Acceptability of Community-Based Tuberculosis Preventive Treatment for People Living with HIV in Zimbabwe

As Zimbabwe expands tuberculosis preventive treatment (TPT) for people living with HIV (PLHIV), the Ministry of Health and Child Care is considering making TPT more accessible to PLHIV via less-intensive differentiated service delivery models such as Community ART Refill Groups (CARGs). We designed a study to assess the feasibility and acceptability of integrating TPT into CARGs among key stakeholders, including CARG members, in Zimbabwe. We conducted 45 key informant interviews (KII) with policy makers, implementers, and CARG leaders; 16 focus group discussions (FGD) with 136 PLHIV in CARGs; and structured observations of 8 CARG meetings. KII and FGD were conducted in English and Shona. CARG observations were conducted using a structured checklist and time-motion data capture. Ninety six percent of participants supported TPT integration into CARGs and preferred multi-month TPT dispensing aligned with ART dispensing schedules. Participants noted that the existing CARG support systems could be used for TB symptom screening and TPT adherence monitoring/support. Other perceived advantages included convenience for PLHIV and decreased health facility provider workloads. Participants expressed concerns about possible medication stockouts and limited knowledge about TPT among CARG leaders but were confident that CARGs could effectively provide community-based TPT education, adherence monitoring/support, and TB symptom screening provided that CARG leaders received appropriate training and supervision. These results are consistent with findings from pilot projects in other African countries that are scaling up both differentiated service delivery for HIV and TPT and suggest that designing contextually appropriate approaches to integrating TPT into less-intensive HIV treatment models is an effective way to reach people who are established on ART but who may have missed out on access to TPT.

Possibilities of colecalciferol therapy for tension type headache combined with hypovitaminosis D

Introduction. Modern studies indicate the therapeutic effect of vitamin D (VD) in chronic pain conditions, but there is no data on the use of VD in chronic tension type headache (CTTH) treatment.Objective: comparative evaluation of the effectiveness of various options for preventive treatment of CTTH: the use of colecalciferol, standard therapy of the disease and a combination of these methods.Materials and methods. 125 women with CTTH and hypovitaminosis D were treated in the study. The frequency, duration and intensity of headache (HF, HD and HI, respectively), HIT index, frequency of analgesics taking, pericranial muscle dysfunction were evaluated. The VD level was measured by the concentration of 25-hydroxyvitamin D [25(OH)D]. The patients received differentiated therapy for 16 weeks: group 1 – colecalciferol, group 2 – amitriptyline, group 3 – a combination of these medicines. Results. In group 1, HF, HD, HIT-index and the frequency of analgesics taking decreased, all p ≤ 0.001. In groups 2 and 3, the values of all CTTH-parameters decreased, all p < 0.05. HF, HIT-index and the frequency of analgesics taking in group 3 decreased more than in group 2, all p >< 0.017. In women who had VD deficiency before treatment, the decrease in HF from the initial one was 36% in group 1, 55% in group 2, and 74% in group 3. In patients who had VD deficiency before treatment, the effectiveness of therapy in group 3 was higher than in group 2: 74% vs. 55%, respectively, p >< 0.001.Conclusions. Treatment of hypovitaminosis D in women with CTTH is accompanied by a decrease in HF, the effect of headache on the quality of life of patients and the frequency of taking analgesics. In CTTH and VD deficiency normalization of 25(OH)D level contributes to higher efficiency of standard therapy.

Real-World Evidence for the Safety and Efficacy of CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA Treatment for Migraine Prevention in Adult Patients With Chronic Migraine

Background: OnabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) target different migraine pathways, therefore, combination treatment may provide additional effectiveness for the preventive treatment of chronic migraine (CM) than either treatment alone. The objective of this study was to collect real-world data to improve the understanding of the safety, tolerability, and effectiveness of adding a CGRP mAb to onabotulinumtoxinA treatment for the preventive treatment of CM.Methods: This was a retrospective, longitudinal study conducted using data extracted from a single clinical site's electronic medical records (EMR) of adult patients (≥18 years) with CM treated with ≥2 consecutive cycles of onabotulinumtoxinA before ≥1 month of continuous onabotulinumtoxinA and CGRP mAb (erenumab, fremanezumab, or galcanezumab) combination treatment. Safety was evaluated by the rate of adverse events (AE) and serious adverse events (SAE). The proportion of patients who discontinued either onabotulinumtoxinA, a CGRP mAb, or combination treatment, and the reason for discontinuation, if available, was collected. The effectiveness of combination preventive treatment was assessed by the reduction in monthly headache days (MHD). Outcome data were extracted from EMR at the first CGRP mAb prescription (index) and up to four assessments at ~3, 6, 9, and 12 months post-index. The final analyses were based on measures consistently reported in the EMR.Results: EMR were collected for 192 patients, of which 148 met eligibility criteria and were included for analysis. Erenumab was prescribed to 56.7% of patients, fremanezumab to 42.6%, and galcanezumab to 0.7%. Mean (standard deviation [SD]) MHD were 20.4 (6.6) prior to onabotulinumtoxinA treatment and 14.0 (6.9) prior to the addition of a CGRP mAb (baseline). After real-world addition of a CGRP mAb, there were significant reductions in MHD at the first assessment (~3 months) (mean −2.6 days/month, 95% CI −3.7, −1.4) and at all subsequent visits. After ~12 months of continuous combination treatment, MHD were reduced by 4.6 days/month (95% CI −6.7, −2.5) and 34.9% of patients achieved ≥50% MHD reduction from index. AEs were reported by 18 patients (12.2%), with the most common being constipation (n = 8, 5.4% [onabotulinumtoxinA plus erenumab only]) and injection site reactions (n = 5, 3.4%). No SAEs were reported. Overall, 90 patients (60.8%) discontinued one or both treatments. The most common reason for discontinuing either treatment was lack of insurance coverage (40%); few (~14%) patients discontinued a CGRP mAb and none discontinued onabotulinumtoxinA due to safety/tolerability.Conclusion: In this real-world study, onabotulinumtoxinA was effective at reducing MHD and the addition of a CGRP mAb was safe, well-tolerated and associated with incremental and clinically meaningful reductions in MHD for those who stayed on the combination treatment. No new safety signals were identified. Of those who discontinued, the majority reported lack of insurance coverage as a reason. Prospective real-world and controlled trials are needed to further evaluate the safety and potential benefits of this combination treatment paradigm for people with CM.

Conception and Clinical Efficacy of an Osmotic, Polymeric, Stable Nasal Filmogen Barrier for Preventive Treatment of Allergen and Pollution Induced Rhinitis and Respiratory Symptoms

Background: Pollution induced allergic rhinitis and respiratory symptoms is becoming a major health problem in the world for which still there is no safe and preventive treatment. Objectives: Conceive and evaluate the allergen preventive properties and clinical efficacy of an osmotic, polymeric, stable filmogen spray, called PCNS. Materials and Methods: Amb A 1 (ragweed), Der P 1 and 2 (dust mite), Bet v 1 (birch), Alt a 1 (Alternaria, fungus), and Fel d 1 (cat dander) allergens were exposed at a concentration of 5µg/ml (20 µl per tube) on the polymeric test product film (120 and 240µl layer) and the allergens crossing the barrier were quantified in the agar gel beneath the film. 0.40% HPMC and PBS solutions, tested identically, served as controls. Clinical efficacy of PCNS nasal spray was evaluated in patients suffering from allergic rhinitis and/or respiratory symptoms (29 in test product v/s 15 in saline controls) for 22 days. Nasal, ocular, respiratory symptoms and Rhino conjunctivitis Quality of Life Questionnaire (RQLQ) were measured. Statistical analyses: The normality of the populations was determined by the Shapiro-Wilk test, then statistical analysis was performed by two-tailed Student’s test for comparisons between two groups and the two-way ANOVA followed by the post hoc Bonferroni’s test for comparisons of multiple groups. p<0.05 was considered statistically significant. The analyses were performed with the software GraphPad Prism (version 8.4.2, La Jolla, USA). NS indicates not significant. Results: PCNS polymeric spray blocked the diffusion of all the allergens while 0.40% HPMC was able to prevent diffusion of only Alt a 1 and Fel d 1 allergens. Mean reflective total nasal symptom scores (rTNSS), reflective total ocular symptom score (rTOSS), and respiratory symptoms including effect on wheezing, cough, dyspnea, and chest tightness were moderately improved in the control saline group, but the improvements were nearly twice better in the PCNS group. RQLQ was improved by 23% in saline spray v/s 46% PCNS group. 4/15 patients in saline group v/s 1/29 in PCNS group required rescue medication during the study. PCNS was highly effective in reducing allergen and pollution induced respiratory symptoms. Conclusion: a polymeric, osmotic, and stable nasal barrier against pollutants and allergens represents an innovative approach against pollution induced respiratory symptoms.

Risk Assessment and Preventive Treatment for Peritoneal Recurrence Following Radical Resection for Gastric Cancer

As the most common recurrence pattern after radical gastric cancer resection, peritoneal recurrence is a major cause of mortality, which affects the prognosis of patients to a very large extent. Peritoneal status and risk of peritoneal recurrence can be evaluated by peritoneal lavage cytology, photodynamic diagnosis, imaging examination, and pathologic analysis. Presently, there is no standard approach for preventing peritoneal recurrence after radical surgery; furthermore, controversies exist regarding the effects of some preventive methods. Among the preventive methods, there are high expectations about the potential of preoperative therapy, surgical skill improvement, hyperthermic intraperitoneal chemotherapy, and postoperative treatment to reduce the incidence of peritoneal recurrence after radical gastrectomy. This study aimed to analyze the results of previous studies on the risk assessment and preventive methods of peritoneal recurrence after radical gastrectomy in recent years. We hope to provide references for better approach to clinical diagnosis and treatment strategies for peritoneal recurrence after radical gastrectomy.

Predictor Naïve Temporal Baseline Hazard of Recurrent Ischemic Stroke

There are established correlation between risk factors and the recurrence of ischemic stroke (IS), however does the hazard of recurrent IS change although without the influence of established risk factors? This study aimed to quantify the hazard of recurrent IS at different time points after the index IS. This was a population cohort study extracted data of 7697 patients with a history of first IS attack registered with National Neurology Registry of Malaysia. A repeated time to recurrent IS model was developed using NONMEM version 7.5. Three baseline hazard models were fitted into the data. The best model was selected using maximum likelihood estimation, clinical plausibility and visual predictive checks. Three hundred and thirty-three (4.32%) patients developed at least one recurrent IS within the maximum 7.37 years follow-up. In the absence of significant risk factors, the hazard of recurrent IS was predicted to be 0.71 within the first month after the index IS and reduced to 0.022 between the first to third months after the index attack. The hazard of IS recurrence accelerated with the presence of typical risk factors such as hyperlipidaemia (HR, 2.64 [2.10-3.33]), hypertension (HR, 1.97 [1.43-2.72], and ischemic heart disease (HR, 2.21 [1.69-2.87]). In conclusion, the absence of significant risk factors, predicted hazard of recurrent IS was prominent in the first month after the index IS and was non-zero even three months after the index IS or later. Optimal secondary preventive treatment should incorporate the ‘nature risk’ IS recurrence.

Differentials in prevalence and correlates on uptake of tetanus toxoid and intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy: A community-based cross-sectional study in The Gambia

Objectives: The study examined the differentials in prevalence and correlates on the uptake of tetanus toxoid and intermittent preventive treatment of malaria among pregnant women in The Gambia. Methods: The 2018 data from The Gambia Multiple Indicators Cluster Survey were analyzed. Data from 6143 women of reproductive age who have given birth were extracted for the analysis. Percentages and Chi-square tests were used. In addition, a multivariable logistic regression model was used to calculate the adjusted odds ratios (with a corresponding 95% confidence interval). The level of significance was set at p < 0.05. Results: The prevalence of tetanus toxoid uptake among women in The Gambia was 88.2%, while that of the adequate tetanus toxoid doses was 34.8%. The prevalence of intermittent preventive treatment with sulfadoxine-pyrimethamine uptake among maternal women in The Gambia was 98.6%, while that of the adequate intermittent preventive treatment with sulfadoxine-pyrimethamine doses taken was 34.3%. The identified statistically significant covariates of tetanus toxoid immunization and intermittent preventive treatment with sulfadoxine-pyrimethamine uptake includes women’s age, local government areas, parity, use of radio, use of newspaper, and antenatal care visits. Conclusion: The current utilization rate for adequate intermittent preventive treatment with sulfadoxine-pyrimethamine and tetanus toxoid immunization during pregnancy in The Gambia is very low and even below universal levels. The country needs to strengthen more and effective mass media advocacy programs that would target both rural and urban populace, and motivate maternal women to ensure adequate vaccination against malaria and tetanus.

Migraine

Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of chronic migraine.

Blackberry phenolic and volatile extracts inhibit cytokine secretion in LPS-inflamed RAW264.7 cells

The anti-inflammatory activity of blackberries has been attributed to phenolic compounds, especially anthocyanins. The present study hypothesized that volatiles could contribute to anti-inflammatory activity as well. The anti-inflammatory properties of three blackberry genotypes varying in total volatile and phenolic contents were assessed by measuring concentrations of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor -α (TNF-α) within LPS-inflamed RAW264.7 murine macrophage cells after a preventive treatment of either a phenolic or a volatile extract. Extracts from blackberry genotypes A2528T, A2587T and Natchez had total phenolic contents of 4315, 3369 and 3680 µg/mL, respectively, and total volatile contents of 283, 852 and 444 ng/mL, respectively. Phenolic and volatile extracts of all genotypes significantly lowered the secretion of NO, IL-6 and TNF-α in ranges varying between 20-42%, 34-60% and 28-73% inhibition, respectively. Volatile extracts exhibited greater anti-inflammatory properties than phenolic extracts, despite being present at much lower concentrations in the berries. Further research is needed to assess bioavailability and anti-inflammatory effect of blackberry volatiles in vivo.