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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.

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)

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.

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.

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 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.

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.

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.

In Karachi, Pakistan, a South Asian megacity with a high prevalence of tuberculosis (TB) and low HIV prevalence, we assessed the effectiveness of fluoroquinolone-based preventive therapy for drug-resistant (DR) TB exposure. During February 2016–March 2017, high-risk household contacts of DR TB patients began a 6-month course of preventive therapy with a fluoroquinolone-based, 2-drug regimen. We assessed effectiveness in this cohort by comparing the rate and risk for TB disease over 2 years to the rates and risks reported in the literature. Of 172 participants, TB occurred in 2 persons over 336 person-years of observation. TB disease incidence rate observed in the cohort was 6.0/1,000 person-years. The incidence rate ratio ranged from 0.29 (95% CI 0.04–1.3) to 0.50 (95% CI 0.06–2.8), with a pooled estimate of 0.35 (95% CI 0.14–0.87). Overall, fluoroquinolone-based preventive therapy for DR TB exposure reduced risk for TB disease by 65%.

AbstractMigraine 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.

Introduction: The increasing tuberculosis cases in children showed management of Tuberculosis itself. There was a finding of TB case in children according to WHO TB report 2019 that not all childrens being well diagnosed, treated or reported each year. This systematic review aims to describes implementation of TB prevention often missed in children with adult TB household contacts. Method: This study uses based on PICO, which contains Participants are family who living household with adult TB, Interventions are CI followed by PT, no comparison, Outcomes are improving the implementation of CI and PT. Searching for article is using the Scopus, PubMed, and Science Direct and found 15 articles in final which limited to the last 3 years (2017-2020). Keywords used in searching are” Tuberculosis”, “Transmission”, and “Preventive Therapy”. The population included were respondents identified as family having child aged ≤ 15 years with TB Household Contacts. The study design varied in rigorousness form of quantitative and mixed studies. Result: Household Contact (HHC) contribute to TB cases in children. Conclusion: Contact Investigation (CI) and Preventive Therapy (PT) could be succesfull strategies to prevent TB transmission to children provided not only by Health Care Workers (HCWs) but also public concerned to community-based approach in order to encouraged family members of TB affected

Abstract Background The prevention of tuberculosis (TB) is key for accelerating current, slow declines in TB burden. The 2018 World Health Organization (WHO) guidelines on eligibility for preventive therapy to treat latent TB infection (LTBI) include people living with human immunodeficiency virus (PLHIV), household contacts of TB patients including children, and those with clinical conditions including silicosis, dialysis, transplantation, etc. and other country-specific groups. We aimed to estimate the potential impact of full implementation of these guidelines in the WHO South-East Asian (SEA) Region, which bears the largest burden of TB and LTBI amongst the WHO regions. Methods We developed mathematical models of TB transmission dynamics, calibrated individually to each of the 11 countries in the region. We modelled preventive therapy in the absence of other TB interventions. As an alternative comparator, reflecting ongoing developments in TB control in the region, we also simulated improvements in the treatment cascade for active TB, including private sector engagement and intensified case-finding. Relative to both scenarios, for each country in the region, we projected TB cases and deaths averted between 2020 and 2030, by full uptake of preventive therapy, defined as comprehensive coverage amongst eligible populations as per WHO guidelines, and assuming outcomes consistent with clinical trials. We also performed sensitivity analysis to illustrate impact under less-than-optimal conditions. Results At the regional level, full uptake of preventive therapy amongst identified risk groups would reduce annual incidence rates in 2030 by 8.30% (95% CrI 6.48–10.83) relative to 2015, in the absence of any additional interventions. If implemented against a backdrop of improved TB treatment cascades, preventive therapy would achieve an incremental 6.93 percentage points (95% CrI 5.81–8.51) of reduction in annual incidence rates, compared to 2015. At the regional level, the numbers of individuals with latent TB infection that need to be treated to avert 1 TB case is 64 (95% CrI 55–74). Sensitivity analysis illustrates that results for impact are roughly proportional to ‘effective coverage’ (the product of actual coverage and effectiveness of the regimen). Conclusions Full implementation of WHO guidelines is important for ending TB in the SEA Region. Although future strategies will need to be expanded to the population level, to achieve large declines in TB incidence, the uptake of current tools can offer a valuable step in this direction.

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.

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 19th 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.

Abstract Background Evidence supports the use of non-invasive vagus nerve stimulation (nVNS; gammaCore®) as a promising therapeutic option for patients with cluster headache (CH). We conducted this audit of real-world data from patients with CH, the majority of whom were treatment refractory, to explore early UK clinical experience with nVNS used acutely, preventively, or both. Methods We retrospectively analysed data from 30 patients with CH (29 chronic, 1 episodic) who submitted individual funding requests for nVNS to the National Health Service. All patients had responded to adjunctive nVNS therapy during an evaluation period (typical duration, 3–6 months). Data collected from patient interviews, treatment diaries, and physician notes were summarised with descriptive statistics. Paired t tests were used to examine statistical significance. Results The mean (SD) CH attack frequency decreased from 26.6 (17.1) attacks/wk. before initiation of nVNS therapy to 9.5 (11.0) attacks/wk. (P

Background: Acute pancreatitis (AP) refers to afflicted inflammation of pancreas with unfavorable adverse effects and developed multiple organ failures. Unfortunately, there is not a certain therapeutic method for this disease. Oxidative stress has a serious role in the pathogenesis of AP. Thus, decreasing of oxidative stress may prevent induction and progression of AP. Punica granatum L. has been extensively used in traditional medicine and possesses various active biological elements. Due to antioxidant and anti-inflammatory properties of pomegranate, it could be considered as a good candidate alternative medicine with beneficial effects on AP. In this study, we decided to study the protective effect of three fractions of pomegranate seeds on cerulein-induced AP. Methods: AP was induced in male Syrian mice by five intraperitoneal (i.p.) injection of cerulein (50 μg/kg) with 1 h intervals. Treatments with pomegranate freeze-dried powder (PFDP) and hydroalcoholic pomegranate seeds extract (PSE) at doses of 125, 250, 500 mg/kg (i.p.) were started 30 min before pancreatitis induction. Pomegranate seed oil fraction (PSOF) was orally administered (50, 100, 200 μL/kg) and continued for 10 days. Pancreatic tissue was evaluated for histopathological parameters and pancreatic myeloperoxidase (MPO) activity as well as lipase and amylase levels were measured in plasma. Results: The higher doses of three fractions (250 and 500 mg/kg for PFDP and PSE and doses of 100, 200 μL/kg for PSOF) significantly reduced amylase and lipase activity in serum (at least P < 0.01), pancreatic MPO activity (P < 0.001), edema, leukocyte infiltration and vacuolization in comparison to the control group (P < 0.05). Conclusions: These results propose that pomegranate seeds fractions can prevent and/or treat the AP.