preventive therapy
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The objective: to evaluate effectiveness of mass screening for tuberculosis infection in children aged 1 to 7 years in different periods – before and after the use of tuberculosis recombinant allergen skin test (TRA) in primary health care as an additional diagnostic method.Subjects and Methods. The study was designed as continuous observational prospective-retrospective study. Two different periods were assessed: the first one was 2014-2016 when screening for tuberculosis infection was performed in all children from 1 to 17 years (inclusive) using Mantoux test with 2 TU PPD-L in pediatric primary health care, and then children suspected to have a positive reaction were referred to TB dispensary where they were examined with a skin test with TRA if necessary. The second period was from 2018 to 2020 when children of 1-7 years old were given Mantoux test and if tuberculosis infection was suspected, a skin test with TRA was done both in primary health care network and TB units. In the first 3 years, 1,864,137 children were examined and in the second 3 years, 2,078,800 children from 1 to 7 years old were examined.Results. Among children of 1-7 years old who were screened by two stages (initial Mantoux test, and then in those who had a positive reaction, the TRA test was used), only 10-12% of those referred to a phthisiologist were subject to dispensary follow-up. Thus, with the implementation of the new edict on screening for tuberculosis infection in children with two tests, this proportion has not changed compared to previous years, when screening was carried out only with one Mantoux test. The reason why almost 90% of the children who were referred to TB Dispensary were not subject to dispensary follow-up is the following: children who have had previous conversion of tuberculin tests, along with everyone else are again screened with Mantoux test despite being previously followed up by TB dispensary due to the primary infection.Recommendations:Currently, there is no division of Group VI into Subgroups A, B, C in the dispensary follow up grouping. Why should conversion of Mantoux test reaction from negative into positive not be considered an infection, and the increase in the reaction must be at least 6 mm.Since Order No. 124n of the Russian Ministry of Health allows testing with TRA in the primary health care in case of suspected infection, it is advisable to refer those who have already had this test to a phthisiologist.A child with conversion of Mantoux test should not be re-screened with Mantoux test but the TRA test should be used. If a positive reaction to the TRA test occurs for the first time, it should be considered as conversion of this test, and in this case the child should be examined by computed tomography (CT), and preventive therapy should be prescribed. If in subsequent years the TRA reaction increases by at least 6 mm after previous preventive therapy, the child should be re-referred for CT to rule out the development of active tuberculosis.

Introduction. Patients with cardiovascular diseases have endothelial dysfunction and a higher risk of severe course of COVID-19, and thrombotic complications. Associated endotheliitis caused by virus penetration and cytokines storm leads to the release of tissue factor, the formation of excess thrombin and fibrin and thrombosis. The aim. To identify the potential of high-frequency ultrasound Dopplerography (HFUDG) for the assessment of microcirculatory disorders in post-COVID-19 patients with cardiovascular profile and to assess the microcirculatory bed condition before and after treatment with sulodexide. Materials and methods. 49 patients recovered from moderate-severe COVID-19 one month ago, aged 20–80, were examined. 24 patients, received prophylaxis with POACs for 1 month, formed group I, group II – 25 patients without prophylaxis. The nail bed of the upper limb 1st finger was examined using HFUDG and a 25 MHz sensor. Shape and spectrum of curves taken from dopplerograms were analyzed. The control examination was performed 4 weeks after therapy. Results. In patients after COVID19, depletion of spectral characteristics was revealed in comparison with dopplerograms of healthy individuals. The predominantly red part of the spectrum corresponding to the fastest particles was recorded. Slow-moving particles corresponding to the lighter part of the spectrum were nearly non-existent. In patients administrated POAC prophylaxis, amplitude indices were higher. Significant increase in D-dimer, antithrombin III, and soluble fibrin monomer complexes (SFMC) was also detected. The remaining parameters of the coagulogram were within the norm before and after treatment. After a course of sulodexide therapy, the spectral characteristics and coagulogram parameters returned to normal. Conclusion. HFUDG allows to detect stasis of capillary blood flow, the appearance of shunt blood flow corresponding to microtrombosis. Microcirculation indicators in post-COVID-19 patients improved after a course of preventive therapy with sulodexide.

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.

In diabetic retinopathy (DR), high blood glucose drives chronic oxidative stress and inflammation that trigger alterations of the neurovascular balance finally resulting in vascular abnormalities and retinal cell death, which converge towards altered electroretinogram (ERG). In the last years, a growing body of preclinical evidence has suggested that nutrients with anti-inflammatory/antioxidant properties can be able to hamper DR progression since its very early stages. In the present study, we used a streptozotocin-induced rat model of DR, which mimics most aspects of the early stages of human DR, to test the preventive efficacy of a novel compound containing cyanidin-3-glucoside (C3G), verbascoside and zinc as nutrients with antioxidant and anti-inflammatory properties. Western blot, immunofluorescence and electroretinographic analyses demonstrated a dose-dependent inhibition of oxidative stress- and inflammation-related mechanisms, with a significant counterpart in preventing molecular mechanisms leading to DR-associated vasculopathy and its related retinal damage. Preventive efficacy of the compound on dysfunctional a- and b-waves was also demonstrated by electroretinography. The present demonstration that natural compounds, possibly as a consequence of vascular rescue following ameliorated oxidative stress and inflammation, may prevent the apoptotic cascade leading to ERG dysfunction, adds further relevance to the potential application of antioxidants as a preventive therapy to counteract DR progression.

Introduction. Tension-type headache (TTH) represents a widespread and recurrent disease in adults, children, and adolescents, adversely affecting the quality of life, learning achievements, and social functioning. In recent publications, a high incidence of comorbid disorders in patients with TTH is discussed, in particular sleep disorders. The aim of the study was to assess the nature and prevalence of sleep disorders in children and adolescents with frequent episodic TTH and chronic TTH. Materials and methods. One hundred fifty patients aged from 8 years to 16 years 11 months with TTH were examined. Of them, 91 (49 boys, 42 girls) had frequent episodic TTH, 59 (26 boys, 33 girls) had chronic TTH. There was used Sleep Disturbance Scale for Children including 26 questions for parents. Results. The present study confirms the high incidence of sleep disorders among TTH children and adolescents. TTH was diagnosed in 129 (86.0%) out of 150 patients. The most frequently diagnosed varying degrees of severity (clinically relevant and borderline, when assessing sleep disorders in children) were insomnia (disorders of initiating and maintaining sleep) - in 65.3% of patients (including 60.4% with frequent episodic TTH and 72.9% with chronic TTH), excessive somnolence - in 74.7% (67.1% and 86.4%), sleep breathing disorders - in 26.7% (23.1% and 32.2%), disorders of arousal/nightmares - in 46.0% (42.9% and 50.8%), sleep-wake transition disorders - in 65.3% (67.1% and 62.7%), sleep hyperhidrosis - in 31.3% (26.4% and 39.0%). Thus, all sleep disorders (except for sleep-wake transition disorders) were significantly more common among the patients with chronic TTH. At the same time, in the subgroup of patients with TTH and any sleep disorders, significantly more prominent indicators of the frequency, the intensity of TTH and its negative impact on the daily activity were revealed, compared to patients with TTH lacking sleep disorders. Conclusion. The results of the assessment of children and adolescents with TTH show that when planning preventive therapy for TTH and evaluating its results, not only main clinical characteristics of TTH should be taken into account, but also the manifestations and severity of comorbid disorders, including sleep disorders observed in most patients with TTH. The revealed prevalence of various sleep disorders in the subgroup of patients with chronic TTH confirms that sleep disorders and anxiety disorders refer to significant risk factors for the transition of TTH to a chronic form, and such patients need more active multimodal treatment.

TB preventive treatment (TPT) is recommended for high-risk and hard-to-reach populations such as incarcerated people living with HIV (PLHIV). To assess implementation of TPT delivery in correctional settings, we conducted an exploratory analysis of data from a multisite cohort study in South Africa and Zambia. From 975 participants, 648 were screened for TB, and 409 initiated TPT mostly within a month after initiation of antiretroviral therapy (190/409, 46.5%). We observed a median gap of one month (IQR 0.6–4.7) in TPT delivery to incarcerated PLHIV. Future research should examine standardised quality improvement tools and new strategies such as short-course regimens to improve TPT initiation in this population.

Introduction In resource-limited settings, the mortality rate among tuberculosis and human Immunodeficiency virus co-infected children is higher. However, there is no adequate evidence in Ethiopia in general and in the study area in particular. Hence, this study aims to estimate lifetime survival and predictors of mortality among TB with HIV co-infected children after test and treat strategies launched in Northwest Ethiopia Hospitals, 2021. Methods Institution-based historical follow-up study was conducted in Northwest Ethiopia Hospitals among 227 Tuberculosis and Human Immunodeficiency Virus co-infected children from March 1, 2014, to January 12, 2021. The data were entered into Epi info-7 and then exported to STATA version 14 for analysis. The log-rank test was used to estimate the curve difference of the predictor variables. Bivariable cox-proportional hazard models were employed for each predictor variable. Additionally, those variables having a p-value < 0.25 in bivariate analysis were fitted into a multivariable cox-proportional hazards model. P-value < 0.05 was used to declare significance associated with the dependent variable. Results From a total of 227 TB and HIV co-infected children, 39 died during the follow-up period. The overall mortality rate was 3.7 (95% CI (confidence interval): 2.9–4.7) per 100 person-years with a total of 1063.2-year observations. Cotrimoxazole preventive therapy (CPT) non-users [Adjusted Hazarded Ratio (AHR) = 3.8 (95% CI: 1.64–8.86)], presence of treatment failure [AHR = 3.0 (95% CI: 1.14–78.17)], and Cluster of differentiation 4(CD4) count below threshold [AHR = 2.7 (95% CI: 1.21–6.45)] were significant predictors of mortality. Conclusion In this study, the mortality rate among TB and HIV co-infected children was found to be very high. The risk of mortality among TB and HIV co-infected children was associated with treatment failure, CD4 count below the threshold, and cotrimoxazole preventive therapy non-users. Further research should conduct to assess and improve the quality of ART service in Northwest Ethiopia Hospitals.

BACKGROUND and OBJECTIVE: Isoniazid preventive therapy (IPT) is known to reduce the risk of developing active TB in about 59% in children aged 15 years. We assessed adherence, completion and adverse events among children who were household contacts of a newly diagnosed adult with smear-positive TB in Bamako, Mali.METHODS: Children aged <15 years living in the same house with an adult smear-positive index case were enrolled in the study in the Bamako Region after consent was obtained from the parent or legal guardian. Adherence was assessed based on the number of tablets consumed during 6 months.RESULTS: A total of 260 children aged <15 years were identified as household contacts of 207 adult patients with smear-positive TB during the study period. Among all child contacts, 130/260 (50.0%) were aged 0–4 years and were eligible for IPT; 128/130 (98.5%) were started on IPT and 83/128 (64.8%) completed with good adherence at the end of the 6 months, and without any significant adverse events.CONCLUSION: We successfully implemented IPT with good acceptance, but low completion rate. The Mali National TB Program and partners should expand this strategy to reach more children in Bamako and the whole country and create greater awareness in the population.

In Canada, preventive therapy for latent tuberculosis infection (LTBI) has required multiple doses of medication over an extended period of time. Such regimens are associated with poor adherence and completion rates. A shortened treatment regimen of once weekly isoniazid plus rifapentine for 3 months (3HP), is now available, and holds promise in populations facing challenges to treatment adherence. Although many factors impact treatment adherence, a knowledge gap exists in describing these factors in the context of this regimen. We present findings from a qualitative descriptive study, involving semi-structured interviews with unstably housed or homeless individuals in Edmonton and Fort McMurray, Alberta, Canada who were offered directly-observed preventive therapy (DOPT) with 3HP, and their health care providers. Latent content analysis revealed incomplete understandings of LTBI and about the need for preventive therapy. Clients’ motivation to be healthy, alongside education, health care outreach, relationships developed in the context of DOPT, ease of treatment regimen, incentives, and collaboration were all described as supporting treatment completion. Competing priorities, difficulty in reaching clients, undesirable aspects of the regimen and difficulties obtaining and initiating 3HP were identified as barriers. Perceptions of stigma related to LTBI and TB were described by clients in addition to feelings of shame related to their diagnosis. Our study provides insight into LTBI and indicates that multiple interacting psychosocial factors influence preventive therapy access, uptake, and adherence. Findings from this study of both client and provider perspectives can be used to inform and address inequities among individuals experiencing homelessness, and ultimately contribute to a diminished reservoir of LTBI.