Nevin Manimala

Clinics (Sao Paulo). 2021 Apr 9;76:e2501. doi: 10.6061/clinics/2021/e2501. eCollection 2021.

ABSTRACT

OBJECTIVES: Antineutrophil cyto plasmic antibody-associated vasculitis (AAV) is a fatal disease. Currently, predictors of mortality due to AAV are based on the distribution of organ involvement. The novel fibrosis index (NFI) is an index composed of laboratory results that reflect the degree of liver fibrosis. This study aimed to evaluate whether NFI can predict poor outcomes in patients with AAV without substantial liver disease.

METHODS: A total of 210 patients with immunosuppressive drug-naïve AAV were retrospectively reviewed. NFI was calculated as follows: NFI=(serum bilirubin × (alkaline phosphatase)2)/(platelet count×(serum albumin)2). NFI cut-off was set at 1.24 (the highest quartile). Poor outcomes were defined as all-cause mortality, relapse, and end-stage renal disease (ESRD).

RESULTS: During the median 34.5 months of follow-up, 21 patients (10%) died, 72 patients (34.3%) relapsed, and 38 patients (18.1%) had ESRD due to AAV progression. The median calculated NFI was 0.61, and it was higher in AAV patients with all-cause mortality than in those without mortality, but the difference was not statistically significant (1.26 vs. 0.59). AAV patients with NFI at diagnosis ≥1.24 exhibited a significantly lower cumulative patient survival rate than those with NFI at diagnosis <1.24 (p=0.002). Multivariate Cox hazard model analysis showed that NFI at diagnosis ≥1.24 was an independent predictor of all-cause mortality in AAV (hazard ratios [HR] 2.850, 95% confidence interval [CI] 1.026, 7.910).

CONCLUSIONS: NFI ≥1.24, which may be an independent predictive marker for all-cause mortality in AAV patients without substantial liver disease.

PMID:33852653 | DOI:10.6061/clinics/2021/e2501

Clinics (Sao Paulo). 2021 Apr 9;76:e2189. doi: 10.6061/clinics/2021/e2189. eCollection 2021.

ABSTRACT

OBJECTIVES: This study explored the effects of the timing of laparoscopic cholecystectomy (LC) after endoscopic retrograde cholangiopancreatography (ERCP) on liver function, bile biochemical indices, inflammatory reactions, and cholecysto-choledocholithiasis patient prognoses.

METHODS: A total of 103 cholecysto-choledocholithiasis patients were stratified into control (CG; n=51; LC at 4-7 d after ERCP) and observation groups (OG; n=52; LC at 1-3 d after ERCP) using a random number table.

RESULTS: The surgical time was shorter and intraoperative blood loss was less in OG than in CG, and the two groups were not statistically different in terms of time to the first passage of gas through anus, length of postoperative hospital stay, conversion rate to laparotomy, and stone-free rate. Four weeks after LC, alanine aminotransferase (ALT), total bilirubin (TBil), albumin (ALB), and glutamyl transpeptidase (GGT) levels declined in both groups, but the difference was not statistically significant. Three days after LC, total bile acid (TBA) levels increased, and cholesterol (CHO), unconjugated bilirubin (UCB), and TBiL levels were reduced in both groups, but were not statistically different (p>0.05). Three days after LC, interleukin (IL)-6, procalcitonin (PCT), and high-sensitivity C-reactive protein (hs-CRP) levels in the serum and bile increased in both groups and were lower in OG. The total incidence of perioperative complications was 1.92% in OG, which was lower than 15.69% in the CG.

CONCLUSION: For cholecysto-choledocholithiasis patients, LC at 1-3 d after ERCP can shorten surgical times, reduce intraoperative blood loss, improve liver function and bile biochemistry, relieve inflammatory reactions, reduce complications, and improve prognoses.

PMID:33852651 | DOI:10.6061/clinics/2021/e2189

PLoS One. 2021 Apr 14;16(4):e0250110. doi: 10.1371/journal.pone.0250110. eCollection 2021.

ABSTRACT

BACKGROUND: Prediction of the dynamics of new SARS-CoV-2 infections during the current COVID-19 pandemic is critical for public health planning of efficient health care allocation and monitoring the effects of policy interventions. We describe a new approach that forecasts the number of incident cases in the near future given past occurrences using only a small number of assumptions.

METHODS: Our approach to forecasting future COVID-19 cases involves 1) modeling the observed incidence cases using a Poisson distribution for the daily incidence number, and a gamma distribution for the series interval; 2) estimating the effective reproduction number assuming its value stays constant during a short time interval; and 3) drawing future incidence cases from their posterior distributions, assuming that the current transmission rate will stay the same, or change by a certain degree.

RESULTS: We apply our method to predicting the number of new COVID-19 cases in a single state in the U.S. and for a subset of counties within the state to demonstrate the utility of this method at varying scales of prediction. Our method produces reasonably accurate results when the effective reproduction number is distributed similarly in the future as in the past. Large deviations from the predicted results can imply that a change in policy or some other factors have occurred that have dramatically altered the disease transmission over time.

CONCLUSION: We presented a modelling approach that we believe can be easily adopted by others, and immediately useful for local or state planning.

PMID:33852642 | DOI:10.1371/journal.pone.0250110

PLoS One. 2021 Apr 14;16(4):e0250158. doi: 10.1371/journal.pone.0250158. eCollection 2021.

ABSTRACT

While the world awaits a widely available COVID-19 vaccine, availability of testing is limited in many regions and can be further compounded by shortages of reagents, prolonged processing time and delayed results. One approach to rapid testing is to leverage the volatile organic compound (VOC) signature of SARS-CoV-2 infection. Detection dogs, a biological sensor of VOCs, were utilized to investigate whether SARS-CoV-2 positive urine and saliva patient samples had a unique odor signature. The virus was inactivated in all training samples with either detergent or heat treatment. Using detergent-inactivated urine samples, dogs were initially trained to find samples collected from hospitalized patients confirmed with SARS-CoV-2 infection, while ignoring samples collected from controls. Dogs were then tested on their ability to spontaneously recognize heat-treated urine samples as well as heat-treated saliva from hospitalized SARS-CoV-2 positive patients. Dogs successfully discriminated between infected and uninfected urine samples, regardless of the inactivation protocol, as well as heat-treated saliva samples. Generalization to novel samples was limited, particularly after intensive training with a restricted sample set. A unique odor associated with SARS-CoV-2 infection present in human urine as well as saliva, provides impetus for the development of odor-based screening, either by electronic, chemical, or biological sensing methods. The use of dogs for screening in an operational setting will require training with a large number of novel SARS-CoV-2 positive and confirmed negative samples.

PMID:33852639 | DOI:10.1371/journal.pone.0250158

PLoS One. 2021 Apr 14;16(4):e0249953. doi: 10.1371/journal.pone.0249953. eCollection 2021.

ABSTRACT

INTRODUCTION: New HIV infection during pre-conception and pregnancy is a significant contributor of mother-to-child transmission of HIV in South Africa. This study estimated HIV incidence (defined as new infection within the last one year from the time of the survey which included both new infections occurred during pregnancy or just before pregnancy) among pregnant women and described the characteristics of recently infected pregnant women at national level.

METHODS: Between 1 October and 15 November 2017, we conducted a national cross-sectional survey among pregnant women aged 15-49 years old attending antenatal care at 1,595 public facilities. Blood specimens were collected from pregnant women and tested for HIV in a centralised laboratory. Plasma viral load and Limiting Antigen Avidity Enzyme Immunosorbent Assay (LAg) tests were further performed on HIV positive specimens to differentiate between recent and long-term infections. Recent infection was defined as infection that occurred within one year from the date of collection of blood specimen for the survey. Data on age, age of partner, and marital status were collected through interviews. Women whose specimens were classified as recent by LAg assay and with viral loads >1,000 copies/mL were considered as recently infected. The calculated proportion of HIV positive women with recent infection was adjusted for assay-specific parameters to estimate annual incidence. Survey multinomial logistic regression was used to examine factors associated with being recently infected using HIV negative women as a reference group. Age-disparate relationship was defined as having a partner 5 or more years older.

RESULTS: Of 10,049 HIV positive participants with LAg and viral load data, 1.4% (136) were identified as recently infected. The annual HIV incidence was 1.5% (95% confidence interval (CI): 1.2-1.7). In multivariable analyses, being single (adjusted odds ratio, aOR: 3.4, 95% CI: 1.8-6.2) or cohabiting (aOR: 3.8, 95% CI: 1.8-7.7), compared to being married as well as being in an age-disparate relationship among young women (aOR: 3.1, 95% CI: 2.0-4.7; reference group: young women (15-24years) whose partners were not 5 years or more older) were associated with higher odds of recent infection.

CONCLUSIONS: Compared to previous studies among pregnant women, the incidence estimated in this study was substantially lower. However, the UNAIDS target to reduce incidence by 75% by 2020 (which is equivalent to reducing incidence to <1%) has not been met. The implementation of HIV prevention and treatment interventions should be intensified, targeting young women engaged in age-disparate relationship and unmarried women to fast track progress towards the UNAIDS target.

PMID:33852629 | DOI:10.1371/journal.pone.0249953

Cochrane Database Syst Rev. 2021 Apr 14;4:CD007694. doi: 10.1002/14651858.CD007694.pub3.

ABSTRACT

BACKGROUND: Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta₂-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta₂-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments.

OBJECTIVES: To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid.

SEARCH METHODS: We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers’ websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was 24 February 2021.

SELECTION CRITERIA: We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks’ duration.

DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect.

MAIN RESULTS: Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-related serious adverse events were reported in these studies. Four all-cause serious adverse events were reported: three in the formoterol arm, and one in the salmeterol arm (Peto OR 2.72, 95% CI 0.38 to 19.46; 548 participants, 2 studies; low-certainty evidence).

AUTHORS’ CONCLUSIONS: Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.

PMID:33852162 | DOI:10.1002/14651858.CD007694.pub3

Obes Surg. 2021 Apr 14. doi: 10.1007/s11695-021-05360-7. Online ahead of print.

ABSTRACT

INTRODUCTION: Obesity increases the risk of pelvic floor disorders in individuals with obesity, including faecal incontinence. Faecal incontinence (FI) is a condition with important clinical and psychosocial consequences. Though it is associated with obesity, the effect of bariatric surgery on the prevalence and severity of FI is not well reported.

OBJECTIVE: To assess the effect of bariatric surgery on the prevalence and severity of FI in adult patients with obesity.

METHODS: This systematic review was conducted in accordance with the PRISMA statement. Two independent reviewers performed a literature search in MEDLINE, PubMed, Cochrane and Embase from 1 January 1980 to 12 January 2019. We included published English-language randomized control trials and observational studies assessing pre- and post-bariatric surgery prevalence or severity of FI. Random-effects models with DerSimonian and Laird’s variance estimator were used for meta-analysis.

RESULTS: Thirteen studies were included, eight assessing prevalence (678 patients) and 11 assessing severity of FI (992 patients). There was no significant difference in prevalence post-operatively overall, though it trended towards a reduction [pooled OR=0.55; =0.075]. There was a significant reduction of FI prevalence in women post-bariatric surgery [95% CI 0.22 to 0.94, p=0.034]. There was a statistically significant reduction in FI prevalence following Roux-en-Y gastric bypass and one anastomosis gastric bypass [0.46, 95% CI 0.26 to 0.81; p=0.007]. There was no significant reduction of incontinence episodes post-operatively [pooled mean difference =-0.17, 95% CI -0.90 to 0.56; p=0.65]. Quality of life (QOL) was not significantly improved post-bariatric surgery [mean differences for the following facets of QOL: behaviour -0.35, 95% CI -0.94 to 0.24; depression 0.04, 95% CI -0.12 to 0.2; lifestyle -0.33, 95% CI -0.98 to 0.33; p values of 0.25, 0.61 and 0.33, respectively].

DISCUSSION: There was a significant reduction in FI prevalence in women and those who underwent Roux-en-Y or one anastomosis gastric bypass. Our results for FI prevalence overall, FI severity and impact on quality of life were not statistically significant. Larger studies are needed in this under-researched area to determine the true effect of bariatric surgery on FI.

PMID:33852150 | DOI:10.1007/s11695-021-05360-7

J Racial Ethn Health Disparities. 2021 Apr 14. doi: 10.1007/s40615-021-01037-0. Online ahead of print.

ABSTRACT

BACKGROUND: Understanding concerns for receiving COVID-19 vaccines is key to ensuring appropriately tailored health communications to increase vaccine uptake. However, limited data exists about vaccine concerns among Asian Americans and Pacific Islanders (AAPI).

METHODS: Data from the COVID-19 Effects on the Mental and Physical Health of AAPI Survey Study (COMPASS), a cross-sectional, national survey for AAPI adults in the U.S. were used (N=1,646). Descriptive statistics were used to assess sample characteristics including proportions of AAPI with various COVID-19 vaccine concerns, categorized as none, side-effects only, unsafe only, and multiple reasons, and differences in vaccine concerns by socio-demographics. Ordinary multivariable logistic regression analyses were conducted to evaluate associations between a characteristic and having any vaccine concerns.

RESULTS: Overall, 76% of the respondents reported having at ≥1 concerns about the vaccine. The most common concern was side effects (65%). Vietnamese Americans reported less concerns (vs. Chinese Americans). Those who were 30-39 and 40-49 years old (vs. <30), females (vs. males), and experienced mild negative impacts from COVID-19 on family income/employment (vs. no change) reported more concerns about the vaccine. Those who had less vaccine concerns were those who reported higher (vs. low) health status, ≥60 years old (vs. <30), and separated/divorced/widowed (vs. single).

DISCUSSION: AAPI is a diverse population and this study revealed differences in vaccine concerns across AAPI groups. Findings revealed potential targets for patient education needs. Effective strategies to address various vaccine concerns across subgroups of AAPI will be crucial to ensure equity in vaccination uptake.

PMID:33852148 | DOI:10.1007/s40615-021-01037-0

Reprod Sci. 2021 Apr 14. doi: 10.1007/s43032-021-00576-5. Online ahead of print.

ABSTRACT

A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel compounds for their tocolytic and uterotonic efficacy is the isometric organ bath contractility assay. Unfortunately, water-insoluble compounds can be difficult to test using the physiological, buffer-based, organ bath assay. Common methods for overcoming solubility issues include solvent variation, cosolvency, surfactant or complexion use, and emulsification. However, these options for drug delivery or formulation can impact tissue function. Therefore, the goal of this study was to evaluate the ability of common solvents, surfactants, cosolvents, and emulsions to adequately solubilize compounds in the organ bath assay without affecting mouse myometrial contractility. We found that acetone, acetonitrile, and ethanol had the least effect, while dimethylacetamide, ethyl acetate, and isopropanol displayed the greatest inhibition of myometrial contractility based on area under the contractile curve analyses. The minimum concentration of surfactants, cosolvents, and human serum albumin required to solubilize nifedipine, a current tocolytic drug, resulted in extensive bubbling in the organ bath assay, precluding their use. Finally, we report that an oil-in-water base emulsion containing no drug has no statistical effect beyond the control (water), while the drug emulsion yielded the same potency and efficacy as the freely solubilized drug.

PMID:33852137 | DOI:10.1007/s43032-021-00576-5

Eur J Drug Metab Pharmacokinet. 2021 Apr 14. doi: 10.1007/s13318-021-00671-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Population pharmacokinetic analysis explored the pharmacokinetics of sunitinib and its primary active metabolite, SU012662, in children and evaluated the sunitinib dose(s) that produce comparable plasma exposures to adults receiving the approved daily dose.

METHODS: Data were from 65 children with gastrointestinal stromal tumors (GIST) or solid tumors. Pharmacokinetic models of sunitinib and SU012662 were developed using a systematic multi-step approach employing nonlinear mixed-effects modeling. The effect of predefined covariates on pharmacokinetic parameters was assessed. Final models were validated using visual predictive check and statistical techniques.

RESULTS: The final dataset comprised 439 sunitinib and 417 SU012662 post-baseline plasma observations. Base models were characterized by two-compartment models with first-order absorption and lag time. Body surface area (BSA) was the only covariate that affected (P < 0.001) pharmacokinetic parameters for sunitinib and SU012662 and was incorporated into the final models. Bootstrap results indicated that the final models represented the final dataset adequately. Based on the final models, a sunitinib dose of ~ 20mg/m²/day in children with GIST aged 6-17 years would be expected to lead to similar total plasma exposures of sunitinib and SU012661 as a dose of 50 mg/day in an adult with GIST on schedule 4/2.

CONCLUSIONS: In children with GIST or solid tumors receiving sunitinib, population pharmacokinetic analysis identified BSA as the only covariate that affected pharmacokinetic parameters and predicted a dose of ~ 20 mg/m²/day as achieving equivalent exposure to 50 mg/day in adults with GIST on schedule 4/2.

TRIAL REGISTRATION: ClinicalTrials.gov identifiers (date registered): NCT01396148 (July 2011); NCT01462695 (October 2011); NCT00387920 (October 2006).

PMID:33852135 | DOI:10.1007/s13318-021-00671-7