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Nevin Manimala Statistics

Incidence of Duchenne muscular dystrophy in the modern era; an Australian study

Eur J Hum Genet. 2022 Jun 27. doi: 10.1038/s41431-022-01138-2. Online ahead of print.

ABSTRACT

Duchenne muscular dystrophy (DMD), an X-linked recessive condition is maternally inherited in two-thirds of affected boys. It is important to establish carrier status of female relatives to restore reproductive confidence for non-carriers and facilitate reproductive options and cardiac surveillance for carriers. This study investigates disease incidence within an Australian model of cascade screening and evolving genetic diagnostic technologies. A retrospective population-based cohort study of all genetically and/or histopathologically confirmed males with DMD, born in New South Wales and the Australian Capital Territory was undertaken from 2002-2012. Cases were identified using state-wide molecular laboratory and clinical databases. The annual disease incidence and “theoretically” preventable cases were extrapolated over the study period. Proband genotype/phenotype, pedigree analysis, carrier-risk and extent of cascade screening were also determined. The cumulative incidence of disease was 19.7 per 100,000 male live births and 1 in 5076 live born males were diagnosed with DMD. Differences in disease incidence were not statistically different when compared between 2002-2007 and 2008-2012 (incidence rate ratio = 1.13, 95% CI 0.76-1.69, p = 0.52). The incidence rate ratio of theoretically preventable cases did not significantly change between 2002-2007 and 2008-2012 (incidence rate ratio = 2.07, 95% CI 0.58-9.21, p = 0.23). Current diagnostic and cascade screening models have limitations in their impact on disease incidence, due to a spectrum of logistical, patient and condition related factors. Innovative approaches to reduce DMD incidence may be better achieved by preconception or early pregnancy carrier screening, prenatal exome sequencing and newborn screening.

PMID:35754057 | DOI:10.1038/s41431-022-01138-2

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Prevalence, incidence, and risk factors associated with cytomegalovirus infection in healthcare and childcare worker: a systematic review and meta-analysis

Syst Rev. 2022 Jun 27;11(1):131. doi: 10.1186/s13643-022-02004-4.

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) is transmitted by direct contact with body fluids from infected individuals. Transmission of CMV in households, particularly those with young children, contributes significantly to CMV infection in the general population. However, little is known about the contribution of occupational healthcare or childcare exposure to risk of CMV infection.

OBJECTIVES: To determine CMV seroprevalence, incidence of primary infection, and associated risk factors in healthcare and childcare workers.

METHODS: Six electronic databases were searched systematically for publications on CMV infection in healthcare and childcare workers until March 7, 2022. Two authors independently evaluated the literature for quality and inclusion in our analyses. The pooled results for seroprevalence, incidence, and relative risk (RR) were determined using a random effects model. Heterogeneity among studies was quantified and further investigated in subgroup analysis and meta-regression. Publication bias was assessed using funnel plot. Statistical analyses were preformed using R version 4.05.

RESULTS: Forty-eight articles were included in this meta-analysis (quality assessment: 18 good, 14 fair, and 16 poor). Pooled CMV seroprevalence was 59.3% (95% CI: 49.8-68.6) among childcare workers and 49.5% (95% CI: 40.3-58.7) among healthcare workers, and pooled incidences of primary CMV infection per 100 person-years were respectively 7.4 (95% CI: 3.9-11.8) and 3.1 (95% CI: 1.3-5.6). RR for primary infection compared to controls were 3.4 (95% CI: 1.3-8.8) and 1.3 (95% CI: 0.6-2.7) for healthcare and childcare workers, respectively. The odds of CMV seropositivity were 1.6 (95% CI: 1.2-2.3) times higher for childcare workers compared to controls, but not significantly different between healthcare workers and controls (0.9; 95% CI: 0.6-1.2). CMV seropositivity in both groups was significantly associated with having one or more children residing at home, marital status, ethnicity, and age.

CONCLUSIONS: Childcare workers, but not healthcare workers, have an increased risk of prevalent and incident CMV infection, a risk that is further increased with the presence of at least one child living at home. These findings suggest that enforcing simple, conventional hygienic measures in childcare settings could help reduce transmission of CMV, and that special precautionary measures for preventing CMV infection may not be required for pregnant healthcare workers.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020139756.

PMID:35754052 | DOI:10.1186/s13643-022-02004-4

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Differential vulnerability of anterior cingulate cortex cell types to diseases and drugs

Mol Psychiatry. 2022 Jun 27. doi: 10.1038/s41380-022-01657-w. Online ahead of print.

ABSTRACT

In psychiatric disorders, mismatches between disease states and therapeutic strategies are highly pronounced, largely because of unanswered questions regarding specific vulnerabilities of different cell types and therapeutic responses. Which cellular events (housekeeping or salient) are most affected? Which cell types succumb first to challenges, and which exhibit the strongest response to drugs? Are these events coordinated between cell types? How does disease and drug effect this coordination? To address these questions, we analyzed single-nucleus-RNAseq (sn-RNAseq) data from the human anterior cingulate cortex-a region involved in many psychiatric disorders. Density index, a metric for quantifying similarities and dissimilarities across functional profiles, was employed to identify common or salient functional themes across cell types. Cell-specific signatures were integrated with existing disease and drug-specific signatures to determine cell-type-specific vulnerabilities, druggabilities, and responsiveness. Clustering of functional profiles revealed cell types jointly participating in these events. SST and VIP interneurons were found to be most vulnerable, whereas pyramidal neurons were least. Overall, the disease state is superficial layer-centric, influences cell-specific salient themes, strongly impacts disinhibitory neurons, and influences astrocyte interaction with a subset of deep-layer pyramidal neurons. In absence of disease, drugs profiles largely recapitulate disease profiles, offering a possible explanation for drug side effects. However, in presence of disease, drug activities, are deep layer-centric and involve activating a distinct subset of deep-layer pyramidal neurons to circumvent the disease state’s disinhibitory circuit malfunction. These findings demonstrate a novel application of sn-RNAseq data to explain drug and disease action at a systems level.

PMID:35754044 | DOI:10.1038/s41380-022-01657-w

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Sutureless socket technique after removal of third molars: a multicentric, open, randomized controlled trial

BMC Oral Health. 2022 Jun 26;22(1):256. doi: 10.1186/s12903-022-02287-y.

ABSTRACT

BACKGROUND: Although wisdom-tooth extraction is a routine intervention, the postoperative period remains marked by local inflammation classically manifesting as pain, edema and trismus. Furthermore, there is no consensus on the best operative techniques, particularly for the mucosal closure stage on impacted mandibular wisdom teeth.

METHODS: This parallel, randomized, non-blinded study compared pain following removal of impacted third molars, with and without sutures. Patients were electronically allocated 1:1 to extraction with versus without sutures. Patients ≥ 14 years’ old scheduled for extraction of four impacted wisdom teeth under general anesthesia at three French hospitals were eligible for inclusion. Exclusion criteria included taking antiplatelet agents or anticoagulants, coagulation disorders or immunosuppression, and planned orofacial surgical procedures or emergency pain/infection. The primary objective was pain evaluated by Visual Analogue Scale on Day 3. Secondary outcomes were edema, trismus, healing, complications, painkiller consumption and quality of life on Day 3 and 31.

RESULTS: Between June 2016 and November 2018, 100 patients were randomized. Finally, 44 patients in the Suture group and 50 patients in the Without Suture group were analyzed. Mean age was 16.5 years and 66.6% of patients were female. After adjustment on center, age and smoking, no statistical difference was seen between groups for pain on Day 3 (p = 0.904). No differences were seen for swelling, trismus, consumption of painkillers, healing, complications or quality of life. Smokers had a 3.65 times higher complications rate (p = 0.0244).

CONCLUSIONS: Sutureless removal of third molars is thus a reliable technique without negative consequence on outcomes, and allows shorter operating time. Smoking is a risk factor for postoperative complications. Trial registration www.

CLINICALTRIALS: gov (NCT02583997), registered 22/10/2015.

PMID:35754043 | DOI:10.1186/s12903-022-02287-y

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Increasing incidence rates of sexually transmitted infections from 2010 to 2019: an analysis of temporal trends by geographical regions and age groups from the 2019 Global Burden of Disease Study

BMC Infect Dis. 2022 Jun 26;22(1):574. doi: 10.1186/s12879-022-07544-7.

ABSTRACT

BACKGROUND: World Health Organization announced its goal of ending sexually transmitted infection (STI) epidemics by 2030. To provide a reference for tailored prevention strategies, we analyzed trends and differences in STIs by geographical regions and age groups from 1990 to 2019.

METHODS: Annual number of new infections and age-standardized incidence rates (ASRs) of syphilis, chlamydia, gonorrhea, trichomoniasis, and genital herpes were recorded from the 2019 Global Burden of Disease study. We quantified the temporal trends of STIs by calculating changes in new infections and estimated annual percentage changes (EAPCs) of ASR.

RESULTS: The ASRs of syphilis, chlamydia, trichomoniasis, and genital herpes increased by 1.70% (95% confidence interval [CI], 1.62-1.78%), 0.29% (95% CI 0.04-0.54%), 0.27% (95% CI 0.03-0.52%), and 0.40% (95% CI 0.36-0.44%) per year from 2010 to 2019 worldwide, respectively, while that of gonorrhea did not. The American regions had the greatest increase in ASR for syphilis (tropical Latin America: EAPC, 5.72; 95% CI 5.11-6.33), chlamydia (high-income North America: EAPC, 1.23; 95% CI 0.73-1.73), and gonorrhea (high-income North America: EAPC, 0.77; 95% CI 0.12-1.41). Additionally, southern sub-Saharan Africa and East Asia had the greatest increase in ASR for trichomoniasis (EAPC, 0.88; 95% CI 0.57-1.20) and genital herpes (EAPC, 1.44; 95% CI 0.83-2.06), respectively. In the most recent years, the population with the greatest incidence of syphilis tended to be younger globally (25-29 years in 2010 vs. 20-24 years in 2019) but older in North Africa and Middle East (20-24 year vs. 25-29 years); with chlamydia tended to be older in southern sub-Saharan Africa (25-29 years vs. 30-34 years) but younger in Australasia (40-44 years vs. 25-29 years); with genital herpes tended to be older in high-income North America (20-24 years vs. 25-29 years) and South Asia (25-29 years vs. 30-34 years).

CONCLUSIONS: Syphilis, chlamydia, trichomoniasis, and genital herpes showed a trend of increasing ASR from 2010 to 2019. The differences in trends by geographical regions and age groups point to the need for more targeted prevention strategies in key regions and populations.

PMID:35754034 | DOI:10.1186/s12879-022-07544-7

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Evaluation of the effectiveness of the standard traditional Korean medicine-based health promotion program for disadvantaged children in South Korea

BMC Complement Med Ther. 2022 Jun 26;22(1):175. doi: 10.1186/s12906-022-03634-w.

ABSTRACT

BACKGROUND: Traditional Korean Medicine (TKM) is highly integrated with the modern health care system of South Korea and is actively used in the public health field. Since 2014, the Ministry of Health and Welfare of South Korea has supported the development of standard models for TKM-based health promotion programs. This study aimed to develop and evaluate a standard TKM-based health promotion program for disadvantaged children.

METHODS: Using convenience sampling, we recruited 16 Community Children’s Centers (CCCs) located in Busan and Yangsan, South Korea, which are welfare daytime facilities for children from socially disadvantaged families. The CCCs were divided into two groups of eight CCCs-intervention CCCs and control CCCs-through random allocation, and children in each group were selected as subjects for the study. For 12 weeks, the TKM-based health promotion program developed in this study along with the basic services of CCCs were applied to children in the intervention group, and only the basic services of CCCs were provided to children in the control group. Data were obtained through pre- and post-surveys with the legal representatives of the children prior to implementing the program and after the 12-week program, respectively. The outcome variables-the number of outpatient visits, absences, lateness/early leaves, infectious symptoms, and EuroQol-5D and EQ-visual analog scale scores-were measured and statistically compared between the groups by descriptive analysis, chi-square test, t-test, and difference-in-differences model with regression analysis.

RESULTS: At baseline, there were 156 children in the intervention group and 153 children in the control group, among which 155 and 147 children, respectively, were included in the analysis. Results indicated that the number of outpatient visits was significantly lower (by 65%) in the intervention group than in the control group (p = 0.03), and this was similar in the sensitivity analysis. Regarding other outcome variables, the effects were not consistently significant.

CONCLUSIONS: A standard TKM-based health promotion program has the potential to improve the health of disadvantaged children. In the future, studies with long-term interventions and a larger sample are needed to enhance the applicability of these programs in communities.

PMID:35754023 | DOI:10.1186/s12906-022-03634-w

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Participation of children and young people with cerebral palsy in activities of daily living in rural Uganda

Dev Med Child Neurol. 2022 Jun 26. doi: 10.1111/dmcn.15323. Online ahead of print.

ABSTRACT

AIM: To compare the participation attendance and involvement of children and young people with and without cerebral palsy (CP) in a low-resource area of Uganda.

METHOD: Eighty-two children and young people with CP aged 6 to 22 years (49 males, 33 females) and 81 age- and sex-matched peers without CP (6 to 22 years; 48 males, 33 females) participated in this population-based, cross-sectional study. Data on attendance and involvement in 20 home and community activities were obtained using Picture My Participation, an instrument intended to measure participation in children with disabilities, particularly in low- and middle-income countries. Non-parametric statistical methods were used to assess between-group differences. Effect size estimates were calculated.

RESULTS: Pooled attendance across all activities was lower in children and young people with CP than in children and young people without CP (p < 0.001) and for each activity item (p = 0.004 to p < 0.001). The effect sizes for each activity were 0.2 to 0.7. Between-group differences were larger for community activities than for home activities. Pooled involvement across all activities was less in the group with CP (p < 0.001) and for each activity (p = 0.014 to p < 0.001). The effect sizes for each activity were 0.2 to 0.5. Children and young people in Gross Motor Function Classification System (GMFCS) levels I and II had higher attendance (p < 0.001) and involvement (p = 0.023) than those in GMFCS levels III to V.

INTERPRETATION: Participation of young people living with CP in Uganda was restricted, especially for community activities. There is a need to identify context-specific participation barriers and develop strategies to overcome them.

PMID:35754006 | DOI:10.1111/dmcn.15323

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Systemic Immunological Determinants of Oncological Outcomes After Surgery for Localized Renal Cell Carcinoma

Clin Genitourin Cancer. 2022 May 25:S1558-7673(22)00123-9. doi: 10.1016/j.clgc.2022.05.010. Online ahead of print.

ABSTRACT

INTRODUCTION & OBJECTIVES: In systemic therapy trials, a decreasing neutrophil-to-lymphocyte ratio (NLR) after treatment for metastatic renal cell carcinoma (RCC) has been associated with improved oncologic outcomes. Paradoxically, for patients with localized RCC treated with upfront surgery the opposite effect has been reported. We thus aimed to evaluate NLR dynamics on localized RCC recurrence.

MATERIALS AND METHODS: Treatment naïve patients with localized RCC managed surgically between 2005 and 2020 were included. Preoperative NLR was calculated within 6-weeks prior to surgery and postoperative NLR was calculated between 4 and twelve-weeks after surgery. Patients were followed for disease recurrence, noting metastatic sites and postoperative infections. Cox regression were used to determine whether the relative change in postoperative NLR was associated with metastasis-free survival (MFS) and cancer-specific survival (CSS), adjusted for preoperative NLR.

RESULTS: In the cohort of 3310 patients, 996 (30%) had postoperative NLR available. These patients generally had more advanced disease, with 100 developing metastases and 38 dying from kidney cancer. Median MFS follow-up was 4.4 years. Decreasing 2-month postoperative NLR was associated with non-statistically significant worse MFS and CSS (HR 0.79, 95% 0.50, 1.24, P = .3; HR 0.83, 95% C.I. 0.40, 1.73; P = .6). On sensitivity analysis, across all NLR measurements, with NLR as a time-dependent covariate, results were similar, with a declining NLR associated with adverse MFS (HR 0.85, 95% CI 0.69, 1.30, P-value = .10), though not meeting conventional levels of significance.

CONCLUSION: In higher-risk localized RCC patients, postoperative NLR is not suitable as a biomarker for predicting recurrences.

PMID:35753989 | DOI:10.1016/j.clgc.2022.05.010

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Predicting Patients With Troponin Positive Chest Pain and Unobstructed Coronary Arteries With Electrocardiogram, Troponin Kinetics and GRACE Score

Heart Lung Circ. 2022 Jun 23:S1443-9506(22)00268-2. doi: 10.1016/j.hlc.2022.05.040. Online ahead of print.

ABSTRACT

BACKGROUND: Troponin positive chest-pain with unobstructed coronary arteries (TPCP-UCA), occurs in 6% of cases of patients presenting with acute coronary syndrome (ACS). Whilst TPCP-UCA patients are known to be younger with less cardiovascular risk factors when compared to obstructive coronary disease (MICAD), no validated methods exist to reliably delineate these two conditions prior to coronary angiography.

METHODS: We analysed 142 patients with MICAD and 127 patients with TPCP-UCA from 2015 to 2019. Several key predetermined clinical, biochemical and electrocardiograph (ECG) parameters, as well as Global Registry of Acute Coronary Events (GRACE) score, were collected for all patients. All TPCP-UCA patients underwent cardiac magnetic resonance imaging (cMRI).

RESULTS: Patients with TPCP-UCA were younger than MICAD (44 vs 68 yrs, p<0.01), and with less cardiac risk factors of hypertension (31% vs 68%, p<0.01), hypercholesterolaemia (23% vs 56%, p<0.01), diabetes (11% vs 45%, p<0.01), prior ischaemic heart disease (8% vs 42%, p<0.01) and smoking history (29% vs 50%, p<0.01). Peak troponin (MICAD 2,084.5 ng/L vs TPCP-UCA 847.0 ng/L, p=0.02), serial-to-initial troponin ratio (MICAD 13.5 vs TPCP-UCA 5.1, p<0.01), and peak-to-initial troponin ratio (MICAD 69.6 vs TPCP-UCA 14.0, p<0.01) were all higher in the MICAD group. GRACE scores were significantly different across the two cohorts (TPCP UCA 74 vs MICAD 106, p<0.01), with a receiver operator characteristic (ROC) curve statistic of 0.794 (95% CI 0.739-0.850). On ECG analysis, MICAD had greater prevalence and sum of ST depression (40% vs 19% p<0.01; 1.6 mm vs 0.44 mm, p<0.01) and T wave inversion (37% vs 17%, p<0.01), whilst TPCP-UCA had greater presence of PR depression (20% vs 3% p<0.01), and longer repolarisation (T wave peak to end 89 ms vs 83 ms, p=0.04; T wave peak to end/corrected QT 0.208 ms vs 0.193 ms, p=0.03). All TPCP-UCA patients underwent cMRI. Aetiology was found in 82% of cases, with the leading diagnosis being myocarditis (58%), followed by infarction (8%), whilst 18% had a normal cMRI.

CONCLUSIONS: TPCP-UCA is an important differential for patients presenting with ACS, and has several key demographic, biochemical and electrocardiographic differences. The present findings are hypothesis generating, thus prospective studies are required to determine and validate potential clinical utility.

PMID:35753985 | DOI:10.1016/j.hlc.2022.05.040

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Oral anticoagulant adherence and switching in patients with atrial fibrillation: A prospective observational study

Res Social Adm Pharm. 2022 Jun 11:S1551-7411(22)00180-2. doi: 10.1016/j.sapharm.2022.06.002. Online ahead of print.

ABSTRACT

BACKGROUND: Adherence to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) is important in preventing stroke. The dominance of retrospective studies using administrative data has led to a lack of data on psychosocial determinants of adherence and prevented comparison of adherence between OAC drug classes. OAC switching is another aspect of adherence that is unexplored.

METHODS: A prospective design was utilized to measure AF patients’ self-reported adherence and OAC switching, and to identify their clinical, demographic, and psychosocial determinants. Participants were recruited from specialized AF clinics in Canada and followed for up to 2 years. Data were collected via telephone every 3-4 months using a structured survey. Adherence was measured using the Morisky Medication Adherence scale (©MMAS-8).

RESULTS: The included participants (N = 306) were followed for a median follow up time of 14.1 months and had an average of 3.2(SD 1.4) study visits. The mean self-reported adherence on the ©MMAS-8 was 7.28(SD 0.71) for patients receiving care at specialized AF clinics. Older age, experiencing a bleed, and higher satisfaction with the burden of medications were significantly associated with higher adherence. Drug class did not have any significant impact on adherence. 7.8% of the cohort experienced a switch with most of them being from warfarin to DOAC. Taking warfarin as the index medication, experiencing a bleed and older age were significantly associated with higher odds of switching.

CONCLUSION: Patients with AF reported high adherence to their OAC therapy however being on DOAC may not translate to better adherence compared to VKA. Improving satisfaction with the burden of therapy is important in improving adherence.

PMID:35753963 | DOI:10.1016/j.sapharm.2022.06.002