Impact of age and sex on the efficacy of fremanezumab in patients with difficult-to-treat migraine: results of the randomized, placebo-controlled, phase 3b FOCUS study

Background Migraine prevalence is age and sex dependent, predominating in women in early and middle adulthood; however, migraine also represents a substantial burden for men and adults of all ages. Thus, understanding this burden and the efficacy of migraine preventive medications in both sexes and across age groups is critical. The randomized, placebo-controlled, double-blind, phase 3b FOCUS study demonstrated the safety and efficacy of fremanezumab, a fully humanized monoclonal antibody (IgG2∆a) that selectively targets calcitonin gene-related peptide as a migraine preventive treatment for individuals with migraine and prior inadequate response to 2 to 4 migraine preventive medication classes. Here, we assessed the efficacy of fremanezumab in participants from FOCUS subgrouped by age (18–45 years and > 45 years) and sex. Methods In the FOCUS study, eligible participants were randomized (1:1:1) to 12 weeks of double-blind treatment with quarterly fremanezumab, monthly fremanezumab, or matched monthly placebo. In this post hoc analysis, we evaluated changes from baseline in monthly migraine days (primary endpoint of FOCUS) and other secondary and exploratory efficacy outcomes in prespecified age (18–45 and > 45 years) and sex subgroups. Results The modified intention-to-treat population (received ≥ 1 dose of study drug and had ≥ 10 days of postbaseline efficacy assessments for the primary endpoint) totaled 837 participants (18–45 years, n = 373; > 45 years, n = 464; male, n = 138; female, n = 699). Consistent reductions in monthly average number of migraine days during 12 weeks were observed, regardless of age (18–45 years: quarterly fremanezumab, − 4.1 days; monthly fremanezumab, − 4.7 days; placebo, − 0.9 days; P < 0.001; > 45 years: quarterly fremanezumab, − 3.6 days; monthly fremanezumab, − 3.7 days; placebo, − 0.3 days; P < 0.001) and sex (male: quarterly fremanezumab, − 4.1 days; monthly fremanezumab, − 4.6 days; placebo, − 0.3 days; P < 0.001; female: quarterly fremanezumab, − 3.6 days; monthly fremanezumab, − 3.9 days; placebo, − 0.6 days; P < 0.001). Fremanezumab also reduced monthly headache days of at least moderate severity, monthly days of acute medication use, and improved Migraine Disability Assessment scores across subgroups. Conclusions These results demonstrate the efficacy of fremanezumab in patients with difficult-to-treat migraine for reducing migraine and headache days, acute medication use, and disability, regardless of age or sex. Trial registration ClinicalTrials.gov Identifier NCT03308968 (FOCUS), registered October 13, 2017.

Dealing with being prescribed cardiovascular preventive medication: a narrative analysis of qualitative interviews with patients with recent acute coronary heart disease in Sweden

ObjectiveTo explore how patients with experience of acute coronary heart disease make sense of, and deal with, the fact of being prescribed cardiovascular preventive medication.DesignQualitative interview study.SettingSwedish primary care.ParticipantsTwenty-one participants with experience of being prescribed cardiovascular preventive medication, recruited from a randomised controlled study of problem-based learning for self-care for coronary heart disease.MethodsThe participants were interviewed individually 6–12 months after their hospitalisation for acute coronary disease. A narrative analysis was conducted of their accounts of being prescribed cardiovascular preventive medication.ResultsFour themes shape the patients’ experiences: ‘A matter of living’ concerns an awareness of the will to live linked to being prescribed cardiovascular preventive medication regarded in the light of the recent hospitalisation. In ‘Reconciliation of conflicting self-images’, patients dealt with being prescribed preventive medication through work to restore an identity of someone responsible in spite of viewing the taking of medication as questionable. The status of feeling healthy, while being someone in need of medication, also constituted conflicting self-images. Following this, taking medication was framed as necessary, not as an active choice. ‘Being in the hands of expertise’ is about the seeking of an answer from a reliable prescriber to the question: ‘Is this medication really necessary for me?’ Existential labour was done to establish that the practice of taking cardiovascular preventive medication was an inevitable necessity, rather than an active choice. ‘Taking medicines no longer a big deal’ could be the resulting experience of this process.ConclusionsUnmet existential needs when being prescribed cardiovascular preventive medication seem to be a component of the burden of treatment. A continuous and trustful relationship with the prescribing doctor may facilitate the reconciliation of conflicting self-images, and support patients in their efforts to incorporate their medicines taking into daily life.

Acceptability and feasibility of malaria prophylaxis for forest goers: findings from a qualitative study in Cambodia

Background In the Greater Mekong Subregion, adults are at highest risk for malaria, particularly those who visit forests. The absence of effective vector control strategies and limited periods of exposure during forest visits suggest that chemoprophylaxis could be an appropriate strategy to protect forest goers against malaria. Methods Alongside a clinical trial of anti-malarial chemoprophylaxis in northern Cambodia, qualitative research was conducted, including in-depth interviews and observation, to explore the acceptability of malaria prophylaxis for forest goers, the implementation opportunities, and challenges of this strategy. Results Prophylaxis with artemether–lumefantrine for forest goers was found to be acceptable under trial conditions. Three factors played a major role: the community’s awareness and perception of the effectiveness of prophylaxis, their trust in the provider, and malaria as a local health concern. The findings highlight how uptake and adherence to prophylaxis are influenced by the perceived balance between benefits and burden of anti-malarials which are modulated by the seasonality of forest visits and its influence on malaria risk. Conclusions The implementation of anti-malarial prophylaxis needs to consider how the preventive medication can be incorporated into existing vector-control measures, malaria testing and treatment services. The next step in the roll out of anti-malarial prophylaxis for forest visitors will require support from local health workers.

Comparison of Coronary Heart Disease Prediction models using various Machine Learning Algorithms

In the health sector, Data Analytics and Machine Learning (ML) methods are taking over role of skill and experience of a doctor especially in diagnosing diseases and preventive health measures. The health care industry is collecting very large amount of data related to patients, his medical history for preventive medication and diagnosing disease well in time and more accurately. In this paper, a comparison of five classification machine learning methods viz. Decision Tree, Random Forests, Support Vector Machine, Artificial Neural Network and Fuzzy Logic based soft computing method is done for heart disease diagnosis on the basis of data available on public domain. Out of 76 parameters collected for a patient, only 15 medical parameters such as blood pressure, sex, age, obesity and cholesterol level are used for predicting heart disease of patients.

Efficacy of galcanezumab in patients with migraine and history of failure to 3–4 preventive medication categories: subgroup analysis from CONQUER study

Background Chronic migraine (CM) and episodic migraine (EM) are associated with substantial headache-related disability, poor quality of life and global societal burden. In this subgroup analysis from the CONQUER study, we report efficacy outcomes from a pre-specified analysis of galcanezumab versus placebo in patients with CM or EM and 3–4 prior preventive medication category failures due to inadequate efficacy (after at least 2 months at maximum tolerated dose), or safety or tolerability reasons. The patient population is of particular interest due to evidence of decreased quality of life and increased economic burden among patients with migraine that is inadequately managed and is of interest to decision-makers globally. Methods Key outcomes included overall mean change from baseline in monthly migraine headache days and proportions of patients achieving ≥30% (CM), ≥50%, and ≥ 75% reduction (response rates) in monthly migraine headache days across Months 1–3. Patient functioning and disability were evaluated at Month 3. Results Of the 462 randomized patients, 186 (40.3%) had a history of 3–4 preventive category failures. Galcanezumab versus placebo resulted in significantly (P ≤ .001) larger overall mean reduction in monthly migraine headache days (total: − 5.49 versus − 1.03; CM: − 6.70 versus − 1.56; EM: − 3.64 versus − 0.65). Similarly, the ≥50% response rate was significantly (P ≤ .001) higher with galcanezumab versus placebo (total: 41.0 versus 12.7; CM: 41.5 versus 8.4; EM: 41.1 versus 16.5). In the CM group, the ≥30% response rate was significantly higher in the galcanezumab group than the placebo group (CM, 57.5 versus 19.8, P ≤ .0001) as was the ≥75% response rate (13.3 versus 2.6, P ≤ .05). Galcanezumab also resulted in significant (P < .0001) improvements in patient functioning and reductions in disability. Conclusions Galcanezumab was effective in a difficult-to-treat population of patients with CM or EM who had failed 3–4 prior preventive medication categories. Trial registration CONQUER. Clinicaltrials.gov identifier: NCT03559257.

Secondary Stroke Prevention in Polish Adults: Results from the LIPIDOGRAM2015 Study

Background: The purpose of the study was to evaluate secondary stroke prevention in Poland and its association with sociodemographic factors, place of residence, and concomitant cardiovascular risk factors. Material and methods: From all patients in LIPIDOGRAM2015 Study (n = 13,724), 268 subjects had a history of ischaemic stroke and were included. Results: 165 subjects (61.6%) used at least one preventive medication. Oral antiplatelet and anticoagulation agents were used by 116 (43.3%) and 70 (26.1%) patients, respectively. Only 157 (58.6%) participants used lipid-lowering drugs, and 205 (76.5%) were treated with antihypertensive drugs. Coronary heart disease (CHD) and dyslipidaemia were associated with antiplatelet treatment (p = 0.047 and p = 0.012, respectively). A history of atrial fibrillation, CHD, and previous myocardial infarction correlated with anticoagulant treatment (p = 0.001, p = 0.011, and p < 0.0001, respectively). Age, gender, time from stroke onset, place of residence, and level of education were not associated with antiplatelet or anticoagulant treatment. Only 31.7% of patients were engaged in regular physical activity, 62% used appropriate diet, and 13.6% were current smokers. Conclusions: In Poland drugs and lifestyle modification for secondary stroke prevention are not commonly adhered to. Educational programmes for physicians and patients should be developed to improve application of effective secondary prevention of stroke.