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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.

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. Plain Language Summary: Numerous studies have shown that eptinezumab is effective for migraine prevention, but there have been limited studies in Asian patients. In this six‐month real‐world study of eptinezumab treatment in 30 Asian patients with chronic migraine (CM), patients were treated with eptinezumab (one dose each at Months 1 and 3) and they reported fewer migraine days per month and improvement in their symptoms, lessened impact of migraine on daily life, and reduced use of medication for acute headache relief after 6 months. These findings support eptinezumab's potential effectiveness as a preventive treatment option in Asian patients with CM. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) preventive therapy is crucial in combating the global TB epidemic. However, adverse drug reactions (ADRs) remain a significant barrier to its successful implementation. Methods: This prospective observational study involved 152 participants on TB preventive therapy, monitored over nine months to identify the incidence, type, and severity of ADRs, and assess the impact on treatment adherence. Results: A high incidence of ADRs was observed, with 88.2% of participants experiencing at least one ADR. Gastrointestinal side effects were the most common (41.4%), followed by hepatotoxicity (21.7%). The study also found an increased risk of ADRs among older adults (P=0.033), individuals with a higher BMI (P=0.015), and patients with diabetes mellitus (P=0.042). Despite this, high rates of treatment adherence and completion (92.1%) were achieved, indicating effective management of ADRs. Conclusion: The study highlights the prevalence of ADRs in TB preventive therapy but also demonstrates the effectiveness of current management strategies. Tailored monitoring and management strategies for high-risk groups are essential to enhance treatment safety and efficacy. [ABSTRACT FROM AUTHOR]

Background. Human papillomavirus refers to one of the most common sexually transmitted infections with the majority of viruses in the host being transient carriers, the so-called latent forms of papillomavirus infection. Persistence of cancer-associated human papillomavirus is fraught with cervical intraepithelial neoplasia, and subsequent cervical cancer. Measures for secondary prevention of cervical cancer in latent forms of papillomavirus infection are yet to be developed, which predetermined the present study.Objectives. To increase the effectiveness of secondary prevention of cervical cancer by improving the algorithm for managing latent forms of papillomavirus infection in women. Methods. A randomized controlled trial enrolled 152 patients diagnosed with a latent papillomavirus infection. Patient examination and data analysis were carried out at clinical trial centers of the Department of Obstetrics, Gynecology and Perinatology of Kuban State Medical University (Russia) in 2020–2024. The trial involved patients aged 18 to 35 years. Patients were divided into 2 groups using the sealed code envelope method: Group I (comparison group) (n = 74) — microbiological sanitation of the cervicovaginal zone (as indicated) and observation for 36 months with annual control of viral load, colposcopy and oncocytology; Group II (study group) (n = 78) — microbiological sanitation of the cervicovaginal zone (as indicated) and administration of quadrivalent recombinant human papillomavirus vaccine (types 6, 11, 16, 18) (3 doses intramuscularly: second and third doses were administered 1 and 3 months after the first one). Each patient was analyzed for the effectiveness of preventive therapy according to the dynamics of indicators: colposcopy, cytology (Papanicolau staining), and molecular biological analysis (polymerase chain reaction). The indicators were evaluated after 12, 24, and 36 months. Statistical analysis of the results was carried out using IBM SPSS Statistics 26 (IBM, USA) variation statistics programs.Results. Vaccination with a quadrivalent recombinant vaccine against human papillomavirus of types 6, 11, 16, 18 against the background of correction of dysbiotic vaginal and cervical disorders in latent forms of papillomavirus infection in women was revealed to cause a 9.3-fold decrease (compared to the study group) in realization of latent persistence of viruses into subclinical (25.7 % in group I vs. 9.0 % in group II) and clinical forms of papillomavirus infection (cervical intraepithelial neoplasia) — 12.1 % in group I vs. 1.3 % in group II, to reduce the persistence of human papillomavirus and the appearance of their new genotypes, the viral load of highly oncogenic types of human papillomavirus (1.9 times —3.2 ± 2.4 geq/ml in group I versus 1.7 ± 2.1 geq/ml in group II).Conclusion. The trial has shown that human papillomavirus vaccination is associated with a reduced risk of realization of latent forms of papillomavirus infection into clinical forms as cervical intraepithelial neoplasia and, consequently, cervical cancer, thereby being considered promising for secondary prevention of this pathology.

Abstract 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.

Chronic migraine is a disease that significantly reduces the quality of life of patients. It affects millions of people around the world, and is common particularly among young women. Family physicians often encounter the problem of migraine headaches in their daily practice. The diagnostic problem results from absence of tests or imaging studies that can clearly indicate the cause of the headache. In order to establish a diagnosis and exclude secondary sources of pain, doctors focus on a detailed medical history and analysis of symptoms presented over time. Preventive treatment of migraine requires appropriate drug selection after weighing the benefits and risks for each patient. This review paper presents and briefly discusses selected pharmacological and non-pharmacological methods used in migraine prevention. They were selected by searching the PubMed Internet database. The presented non-pharmacological methods include the use of nutraceutics, acupuncture and behavioral therapy. The discussed pharmacological methods include treatment with beta-blockers, topimarate, flunarizine or one of the latest methods - the use of monoclonal antibodies against CGRP. In addition, the use of botulinum toxin type A in the treatment of chronic migraine has also been demonstrated. It should be remembered that the type of therapy chosen should be individualized: according to the patient's preferences, treatment effectiveness, possible side effects or accompanying diseases. Proper management of chronic migraine prophylaxis can significantly improve the quality of life of patients and reduce the frequency of headache attacks. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Shin splints are a common injury in the world of sports, causing pain along the inner edge of the tibial and impacting an athlete’s performance and well-being. The study aims to examine how kinesio taping application affects pain, postural control, and plantar pressure parameters in athletes with shin splints. Methods: A placebo-controlled trial design was used, with 32 athletes with shin splints randomly assigned to either the kinesio taping group (KT=16) or the placebo group (PC=16). The KT group received kinesio tape with 75% tension applied to the affected shin, while the PC group received the same application without tension. Before and after the taping intervention, pain levels, postural control, and plantar pressure parameters were evaluated. Results: Results indicated that the KT group experienced a significant pain reduction and improved postural control and plantar pressure parameters compared to the PC group. Conclusion: These results suggest that kinesio tape can relieve pain in the short term and enhance postural control and plantar pressure distribution in athletes with shin splints. Further research is necessary to explore the long-term effects and underlying mechanisms.

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Shin splints are a common injury in the world of sports, causing pain along the inner edge of the tibial and impacting an athlete's performance and well-being. The study aims to examine how kinesio taping application affects pain, postural control, and plantar pressure parameters in athletes with shin splints. Methods: A placebo-controlled trial design was used, with 32 athletes with shin splints randomly assigned to either the kinesio taping group (KT=16) or the placebo group (PC=16). The KT group received kinesio tape with 75% tension applied to the affected shin, while the PC group received the same application without tension. Before and after the taping intervention, pain levels, postural control, and plantar pressure parameters were evaluated. Results: Results indicated that the KT group experienced a significant pain reduction and improved postural control and plantar pressure parameters compared to the PC group. Conclusion: These results suggest that kinesio tape can relieve pain in the short term and enhance postural control and plantar pressure distribution in athletes with shin splints. Further research is necessary to explore the long-term effects and underlying mechanisms. [ABSTRACT FROM AUTHOR]

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.

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)

Introduction: Loss to follow up remains one of the main problems in the treatment of latent tuberculosis infection (LTBI) in the state of Sabah, Malaysia. This study aims to identify the risk factors for loss to follow-up among LTBI treated TB contacts in children under 5 years of age, who did not complete 180 dosages of treatment within 6 to 9 months. Methods: This retrospective cohort study used anonymised data taken from the Malaysia national case-based TB registry (MyTB) between 2017 and 2019. To identify factors related with loss to follow-up, a logistic regression analysis was performed. Results: Of the 1334 treated LTBI cases, 10.4% were loss-to-follow-up. The mean age of study participants was 2.3 years, with 50.2% males. Factors associated with loss to follow-up include index-contact relationship i.e., Extended family (aOR = 1.82, 95% CI = 1.19, 2.77) and PTB index in whom the treatment outcome is loss to follow up (aOR = 4.84, 95% CI = 1.96, 11.95). Rural living was associated with less loss to follow (adjusted odds ratio (aOR) = 0.40, 95% confidence interval (CI) = 0.26, 0.61). Conclusion: Despite commendable efforts, the problem of loss to follow during LTBI treatment in children persisted. In spite of the inherent limitations of the study, the associated factors identified in this study can be used as a basis for future initiatives to strengthen LTBI management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chronic migraine is a disease that significantly reduces the quality of life of patients. It affects millions of people around the world, and is common particularly among young women. Family physicians often encounter the problem of migraine headaches in their daily practice. The diagnostic problem results from absence of tests or imaging studies that can clearly indicate the cause of the headache. In order to establish a diagnosis and exclude secondary sources of pain, doctors focus on a detailed medical history and analysis of symptoms presented over time. Preventive treatment of migraine requires appropriate drug selection after weighing the benefits and risks for each patient. This review paper presents and briefly discusses selected pharmacological and non-pharmacological methods used in migraine prevention. They were selected by searching the PubMed Internet database. The presented non-pharmacological methods include the use of nutraceutics, acupuncture and behavioral therapy. The discussed pharmacological methods include treatment with beta-blockers, topimarate, flunarizine or one of the latest methods - the use of monoclonal antibodies against CGRP. In addition, the use of botulinum toxin type A in the treatment of chronic migraine has also been demonstrated. It should be remembered that the type of therapy chosen should be individualized: according to the patient's preferences, treatment effectiveness, possible side effects or accompanying diseases. Proper management of chronic migraine prophylaxis can significantly improve the quality of life of patients and reduce the frequency of headache attacks.

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.

Abstract 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.

BackgroundA 12-dose, once-weekly regimen of isoniazid and rifapentine (3HP) is effective in preventing tuberculosis (TB) among people living with HIV (PLHIV). We sought to identify potential barriers to and facilitators of acceptance and completion of 3HP treatment from the perspective of people living with HIV (PLHIV) and health workers in a routine HIV care setting in Kampala, Uganda.MethodsWe conducted semi-structured interviews with 25 PLHIV and 10 health workers at an HIV/AIDS clinic in Kampala, Uganda. For both groups, we explored their understanding and interpretations of TB and TB preventive therapy (TPT), and perceptions about social and contextual factors that might influence the willingness of PLHIV to initiate and complete 3HP. We analyzed the data using an inductive thematic approach and aligned the emergent themes to the Behavior Change Wheel framework to identify sources of behavior and targeted behavior change interventions.ResultsFacilitators of acceptance and completion of 3HP treatment among PLHIV were fear of contracting TB, awareness of being at risk of getting TB, willingness to take TPT, trust in health workers, and the perceived benefits of directly observed therapy (DOT) and self-administered therapy (SAT) 3HP delivery strategies. Barriers included inadequate understanding of TPT, fear of potential side effects, concerns about the effectiveness of 3HP, and the perceived challenges of DOT or SAT. Among health workers, perceived facilitators included knowledge that TB is a common cause of mortality for PLHIV, fear of getting TB, and trust in the health workers by PLHIV, the advantages of once-weekly 3HP dosing, and the benefits of DOT and SAT 3HP delivery strategies. Health worker-reported barriers for PLHIV included inadequate understanding of TB and benefits of TPT, TB-associated stigma, potential side effects pill burden, and challenges of DOT and SAT 3HP delivery strategies. Lack of experience in the use of digital technology to monitor patient care was identified as a health worker-specific barrier. Identified intervention functions to address the facilitators or barriers included education, persuasion, environmental restructuring, enablement, and training.ConclusionsUsing a formative qualitative and comprehensive theoretical approach, we identified key barriers, facilitators, and appropriate interventions, including patient education, enhancing trust, and patient-centered treatment support that could be used to optimize the delivery of 3HP to PLHIV in our setting. These interventions are likely generalizable to other clinical interventions in similar populations in sub-Saharan Africa and other TB high-burden settings.

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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.

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine which type of prophylaxis was effective for postoperative symptomatic venous throm- boembolism (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 post- operative 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 com- pared 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 selec- tive LMWH administration were significantly preventive against postoperative symptomatic VTE. [ABSTRACT FROM AUTHOR]

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.

Abstract 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.

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.

Supplemental Digital Content is Available in the Text. Background: Tuberculosis preventive therapy (TPT) is recommended for people with HIV infection, including during pregnancy. The effect of TPT exposure at conception and during pregnancy is poorly documented. Methods: We report pregnancy outcomes among South African women with HIV enrolled in a randomized trial of 4 TPT regimens (two 3-month regimens, rifapentine/isoniazid [3HP] or rifampin/isoniazid [3HR], isoniazid for 6 months, or isoniazid continuously). Descriptive statistics and risk ratios were assessed to examine relationships between study regimens and outcomes. Results: 216/896 women (24%) conceived during the study. Women who conceived were younger (27.9 vs 31.3 years) and had higher mean CD4 counts (589.1 vs 536.7). The odds of pregnancy were higher in women in the rifamycin-isoniazid arms than those in the isoniazid arms (3HP: relative risk [RR] 1.73, P = 0.001; 3HR:RR 1.55, P = 0.017) despite increased contraceptive use compared with the standard 6H therapy. Thirty-four women became pregnant while taking preventive treatment (8 rifamycin and 26 isoniazid monotherapy). Pregnancy outcomes in these women were as follows: 17 (50%) mother/baby healthy, 3 (9%) spontaneous abortions, 6 (18%) elective abortions, 1 (3%) premature delivery, 2 (6%) neonatal deaths [1 rifamycin-isoniazid and 1 isoniazid], and 5 (15%) unknown. Conclusions: Pregnancy was common in women who had received TPT and more frequent in women who had received rifamycin-isoniazid–based regimens. [ABSTRACT FROM AUTHOR]

• Tuberculosis (TB) infection accounts for 2 billion people worldwide • TB infection is defined by immune response detection without clinical active disease • Tests for TB infection diagnosis lack accuracy to identify progressors to disease • Preventive therapy is a strategy to control TB spread worldwide • A TB infection registry is crucial for public health issues of TB control 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction. Migraine is one of the most common disabling neurological disorders. Recently developed monoclonal antibodies to calcitonin gene-related peptide (CGRP) or its receptor are the first targeted medication for preventive therapy of both episodic and chronic migraine. They have been thoroughly investigated in clinical trials; however, there is little data from real-world clinical practice available to date. The aim of this study is to assess the efficacy and safety of 6 months of treatment with erenumab in real-world clinical practice and investigate the effect of the drug on the patients’ sensitivity to medicines for migraine headaches relief and patient satisfaction after treatment.Materials and methods. Our observational cohort prospective study included patients in our Headache Clinic prescribed monoclonal antibodies blocking the CGRP-receptor – erenumab. During the investigation, we evaluated the previous preventive therapy and its efficacy, the number of days with migraine per month, adverse events occurring during the erenumab treatment, depression and anxiety (HADS), migraine disability (MIDAS), the presence of allodynia (ACS-12) and improved response to acute therapy after treatment. A total of 42 patients participated in the study: 6 men, 36 women, the average age was 43.9 ± 12.2. Of them, 38 patients (90%) had chronic migraine. Thirty-two patients (76%) had previously been prescribed preventive therapy, which proved ineffective, and 10 patients (24%) had not once received any type of migraine prevention.Results. Among our patients, we identified 11 patients with resistant migraine and one patient with refractory migraine. During the study, two patients dropped out due to adverse events (constipation). Thirty patients continued the administration of erenumab 70 mg for at least six months. The average number of migraine days per month before treatment was 22.8, and after six months of treatment, it dropped to 7.3. Twenty-nine patients (72.5%) also noted that the response to acute headache treatment improved after the therapy.Conclusion. The results of our study are consistent with the international experience of using erenumab and confirm its effectiveness for migraine preventive therapy, including difficult-to-treat migraine cases. However, further studies with more participants and evaluation of predictors of successful monoclonal antibody therapy are still needed.

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). 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). 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. 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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Trigeminal autonomic cephalalgias (TACs) are rare but are the most intense primary headaches that severely limit patients’ ability to work and be socially active. This article reviews the modern classification of TACs, based on the International Classification of Headache Disorders-3, and the key differences between TAC types, as well as the pathophysiological mechanisms – the role of the trigeminovascular system, autonomic nervous system, hypothalamus and vagus nerve – and their relation to circadian rhythms. The sleep disturbances that can occur in patients with TACs, exacerbating the course of the disease, and the role of melatonin, hypothalamus and suprachiasmatic nucleus in these conditions are also discussed. In addition, current therapies for cluster headache are described, which include acute therapy and prophylactic therapy, with recommendations regarding the timing of prophylactic therapy discontinuation. The review also includes the available data on melatonin as well as new therapies such as CGRP monoclonal antibodies and neuromodulation, which includes the two most promising techniques: non-invasive vagus nerve stimulation and sphenopalatine ganglion microstimulation. Furthermore, the authors present the clinical case of a patient with chronic cluster headache, which was significantly reduced in frequency and intensity when melatonin was added to the therapy.

Abstract 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.

ABSTRACT: 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Liver cancer has become the second most deadly malignant disease, with no efficient targeted or immune therapeutic agents available yet. While dissecting the roles of cytoplasmic signaling molecules in hepatocarcinogenesis using an inducible mouse gene targeting system, Mx1-cre, we identified a potent liver tumor-inhibitory effect of synthetic double-stranded RNA (dsRNA), polyinosinic-polycytidylic acid (pIC), an inducer of the Mx1-cre system. Injection of pIC at the pre-cancer stage robustly suppressed liver tumorigenesis either induced by chemical carcinogens or by Pten loss and associated hepatosteatosis. The immunostimulatory dsRNA inhibited liver cancer initiation, apparently by boosting multiple anti-tumor activities of innate immunity, including induction of immunoregulatory cytokines, activation of NK cells and dendritic cells, and reprogramming of macrophage polarization. This study paves the way for the development of preventive and early interfering strategies for liver cancer to reduce the rapidly increasing incidences of liver cancer in an ever-growing population with chronic liver disorders.

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.

The drug's activity at the target tissue could help to define the minimal effective dose to promote cancer preventive therapy. Here we present exemestane and sex hormone concentrations within breast tissue from a pre-surgical study of alternative exemestane schedules. Postmenopausal women candidate for breast surgery for estrogen receptor-positive breast cancer were randomized to exemestane 25 mg once daily (QD), 25 mg three times/week (TIW), or 25 mg per/week (QW) for 4-6 weeks before surgery. Drug and sex hormones were analyzed from homogenized frozen tissue using a QTRAP 6500+ LC-MS/MS System. Tissue drug concentrations were detectable only in the QD arm with higher concentrations in non-malignant tissue. Estradiol was nearly suppressed in all groups in the non-malignant tissue (QD vs TIW p = .364 and QD vs QW p = .693). In contrast, a dose-response trend was observed in cancer tissue. Based on estradiol suppression in non-malignant tissue, lower exemestane schedules should be explored for breast cancer preventive therapy., (© The Author(s) 2024. Published by Oxford University Press.)