandemic.

PMID:34242378 | DOI:10.1371/journal.pone.0254446