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Noise pollution is a known health risk factor and evidence for cardiovascular diseases associated with traffic noise is growing. At least 20% of the European Union's population lives in noise-polluted areas with exposure levels exceeding the recommended limits of the World Health Organization, which is considered unhealthy by the European Environment Agency. This results in the annual loss of 1.6 million healthy life years. Here, we investigated the protective effects of cardiovascular drug interventions against aircraft noise-mediated cardiovascular complications such as elevated oxidative stress or endothelial dysfunction. Using our established mouse exposure model, we applied mean sound pressure levels of 72 dB(A) for 4 d. C57BL/6 mice were treated with the beta-blocker propranolol (15 mg/kg/d s.c. for 5 d) or the alpha-blocker phenoxybenzamine (1.5 mg/kg/d s.c. for 5 d) and noise-exposed for the last 4 d of the drug administration. Short-term noise exposure caused hypertension (measured by tail-cuff blood pressure monitoring) and impaired endothelial function (measured by isometric tension recording in the aorta and video microscopy in cerebral arterioles in response to acetylcholine). Noise also increased markers of oxidative stress and inflammation. Treatment of mice with propranolol and phenoxybenzamine prevented endothelial and microvascular dysfunction, which was supported by a decrease in markers of inflammation and oxidative stress in heart tissue and the brain. Amelioration of noise-induced hypertension (systolic blood pressure) was not observed, whereas pulse pressure was lowered by trend. This study provides a novel perspective mitigating the adverse effects of noise pollution, especially in vulnerable groups with medication, a rationale for further pharmacological human studies.

Background: Malaria prevention during pregnancy significantly minimizes maternal-fetal adverse events. However, optimal uptake of malaria preventive therapy in pregnancy (MPTp) remains a major challenge for both women living with HIV and those without. In Uganda, suboptimal uptake of MPTp is primarily due to inadequate knowledge among women. This study aimed to develop and assess the feasibility and acceptability of an educational video to improve knowledge of MPTp among pregnant women living with and without HIV., Methods: This study describes the second phase of a mixed methods study conducted among pregnant women (living with and without HIV) and midwives from a public antenatal care clinic in Kampala, Uganda. The study was conducted from October 2022 to Jan 2024, and the first phase involved qualitative data collection from pregnant women, health workers, and Ministry of Health officials to develop a video-based intervention to enhance uptake of MPTp. The second phase involved administration of the developed intervention to a group of purposively selected pregnant women living with and without HIV. Questionnaires, focus group discussions, and interviews were used to collect data among women and midwives, and to assess feasibility and acceptability of the intervention. Quantitative data were summarized using descriptive statistics and analysed using different scales of measurement including the modified system usability scale and the Evidence-based Practice and Attitude Scale (EBPAS), which assessed acceptability among pregnant women and midwives, respectively. The qualitative data were coded and analysed using inductive and deductive thematic methods in Atlas ti.8., Results: A total of 45 women and six midwives were enrolled in the current study phase. The mean age (± standard deviation, SD) of the women was 26 ± 6 years, and the median gestational age (interquartile range, IQR) was 24 (20-32) weeks, and less than half (42%, n = 19) were living with HIV. On the system usability scale, most women (91%, n = 41) rated the intervention as good or excellent, and most (93%, n = 42) were satisfied or very satisfied with the intervention. On the EBPAS, midwives perceived the intervention as reliable with Cronbach's alpha of 0.74, and all midwives found the intervention appropriate and feasible in their facility. All women comprehended and highly accepted the intervention., Conclusion: The video-based intervention for uptake of MPTp was found acceptable among women and midwives and was feasible and appropriate to a public health facility. Future studies would test the effectiveness of the intervention in improving knowledge and uptake of MPTp., Competing Interests: Declarations. Ethics approval and consent to participate: Approval to conduct this study was obtained from the Makerere University School of Medicine Research Ethics Committee (Mak-SOMREC-2021-279) and the Uganda National Council for Science and Technology (NS384ES). Administrative clearance was obtained from the Director of Health Services at KCCA and from KHCIV administration. Written informed consent was obtained from all participants; confidentiality and anonymity were strictly observed. Informed consent for illiterate participants was obtained in the presence of an impartial witness (a guardian or other literate person not part of the study team). The procedure of obtaining informed consent from illiterate participants was approved by the Makerere University School of Medicine Research Ethics Committee IRB. All methods were performed in accordance with the relevant guidelines and regulations of good clinical practice and human subject protection for ICH-6 patients. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Burnout syndrome represents a significant challenge in healthcare, impacting dental professionals globally across all geographic, demographic, or socioeconomic backgrounds. Pervasive work-related stress and insufficient management practices highlight the urgent need for enhanced awareness and targeted interventions., Objectives: This systematic review aimed to evaluate the prevalence, causes, and impacts of burnout among dental professionals and to explore the effectiveness of various occupational health interventions aimed at managing and preventing burnout in the dental sector during different phases of the COVID-19 pandemic., Methods: We conducted a systematic review following the PRISMA guidelines, searching electronic databases, including PubMed, Scopus, and Web of Science, from January 2014 to April 2024. The eligibility criteria included studies reporting on the prevalence of burnout, interventions to reduce burnout, and the impact of burnout on dental practices. A quality assessment was performed using the Newcastle-Ottawa Scale for observational studies., Results: The findings indicate high levels of emotional exhaustion, depersonalization, and reduced personal accomplishment among dental practitioners, with significant variations influenced by workplace factors, professional relationships, and pandemic-related stresses. Differential effects based on educational level and age were also evident., Conclusions: This review highlights the urgent need for targeted public health initiatives and occupational health strategies to address and mitigate burnout in dentistry. Emphasizing professional relationships and workplace dynamics could play a crucial role in the prevention and management of burnout (PROSPERO registration no. CRD42024586616).

Objectives: The weekly rifapentine plus isoniazid for 3 months (3HP) improves completion rate of latent tuberculosis infection treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in HIV-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations., Methods: This randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites., Results: A total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46-50.79] vs. 22.94 [14.67-31.65], p 0.018) and 6 hours (26.13 [15.80-53.06] vs. 29.83 [18.13-34.01], p 0.047) after dosing., Discussion: In non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Intervention for severe aortic stenosis (AS) has dramatically progressed since the introduction of transcatheter aortic valve replacement (TAVR). Decades ago, controversies existed regarding comparing clinical outcomes between TAVR and surgical aortic valve replacement (SAVR) in various risk profiles. Recently, we discussed the durability of transcatheter heart valves and their lifetime management after aortic valve replacement (AVR). Regarding the management of AS, we discuss the appropriate timing of intervention for severe aortic stenosis, especially in asymptomatic patients. In spite of dramatic progression of intervention for AS, there are no established medications available to prevent or slow the progression of AS at present. Basic research and genome studies have suggested several targets associated with the progression of aortic valve calcification. Randomized controlled trials evaluating the efficacy of medications to prevent AS progression are ongoing, which might lead to new strategies for AS management. In this review, we summarize the current management of AS and the drugs expected to prevent the progression of AS.

Objective: The present systematic review with a network meta-analysis (NMA) aimed to evaluate the effect of high-power lasers, associated or not with fluoride compounds, to control and prevent Erosive Tooth Wear (ETW)., Methods: The review was registered in the PROSPERO (CRD42021242547) and followed the PICO question: P (population): enamel and dentin substrate; I (Intervention): high-power laser irradiation, associated or not with fluoride compounds; C (Control): no-treatment; and O (Outcomes): prevention/control of ETW. The electronic databases PubMed, Scopus, and EMBASE were searched. Two independent reviewers evaluated in vitro and in situ studies. The risk of bias was assessed using the RoBDEMAT tool. The estimated treatment effect derived from direct and indirect comparisons were analyzed and the difference between these effects was calculated based on the data of enamel and dentin surface loss (in μm)., Results: A total of 179 studies were retrieved and after the exclusion of duplicates, 103 studies had their titles and abstracts evaluated. Thirty-nine studies had their full text analyzed for data extraction (Cohen Kappa = 0.88). For sound enamel, the laser irradiation (L), fluoride application (F) and, the association of treatments (L + F) promoted higher protection than No-Treatment (NT). For eroded enamel, L + F and F did not differ, but both treatments reduced surface loss compared to NT and L. For sound and eroded dentin, treatments with laser increased surface loss., Conclusions: Although a high-power laser has some potential to prevent erosive tooth wear, this effect is not better than that of standard fluoride. The use of laser in the management of dentin erosive wear can be harmful., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Three months of isoniazid-rifapentine (3HP) is being scaled up for tuberculosis (TB) preventive treatment (TPT) among people living with HIV (PLHIV) in high-burden settings. More evidence is needed to identify factors influencing successful 3HP delivery. We conducted a qualitative assessment of 3HP delivery nested within the 3HP Options Trial, which compared three optimized strategies for delivering 3HP: facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), and patient choice between facilitated DOT and facilitated SAT at the Mulago HIV/AIDS clinic in Kampala, Uganda. We conducted 72 in-depth interviews among PLHIV purposively selected to investigate factors influencing 3HP acceptance and completion. We conducted ten key informant interviews with healthcare providers (HCPs) involved in 3HP delivery to identify facilitators and barriers at the clinic level. We used post-trial 3HP delivery data to assess sustainability. We conducted an inductive thematic analysis and aligned the emergent themes with the RE-AIM framework dimensions to report implementation outcomes. Understanding the need for TPT, once-weekly dosing, shorter duration, and perceived 3HP safety enhanced acceptance overall. Treatment monitoring by HCPs and reduced risk of HIV status disclosure enabled DOT acceptance. Dosing autonomy enabled SAT acceptance. Switching between DOT and SAT as required enabled acceptance for patient choice. Dosing reminders, reimbursement for clinical visits, and social support enabled 3HP completion; pill burden, side effects, and COVID-19-related treatment restrictions hindered completion. All HCPs were trained and participated in 3HP delivery with high fidelity. Training, care integration, and collaboration among HCPs enabled, whereas initial concerns about 3HP safety among HCPs delayed 3HP adoption and implementation. SAT was maintained post-trial; DOT was discontinued due to inadequate ongoing financial support beyond the study period. Facilitated delivery strategies made 3HP treatment convenient for PLHIV and were feasible and implemented with high fidelity by HCPs. However, the costs of 3HP facilitation may limit wider scale-up.

Objective: Migraine, as a primary headache disorder, stands as one of the primary causes of disability worldwide. Consequently, prophylactic treatments are highly recommended for individuals experiencing recurrent migraine episodes. Our study aimed to compare the efficacy and safety profiles of venlafaxine and nortriptyline in the prophylactic management of migraine., Methods: In this single-center, randomized, double-blind clinical trial, 210 migraine patients were allocated into two groups in a 1:1 ratio. One group received venlafaxine (37.5 mg, orally twice daily), while the other group administered nortriptyline (25 mg, orally once daily). A neurologist documented (1) headache intensity using the Visual Analog Scale (VAS) and 6-point Behavioral Rating Scale (BRS-6), (2) headache frequency (per month), and (3) headache duration (in hours) of participants on days 0, 45, and 90 of the intervention., Results: Following the 90-day intervention, a significant decrease was observed in VAS, BRS-6, frequency, and duration of headaches within both groups (all with p-values <0.001). No difference in VAS, BRS-6, or headache durations was observed between the two groups after 45 and 90 days of treatment (all p-values > 0.05). Although the headache frequency exhibited no difference between the groups after 45 days (p-value = 0.097), a significantly lower frequency in the venlafaxine group was observed at day 90 of the intervention (p-value = 0.011). The reductions in attack parameters in the 0-45- and 0-90-day intervals did not meet statistical significance between the two groups (p-values > 0.05). 77.0 % of the participants in the venlafaxine group and 79.2 % in the nortriptyline group experienced a minimum of 50 % improvement in all attack parameters. Venlafaxine demonstrated a statistically significant lower incidence of adverse reactions in comparison to nortriptyline (p-value = 0.005). A total of 33 adverse drug reactions were documented in the venlafaxine group and 53 in the nortriptyline group, with insomnia observed in the former and xerostomia in the latter as the most prevalent side effects., Conclusions: Venlafaxine and nortriptyline demonstrate clinically significant and comparable therapeutic efficacy for migraine patients in reducing the intensity, frequency, and duration of headache attacks. Venlafaxine may be preferred to nortriptyline in the context of migraine preventive treatment under comparable conditions due to its lower incidence of adverse effects., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate the real-world effectiveness of eptinezumab for migraine prevention in Asian patients., Background: Eptinezumab is a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), a potent vasodilator with an important role in migraine pathophysiology. Although there is robust clinical evidence from pivotal Phase 3 placebo-controlled trials of the efficacy of eptinezumab for migraine prevention, there are limited data on the real-world effectiveness of eptinezumab in Asian patient cohorts., Methods: This was a non-interventional, prospective, multisite cohort study of adults with migraine (International Classification of Headache Disorders, 3rd edition criteria) in Singapore who were prescribed eptinezumab (100 mg at baseline and Month 3, administered intravenously) and were followed until Month 6. The primary endpoint was change from baseline in monthly migraine days (MMDs) at Month 3 and Month 6. Secondary endpoints were ≥30% and ≥50% responder rates, and change from baseline in the Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), Migraine-Specific Quality of Life (MSQ), patient-identified most bothersome symptom (PI-MBS), acute medication use at Month 3 and Month 6, and safety., Results: Enrolled patients (completed = 29/30) had on average 3.4 (SD 2.9) previous preventive treatments; 29/30 of the patients had trialed at least one previous preventive treatment without benefit. Most had previously trialed oral preventives (87%, 26/30) and anti-CGRP (70%, 21/30). Relative to baseline, mean MMDs decreased by 4.3 days (95% CI 2.1-6.4; p < 0.001) at Month 3 and 4.9 days (95% CI 2.1-7.7; p < 0.001) at Month 6. At Month 3 and Month 6, 14/30 (47%) and 15/29 (52%) of the patients were ≥30% responders, and 6/30 (20%) and 8/29 (28%) patients were ≥50% responders, respectively. The number of patients with severe life impairment based on the HIT-6 score (total score 60-78) decreased from 24/30 (80%) at baseline to 19/30 (63%) at Month 3 and 19/29 (66%) at Month 6. The mean MIDAS score decreased by 24.6 points (95% CI 2.82-46.38; p = 0.028) at Month 6, and the mean MSQ score increased by 12.2 points (95% CI 5.18-19.20; p = 0.001) at Month 3 and 13.6 points (95% CI 4.58-22.66; p = 0.004) at Month 6. Most patients reported improvement in the PI-MBS at Month 3 (73%, 22/30) and Month 6 (55%, 16/29). Acute medication use for headache relief decreased by 3.3 days/month (95% CI 1.0-5.6; p = 0.007) at Month 3 and 4.7 days/month (95% CI 1.7-7.7; p = 0.003) at Month 6. Treatment-emergent adverse events (TEAEs) were reported in 16/30 (54%) patients, mostly mild/moderate in severity. No serious TEAEs led to treatment discontinuation., Conclusion: Quarterly eptinezumab administration was effective and well-tolerated in Asian patients with chronic migraine., (© 2024 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Colorectal cancer (CRC) is the third most common cancer worldwide, with 1.9 million new cases in 2020 and a predicted rise to 3.2 million in 2040. Screening programmes are already in place to aid early detection and secondary prevention of CRC, but the rising prevalence means additional approaches are required in both primary and secondary prevention settings. Preventive therapy, whereby natural or synthetic agents are used to prevent, reverse or delay disease development, could be an effective strategy to further reduce cancer risk and potential agents have already been identified in conventional observational studies. However, as such studies are vulnerable to confounding and reverse causation, we aim to evaluate these observed relationships using Mendelian randomization (MR), an alternative causal inference approach which should be less susceptible to these biases., Methods and Analysis: We will use two-sample MR, which uses two independent samples for the exposure and outcome data, to investigate previously reported observational associations of multiple potential preventive agents with CRC risk. We define preventive agents as any synthetic (e.g. approved medication) or natural (e.g. micronutrient, endogenous hormone) molecule used to reduce the risk of cancer. We will first extract potential preventive agents that have been previously linked to CRC risk in observational studies from reviews of the literature. We will then evaluate whether we can develop a genetic instrument for each preventive agent from previously published genome-wide association studies (GWASs) of direct measures of molecular traits (e.g. circulating levels of protein drug targets, blood-based biomarkers of dietary vitamins). The summary statistics from these GWASs, and a large GWAS of CRC, will be used in two-sample MR analyses to investigate the causal effect of putative preventive therapy agents on CRC risk. Sensitivity analyses will be conducted to evaluate the robustness of findings to potential violations of MR assumptions., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Fryer E et al.)

Background: The objective of this study was to investigate timing and risk factors for discontinuation of short-course tuberculosis preventive therapy (TPT) comparing directly observed 3-month isoniazid/rifapentine (3HP) vs self-administered 4-month rifampin (4R)., Methods: This was a subanalysis of a 6-month health department cohort (2016-2017) of 993 latent tuberculosis infection (LTBI) patients initiating 3HP (20%) or 4R (80%). Time at risk of TPT discontinuation was compared across regimens. Risk factors were assessed using mixed-effects Cox models., Results: Short-course TPT discontinuation was higher with 4R (31% vs 14%; P < .0001), though discontinuation timing was similar. Latino ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and adverse events (HR, 4.30; 95% CI, 2.60-7.30) increased 3HP discontinuation risk. Social-behavioral factors such as substance misuse (HR, 12.00; 95% CI, 2.20-69.00) and congregate living (HR, 21.00; 95% CI, 1.20-360.00) increased 4R discontinuation risk., Conclusions: TPT discontinuation differed by regimen, with distinct risk factors. Addressing social determinants of health within TPT programs is critical to enhance completion rates and reduce TB disease risk in marginalized populations., Competing Interests: Potential conflicts of interest. The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Mortality associated with HIV-associated cryptococcal meningitis remains high even in the context of clinical trials (24-45% at 10 weeks); mortality at 12-months is up to 78% in resource limited settings. Co-prevalent tuberculosis (TB) is common and preventable, and likely contributes to poor patient outcomes. Innovative strategies to increase TB preventative therapy (TPT) provision and uptake within this high-risk group are needed., Protocol: The IMPROVE trial (Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease) is a nested open label, two arm, randomised controlled strategy trial to evaluate the safety (adverse events) and feasibility (adherence and tolerability) of two ultra-short course TPT strategies, in the context of recent diagnosis and treatment for cryptococcal meningitis. We will enrol 205 adults with HIV-associated cryptococcal meningitis from three hospitals in Uganda. Participants will be randomised to either inpatient initiation (early) or outpatient initiation (standard, week 6) of 1HP (one month of isoniazid and rifapentine). Participant follow-up is to include TB screening, 1HP pill counts and tolerability reviews on alternate weeks until week-18. The trial primary endpoint is TB-disease free 1HP treatment completion at 18-weeks, secondary endpoints: 1HP treatment completion, 1HP discontinuation, grade ≥3 adverse events and serious adverse events, drug-induced liver injury, incident active TB, 18-week survival; rifapentine, fluconazole and dolutegravir concentrations will be measured with intensive sampling in a pharmacokinetic sub-study of 15 eligible participants., Discussion: The IMPROVE trial will provide preliminary safety and feasibility data to inform 1HP TPT strategies for adults with advanced HIV disease and cryptococcal meningitis. The potential impact of demonstrating that inpatient initiation of 1HP TPT is safe and feasible amongst this high-risk subpopulation with advanced HIV disease, would be to expand the range of clinical encounters in which clinicians can feasibly provide 1HP, and therefore increase the reach of TPT as a preventative intervention., Isrctn Registration: ISRCTN18437550 (05/11/2021)., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Ellis J et al.)

Objective: Objectives. To assess the impact of training for emergency department (ED) nurses on adequate thromboprophylaxis for patients admitted to hospital from the ED for medical conditions. Methods. Multicenter quasiexperimental pre-post study of an ED nurse training intervention in 8 hospitals. Patients were recruited from January 2022 through May 2023 in 3 phases: before nurse training, in the first month after training, and in the sixth month after training. Included were patients attended in the ED for medical conditions. Adequate thromboprophylaxis was defined as 1) use of prophylactic drugs in patients at high risk for venousthromboembolism according to the Padua Prediction Score (PPS), and 2) nonuse in patients at low risk. We compared the percentage of adequate prophylaxis in the first phase to the percentages in the second and third phases. Results. A total of 928 patients were included (326 in phase 1, 295 in phase 2, and 307 in phase 3). PPS scores indicated that 238 (73%) of the patients were at high risk in phase 1 vs 189 (64.1%, P = .016) in phase 2 and 207 (67.4%, P = .125) in phase 3. A total of 187 patients (57.4%, 95% CI, 51.8%-62.8%) were adequatelythromboprophylaxed in phase 1 vs 178 (60.%, 95% CI, 54.5%-66%) in phase 2 (absolute difference in proportions, 3.0% (95% CI, -4.8% to 10.6%; P = .462)]. In phase 3, 166 patients (54.1%, 95% CI, 48.3%-59.7%) received adequate prophylaxis (difference, -3.3% (95% CI, -11.0% to 4.4%; P = .405). Conclusions. A training intervention for ED nurses, implemented as an isolated strategy, had no impact on the adequacy of thromboprophylaxis in patients admitted from the ED for medical conditions.

Background: Malaria in pregnancy remains a major global public health problem. Intermittent prophylaxis treatment of malaria in pregnancy with Sulphadoxine-pyrimethamine and co-trimoxazole is efficacious for prevention of malaria in pregnancy HIV negative and positive women, respectively. However, uptake of the recommended doses of therapies has remained suboptimal in Uganda, majorly due to inadequate knowledge among pregnant women. Therefore, this study aimed to explore attitudes and perceptions towards developing an educational video for malaria preventive therapy., Methods: We conducted an exploratory study with qualitative methods among pregnant women attending antenatal care at Kisenyi Health Center IV (KHCIV), health workers from KHCIV, and officials from the Ministry of Health. The study was conducted at KHCIV from October 2022 to March 2023. Focus group discussions (FGD) were conducted among purposively selected pregnant women and key informant interviews (KII) among health workers and Ministry of Health officials. Data were analyzed using inductive and deductive thematic methods in atlas ti.8., Results: A total of five FGDs comprising of 7-10 pregnant women were conducted; and KIIs were conducted among four mid-wives, two obstetricians, and two Ministry of Health officials. Generally, all respondents mentioned a need for interventions to improve malaria preventive knowledge among pregnant women; were positive about developing an educative video for malaria preventive therapy in pregnancy; and suggested a short, concise, and edutaining video focusing both the benefits of taking and risks of not taking malaria preventive therapy. They proposed that women may be encouraged to view the video as soon as they conceive and throughout the pregnancy. It also was suggested that the video may be viewed on television sets in maternal and reproductive health clinics and homes, and on smart phones., Conclusion: Pregnant women, health workers, and Ministry of Health officials were positive about the development of a short edutaining video on malaria preventive therapy that focuses on both benefits of taking and risks of not taking the malaria preventive therapy in pregnancy. This information guided the video development and therefore, in the development of health educative videos, client and stakeholder inputs may always be solicited., (© 2024. The Author(s).)

Introduction: The increased life expectancy of patients with haemophilia A (HA) has led to a growing prevalence of cardiovascular risk factors and events. There is still scarce evidence on the safety and appropriate duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) in HA patients., Aim: We describe our experience on the clinical management of Italian HA patients after ACS., Methods: Nine patients with congenital HA treated with DAPT after a revascularization procedure performed for ACS have been enrolled and followed at the Angelo Bianchi Bonomi Haemophilia and Thrombosis Center in Milan between 2005 and September 2022. The safety and efficacy of DAPT with or without FVIII prophylaxis were assessed., Results: Ten ACS events occurred in the nine HA patients (four mild and five severe). All events were treated with percutaneous transluminal coronary angioplasty with deployment of 1 to 3 drug-eluting stents followed by DAPT for 1-12 months. All patients except one were treated with FVIII prophylaxis during DAPT aimed at achieving FVIII trough levels ≥20-30 IU/dL. DAPT was effective in all cases in preventing early ACS recurrence, with only a late recurrence. We observed two clinically relevant non-major bleeds (one in a patient without FVIII prophylaxis) and three minor bleeds. No venous thrombosis occurred., Conclusion: The long-term secondary antithrombotic prevention consisting of DAPT and FVIII prophylaxis achieving a trough level of 20-30 IU/dL can be effective and safe in HA patients., (© 2024 John Wiley & Sons Ltd.)

Controlling tuberculosis (TB) among immigrants from high-incidence countries presents a public health concern as well as a medical challenge. In this article, we investigate a TB outbreak in a community of people of Jewish descent who emigrated from Ethiopia to Israel (Israeli Ethiopians) that started in June 2022. The index case was a 20-year-old female who had recently immigrated to Israel with her family. Her pre-immigration tuberculin skin test was positive. After excluding active TB, treatment with daily isoniazid for latent TB (LTB) was started shortly after her arrival. A year later, she was diagnosed with smear-positive, culture-positive, pulmonary TB. Investigation of 83 contacts revealed five additional patients with active TB, and three of whom were members were of her household. In this article, we report the current TB outbreak, review previously published TB outbreaks involving Israeli Ethiopians, analyze the factors that triggered each of these outbreaks, and discuss the challenges that face the Israeli TB control program in an era of declining TB incidence and diminishing resources available for TB control.

Background: Interventions that are co-created with end-users, and that are informed by behavior change or implementation theories, support implementation in real world settings. However, injury prevention programs for youth athletes have typically been developed by experts with no, or insufficiently described, end-user involvement and without guidance by theories. The aim of the current study was to describe the development of a holistic injury prevention intervention for youth handball targeting end-users at different levels, through using knowledge from end-users and researchers/experts and applying relevant behavior change and implementation theories., Methods: Knowledge from researchers/experts (sports medicine, sport psychology, handball, physical therapy, strength and conditioning (n = 14)) and end-users (coaches, players, club administrators, n = 16), and applying relevant implementation (Consolidated Framework for Implementation Research, CFIR), behavior change (Health Action Process Approach, HAPA) and motivational (Self-Determination Theory, SDT) theories, were used to co-design the intervention. Early end-users (coaches (n = 6), players (n = 3) and a club administrator (n = 1)) were interviewed for initial feedback., Results: The intervention consisted of end-user-targeted information and training that was made available in a specifically developed interactive mobile application with modules for players, coaches, club administrators, and caregivers. Information for all end-users included benefits and principles of physical and psychological injury prevention training, load-management, motivation, and communication. Information about implementation was developed for club administrators specifically. For coaches, training to do with their teams included handball-specific injury prevention exercises (legs, shoulders, core) combined with psychological aspects (motivation, task focus, body awareness) to integrate within warm-up and handball skills training. Training for players included handball-specific multi-joint strength, power, and explosive exercises (legs, shoulders, core) and sport psychology exercises (self-awareness, relaxation, being in the present moment, prevent and handle stress). To support self-management, adoption, and motivation, programs were provided, and players and coaches could change, add, progress the difficulty of exercises, and build their own programs. Initial feedback from early end-users was generally positive., Conclusions: Utilizing an approach where researchers/experts and end-users co-created injury prevention training specifically for youth handball, an intervention was generated that included information and holistic training targeting end-users at the individual (players, caregivers), team (coaches), and organizational (club administrators) levels., (© 2024. The Author(s).)

Despite high prevalence of cardiovascular disease (CVD) and CVD risk factors among American Indian or Alaska Native adults (AI/AN), there is little information on aspirin use in this population. This survey-based study seeks to understand prevalence of aspirin use in a sample of AI/AN adults in the Upper Midwestern United States. In-person and telephone based surveys were conducted querying self-reported CVD and CVD risk factors, aspirin use, and aspirin related discussion with clinicians. A total of 237 AI/AN participants were included: mean age (SD) was 60.8 (8.4) years; 143 (60 %) were women; 59 (25 %) reported CVD history. CVD risk factors were common particularly smoking (37 %) and diabetes (37 %). Aspirin use was much higher among those with CVD (secondary prevention, 76 %) than those without (primary prevention, 33 %). Primary prevention aspirin use was significantly associated with age and all CVD risk factors in unadjusted analyses. After adjustment for demographics and CVD risk factors, only age (aRR 1.13 per 5 years, 95 % CI 1.02, 1.25) and diabetes (aRR 2.44, 95 % CI 1.52, 3.92) remained significantly associated with aspirin. Regardless of CVD status, a higher proportion of those taking aspirin reported a conversation about aspirin with their doctor compared to those not taking aspirin. Among participants with no CVD, those who had such a conversation were 2.6 times more likely to use aspirin than those who did not have a conversation (aRR 2.64, 95 % CI 1.58, 4.44). The findings of this study emphasize the importance of the patient-provider relationship for preventive therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

This review discusses both preventive measures and clinically implemented therapy procedures that have been developed recently for the prevention and treatment of tooth erosion., Methods: The databases PubMed, Scopus, and Web of Science were used for a thorough search. Studies on the prevention and treatment of dental erosion that were conducted in English and used in vitro were among the inclusion criteria., Results: The search turned up 391 papers in total, with 34 of those publications matching the requirements for inclusion. Varnishes, toothpastes, and solutions containing fluoride and other substances were used as preventive measures., Conclusions: Dental erosion is a significant issue, and taking preventative steps is crucial to lessening the disease's spread and its effects. Interventions based on fluoride seem to be successful at halting erosion and encouraging remineralization. To effectively address severe tooth erosion, therapeutic methods, including composite restorations, prosthetic crowns, and veneers, are available. Dental erosion causes aesthetic and functional issues that are best addressed with less invasive treatments like direct composite restorations. To improve and broaden the range of available treatments for this common dental issue, additional research and development are required.

Background: South African national tuberculosis (TB) guidelines, in accordance with the World Health Organization, recommend conducting routine household TB contact investigation with provision of TB preventive therapy (TPT) for those who qualify. However, implementation of TPT has been suboptimal in rural South Africa. We sought to identify barriers and facilitators to TB contact investigations and TPT management in rural Eastern Cape, South Africa, to inform the development of an implementation strategy to launch a comprehensive TB program., Methods: We collected qualitative data through individual semi-structured interviews with 19 healthcare workers at a district hospital and four surrounding primary-care clinics referring to the hospital. The consolidated framework for implementation research (CFIR) was used to develop interview questions as well as guide deductive content analysis to determine potential drivers of implementation success or failure., Results: A total of 19 healthcare workers were interviewed. Identified common barriers included lack of provider knowledge regarding efficacy of TPT, lack of TPT documentation workflows for clinicians, and widespread community resource constraints. Facilitators identified included healthcare workers high interest to learn more about the effectiveness of TPT, interest in problem-solving logistical barriers in provision of comprehensive TB care (including TPT), and desire for clinic and nurse-led TB prevention efforts., Conclusion: The use of the CFIR, a validated implementation determinants framework, provided a systematic approach to identify barriers and facilitators to TB household contact investigation, specifically the provision and management of TPT in this rural, high TB burden setting. Specific resources-time, trainings, and evidence-are necessary to ensure healthcare providers feel knowledgeable and competent about TPT prior to prescribing it more broadly. Tangible resources such as improved data systems coupled with political coordination and funding for TPT programming are essential for sustainability., (© 2023. BioMed Central Ltd.)

Background: Adherence to tuberculosis preventive treatment (TPT) is an important determinant of clinical benefit. We assessed the association of participant behaviors early in TPT with subsequent discontinuation., Methods: We used data from a phase 3 randomized trial and the preceding phase 2 trial to compare 4 months of rifampin to 9 months of isoniazid for TPT. We excluded participants whose providers discontinued TPT due to adverse events or tuberculosis disease. We analyzed 4 outcomes: discontinuing TPT within the first month of treatment, discontinuing TPT between the first and second month, discontinuing TPT after the second month, and completing treatment but not per protocol. We analyzed the association of outcomes with regimen and participant characteristics and 4 behavioral predictors of discontinuation recorded at the month 1 and month 2 follow-up visits: reporting symptoms of intolerance, missing >20% of doses, rescheduling appointments, and not bringing their medication bottle., Results: Overall, 6656 participants were included (phase 3, 5848; phase 2, 808), of whom 4318 (64.9%) completed treatment per protocol. Participant characteristics were inconsistently associated with discontinuation. Phase 3 trial participants with 1, 2, or 3-4 behavioral predictors at the month 1 follow-up had 5.0 (95% confidence interval, 3.6-6.7), 18.6 (13.3-26.1), and 79.4 (38.2-165.0), respectively, higher odds of discontinuing before the second month. The corresponding number of predictors at the month 2 follow-up had 1.8 (1.4-2.2), 4.7 (3.6-6.2), and 7.4 (4.6-11.9) higher odds of discontinuing before completing treatment; phase 2 findings were similar., Conclusions: Four behavioral predictors recorded early in therapy were more strongly associated with subsequent discontinuation than participant characteristics, particularly when more than 1 behavioral predictor was recorded. Clinical Trials Registration. NCT00170209; NCT00931736., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hereditary angioedema (HAE) is a rare disorder that causes unpredictable and debilitating cutaneous and submucosal edema and can lead to death. HAE can impair patients' ability to perform daily activities, proportional to pain severity, with patients reporting lower productivity, missed time from work or school and potentially resulting in missed career and educational opportunities. Many patients with HAE experience a significant psychological burden, including anxiety and depression. Available treatment aims to prevent and/or treat HAE attacks as they occur, to reduce morbidity and mortality and, finally, to improve health-related quality of life. Two different validated specific angioedema instruments are available to assess patients' quality of life. The Angioedema Quality of Life Questionnaire (AE-QoL) examines diagnosed patients' quality of life but is not specific for HAE. The disease-specific questionnaire is the Hereditary Angioedema Quality of Life (HAE-QoL), and the first used for hereditary angioedema with C1 inhibitors (C1-INH) deficiency. These quality-of-life instruments are helpful to the HAE patients' assessment and to the development of better therapeutic strategies as clinical tools, as defined by international guidelines. Considering this context, this review was conducted to compare the effects of acute vs. long-term prophylaxis on HAE patients' health-related quality of life. In addition, the prevalence of anxiety and depression among these individuals was also reviewed., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Author(s).)

Background: Children and adolescents with household exposure to multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) are at high risk of developing TB disease. Tuberculosis preventive therapy (TPT) is recommended, but programmatic experience is limited, particularly for adolescents., Methods: We conducted a prospective cohort study to describe MDR/RR-TB diagnosis and TPT provision for individuals aged <18 years with MDR/RR-TB exposure. Participants were assessed for TB either in homes or health facilities, with referral for chest x-ray or specimen collection at clinician discretion. The TPT regimens included levofloxacin, isoniazid, or delamanid monotherapy for 6 months, based on source patient drug-resistance profile., Results: Between March 1, 2020 and July 31, 2021, 112 participants were enrolled; median age was 8.5 years, 57 (51%) were female, and 6 (5%) had human immunodeficiency virus. On screening, 11 (10%) were diagnosed with TB: 10 presumptive MDR/RR-TB and 1 drug-susceptible TB. Overall, 95 (94% of 101) participants started TPT: 79 with levofloxacin, 9 with isoniazid, and 7 with delamanid. Seventy-six (80%) completed TPT, 12 (13%) were lost to follow up, and 7 (7%) stopped TPT early due to adverse events. Potential adverse events were reported for 12 (13%) participants; none were serious. There were no further TB diagnoses (200 days median follow up)., Conclusions: Post-MDR/RR-TB exposure management for children and adolescents resulted in significant MDR/RR-TB detection and both high TPT initiation and completion. Tuberculosis preventive monotherapy was well tolerated and there were no further TB diagnoses after initial assessment. Key factors supporting these outcomes included use of pediatric formulations for young children, monotherapy, and community-based options for assessment and follow up., Competing Interests: Potential conflicts of interest. JF received a grant from the Stop TB Partnership's Global Drug Facility to support the roll out of child-friendly formulations of second-line TB medications. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The treatment of latent tuberculosis infection (LTBI) among high-risk populations is an essential component of Tuberculosis (TB) elimination. However, non-compliance with LTBI treatment remains a major obstacle hindering TB elimination efforts. We have previously reported high treatment compliance with nurse-managed, twice-weekly, directly observed Isoniazid treatment (DOT) for LTBI among hard-to-reach Ethiopian immigrants (EI's)., Objectives: to compare rate of completion of treatment, cost, and major adverse drug events with daily self-administered Isoniazid treatment (SAT) to nurse-managed Isoniazid DOT among hard-to-reach EIs., Materials and Methods: We conducted a retrospective study and compared self-administered LTBI treatment outcomes among EIs housed in reception centers during 2008-2012 to EIs treated with DOT., Results: Overall, 455 EIs were included (231 DOT, 224 SAT) in the study. We found no significant difference in treatment completion rates between the two groups (93.0% DOT vs. 87.9% SAT, p = 0.08). However, cases of grade III, drug-induced hepatitis were significantly fewer and treatment costs were significantly lower with the nurse-managed DOT compared with SAT (0% vs. 2.2%, p = 0.028, 363 vs. 521 United States Dollars, p < 0.001, respectively)., Conclusions: Nurse-managed, twice-weekly DOT among hard-to-reach EIs housed in reception centers had less severe drug-related adverse events and reduced treatment cost compared with daily isoniazid SAT, yet we found no significant difference in treatment completion between the two strategies in this population.

Background: Preventive therapy of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control. Research on acceptance of TB preventive therapy (TPT) is an important topic. Current studies focus on acceptability and compliance. However, it is unclear whether LTBI patients will start TPT after accepting treatment. The study assessed the factors associated with TPT refusal after initial willingness to accept treatment., Methods: Data were derived from a baseline survey of prospective study of LTBI treatment among college students in Shandong Province, China. A total of 723 students initially willing to accept TPT were included in the analysis. Stepwise logistic regression was used to explore the individual- and family-level characteristic variables that factors associated with TPT refusal after initial willingness to accept treatment., Results: Of the 723 LTBI college students who initially had acceptance willingness, 436 (60.3%) finally refused TPT. At the individual level, non-medical students were more likely to refuse TPT [odds ratio (OR) = 4.87, 95% confidence interval (CI): 3.10-7.67)], as were students with moderate physical activity (OR = 1.45, 95% CI: 1.04-2.04). Students with boarding experience (OR = 0.49, 95% CI: 0.31-0.78) and a high level of knowledge about TB (OR = 0.97, 95% CI: 0.95-0.99) were less likely to refuse TPT. At the family level, those with high father's educational level (OR = 1.50, 95% CI: 1.07-2.10) or high household income (OR = 1.80, 95% CI: 1.20-2.71) were more likely to refuse TPT after initially accepting treatment., Conclusions: Factors associated with TPT refusal after initial willingness to accept treatment, such as personal (type of students, physical activity, boarding experiences, knowledge of TB) and family characteristics (father's education level, household income) among college student with LTBI, might help identify persons for whom tailored interventions could improve the start of LTBI treatment., (© 2023. The Author(s).)

Introduction Adolescent migraines is a public health problem, and effective prophylactic treatment is needed. In Japan, three types of calcitonin gene-related peptide-related monoclonal antibodies (CGRP-mABs) are available. Galcanezumab, fremanezumab, and erenumab can be used for migraine prevention in ages 15 years or older, but reports on adolescent migraine treated with CGRP-mABs remain few. We described this study to report the real-world data of CGRP-mABs' efficacy for adolescents with migraines aged from 15 to 17 years old. Methods We retrospectively investigated ten adolescent migraine patients aged from 15 to 17 years old treated with CGRP-mABs. Headache impact test-6 (HIT-6), monthly headache days (MHD), and monthly acute medication intake days (AMD) before and three months after CGRP-mABs treatment were evaluated. Results Six females and four males were included. Seven had episodic migraines (EM), three had EM and tension-type headaches, one had chronic migraines (CM), and one had CM and medication-overuse headaches. As chief obstacles to life due to headaches, five reported them as detrimental to study, one reported them as detrimental to playing sports, and four reported missing school. The median HIT-6 was 63 (46-68) and 44 (36-65) before and three months after treatment, respectively. Median of MHD was 5.5 (1-29) and 1.5 (1-30), respectively, and the median of AMD was 5.5 (1-30) and 1 (0-30), respectively. A significant reduction of HIT-6 was observed at three months (p=0.008). Six (60%) of the ten patients experienced therapeutic effectiveness. Patients with missing school as the chief obstacle to life due to headaches seemed ineffective compared to those with other obstacles (p=0.048). There were no side effects of CGRP-mABs. Conclusion We herein described the ten adolescent migraine patients treated with CGRP-mABs. HIT-6 score significantly decreased at three months, and six of the ten patients experienced therapeutic effectiveness measured by HIT-6. Now several trials have been ongoing to test the efficacy of CGRP-mABs for adolescents. Urgent evidence accumulation is needed about CGRP-mABs for adolescents., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Katsuki et al.)

The aim of this study was to determine which type of prophylaxis was effective for postoperative symptomatic venous thromboembolism (VTE) in patients with gynecological malignancies. A total of 1756 consecutive patients undergoing laparotomy as first-line treatment were included. In Period 1 (2004-2009), low-molecular weight heparin (LMWH) was not available for postoperative VTE prophylaxis, but available in after Period 2 (2009-2013). In Period 3 (2013-2020), patients with pretreatment VTE could switch from LMWH to direct oral anticoagulant (DOAC) as of 2015. Preoperative VTE was screened by measuring D-dimer, followed by venous ultrasound imaging, and computed tomography and/or perfusion lung scintigraphy. Postoperative symptomatic VTE occurred with an incidence of 2.8% by the measures without prophylactic LMWH administration in Period 1. The incidence of postoperative symptomatic VTE was 0.6% in Period 2 and 0.3% in Period 3, being significantly reduced compared with Period 1 ( P  < .01 and < .0001). The incidences were not significantly different between Periods 2 and 3, but no patient switching to DOAC in Period 3 (n  =  79) developed symptomatic VTE. Our preoperative VTE screening and postoperative selective LMWH administration were significantly preventive against postoperative symptomatic VTE.

The WHO recommends preventive treatment for all pediatric contacts of a confirmed TB case, but coverage remains low in many high TB burden countries. We aimed to assess the coverage and adherence of the isoniazid preventive therapy (IPT) program among children under 5 years of age with household exposure to an adult pulmonary TB case in a rural district of Southern Mozambique. The estimated IPT coverage was 11.7%. A longer distance to the health center and lower age of the children hindered IPT initiation. Among patients who started IPT, 12/18 (69.9%) were adherent to the 6-month treatment., (© The Author(s) [2023]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The World Health Organization estimated that a quarter of the global population is infected by Mycobacterium tuberculosis (Mtb). A better control of tuberculosis (TB) is based on the ability to detect Mtb infection, identifying the progressors to TB disease, undergoing to preventive therapy and implementing strategies to register the infections and treatment completion., Design: we reviewed the literature regarding the tests available for TB infection diagnosis, the preventive therapies options and the cascade of care for controlling TB at a public health level., Results: current tests for TB infection diagnosis as IFN-γ release assays or tuberculin skin tests are based on the detection of an immune response to Mtb in the absence of clinical disease. The main limit is their low accuracy to detect progressors to disease. New preventive treatments are available with short duration that are associated with better adherence. Options to register TB infections are presented., Conclusions: Tests to diagnose TB infection are available but they lack accuracy to identify the progressors from infection to TB disease. Shorter preventive TB therapy are available but need to be implemented worldwide. A TB infection registry is crucial for improving the cascade of care leading to a better TB control., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Rationale: Although World Health Organization guidelines emphasize contact investigation for tuberculosis (TB)-exposed children, data that support chest radiography as a useful tool are lacking. Objectives: We evaluated the diagnostic and prognostic information of chest radiography in children exposed to TB and measured the efficacy of isoniazid preventive therapy (IPT) in those with relevant radiographic abnormalities. Methods: Between September 2009 and August 2012, we enrolled 4,468 TB-exposed children who were screened by tuberculin skin testing, symptom assessment, and chest radiography. Those negative for TB disease were followed for 1 year for the occurrence of new TB diagnoses. We assessed the protective efficacy of IPT in children with and without abnormal chest radiographs. Measurements and Main Results: Compared with asymptomatic children with normal chest films, asymptomatic children with abnormal radiographs were 25.1-fold more likely to have coprevalent TB (95% confidence interval [CI], 1.02-613.76) and 26.7-fold more likely to be diagnosed with incident TB disease during follow-up (95% CI, 10.44-68.30). Among the 29 symptom-negative and CXR-abnormal child contacts, 20% (3/15) of the isoniazid recipients developed incident TB, compared with 57% (8/14) of those who did not receive IPT (82% IPT efficacy). Conclusions: Our results strongly support the use of chest radiography as a routine screening tool for the evaluation of child TB contacts, which is readily available. Radiographic abnormalities not usually considered suggestive of TB may indicate incipient or subclinical disease, although TB preventive treatment is adequate in most cases.

Migraine is a common neurologic disorder with clinical phenotypes encompassing a variety of symptoms which all contribute to the burden felt by patients. In addition to negative impacts on a patient's quality of life, migraine has both direct medical costs and indirect costs related to missed work and decreased productivity that affect individuals as well as society at large. Unfortunately, migraine diagnoses are often missed, and many patients do not receive appropriate treatment. Primary care providers are in a key position to provide timely diagnosis and effectively manage migraine for many patients. This review aims to be a guide for improving migraine management in the primary care setting by providing strategies to overcome common challenges in migraine diagnosis; summarizing current knowledge on the mechanism of action, efficacy, and safety of calcitonin gene-related peptide (CGRP) pathway-targeting therapies; and reviewing approaches to incorporate traditional and emerging treatment options into a patient-centric migraine management strategy., Competing Interests: LD has served as a consultant/on an advisory board for Abbvie, Amgen, Lilly, Novartis, and Teva and as a speaker for Lilly. BT has served as a consultant on, and as an advisory board member for, Amgen, Biohaven, Lilly, Novartis, Teva, and Theranica, and as a speaker for Abbvie, Amgen, Biohaven, Lilly, Lundbeck, Novartis, Teva, and Supernus. He has performed clinical research for Amgen and Theranica. The authors declare that there is no conflict of interest., (© The British Pain Society 2022.)

Background: In 2017, Korea implemented a nationwide project to screen and treat latent tuberculosis infection (LTBI) in high-risk for transmission public congregate settings. We aimed to assess programme success using a cascade of care framework., Materials and Methods: We undertook a cohort study of people from three congregate settings screened between March 2017 and December 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities. We report percentages of participants with LTBI completing each step in the cascade of care model. Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment., Results: Among the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively. Compared to those aged 20-34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated. Using public health centres rather than private hospitals was associated with people "not initiating treatment" (adjusted risk ratio [aRR], 3.72; 95% confidence interval [CI], 3.95-3.86). Nine-month isoniazid monotherapy therapy was associated with "not completing treatment," compared to 3-month isoniazid and rifampin therapy (aRR, 1.28; 95% CI, 1.16-1.41)., Conclusion: Among participants with LTBI from three congregate settings, less than one third completed treatment. Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Min, Kim, Stagg, Rangaka, Lipman, Abubakar, Lee, Myong, Jeong, Bae, Shin, Kang, Lee, Park, Yim and Kim.)

During the COVID-19 pandemic in 2020, a tuberculosis outbreak occurred in a university in eastern China, with 4,488 students and 421 staff on the campus. A 19-year-old student was diagnosed in August 2019. Later, the first round of screening was initiated among close contacts, but no active cases were found. Till September 2020, four rounds of screening were performed. Four rounds of screening were conducted on September 9, November 8, November 22-25 in 2019 and September 2020, with 0, 5, 0 and 43 cases identified, respectively. A total of 66 active tuberculosis were found in the same university, including 4 sputum culture-positive and 7 sputum smear-positive. The total attack rate of active tuberculosis was 1.34% (66/4909). The whole-genome sequencing showed that the isolates belonged to the same L2 sub-specie and were sensitive to all tested antituberculosis drugs. Delay detection, diagnosis and report of cases were the major cause of this university tuberculosis epidemic. More attention should be paid to the asymptomatic students in the index class. After the occurrence of tuberculosis cases in schools, multiple rounds of screening should be carried out, and preventive therapy should be applied in a timely manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Zhu, Yu, Liu, Ding, Lu, Wu, Sun, Martinez, Lu and Wang.)

Background: The National Institute for Health and Care Excellence (NG151) recommends considering daily aspirin for people with Lynch syndrome to reduce colorectal cancer risk. However, deciding whether to initiate aspirin could be a complex decision for patients and their healthcare providers, as both the potential benefits and harms need to be considered., Methods: We conducted semi-structured interviews to explore the barriers and facilitators to using aspirin for preventive therapy. We recruited 15 people with Lynch syndrome, and 23 healthcare providers across multiple professions in primary, and specialist care (e.g. clinical genetics) in the United Kingdom. Interview schedules were informed by the Theoretical Domains Framework., Results: There were three themes: 1) Considering potential harms and benefits; 2) Healthcare pathway; 3) Patients' level of interest in aspirin. All healthcare providers, across primary and specialist care, viewed general practitioners (GPs) as being responsible for prescribing and overseeing the use of aspirin. However, GPs were unfamiliar with aspirin for preventive therapy, and concerned about prescribing at higher doses (300-600 mg). To support decision-making, GPs wanted clarification from specialist clinicians on the evidence and dose to prescribe. Not all participants with Lynch syndrome received information on aspirin from their healthcare provider, and several were unsure who to discuss aspirin with. GPs were more inclined to prescribe aspirin for patients with expressed preferences for the medication, however several patients were uncertain and wanted further guidance., Conclusions: Coordinated and multilevel strategies are needed, addressing the needs of both GPs and people with Lynch syndrome, to ensure consistent implementation of national guidance on aspirin for preventive therapy., (© 2022. The Author(s).)

Introduction: Isoniazid preventive therapy (IPT) can reduce the risk of tuberculosis (TB) in children living with HIV (CLHIV), but data on the outcomes of the IPT cascade in CLHIV are limited., Methods: We evaluated the IPT cascade among CLHIV aged <15 years and newly enrolled in HIV care in eight HIV clinics in western Kenya. Medical record data were abstracted from September 2015 through July 2019. We assessed the proportion of CLHIV completing TB symptom screening, IPT eligibility assessment, IPT initiation and completion. TB incidence rate was calculated stratified by IPT initiation and completion status. Risk factors for IPT non-initiation and non-completion were assessed using Poisson regression with generalized linear models., Results: Overall, 856 CLHIV were newly enrolled in HIV care, of whom 98% ([95% CI 97-99]; n = 841) underwent screening for TB symptoms and IPT eligibility. Of these, 13 (2%; 95% CI 1-3) were ineligible due to active TB and 828 (98%; 95% CI 97-99) were eligible. Five hundred and fifty-nine (68%; 95% CI 64-71) of eligible CLHIV initiated IPT; median time to IPT initiation was 3.6 months (interquartile range [IQR] 0.5-10.2). Overall, 434 (78%; 95% CI 74-81) IPT initiators completed. Attending high-volume HIV clinics (aRR = 2.82; 95% CI 1.20-6.62) was independently associated with IPT non-initiation. IPT non-initiation had a trend of being higher among those enrolled in the period 2017-2019 versus 2015-2016 (aRR = 1.91; 0.98-3.73) and those who were HIV virally non-suppressed (aRR = 1.90; 95% CI 0.98-3.71). Being enrolled in 2017-2019 versus 2015-2016 (aRR = 1.40; 1.01-1.96) was independently associated with IPT non-completion. By 24 months after IPT screening, TB incidence was four-fold higher among eligible CLHIV who never initiated (8.1 per 1000 person years [PY]) compared to CLHIV who completed IPT (2.1 per 1000 PY; rate ratio [RR] = 3.85; 95% CI 1.08-17.15), with a similar trend among CLHIV who initiated but did not complete IPT (8.2/1000 PY; RR = 4.39; 95% CI 0.82-23.56)., Conclusions: Despite high screening for eligibility, timely IPT initiation and completion were suboptimal among eligible CLHIV in this programmatic cohort. Targeted programmatic interventions are needed to address these drop-offs from the IPT cascade by ensuring timely IPT initiation after ruling out active TB and enhancing completion of the 6-month course to reduce TB in CLHIV., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Pressure injuries (PIs), especially in the sacral region are frequent, costly, and increase morbidity and mortality of patients in an intensive care unit (ICU). These injuries can occur as a result of prolonged pressure and/or shear forces. Neuromuscular electrical stimulation (NMES) can increase muscle mass and improve local circulation, potentially reducing the incidence of PI., Methods: We performed a randomized controlled trial to assess the efficacy and safety of NMES in preventing PI in critically ill patients. We included patients with a period of less than 48 h in the ICU, aged ≥ 18 years. Participants were randomly selected (1:1 ratio) to receive NMES and usual care (NMES group) or only usual care (control group-CG) until discharge, death, or onset of a PI. To assess the effectiveness of NMES, we calculated the relative risk (RR) and number needed to treat (NNT). We assessed the muscle thickness of the gluteus maximus by ultrasonography. To assess safety, we analyzed the effects of NMES on vital signs and checked for the presence of skin burns in the stimulated areas. Clinical outcomes were assessed by time on mechanical ventilation, ICU mortality rate, and length of stay in the ICU., Results: We enrolled 149 participants, 76 in the NMES group. PIs were present in 26 (35.6%) patients in the CG and 4 (5.3%) in the NMES group (p ˂ 0.001). The NMES group had an RR = 0.15 (95% CI 0.05-0.40) to develop a PI, NNT = 3.3 (95% CI 2.3-5.9). Moreover, the NMES group presented a shorter length of stay in the ICU: Δ = - 1.8 ± 1.2 days, p = 0.04. There was no significant difference in gluteus maximus thickness between groups (CG: Δ = - 0.37 ± 1.2 cm vs. NMES group: Δ = 0 ± 0.98 cm, p = 0.33). NMES did not promote deleterious changes in vital signs and we did not detect skin burns., Conclusions: NMES is an effective and safe therapy for the prevention of PI in critically ill patients and may reduce length of stay in the ICU. Trial registration RBR-8nt9m4. Registered prospectively on July 20th, 2018, https://ensaiosclinicos.gov.br/rg/RBR-8nt9m4., (© 2022. The Author(s).)

Aim: Evaluate the efficacy and safety of non-invasive vagus nerve stimulation for migraine prevention., Methods: After completing a 4-week diary run-in period, adults who had migraine with or without aura were randomly assigned to receive active non-invasive vagus nerve stimulation or sham therapy during a 12-week double-blind period., Results: Of 336 enrolled participants, 113 (active, n = 56; sham, n = 57) completed ≥70 days of the double-blind period and were ≥66% adherent with treatment, comprising the prespecified modified intention-to-treat population. The COVID-19 pandemic led to early trial termination, and the population was ∼60% smaller than the statistical target for full power. Mean reduction in monthly migraine days (primary endpoint) was 3.12 for the active group and 2.29 days for the sham group (difference, -0.83; p  = 0.2329). Responder rate (i.e. the percentage of participants with a ≥50% reduction in migraine days) was greater in the active group (44.87%) than the sham group (26.81%; p  = 0.0481). Prespecified subgroup analysis suggested that participants with aura responded preferentially. No serious device-related adverse events were reported., Conclusions: These results suggest clinical utility of non-invasive vagus nerve stimulation for migraine prevention, particularly for patients who have migraine with aura, and reinforce the well-established safety and tolerability profile of this therapy. Trial Registration: ClinicalTrials.gov (NCT03716505).

Background: In 2017, Korea implemented nationwide latent tuberculosis infection (LTBI) project targeting healthcare workers (HCWs). We aimed to assess its performance using the cascade of care model., Methods: We included 45,503 employees of medical institutions with positive interferon-gamma release assay result who participated between March 2017 and December 2018. We described percentages of LTBI participants completing each step in the cascade of care. Poisson regression model was conducted to assess individual characteristics and factors associated with not-visiting clinics for further care, not-initiating LTBI treatment, and not-completing treatment., Results: Proportions of visiting clinics and initiating and completing treatment in HCWs were 54.9%, 38.5%, and 32.0%, respectively. Despite of less likelihood of visiting clinics and initiating LTBI treatment, older age ≥ 65 years were more likely to complete treatment (adjusted relative risk [aRR], 0.80; 95% confidence interval [CI], 0.64-0.99), compared to young age < 35 years. Compared to nurses, doctors were less likely to visit clinic; however, were more likely to initiate treatment (aRR, 0.88; 95% CI, 0.81-0.96). Those who visited public health centers were associated with not-initiating treatment (aRR, 1.34; 95% CI, 1.29-1.40). When treated at private hospitals, 9-month isoniazid monotherapy was less likely to complete treatment, compared to 3-month isoniazid and rifampicin combination therapy (aRR, 1.33; 95% CI, 1.16-1.53)., Conclusion: Among employees of medical institutions with LTBI, only one third completed treatment. Age, occupation, treatment center, and initial regimen were significantly related to LTBI treatment performance indicators. Rifampicin-based short treatment regimens were effective under standard of care., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: Recent years have seen important improvements in available preventive treatment regimens for tuberculosis (TB), and research is ongoing to develop these further. To assist with the formulation of target product profiles for future regimens, we examined which regimen properties would be most influential in the epidemiological impact of preventive treatment., Methods: Following expert consultation, we identified 5 regimen properties relevant to the incidence-reducing impact of a future preventive treatment regimen: regimen duration, efficacy, ease-of-adherence (treatment completion rates in programmatic conditions), forgiveness to non-completion and the barrier to developing rifampicin resistance during treatment. For each regimen property, we elicited expert input for minimally acceptable and optimal (ideal-but-feasible) performance scenarios for future regimens. Using mathematical modelling, we then examined how each regimen property would influence the TB incidence reduction arising from full uptake of future regimens according to current WHO guidelines, in four countries: South Africa, Kenya, India and Brazil., Results: Of all regimen properties, efficacy is the single most important predictor of epidemiological impact, while ease-of-adherence plays an important secondary role. These results are qualitatively consistent across country settings; sensitivity analyses show that these results are also qualitatively robust to a range of model assumptions, including the mechanism of action of future preventive regimens., Conclusions: As preventive treatment regimens against TB continue to improve, understanding the key drivers of epidemiological impact can assist in guiding further development. By meeting these key targets, future preventive treatment regimens could play a critical role in global efforts to end TB., (© 2022. The Author(s).)

Despite the growing disease burden of non-alcoholic fatty liver disease (NAFLD), approved medical treatments to improve or prevent liver fibrosis are effective only in a small number of patients. Recent studies have found the new use of antiplatelet agents for antifibrotic benefits in NAFLD, but human studies are still limited. The goal of this meta-analysis was to combine the findings of existing relevant studies to investigate the effects of antiplatelet therapy in reducing or preventing advanced liver fibrosis in patients with NAFLD. We conducted a systematic literature search in PubMed, EMBASE, and Web of Science databases from inception to January 2021 to identify all original studies that investigated the use of antiplatelet agents in patients with NAFLD. We used the National Institutes of Health's quality assessment tool for observational cohort and cross-sectional studies to assess study quality and risk of bias. The primary outcome was the prevalence of advanced liver fibrosis stage 3-4. Data from each study was combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate pooled odds ratio (OR) and 95% confidence intervals (CIs). Of the 2,498 studies identified, 4 studies involving 2,593 patients with NAFLD were included in this study (949 antiplatelet agent users and 1,644 non-antiplatelet agent users). The use of aspirin and/or P2Y12 receptor inhibitors was associated with a lower pooled OR of advanced liver fibrosis in patients with NAFLD (pooled OR = 0.66; 95% CI: 0.53-0.81, I 2  = 0.0%; p < 0.001). This study focuses on the outcome of advanced liver fibrosis in patients with NAFLD. Our study is limited by the small number of studies that were included. Preliminary evidence from this meta-analysis suggests a protective association between antiplatelet therapy and the prevalence of advanced liver fibrosis in patients with NAFLD. Our findings support future research into repositioning an antiplatelet agent as a novel NAFLD treatment., (© 2022. Indian Society of Gastroenterology.)

Delays in diagnosis and treatment of pulmonary tuberculosis (TB) can lead to more severe disease and increased transmission. Contact investigation among household contacts (HHCs) of TB patients is crucial to ensure optimal outcomes. In the context of a prospective cohort study in Palamaner, Southern India, this study attempted to assess the potential of 27 different soluble immune markers to accurately assign HHCs for appropriate treatment. A multiplex bead assay was applied on QuantiFERON (QFT)-nil supernatants collected from 89 HHCs grouped by longitudinal QFT status; M. tuberculosis ( Mtb ) infected (QFT positive at baseline and follow-up, n = 30), recent QFT converters (QFT-negative at baseline, n = 27) and converted to QFT-positivity within 6 months of exposure (at follow-up, n = 24) and QFT consistent negatives (n = 32). The 29 TB index cases represented Active TB. Active TB cases and HHCs with Mtb infection produced significantly different levels of both pro-inflammatory (IFNγ, IL17, IL8, IP10, MIP-1α, MIP1β, and VEGF) and anti-inflammatory (IL9 and IL1RA) cytokines. We identified a 4-protein signature (bFGF, IFNγ, IL9, and IP10) that correctly classified HHCs with Mtb infection vs. Active TB with a specificity of 92.6%, suggesting that this 4-protein signature has the potential to assign HHCs for either full-length TB treatment or preventive TB treatment. We further identified a 4-protein signature (bFGF, GCSF, IFNγ, and IL1RA) that differentiated HHCs with Mtb infection from QFT consistent negatives with a specificity of 62.5%, but not satisfactory to safely assign HHCs to no preventive TB treatment. QFT conversion, reflecting new Mtb infection, induced an elevated median concentration in nearly two-thirds (19/27) of the analyzed soluble markers compared to the levels measured at baseline. Validation in other studies is warranted in order to establish the potential of the immune biosignatures for optimized TB case detection and assignment to therapeutic and preventive treatment of Mtb infected individuals., Competing Interests: TMD is an employee of and holds shares in the GSK group of companies but participated in the current work as an independent investigator. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sivakumaran, Jenum, Ritz, Vaz, Doherty and Grewal.)

Migraine continues second among the world's causes of disability. Diagnosis is based on the history and clinical examination and imaging is usually not necessary. Migraine can be subdivided depending on whether there is an aura or not and based on the frequency of the headaches. The number of headache days determines whether the patient has episodic migraine or chronic migraine. Treating migraines can be done to treatment the migraine itself and to prevent its appearance. In this review we approach the migraine from a practical point of view with updated information., (Copyright © 2021 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

We undertook a systematic review to synthesise the data on attitudes and behaviour towards the use of aspirin for cancer prevention, and healthcare providers' attitudes towards implementing aspirin in practice. Searches were carried out across 12 databases (e.g. MEDLINE, EMBASE). We used the Mixed Methods Appraisal Tool to evaluate study quality, and conducted a narrative synthesis of the data. The review was pre-registered (PROSPERO: CRD42018093453). Thirty-eight studies were identified. Uptake and adherence data were all from trials. Trials recruited healthy participants, those at higher risk of cancer, and those with cancer. Four studies reported moderate to high (40.9-77.7%) uptake to an aspirin trial among people who were eligible. Most trials (18/22) reported high day-to-day adherence (≥80%). Three trials observed no association between gender and adherence. One trial found no association between adherence and colorectal cancer risk. Three studies reported moderate to high (43.6-76.0%) hypothetical willingness to use aspirin. Two studies found that a high proportion of healthcare providers (72.0-76.0%) perceived aspirin to be a suitable cancer prevention option. No qualitative studies were identified. The likelihood that eligible users of aspirin would participate in a trial evaluating the use of aspirin for preventive therapy was moderate to high. Among participants in a trial, day-to-day adherence was high. Further research is needed to identify uptake and adherence rates in routine care, the factors affecting aspirin use, and the barriers to implementing aspirin into clinical care., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Short-course, rifamycin-based regimens could facilitate scale-up of tuberculosis preventive therapy (TPT), but it is unclear how stringently tuberculosis (TB) disease should be ruled out before TPT use., Methods: We developed a state-transition model of a TPT intervention among two TPT-eligible cohorts: adults newly diagnosed with HIV in South Africa (PWH) and TB household contacts in Pakistan (HHCs). We modeled two TPT regimens-4 months of rifampicin [4R] or 6 months of isoniazid [6H]-comparing each to a reference of no intervention. Before initiating TPT, TB disease was excluded either through symptom-only screening or with additional radiographic screening that could detect subclinical TB but might limit access to the TPT intervention. TPT's potential curative effects on both latent and subclinical TB were modeled, as were both acquisitions of resistance and prevention of drug-resistant disease. Although all eligible individuals received the screening and/or TPT interventions, the modeled TB outcomes comprised only those with latent or subclinical TB that would have progressed to symptomatic disease if untreated., Results: When prescribed after only symptom-based TB screening (such that individuals with subclinical TB were included among TPT recipients), 4R averted 45 active (i.e., symptomatic) TB cases (95% uncertainty range 24-79 cases or 40-89% of progressions to active TB) per 1000 PWH [17 (9-29, 43-94%) per 1000 HHCs]; 6H averted 37 (19-66, 52-73%) active TB cases among PWH [13 (7-23, 53-75%) among HHCs]. With this symptom-only screening, for each net rifampicin resistance case added by 4R, 12 (3-102) active TB cases were averted among PWH (37 [9-580] among HHCs); isoniazid-resistant TB was also reduced. Similarly, 6H after symptom-only screening increased isoniazid resistance while reducing overall and rifampicin-resistant active TB. Screening for subclinical TB before TPT eliminated this net increase in resistance to the TPT drug; however, if the screening requirement reduced TPT access by more than 10% (the estimated threshold for 4R among HHCs) to 30% (for 6H among PWH), it was likely to reduce the intervention's overall TB prevention impact., Conclusions: All modeled TPT strategies prevent TB relative to no intervention, and differences between TPT regimens or between screening approaches are small relative to uncertainty in the outcomes of any given strategy. If most TPT-eligible individuals can be screened for subclinical TB, then pairing such screening with rifamycin-based TPT maximizes active TB prevention and does not increase rifampicin resistance. Where subclinical TB cannot be routinely excluded without substantially reducing TPT access, the choice of TPT regimen requires weighing 4R's efficacy advantages (as well as its greater safety and shorter duration that we did not directly model) against the consequences of rifampicin resistance in a small fraction of recipients., (© 2021. The Author(s).)

Migraine is a chronic neurologic disease estimated to affect approximately 50 million Americans. It is associated with a range of symptoms, which contribute to disability and substantial negative impacts on quality of life for many patients. Still, migraine continues to be underdiagnosed, undertreated, and optimising treatment for individual patients has proven difficult. As many migraine patients will be seen first in primary care settings, internists and other primary care providers are ideally positioned to improve diagnosis and migraine management for many patients. In this review, we discuss some of the challenges in diagnosing migraine and suggest strategies to overcome them, summarise the current understanding of migraine pathophysiology and clinical evidence on acute and preventive treatment options, and offer practical approaches to diagnosis and contemporary management of migraine in the primary care setting.Key messagesMigraine is a prevalent disease with substantial impact. Primary care providers are ideally positioned to improve care for migraine patients with streamlined approaches to diagnosis and management.A stepwise diagnostic approach to migraine involves taking a thorough headache history, excluding secondary headache, and identifying primary headache disorder using screening tools or ICHD-3 criteria.The FDA approved seven new migraine therapies from 2018 to 2020 (four monoclonal antibodies, two gepants, one ditan), expanding acute and preventive therapeutic options.

Latent tuberculosis infection affects one quarter of the world's population, and effective therapies are available. However, scale-up of tuberculosis preventive treatment (TPT) remains limited. We describe strategies to support scale-up of TPT in high-prevalence settings, where the potential benefit for affected individuals is considerable. Patients must be at the centre of policies to scale-up TPT. Addressing the health system requirements for scale-up will ensure that programs can deliver treatment safely, efficiently and sustainably. Further research is required to adapt TPT to local contexts, and develop new shorter treatments that will be suitable for wide-scale deployment., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Background: Young children (<5 years) and children living with HIV in contact with an adult with tuberculosis (TB) should receive TB preventive therapy (TPT), but uptake is low., Aims: To determine gaps in the uptake of and adherence to TPT in child TB contacts under routine primary care clinic conditions., Methods: A cohort of child TB contacts (age <5 years or living with HIV <15 years) was followed at a primary care clinic in Johannesburg, South Africa., Results: Of 170 child contacts with 119 adult TB cases, only 45% (77/170) visited the clinic for TPT eligibility screening, two of whom had already initiated TPT at another clinic. Of the 75 other children, 18/75 (24%) commenced TB treatment and 56/75 (75%) started TPT. Health-care workers followed the guidelines, with 96% (64/67) of children screened for symptoms of TB and 97% (36/37) of those symptomatic assessed for TB, but microbiological testing was low (9/36, 25%) and none had microbiologically confirmed tuberculosis. Only half (24/46, 52%) of the children initiating TPT completed the 6-month course. Neither sociodemographic determinants (age, sex) nor clinical factors (HIV status, TB source, time to TPT initiation) was associated with non-adherence to TPT., Conclusion: Most child contacts of an adult TB case do not visit the clinic, and half of those initiating TPT did not adhere to the full 6-month course. These programme failures result in missed opportunities for early diagnosis of active TB and prevention of progression to disease in young and vulnerable children.

Background: Tuberculosis (TB) preventive therapy is recommended for all people living with HIV (PLHIV). Despite the elevated risk of TB amongst PLHIV, most of those eligible for preventive therapy would never develop TB. Tests which can identify individuals at greatest risk of disease would allow more efficient targeting of preventive therapy., Methods: We used mathematical modelling to estimate the potential impact of using a blood transcriptomic biomarker (RISK11) to target preventive therapy amongst PLHIV. We compared universal treatment to RISK11 targeted treatment and explored the effect of repeat screening of the population with RISK11., Results: Annual RISK11 screening, with preventive therapy provided to those testing positive, could avert 26% (95% CI 13-34) more cases over 10 years compared to one round of universal treatment. For the cost per case averted to be lower than universal treatment, the maximum cost of the RISK11 test was approximately 10% of the cost of preventive therapy. The benefit of RISK11 screening may be greatest amongst PLHIV on ART (compared to ART naïve individuals) due to the increased specificity of the test in this group., Conclusions: Biomarker targeted preventive therapy may be more effective than universal treatment amongst PLHIV in high incidence settings but would require repeat screening., (© 2021. The Author(s).)

The COVID-19 pandemic and its virus variants continue to pose a serious and long-lasting threat worldwide. To combat the pandemic, the world's largest COVID-19 vaccination campaign is currently ongoing. As of July 19 th 2021, 26.2% of the world population has received at least one dose of a COVID-19 vaccine (1.04 billion), and one billion has been fully vaccinated, with very high vaccination rates in countries like Israel, Malta, and the UEA. Conversely, only 1% of people in low-income countries have received at least one dose with examples of vaccination frequency as low as 0.07% in the Democratic Republic of Congo. It is thus of paramount importance that more research on alternate methods to counter cell infection and propagation is undertaken that could be implemented in low-income countries. Moreover, an adjunctive therapeutic intervention would help to avoid disease exacerbation in high-rate vaccinated countries too. Based on experimental biochemical evidence on viral cell fusion and propagation, herein we identify (i) extracellular pH (epH), (ii) temperature, and (iii) humidity and osmolarity as critical factors. These factors are here in discussed along with their implications on mucus thick layer, proteases, abundance of sialic acid, vascular permeability and exudate/edema. Heated, humidified air containing sodium bicarbonate has long been used in the treatment of certain diseases, and here we argue that warm inhalation of sodium bicarbonate might successfully target these endpoints. Although we highlight the molecular/cellular basis and the signalling pathways to support this intervention, we underscore the need for clinical investigations to encourage further research and clinical trials. In addition, we think that such an approach is also important in light of the high mutation rate of this virus originating from a rapid increase., Competing Interests: Maria Cristina Albertini is an Academic Editor for PeerJ., (© 2021 Cicconetti et al.)