Moving beyond hotspots of HIV prevalence to geospatial hotspots of UNAIDS 95-95-95 targets in sub-Saharan Africa.

The HIV epidemic in sub-Saharan Africa displays a varied geographical distribution, with particular regions termed as HIV hotspots due to a higher prevalence of infection. Addressing these hotspots is essential for controlling the epidemic. However, these regions, influenced by historical factors, challenge standard interventions. Legacy effects-the lasting impact of past events-play a substantial role in the persistence of these hotspots. To address this challenge of the standard interventions, we propose a shift towards the UNAIDS 95-95-95 targets. Spatial analysis of HIV viral load and antiretroviral therapy coverage can provide a more comprehensive perspective on the epidemic's dynamics. Studies in Zambia and Zimbabwe, using this approach, have revealed disparities in HIV care metrics across regions. By focusing on the UNAIDS 95-95-95 targets, more effective control strategies can be designed, with consideration of both historical and current factors. This approach would offer a solution-oriented strategy, emphasising tailored interventions based on specific regional needs.

RiPP enzyme heterocomplex structure-guided discovery of a bacterial borosin α-N-methylated peptide natural product.

Amide peptide backbone methylation is a characteristic post-translational modification found in a family of ribosomally synthesized and post-translationally modified peptide natural products (RiPPs) called borosins. Previously, we bioinformatically identified >1500 putative borosin pathways in bacteria; however, none of the pathways were associated with a known secondary metabolite. Through in-depth characterization of a borosin pathway in Shewanella oneidensis MR-1, we have now identified a bacterially derived borosin natural product named Shewanellamide A. Borosin identification was facilitated by the creation and analysis of a series of precursor variants and crystallographic interrogation of variant precursor and methyltransferase complexes. Along with assaying two proteases from S. oneidensis, probable boundaries for proteolytic maturation of the metabolite were projected and confirmed via comparison of S. oneidensis knockout and overexpression strains. All in all, the S. oneidensis natural product was found to be a 16-mer linear peptide featuring two backbone methylations, establishing Shewanellamide A as one of the few borosin metabolites yet identified, and the first from bacteria.

Impact of healthcare capacity disparities on the COVID-19 vaccination coverage in the United States: A cross-sectional study.

Background: The impact of the COVID-19 vaccination campaign in the US has been hampered by a substantial geographical heterogeneity of the vaccination coverage. Several studies have proposed vaccination hesitancy as a key driver of the vaccination uptake disparities. However, the impact of other important structural determinants such as local disparities in healthcare capacity is virtually unknown. Methods: In this cross-sectional study, we conducted causal inference and geospatial analyses to assess the impact of healthcare capacity on the vaccination coverage disparity in the US. We evaluated the causal relationship between the healthcare system capacity of 2417 US counties and their COVID-19 vaccination rate. We also conducted geospatial analyses using spatial scan statistics to identify areas with low vaccination rates. Findings: We found a causal effect of the constraints in the healthcare capacity of a county and its low-vaccination uptake. Counties with higher constraints in their healthcare capacity were more probable to have COVID-19 vaccination rates ≤50, with 35% higher constraints in low-vaccinated areas (vaccination rates ≤ 50) compared to high-vaccinated areas (vaccination rates > 50). We also found that COVID-19 vaccination in the US exhibits a distinct spatial structure with defined "vaccination coldspots". Interpretation: We found that the healthcare capacity of a county is an important determinant of low vaccine uptake. Our study highlights that even in high-income nations, internal disparities in healthcare capacity play an important role in the health outcomes of the nation. Therefore, strengthening the funding and infrastructure of the healthcare system, particularly in rural underserved areas, should be intensified to help vulnerable communities. Funding: None.

Association Between Vaccination Coverage Disparity and the Dynamics of the COVID-19 Delta and Omicron Waves in the US.

Objective: The US recently suffered the fourth and most severe wave of the COVID-19 pandemic. This wave was driven by the SARS-CoV-2 Omicron, a highly transmissible variant that infected even vaccinated people. Vaccination coverage disparities have played an important role in shaping the epidemic dynamics. Analyzing the epidemiological impact of this uneven vaccination coverage is essential to understand local differences in the spread and outcomes of the Omicron wave. Therefore, the objective of this study was to quantify the impact of vaccination coverage disparity in the US in the dynamics of the COVID-19 pandemic during the third and fourth waves of the pandemic driven by the Delta and Omicron variants. Methods: This cross-sectional study used COVID-19 cases, deaths, and vaccination coverage from 2,417 counties. The main outcomes of the study were new COVID-19 cases (incidence rate per 100,000 people) and new COVID-19 related deaths (mortality rate per 100,000 people) at county level and the main exposure variable was COVID-19 vaccination rate at county level. Geospatial and data visualization analyses were used to estimate the association between vaccination rate and COVID-19 incidence and mortality rates for the Delta and Omicron waves. Results: During the Omicron wave, areas with high vaccination rates (>60%) experienced 1.4 (95% confidence interval [CI] 1.3-1.7) times higher COVID-19 incidence rate compared to areas with low vaccination rates (<40%). However, mortality rate was 1.6 (95% CI 1.5-1.7) higher in these low-vaccinated areas compared to areas with vaccination rates higher than 60%. As a result, areas with low vaccination rate had a 2.2 (95% CI 2.1-2.2) times higher case-fatality ratio. Geospatial clustering analysis showed a more defined spatial structure during the Delta wave with clusters with low vaccination rates and high incidence and mortality located in southern states. Conclusions: Despite the emergence of new virus variants with differential transmission potential, the protective effect of vaccines keeps generating marked differences in the distribution of critical health outcomes, with low vaccinated areas having the largest COVID-19 related mortality during the Delta and Omicron waves in the US. Vulnerable communities residing in low vaccinated areas, which are mostly rural, are suffering the highest burden of the COVID-19 pandemic during the vaccination era.

Defining the decision problem: a scoping review of economic evaluations for Clostridioides difficile interventions.

BACKGROUND: Clostridioides difficile infection is the leading cause of healthcare-associated infectious diarrhoea. Several preventative and treatment interventions exist; however, decisions for their use are typically made independent of other interventions along the care pathway. AIM: To assess how the scope of the decision problem is defined in economic evaluations of C. difficile interventions. METHODS: A scoping review was conducted following the Joanna Briggs Institute framework using a comprehensive literature search with C. difficile and economic evaluation as key search concepts. Study selection and extraction were performed independently by two reviewers. An in-depth analysis of all cost-utility and cost-effectiveness analyses was conducted. Care pathway domains (i.e. infection prevention and control, antimicrobial stewardship programmes, prevention, diagnostics, treatment) were defined iteratively, and each study was classified according to the scope of the decision problem: (i) one intervention, one domain; (ii) one intervention, multiple domains; (iii) multiple interventions, one domain; and (iv) multiple interventions, multiple domains. RESULTS: In total, 3886 studies were identified. Of these, 116 studies were included in the descriptive overview, and 46 were included in the in-depth analysis. Most studies limited the scope of the decision problem to one intervention (43/46; 93%). Only three studies (3/46; 7%) assessed multiple interventions - either as bundled vs standalone interventions for prevention (i.e. a single domain), or as sequences of treatments for initial and recurrent infection (i.e. multiple domains). No study assessed multiple interventions across prevention and treatment domains. CONCLUSIONS: Economic evaluations for C. difficile infection assess narrowly defined decision problems which may have implications for optimal healthcare resource allocation.

The epidemiological landscape of anemia in women of reproductive age in sub-Saharan Africa.

The role of geographical disparities of health-related risk factors with anemia are poorly documented for women of reproductive age in sub-Saharan Africa (SSA). We aimed to determine the contribution of potential factors and to identify areas at higher risk of anemia for women in reproductive age in SSA. Our study population comprised 27 nationally representative samples of women of reproductive age (15-49) who were enrolled in the Demographic and Health Surveys and conducted between 2010 and 2019 in SSA. Overall, we found a positive association between being anemic and the ecological exposure to malaria incidence [adjusted odds ratio (AOR) = 1.02, 95% confidence interval (CI) 1.02-1.02], and HIV prevalence (AOR = 1.01, CI 1.01-1.02). Women currently pregnant or under deworming medication for the last birth had 31% (AOR = 1.31, CI 1.24-1.39) and 5% (AOR = 1.05, CI 1.01-1.10) higher odds of having anemia, respectively. Similarly, women age 25-34 years old with low education, low income and living in urban settings had higher odds of having anemia. In addition, underweight women had 23% higher odds of suffering anemia (AOR = 1.23, CI 1.15-1.31). Females with low levels of education and wealth index were consistently associated with anemia across SSA. Spatial distribution shows increased risk of anemia in Central and Western Africa. Knowledge about the contribution of known major drivers and the spatial distribution of anemia risk can mitigate operational constraints and help to design geographically targeted intervention programs in SSA.

Dynamics of the COVID-19 epidemic in urban and rural areas in the United States.

PURPOSE: There is a growing concern about the COVID-19 epidemic intensifying in rural areas in the United States (U.S.). In this study, we described the dynamics of COVID-19 cases and deaths in rural and urban counties in the U.S. METHODS: Using data from April 1 to November 12, 2020, from Johns Hopkins University, we estimated COVID-19 incidence and mortality rates and conducted comparisons between urban and rural areas in three time periods at the national level, and in states with higher and lower COVID-19 incidence rates. RESULTS: Results at the national level showed greater COVID-19 incidence rates in urban compared to rural counties in the Northeast and Mid-Atlantic regions of the U.S. at the beginning of the epidemic. However, the intensity of the epidemic has shifted to a rapid surge in rural areas. In particular, high incidence states located in the Mid-west of the country had more than 3,400 COVID-19 cases per 100,000 people compared to 1,284 cases per 100,000 people in urban counties nationwide during the third period (August 30 to November 12). CONCLUSIONS: Overall, the current epicenter of the epidemic is located in states with higher infection rates and mortality in rural areas. Infection prevention and control efforts including healthcare capacity should be scaled up in these vulnerable rural areas.

COVID-19 Stroke Apical Lung Examination Study: A Diagnostic and Prognostic Imaging Biomarker in Suspected Acute Stroke.

BACKGROUND AND PURPOSE: Diagnosis of coronavirus disease 2019 (COVID-19) relies on clinical features and reverse-transcriptase polymerase chain reaction testing, but the sensitivity is limited. Carotid CTA is a routine acute stroke investigation and includes the lung apices. We evaluated CTA as a potential COVID-19 diagnostic imaging biomarker. MATERIALS AND METHODS: This was a multicenter, retrospective study (n = 225) including CTAs of patients with suspected acute stroke from 3 hyperacute stroke units (March-April 2020). We evaluated the reliability and accuracy of candidate diagnostic imaging biomarkers. Demographics, clinical features, and risk factors for COVID-19 and stroke were analyzed using univariate and multivariate statistics. RESULTS: Apical ground-glass opacification was present in 22.2% (50/225) of patients. Ground-glass opacification had high interrater reliability (Fleiss κ = 0.81; 95% CI, 0.68-0.95) and, compared with reverse-transcriptase polymerase chain reaction, had good diagnostic performance (sensitivity, 75% [95% CI, 56-87]; specificity, 81% [95% CI, 71-88]; OR = 11.65 [95% CI, 4.14-32.78]; P < .001) on multivariate analysis. In contrast, all other contemporaneous demographic, clinical, and imaging features available at CTA were not diagnostic for COVID-19. The presence of apical ground-glass opacification was an independent predictor of increased 30-day mortality (18.0% versus 5.7%, P = .017; hazard ratio = 3.51; 95% CI, 1.42-8.66; P = .006). CONCLUSIONS: We identified a simple, reliable, and accurate COVID-19 diagnostic and prognostic imaging biomarker obtained from CTA lung apices: the presence or absence of ground-glass opacification. Our findings have important implications in the management of patients presenting with suspected stroke through early identification of COVID-19 and the subsequent limitation of disease transmission.

Unique pattern of COVID-19 infection in the State of Hawai'i.

This is a brief report on an unusual observation regarding COVID-19 cases. The State of Hawaii is one of the most remote of the Pacific islands and the population is approximately 1.4 million. The racial and ethnic diversity is very high. For example, white Caucasians comprise ∼25%, Asians including Japanese, Chinese, and other Asians account for ∼30%, Hawaiians for 20%, and Pacific Islanders mostly from Micronesia and Samoa comprise ∼4%. We discovered that the COVID-19 rate in the latter group was up to 10 times that in all of the other groups combined and they accounted for almost 30% of cases. Moreover, we are unaware of COVID-19 transmission from Pacific Islanders to islanders with other ethnicities. Thus, there is an epidemic within the epidemic in Hawai'i.

Sustainability in Dentistry: A Multifaceted Approach Needed.

This article provides an introduction to environmentally sustainable dentistry and offers perspectives on managing drivers to reduce carbon emissions and make dentistry more environmentally sustainable. A sustainable world must meet the needs of the present without compromising the ability of future generations to meet their own needs. Global commitment to sustainability and demands for a sustainable world are growing. Within dentistry, travel creates the highest carbon emissions and also contributes to human health damage. Internally, there are a number of ways to reduce impact by decreasing travel and energy use, as well as carefully considering the types of items purchased (and how they are disposed of). Larger dental organizations can influence their suppliers and industry by choosing to purchase from sustainable companies with environmentally friendly products. From an external driver perspective policy, guidance and research are essential. Governments need to reevaluate decontamination policy from an environmental perspective. Decontamination documents need revision to consider both planetary and public health. Dental organizations need to support dental teams in this area. Insurance providers and health care purchasers should review policies to influence the sustainability of dental providers. Sustainability education needs to be considered as part of the curriculum of undergraduate and postgraduate students. Guidance could also be developed for the dental industry to produce sustainable products. Research needs to be prioritized. Identifying hot spots or areas of high environmental contributions using other assessments such as life cycle analysis (LCA) would allow dentistry to identify products or practices that have a disproportionate adverse impact on the environment and might be prioritized for change. This should include an analysis of single-use instruments, chemicals, and products. Building research capacity by training students and creating virtual or physical centers for sustainability is essential. Financial support is needed for priority areas of research.

Spatiotemporal analysis of insecticide-treated net use for children under 5 in relation to socioeconomic gradients in Central and East Africa.

BACKGROUND: Insecticide-treated net (ITN) use is the core intervention among the strategies against malaria in sub-Saharan Africa (SSA) and the percentage of ITN ownership has increased from 47% in 2010 to 72% in 2017 across countries in SSA. Regardless of this massive expansion of ITN distribution, considerable gap between ownership and use of ITNs has been reported. Using data from more than 100,000 households in Central and East Africa (CEA) countries, the main aim of this study was to identify barriers associated with low ITN use and conduct geospatial analyses to estimate numbers and locations of vulnerable children living in areas with high malaria and low ITN use. METHODS: Main sources of data for this study were the Demographic and Health Surveys and Malaria Indicator Surveys conducted in 11 countries in CEA. Logistic regression models for each country were built to assess the association between ITN ownership or ITN use and several socioeconomic and demographic variables. A density map of children under 5 living in areas at high-risk of malaria and low ITN use was generated to estimate the number of children who are living in these high malaria burden areas. RESULTS: Results obtained suggest that factors such as the number of members in the household, total number of children in the household, education and place of residence can be key factors linked to the use of ITN for protecting children against malaria in CEA. Results from the spatiotemporal analyses found that although total rates of ownership and use of ITNs across CEA have increased up to 70% and 48%, respectively, a large proportion of children under 5 (19,780,678; 23% of total number of children) still lives in high-risk malaria areas with low use of ITNs. CONCLUSION: The results indicate that despite substantial progress in the distribution of ITNs in CEA, with about 70% of the households having an ITN, several socioeconomic factors have compromised the effectiveness of this control intervention against malaria, and only about 48% of the households protect their children under 5 with ITNs. Increasing the effective ITN use by targeting these factors and the areas where vulnerable children reside can be a core strategy meant to reducing malaria transmission.

Helicobacter pylori seropositivity is associated with antinuclear antibodies in US adults, NHANES 1999-2000.

Infectious diseases, such as Helicobacter pylori, which produce systemic inflammation may be one key factor in the onset of autoimmunity. The association between H. pylori and antinuclear antibodies (ANA), a marker of autoimmunity, has been understudied. Data from the 1999-2000 National Health and Nutrition Examination Survey were used to evaluate the cross-sectional association between H. pylori seroprevalence and ANA positivity in US adults aged ≥20 years. ANA was measured in a 1:80 dilution of sera by indirect immunofluorescence using HEp-2 cells (positive ⩾3). H. pylori immunoglobulin G enzyme-linked immunosorbent assays were used to categorise individuals as seropositive or seronegative. H. pylori seropositivity and ANA positivity were common in the adult US population, with estimated prevalences of 33.3% and 9.9%, respectively. Both were associated with increasing age. H. pylori seropositivity was associated with higher odds of ANA (prevalence odds ratio = 1.89, 95% confidence interval = 1.08-3.33), adjusted for age, sex, race/ethnicity, educational attainment and body mass index. H. pylori infection may be one key factor in the loss of self-tolerance, contributing to immune dysfunction.

Geospatial assessment of the voluntary medical male circumcision programme in Tanzania, 2011-2016.

INTRODUCTION: Tanzania is one of the 14 priority countries in sub-Saharan Africa scaling up voluntary medical male circumcision (VMMC) for HIV prevention. In this study, we assessed the progress of VMMC by evaluating changes in the spatial structure of male circumcision (MC) prevalence and identifying age groups with low MC uptake. METHODS: We use data from two waves of the Demographic and Health Survey (DHS) conducted in Tanzania in 2011-2012 and 2015-2016. MC incidence rate was estimated using a method developed to calculate incidence rates from two successive cross-sectional surveys. Continuous surface maps of MC prevalence were generated for both DHS waves and compared with identified areas with high MC prevalence changes and high density of uncircumcised males. RESULTS: National MC prevalence in Tanzania increased from 73.5% in 2011-2012 to 80.0% in 2015-2016. The estimated national MC incidence rate was 4.6 circumcisions per 100 person-years (py). The lowest circumcision rate was observed in males aged 20-24 years, with 0.61 circumcisions per 100 py. An estimated 1 567 253 males aged 15-49 years residing in low-MC prevalence areas were uncircumcised in 2015-2016. CONCLUSION: Tanzania has shown substantial progress in the implementation of VMMC. However, extensive spatial variation of MC prevalence still exists in the country, with some areas having an MC prevalence <60%. Here, we identified locations where VMMC needs to be intensified to reach the ~1.5 million uncircumcised males age 15-49 living in these low-MC areas, particularly for men aged 20-34.

Identification of complications in paediatric cerebral palsy treated with intrathecal baclofen pump: a descriptive analysis of 15 years at one institution.

PURPOSE: Intrathecal baclofen (ITB) treatment is used with increasing frequency in the cerebral palsy population. We describe the complications of ITB treatment, the incidence of complications, and our experience with their treatment. METHODS: In a period of 15 years, 341 paediatric patients with cerebral palsy treated with ITB were evaluated. Device problems associated with the catheter or pump, or infection and complications such as cerebrospinal fluid (CSF) leak and postdural spinal headache, were reviewed. Infection was classified as early (≤ 90 days) or late (> 90 days) according to the time of onset. RESULTS: The infection rate was 6.9% per procedure (50/720) and 14.6% per patient (50/341) over a mean 6.3 ± 3.9 years. There was a positive correlation between the risk of infection and preoperative comorbidities including epilepsy/seizure history, feeding tube, and mixed type cerebral palsy (p < 0.05, p = 0.03, p = 0.01, respectively). Eighty-five (24.9%) patients experienced 90 CSF leak episodes; 61 of these 85 patients had headache complaints as a result of CSF leak. There was a positive correlation between the risk of early infection and CSF leak (p < 0.05). CONCLUSIONS: The most common complication related to ITB was associated with pump and catheter problems. The rate of complications with the use of ITB is relatively high; however, based on the literature reports, it is the most effective treatment for severe spasticity and dystonia in patients with severe cerebral palsy. LEVEL OF EVIDENCE: III.

Mass screening for hepatitis B and C in Southern Upper Egypt.

BACKGROUND: It is well documented that Egypt has the highest prevalence of hepatitis C virus (HCV) infection in the world. The recent development of highly effective direct acting antiviral drugs (DAAs), has opened the possibility of treating and curing HCV infection in the Egyptian population on a large scale. METHODS: A screening demonstration project was implemented in southern Egypt in and around the city of Luxor. Free screening and if indicated, treatment, was offered to those 16 years or older for anti-HCV antibodies (anti-HCV) and hepatitis B surface antigen (HBsAg) using third generation enzyme immunoassays (Enzygnost® Anti-HCV and HbsAg). Statistical methods included estimation of odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: There was a large turnout of 67,042 persons who were screened in a 12-month period starting in June 2016. Thirty-one thousand nine hundred sixty-four males (47.7%) and 35,074 females (52.3%) were screened with a mean age of 43.6 ± 14.3 years. Nine thousand seven hundred one patients (14.5%) were positive for anti-HCV and 2950 (4.4%) for HBsAg. Prevalence of anti-HCV was significantly higher in males than females (19.67% vs.9.73% OR = 2.27; CI 2.2 to 2.4; p < 0.001) and the same for HBsAg (6.2% vs. 2.8% OR = 2.3; CI 2.2 to 2.5; p < 0.001). The prevalence of anti-HCV was significantly associated with age (p < 0.001), ranging from between 1 and 4% in individuals below the age of 40 years, then increased steadily to 42% at age 60 followed by a precipitous decline in age specific prevalence. CONCLUSIONS: The results showed unanticipated patterns in the Luxor area of anti-HCV and HBsAg by age and gender in contrast to previous reports on this unique HCV epidemic in Egypt. Moreover, the level and rate of turnout, cost, and other logistical issues, provided essential information for effective planning, design, and evaluation methods for larger national mass screening and treatment programs.

The effect of methadone on postoperative quality of recovery in patients undergoing laparoscopic cholecystectomy: A prospective, randomized, double blinded, controlled clinical trial.

STUDY OBJECTIVES: The aim of the present study was to assess the quality of recovery from anesthesia in patients undergoing laparoscopic cholecystectomy (LC) under total intravenous anesthesia, who received either methadone or morphine for post-surgical analgesia by means of questionnaire Quality of Recovery-40 (QoR-40). DESIGN: Prospective Randomized Clinical Trial. SETTING: The setting was at an operating room, postoperative recovery area and hospital ward. PATIENTS: Seventy patients who underwent LC under remifentanil-based anesthesia were randomly assigned to receive methadone 0.1 mg kg-1 or morphine 0.1 mg kg-1. MEASUREMENTS: The primary outcome was the quality of recovery, using the Quality of Recovery Questionnaire (QoR-40). Secondary outcomes included time to eye opening, the occurrence of nausea and vomiting, pain score, use of supplemental analgesics, and PACU length of stay. MAIN RESULTS: No differences were observed in the total or individual QoR-40 dimension scores. During the PACU stay, the occurrence of PONV and pain scores were similar between groups. Opioid consumption (p < 0.02) and the level of sedation (p < 0.01) were higher in the morphine group. There were no differences in the amount of time required to achieve PACU discharge criteria. The frequency of nausea or emesis, the severity of pain, and tramadol consumption were comparable between both groups while on the ward. CONCLUSIONS: Pain scores and the Quality of Recovery did not differ between patients who underwent LC under total intravenous anesthesia, who received either methadone or morphine for post-surgical analgesia.

Foot and ankle deformities in children with Down syndrome.

PURPOSE: Foot and ankle deformities are common orthopaedic disorders in children with Down syndrome. However, radiographic measurements of the foot and ankle have not been previously reported. The aim of this study is to describe the foot and ankle deformity in children with Down syndrome. METHODS: Children who had foot and ankle radiographs in the standing weight-bearing position were selected. Three groups of patients were identified. The relationship of radiographic measurements with age, body mass index and pain is discussed. In all, 41 children (79 feet) had foot radiographs and 60 children (117 ankles) had ankle radiographs, with 15 children overlapping between Groups I and II. RESULTS: In Group I, hallux valgus deformity was seen before ten years of age and hallux valgus angle increased afterwards. Metatarsus adductus angle showed a significant increase (p = 0.006) with obesity and was higher in patients who had foot pain (p = 0.05). In Group II, none of the ankle measurements showed a significant difference with age or body mass index percentiles. Tibiotalar angle (TTA) and medial distal tibial angle (MDTA) were higher in patients who had ankle pain. In Group III, correlation analysis was performed between the different measurements with the strongest correlations found between TTA and MDTA. CONCLUSION: In children with Down syndrome, radiographic evaluation of the foot and ankle reveals higher prevalence of deformities than clinical examination. However, foot and ankle radiographs are needed only for symptomatic children with pain and gait changes. LEVEL OF EVIDENCE: Level IV - Prognostic Study.