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Nevin Manimala Statistics

Minimally invasive sampling to identify leprosy patients with a high bacterial burden in the Union of the Comoros

PLoS Negl Trop Dis. 2021 Nov 10;15(11):e0009924. doi: 10.1371/journal.pntd.0009924. eCollection 2021 Nov.

ABSTRACT

The World Health Organization (WHO) endorsed diagnosis of leprosy (also known as Hansen’s disease) entirely based on clinical cardinal signs, without microbiological confirmation, which may lead to late or misdiagnosis. The use of slit skin smears is variable, but lacks sensitivity. In 2017-2018 during the ComLep study, on the island of Anjouan (Union of the Comoros; High priority country according to WHO, 310 patients were diagnosed with leprosy (paucibacillary = 159; multibacillary = 151), of whom 263 were sampled for a skin biopsy and fingerstick blood, and 260 for a minimally-invasive nasal swab. In 74.5% of all skin biopsies and in 15.4% of all nasal swabs, M. leprae DNA was detected. In 63.1% of fingerstick blood samples, M. leprae specific antibodies were detected with the quantitative αPGL-I test. Results show a strong correlation of αPGL-I IgM levels in fingerstick blood and RLEP-qPCR positivity of nasal swabs, with the M. leprae bacterial load measured by RLEP-qPCR of skin biopsies. Patients with a high bacterial load (≥50,000 bacilli in a skin biopsy) can be identified with combination of counting lesions and the αPGL-I test. To our knowledge, this is the first study that compared αPGL-I IgM levels in fingerstick blood with the bacterial load determined by RLEP-qPCR in skin biopsies of leprosy patients. The demonstrated potential of minimally invasive sampling such as fingerstick blood samples to identify high bacterial load persons likely to be accountable for the ongoing transmission, merits further evaluation in follow-up studies.

PMID:34758041 | DOI:10.1371/journal.pntd.0009924

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The prevalence of soil transmitted helminth infections in minority indigenous populations of South-East Asia and the Western Pacific Region: A systematic review and meta-analysis

PLoS Negl Trop Dis. 2021 Nov 10;15(11):e0009890. doi: 10.1371/journal.pntd.0009890. eCollection 2021 Nov.

ABSTRACT

INTRODUCTION: Soil transmitted helminth (STH) infections cause one of the most prevalent diseases in man. STHs disproportionately impact socio-economically disadvantaged communities including minority indigenous populations. This systematic review aimed to quantify the prevalence of STH infection within minority indigenous populations of the South-East Asia and Western Pacific Regions.

METHODS: The systematic review was conducted in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines following a published protocol. A random effects meta-analysis was used to estimate the pooled prevalence of STH infection, and meta-regression analysis was used to quantify associations with study characteristics. Where comparative data were available, sub-group analysis was conducted to evaluate the risk of STH infection in minority indigenous people relative to other population groups. The heterogeneity between studies was evaluated visually using Forest plots and was assessed quantitatively by the index of heterogeneity (I2) and Cochran Q-statistics.

RESULTS: From 1,366 unique studies that were identified, 81 were included in the final analysis. The pooled prevalence of infection within minority indigenous populations was 61.4% (95% CI 50.8, 71.4) for overall STH infection; 32.3% (95% CI 25.7, 39.3) for Ascaris.lumbricoides; 43.6% (95% CI 32.6, 54.8) for Trichuris.trichiura; 19.9% (95% CI 15.7, 24.5) for hookworm and 6.3% (95% CI 3.2, 10.2) for Strongyloides.stercoralis. A significant increase in T. trichiura prevalence was observed over time. The stratified analysis showed that the prevalence of infection for STH overall and for each STH species were not significantly different in minority indigenous participants compared to other populations groups.

CONCLUSION: The prevalence of STH infection is high within minority indigenous populations across countries at very different levels of socio-economic development. The increasing prevalence of T. trichiura calls for the implementation of more effective therapies and control strategies.

PMID:34758024 | DOI:10.1371/journal.pntd.0009890

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Impact of the COVID-19 Pandemic on Use of HIV Care, Antiretroviral Therapy Adherence, and Viral Suppression: An Observational Cohort Study From Uganda

J Acquir Immune Defic Syndr. 2021 Dec 15;88(5):448-456. doi: 10.1097/QAI.0000000000002811.

ABSTRACT

INTRODUCTION: Recent studies project thousands of additional AIDS-related deaths because of COVID-19-related disruptions in HIV care. However, the extent to which disruptions in care have materialized since the start of the pandemic is not well understood.

METHODS: We use electronic health records to investigate how the pandemic has affected clinic visits, patients’ antiretroviral therapy (ART) supply, and viral suppression for a cohort of 14,632 HIV clients from a large HIV clinic in Kampala, Uganda. We complement this with an analysis of electronically measured longitudinal ART adherence data from a subcohort of 324 clients.

RESULTS: Clinic visits decreased by more than 50% after a national lockdown started. The risk of patients running out of ART on a given day increased from 5% before the lockdown to 25% 3 months later (Relative Risk Ratio of 5.11, 95% confidence interval: 4.99 to 5.24) and remained higher than prelockdown 6 months later at 13% (Relative Risk Ratio of 2.60; 95% confidence interval: 2.52 to 2.70). There was no statistically significant change in electronically measured adherence or viral suppression.

CONCLUSION: We document substantial gaps in HIV care after the start of the COVID-19 pandemic in Uganda. This suggests that measures to improve access should be explored as the pandemic persists. However, ART adherence was unaffected for the subcohort for whom we measured electronic adherence. This suggests that some clients may have stockpiles of ART tablets from previous prescriptions that allowed them to keep taking their medication even when they could not visit the clinic for ART refills.

PMID:34757973 | DOI:10.1097/QAI.0000000000002811

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Spatio-temporal warping for myoelectric control: an offline, feasibility study

J Neural Eng. 2021 Nov 10. doi: 10.1088/1741-2552/ac387f. Online ahead of print.

ABSTRACT

OBJECTIVE: The efficacy of an adopted feature extraction method directly affects the classification of the electromyographic (EMG) signals in myoelectric control applications. Most methods attempt to extract the dynamics of the multi-channel EMG signals in the time domain and on a channel-by-channel, or at best pairs of channels, basis. However, considering multi-channel information to build a similarity matrix has not been taken into account.

APPROACH: Combining methods of long and short-term memory (LSTM) and dynamic temporal warping (DTW), we developed a new feature, called spatio-temporal warping (STW), for myoelectric signals. This method captures the spatio-temporal relationships of multi channels EMG signals.

MAIN RESULTS: Across four online databases, we show that in terms of average classification error and standard deviation values, the STW feature outperforms traditional features by 5% to 17%. In comparison to the more recent deep learning models, e.g. convolutional neural networks (CNN), STW outperformed by 5% to 18%. Also, STW showed enhanced performance when compared to the CNN+LSTM model by 2% to 14%. All differences were statistically significant with a large effect size.

SIGNIFICANCE: This feasibility study provides evidence supporting the hypothesis that spatio-temporal warping of the EMG signals can enhance the classification accuracy in an explainable way when compared to recent deep learning methods. Future work includes real-time implementation of the method and testing for prosthesis control.

PMID:34757954 | DOI:10.1088/1741-2552/ac387f

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How should we model and evaluate breathing interplay effects in IMPT?

Phys Med Biol. 2021 Nov 10. doi: 10.1088/1361-6560/ac383f. Online ahead of print.

ABSTRACT

Breathing interplay effects in Intensity Modulated Proton Therapy (IMPT) arise from the interaction between target motion and the scanning beam. Assessing the detrimental effect of interplay and the clinical robustness of several mitigation techniques requires statistical evaluation procedures that take into account the variability of breathing during dose delivery. In this study, we present such a statistical method to model intra-fraction respiratory motion based on breathing signals and assess clinical relevant aspects related to the practical evaluation of interplay in IMPT such as how to model irregular breathing, how small breathing changes affect the final dose distribution, and what is the statistical power (number of different scenarios) required for trustworthy quantification of interplay effects. First, two data-driven methodologies to generate artificial patient-specific breathing signals are compared: a simple sinusoidal model, and a precise probabilistic deep learning model generating very realistic samples of patient breathing. Second, we investigate the highly fluctuating relationship between interplay doses and breathing parameters, showing that small changes in breathing period result in large local variations in the dose. Our results indicate that using a limited number of samples to calculate interplay statistics introduces a bigger error than using simple sinusoidal models based on patient parameters or disregarding breathing hysteresis during the evaluation. We illustrate the power of the presented statistical method by analyzing interplay robustness of 4DCT and Internal Target Volume (ITV) treatment plans for a 8 lung cancer patients, showing that, unlike 4DCT plans, even 33 fraction ITV plans systematically fail to fulfill robustness requirements.

PMID:34757958 | DOI:10.1088/1361-6560/ac383f

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Myxomatous mitral valve disease in Miniature Schnauzers and Yorkshire Terriers: 134 cases (2007-2016)

J Am Vet Med Assoc. 2021 Dec 15:1-5. doi: 10.2460/javma.20.05.0291. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize features of myxomatous mitral valve disease (MMVD) in Miniature Schnauzers and Yorkshire Terriers.

ANIMALS: 69 Miniature Schnauzers and 65 Yorkshire Terriers, each with MMVD.

PROCEDURES: Medical record data for each dog were collected; the study period was January 2007 through December 2016. If available, radiographic data were evaluated, and a vertebral heart scale score was assigned for each dog. Statistical analysis was performed with Student t and Fisher exact tests.

RESULTS: Compared with Yorkshire Terriers, the prevalence of MMVD was significantly higher in Miniature Schnauzers and affected dogs were significantly younger at the time of diagnosis. Miniature Schnauzers were significantly more likely to have mitral valve prolapse and syncope, compared with Yorkshire Terriers. Yorkshire Terriers were significantly more likely to have coughing and have had previous or current treatment with cardiac medications, compared with Miniature Schnauzers. There was no statistical difference between breeds with regard to abnormally high vertebral heart scale scores or radiographic evidence of congestive heart failure.

CONCLUSIONS AND CLINICAL RELEVANCE: With regard to MMVD, features of the disease among Miniature Schnauzers and Yorkshire Terriers were similar, but there were also a few discernable differences between these 2 breeds and from historical findings for dogs with MMVD of other breeds. Clinical signs at the time of diagnosis differed between the 2 breeds, which may have reflected concurrent breed-specific conditions (sick sinus syndrome or airway disease [eg, tracheal collapse]). Future work should include prospective studies to provide additional information regarding the natural progression of MMVD in these dog breeds.

PMID:34757932 | DOI:10.2460/javma.20.05.0291

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Familial nephropathy in Bracchi Italiani: 8 cases (2012-2019)

J Am Vet Med Assoc. 2021 Dec 15:1-6. doi: 10.2460/javma.20.07.0420. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize the signalment, clinical signs, clinical pathological and histologic findings, and outcome in 8 related Bracchi Italiani with proteinuric kidney disease.

ANIMALS: 8 client-owned Bracchi Italiani.

PROCEDURES: Health records submitted to the Bracco Italiano Health Foundation and the Bracco Italiano Club of America between 2012 and 2019 were reviewed for dogs with evidence of nephropathy for which histologic diagnoses were obtained. Pedigree, signalment, clinical signs, diagnostic test results (including microscopic examination of kidney tissue samples collected ante- or postmortem), and outcome were acquired. Results were presented as descriptive statistics.

RESULTS: The most common clinical sign in affected dogs was inappetence. All dogs were proteinuric, and 4 dogs were azotemic. Seven dogs developed clinical signs of kidney disease and were euthanized a median of 75 days postdiagnosis. Six dogs had glomerular amyloidosis, and 1 dog each had nephrosclerosis and nonamyloidotic fibrillar glomerulopathy.

CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the clinical presentation may vary in affected dogs, and proteinuria in young or middle-aged Bracchi Italiani should raise the concern for hereditary nephropathy. Prognosis is likely poor once clinical signs are noted.

PMID:34757934 | DOI:10.2460/javma.20.07.0420

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The Role of Inhaled Corticosteroids (ICS) in Critically Ill Patients With COVID-19: A Multicenter, Cohort Study

J Intensive Care Med. 2021 Nov 10:8850666211053548. doi: 10.1177/08850666211053548. Online ahead of print.

ABSTRACT

Background: Severe coronavirus disease 2019 (COVID-19) can boost the systematic inflammatory response in critically ill patients, causing a systemic hyperinflammatory state leading to multiple complications. In COVID-19 patients, the use of inhaled corticosteroids (ICS) is surrounded by controversy regarding their impacts on viral infections. This study aims to evaluate the safety and efficacy of ICS in critically ill patients with COVID-19 and its clinical outcomes. Method: A multicenter, noninterventional, cohort study for critically ill patients with COVID-19 who received ICS. All patients aged ≥ 18 years old with confirmed COVID-19 and admitted to intensive care units (ICUs) between March 1, 2020 and March 31, 2021 were screened. Eligible patients were classified into two groups based on the use of ICS ± long-acting beta-agonists (LABA) during ICU stay. Propensity score (PS)-matched was used based on patient’s Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, systemic corticosteroids use, and acute kidney injury (AKI) within 24 h of ICU admission. We considered a P-value of < 0.05 statistically significant. Results: A total of 954 patients were eligible; 130 patients were included after PS matching (1:1 ratio). The 30-day mortality (hazard ratio [HR] [95% confidence interval [CI]]: 0.53 [0.31, 0.93], P-value = 0.03) was statistically significant lower in patients who received ICS. Conversely, the in-hospital mortality, ventilator-free days (VFDs), ICU length of stay (LOS), and hospital LOS were not statistically significant between the two groups. Conclusion: The use of ICS ± LABA in COVID-19 patients may have survival benefits at 30 days. However, it was not associated with in-hospital mortality benefits nor VFDs.

PMID:34757869 | DOI:10.1177/08850666211053548

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Neuromodulatory effects of HD-tACS/tDCS on the prefrontal cortex: A resting-state fNIRS-EEG study

IEEE J Biomed Health Inform. 2021 Nov 10;PP. doi: 10.1109/JBHI.2021.3127080. Online ahead of print.

ABSTRACT

Transcranial direct and alternating current stimulation (tDCS and tACS, respectively) can modulate human brain dynamics and cognition. However, these modalities have not been compared using multiple imaging techniques concurrently. In this study, 15 participants participated in an experiment involving two sessions with a gap of 10 d. In the first and second sessions, tACS and tDCS were administered to the participants. The anode for tDCS was positioned at point FpZ, and four cathodes were positioned over the left and right prefrontal cortices (PFCs) to target the frontal regions simultaneously. tDCS was administered with 1 mA current. tACS was supplied with a current of 1 mA (zero-to-peak value) at 10 Hz frequency. Stimulation was applied concomitantly with functional near-infrared spectroscopy and electroencephalography acquisitions in the resting-state. The statistical test showed significant alteration (p < 0.001) in the mean hemodynamic responses during and after tDCS and tACS periods. Between-group comparison revealed a significantly less (p < 0.001) change in the mean hemodynamic response caused by tACS compared with tDCS. As hypothesized, we successfully increased the hemodynamics in both left and right PFCs using tDCS and tACS. Moreover, a significant increase in alpha-band power (p < 0.01) and low beta band power (p < 0.05) due to tACS was observed after the stimulation period. Although tDCS is not frequency-specific, it increased but not significantly (p > 0.05) the powers of most bands including delta, theta, alpha, low beta, high beta, and gamma. These findings suggest that both hemispheres can be targeted and that both tACS and tDCS are equally effective in high-definition configurations, which may be of clinical relevance.

PMID:34757916 | DOI:10.1109/JBHI.2021.3127080

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Determination of Microstructural Impact on the Release of Drug from Hydroxypropyl Cellulose Gel by Validated In Vitro Release Test Method

Assay Drug Dev Technol. 2021 Nov 10. doi: 10.1089/adt.2021.078. Online ahead of print.

ABSTRACT

Microstructure of a semisolid system is greatly influenced by the formulation composition and the processing parameters. Different polymers exhibit different three-dimensional structure and these have a great impact on the drug release properties. The current research focuses on studying the impact of hydroxypropyl cellulose gel microstructure on the release properties of chlorhexidine gluconate (CHX G). The two main investigating methods of microstructure were used namely, rheology and texture analysis to determine the differences in the formulations studied. The CHX G drug release study was performed using a developed and validated in vitro release test method, which is reproducible, discriminative, and robust to detect the formulation differences. The drug release results showed that there was appreciable difference in the release rates of the different formulations. The rheology and texture analysis data correlated well with the difference in the release rates. The formulations differences were further confirmed by a statistical approach using analysis of variance.

PMID:34757828 | DOI:10.1089/adt.2021.078