Nevin Manimala

Diabet Med. 2021 Nov 10:e14739. doi: 10.1111/dme.14739. Online ahead of print.

ABSTRACT

OBJECTIVE: Prior to the Continuous Monitoring and Control of Hypoglycaemia (COACH) study described herein, no study had been powered to evaluate the impact of non-adjunctive RT-CGM use on the rate of debilitating moderate or severe hypoglycaemic events.

RESEARCH DESIGN AND METHODS: In this 12-month observational study, adults with insulin-requiring diabetes who were new to RT-CGM participated in a 6-month control phase where insulin dosing decisions were based on self-monitored blood glucose (SMBG) values, followed by a 6-month phase where decisions were based on RT-CGM data (i.e., non-adjunctive RT-CGM use); recommendations for RT-CGM use were made according to sites’ usual care. The primary outcome was change in debilitating moderate (requiring second-party assistance) and severe (resulting in seizures or loss of consciousness) hypoglycaemic event frequency. Secondary outcomes included changes in HbA1c and diabetic ketoacidosis (DKA) frequency.

RESULTS: A total of 519 participants with mean (SD) age 50.3 (16.1) years and baseline HbA1c 8.0% (1.4%) completed the study, of whom 32.8% had impaired hypoglycaemia awareness and 33.5% had type 2 diabetes (T2D). The mean (SE) per-patient frequency of hypoglycaemic events decreased by 63% from 0.08 (0.016) during the SMBG phase to 0.03 (0.010) during the RT-CGM phase (p=0.005). HbA1c decreased during the RT-CGM phase both for participants with type 1 diabetes (T1D) and T2D and there was a trend toward larger reductions among individuals with higher baseline HbA1c.

CONCLUSIONS: Among adults with insulin-requiring diabetes, non-adjunctive use of RT-CGM data is safe, resulting in significantly fewer debilitating hypoglycaemic events than management using SMBG.

PMID:34758142 | DOI:10.1111/dme.14739

Br J Dermatol. 2021 Nov 10. doi: 10.1111/bjd.20882. Online ahead of print.

ABSTRACT

BACKGROUND: Acne vulgaris is widespread across the world. Mapping the latest magnitudes and temporal trends of acne vulgaris provides the essential foundation for targeted public policies at the national, regional, and global levels.

METHODS: Complying with the framework of the Global Burden of Disease 2019 Study, the incidence, prevalence and disability-adjusted life years (DALYs) on acne vulgaris were retrieved in 204 countries and regions from 1990 to 2019. The average annual percentage change was calculated to depict the temporal trends in age-standardized rates (ASRs) of acne vulgaris burden by region, sex, and age.

RESULTS: Globally, 117.4 [95% uncertainty interval (UI): 103.0, 133.7] million incident cases of acne vulgaris, 231.2 million (95% UI: 208.2, 255.5) prevalent cases and 5.0 (95% UI: 3.0, 7.9) million DALYs were estimated in 2019, with about 47% increase compared with 1990. Moreover, the overall ASRs of acne vulgaris increased by around 0.55% annually over the past three decades. We observed huge disparities in ASRs of acne vulgaris with its changing trends in sex, location, and age. The ASR of acne vulgaris among women was around 1.3 times that of men, but the gender difference was narrowed for the pronounced increase among men. The ASRs of acne vulgaris were higher in high-income regions, but the increasing trend was more pronounced in other regions.

CONCLUSION: The burden rate of acne vulgaris continues to increase in almost all countries. Understanding the specific characteristics of acne vulgaris burden is essential to formulate more effective and targeted interventions for controlling acne burden.

PMID:34758111 | DOI:10.1111/bjd.20882

Acta Psychiatr Scand. 2021 Nov 10. doi: 10.1111/acps.13384. Online ahead of print.

ABSTRACT

OBJECTIVE: Longitudinal studies examining the association between adolescent cannabis use and self-harm are rare, heterogenous and mixed in their conclusions. We study this association utilizing a large general population-based sample with prospective data.

METHODS: The Northern Finland Birth Cohort 1986 (n= 6582) with linkage to nationwide register data was used to study the association of self-reported cannabis use at age 15-16 years and self-harm and suicide death until age 33 (until year 2018), based on register information. Cox-regression analysis with Hazard Ratios (HR) and 95% confidence intervals (CI) was used. Psychiatric disorders, parental psychiatric disorders and other substance use were considered as confounders.

RESULTS: In all, 6582 (49.2 % male) were included in the analysis, and 377 adolescents (5.7%) reported any cannabis use until the age of 15-16 years. Based on register information, 79 (55.7 % male) had visited in health care services due to self-harm, and 22 (90.1 % male) had died by suicide. In crude analyses, adolescent cannabis use was associated with self-harm (HR =3.93; 95 % CI 2.24-6.90). The association between cannabis use and self-harm remained statistically significant after adjusting for sex, psychiatric disorders at baseline, frequent alcohol intoxications, other illicit drug use, and parental psychiatric disorders (HR 2.06; 95 % CI 1.07-3.95). In contrast, the association of cannabis use with suicide did not reach statistical significance even in crude analysis (HR 2.60; 95 % CI 0.77-8.78) CONCLUSION: Cannabis use in adolescence may increase risk of self-harm independent of psychopathology and other substance use.

PMID:34758110 | DOI:10.1111/acps.13384

J Gerontol A Biol Sci Med Sci. 2021 Nov 10:glab339. doi: 10.1093/gerona/glab339. Online ahead of print.

ABSTRACT

BACKGROUND: Several guidelines have suggested alternative glycemic markers for hemoglobin A1c among older adults with limited life expectancy or multiple coexisting chronic illnesses. We evaluated associations between fructosamine, albumin-corrected fructosamine (AlbF) and fasting plasma glucose (FPG) and mortality in the diabetic and non-diabetic subpopulations, compared which marker better predicts mortality among participants aged 80 and above.

METHODS: Included were 2,238 subjects from the Healthy Ageing and Biomarkers Cohort Study (2012-2018) and 207 participants had diabetes at baseline. Multivariable Cox proportional hazards regression models investigated the associations of fructosamine, AlbF, FPG and all-cause, cardiovascular disease (CVD), and non-CVD mortality in the diabetic and non-diabetic subpopulations. Restricted cubic splines (RCS) explored potential non-linear relations. C-statistic, integrated discrimination improvement (IDI) and net reclassification improvement (NRI) evaluated the additive value of different glycemic markers to predict mortality.

RESULTS: Overall, 1,191 deaths were documented during 6,793 person-years of follow-up. In the linear model, per unit increases of fructosamine, AlbF and FPG were associated with higher risk of mortality in non-diabetic participants, with hazard ratios of 1.02 (1.00, 1.05), 1.27 (1.14, 1.42) and 1.04 (0.98, 1.11) for all-cause mortality, and 1.04 (1.00, 1.07), 1.38 (1.19, 1.59) and 1.10 (1.01, 1.19) for non-CVD mortality, respectively. Comparisons indicated AlbF better predicts all-cause and non-CVD mortality in non-diabetic participants with significant improvement in IDI and NRI.

CONCLUSIONS: Higher concentrations of fructosamine, AlbF, and FPG were associated with higher risk of all-cause or non-CVD mortality among very elderly where AlbF may constitute an alternative prospective glycemic predictor of mortality.

PMID:34758092 | DOI:10.1093/gerona/glab339

Mod Rheumatol. 2021 Sep 20:roab009. doi: 10.1093/mr/roab009. Online ahead of print.

ABSTRACT

OBJECTIVES: Previous studies suggest that exposure to inflammation in infancy may increase the risk for attention-deficit and hyperactivity disorder (ADHD). We studied the ADHD manifestations among 124 familial Mediterranean fever (FMF) patients and examined the relationship between FMF patient characteristics and ADHD.

METHODS: Clinical, demographic, and genetic data were abstracted from patients’ medical records and supplemented by information obtained during clinic visits. ADHD manifestations were assessed using the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) questionnaire.

RESULTS: ADHD was diagnosed in 42 (32.8%) FMF patients, a rate significantly higher than in unselected populations (∼8%). A majority (n = 27, 64.3%) had combined inattentive, hyperactive-impulsive manifestations. Eight (19%) had predominantly hyperactive-impulsive, and seven (16.6%) had predominantly inattentive symptoms. FMF patients with severe manifestations reported more ADHD symptoms. FMF patients with ADHD symptoms were less adherent to their treatment regimen, with only 61.9% of the patients with ADHD symptoms adhering to colchicine therapy compared to 92.7% of the patients without ADHD symptoms.

CONCLUSION: The high prevalence of ADHD characteristics in children with FMF may support the neuroimmune hypothesis that chronic inflammation increases the risk for ADHD. Children with FMF should be screened for ADHD as its presence may adversely affect adherence to treatment.

PMID:34758078 | DOI:10.1093/mr/roab009

PLoS One. 2021 Nov 10;16(11):e0259574. doi: 10.1371/journal.pone.0259574. eCollection 2021.

ABSTRACT

INTRODUCTION: Rheumatoid arthritis(RA) and osteoarthritis(OA) patients showed systemic manifestations that may lead to a reduction in muscle strength, muscle mass and, consequently, to a reduction in functionality. On the other hand, moderate intensity resistance training(MIRT) and high intensity resistance training(HIRT) are able to improve muscle strength and muscle mass in RA and OA without affecting the disease course. However, due to the articular manifestations caused by these diseases, these patients may present intolerance to MIRT or HIRT. Thus, the low intensity resistance training combined with blood flow restriction(LIRTBFR) may be a new training strategy for these populations.

OBJECTIVE: To perform a systematic review with meta-analysis to verify the effects of LIRTBFR on muscle strength, muscle mass and functionality in RA and OA patients.

MATERIALS AND METHODS: A systematic review with meta-analysis of randomized clinical trials(RCTs), published in English, between 1957-2021, was conducted using MEDLINE(PubMed), Embase and Cochrane Library. The methodological quality was assessed using Physiotherapy Evidence Database scale. The risk of bias was assessed using RoB2.0. Mean difference(MD) or standardized mean difference(SMD) and 95% confidence intervals(CI) were pooled using a random-effects model. A P<0.05 was considered statistically significant.

RESULTS: Five RCTs were included. We found no significant differences in the effects between LIRTBFR, MIRT and HIRT on muscle strength, which was assessed by tests of quadriceps strength(SMD = -0.01[-0.57, 0.54], P = 0.96; I² = 58%) and functionality measured by tests with patterns similar to walking(SMD = -0.04[-0.39, 0.31], P = 0.82; I² = 0%). Compared to HIRT, muscle mass gain after LIRTBFR was reported to be similar. When comparing LIRTBFR with low intensity resistance training without blood flow restriction(LIRT), the effect LIRTBFR was reported to be higher on muscle strength, which was evaluated by the knee extension test.

CONCLUSION: LIRTBFR appears to be a promising strategy for gains in muscle strength, muscle mass and functionality in a predominant sample of RA and OA women.

PMID:34758045 | DOI:10.1371/journal.pone.0259574

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

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

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

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