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Neurology and Therapy Jun 2024Long-term (1-year) fremanezumab treatment proved to be effective, safe, and well tolerated in individuals with migraine and < 2 medication clusters in a randomized...
Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study.
INTRODUCTION
Long-term (1-year) fremanezumab treatment proved to be effective, safe, and well tolerated in individuals with migraine and < 2 medication clusters in a randomized controlled trial (RCT). We aimed to assess real-world evidence (RWE), long-term effectiveness, tolerability, and safety of fremanezumab in people with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and various comorbidities.
METHODS
A 48-week, prospective, multicenter (n = 26), cohort study assessed fremanezumab's effectiveness, safety, and tolerability in consecutive adults with HFEM or CM with > 3 treatment failures. Primary endpoint was variation from baseline in monthly migraine days (MMD) in HFEM and monthly headache days (MHD) in CM at weeks 45-48. Secondary endpoints were changes in monthly analgesic medications, Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), and the Migraine Disability Assessment Scale (MIDAS) scores and ≥ 50%, ≥ 75%, and 100% responder rates.
RESULTS
Of 533 participants who had received ≥ 1 fremanezumab dose, 130 were treated for ≥ 48 weeks and considered for effectiveness analysis. No participant missed any treatment dosage every other consecutive month during the 12-month period.
PRIMARY ENDPOINT
fremanezumab significantly (p < 0.001) reduced both MMD (- 6.4) in HFEM and MHD (- 14.5) in CM. Secondary endpoints: a significant reduction (p < 0.001) was observed in monthly analgesic medications (HFEM - 6.0; CM -16.5), NRS (HFEM - 3.4; CM - 3.4), HIT-6 (HFEM - 16.9; CM - 17.9) and MIDAS score (HFEM - 50.4; CM - 76.6). The ≥ 50%, ≥ 75%, and 100% response rates to fremanezumab were 75.5%, 36.7%, and 2% in HFEM and 71.6%, 44.4%, and 3.7% in CM. Corresponding response rates were 60.5%, 37.2%, and 2.3% in individuals with psychiatric comorbidities, 74.2%, 50%, and 4.8% in CM with medication overuse, and 60.9%, 39.1%, and 4.3% in CM with medication overuse and psychiatric comorbidities. Mild and transient treatment-emergent adverse events occurred in 7.8% of the participants. No subject discontinued the treatment for any reason.
CONCLUSION
This RWE study documents that long-term fremanezumab treatment is highly effective and remarkably well tolerated in subjects with HFEM or CM with multiple (> 3) therapeutic failures, even in the presence of concomitant medication overuse, psychiatric comorbidities, or both. The effectiveness-to-tolerability ratio appears to be better in RWE than in RCTs.
PubMed: 38451463
DOI: 10.1007/s40120-024-00591-z -
Contraception May 2024The Adherence with Continuous Dose Oral Contraceptive: Evaluation of Self-Selection and Use (ACCESS) study assessed whether consumers can adhere to the regimen for a...
OBJECTIVE
The Adherence with Continuous Dose Oral Contraceptive: Evaluation of Self-Selection and Use (ACCESS) study assessed whether consumers can adhere to the regimen for a progestin-only pill (norgestrel 0.075 mg) in an over-the-counter (OTC) setting.
STUDY DESIGN
An actual use study in a simulated OTC environment assessed adherence to directions to take norgestrel 0.075 mg every day at the same time in 883 participants for up to 24 weeks.
RESULTS
Eighty-five percent (747/883) of participants reported ≥85% adherence to taking norgestrel 0.075 mg every day and reported taking their dose within three hours of their scheduled dosing time on 96% of days. When accounting for use of a condom for 48 hours if a pill was missed, participants reported correctly following the label's directed use for 97% of doses overall, with 95% of participants following label directions for ≥85% of doses. The main limitations were related to finding a balance between intensely collecting data to ensure accurate assessment of adherence and leaving users to behave as they would in a real OTC situation without healthcare practitioner intervention. We observed that some participants reported taking more doses than they could have based on the supply of medication given to them. To fully examine the situation, and the impact on the conclusions, additional post hoc sensitivity analyses were performed, and showed remarkably consistent results.
CONCLUSIONS
Consumers were highly adherent to taking norgestrel 0.075 mg when using only the information provided by the proposed OTC label.
IMPLICATIONS
Adherence to a daily oral contraceptive pill was high when obtained OTC. This suggests that effectiveness of an OTC pill is likely to be like that of a prescribed pill and easier access to this effective contraceptive should allow more opportunity to prevent pregnancy.
Topics: Pregnancy; Female; Humans; Progestins; Norgestrel; Contraception; Contraceptive Devices; Nonprescription Drugs; Contraceptives, Oral
PubMed: 38431261
DOI: 10.1016/j.contraception.2024.110388 -
BMC Public Health Mar 2024Ethiopia has made considerable progress toward measles elimination. Despite ongoing efforts, the country remains among those with the highest number of children missing...
BACKGROUND
Ethiopia has made considerable progress toward measles elimination. Despite ongoing efforts, the country remains among those with the highest number of children missing their initial dose of measles vaccine, and the disease continues to be a public health emergency. The barriers within the health system that hinder the first dose of measles immunization have not been thoroughly investigated. This study aims to identify these barriers within the Ethiopian context.
METHODS
Qualitative research, using purposive expert sampling to select key informants from health organizations in Addis Ababa, Ethiopia was employed. We conducted in-depth face-to-face interviews using a semi-structured interview guide. A thematic analysis based on the World Health Organization's health systems building blocks framework was conducted.
RESULTS
The study uncovered substantial health system barriers to the uptake of the first dose of the measles vaccine in Ethiopia. These barriers include; restricted availability of immunization services, vaccine stockouts, shortage of cold chain technologies, data inaccuracy resulting from deliberate data falsification or accidental manipulation of data, as well as data incompleteness.
CONCLUSION
Our research highlighted significant health system barriers to MCV immunization, contributing to unmet EPI targets in Ethiopia. Our results suggest that to accelerate the country towards measles elimination, there is an urgent need to improve the health systems components such as service delivery, information systems, as well as access to vaccine and cold chain technologies.
Topics: Child; Humans; Ethiopia; Vaccination; Measles; Measles Vaccine; Immunization; Qualitative Research; Immunization Programs
PubMed: 38429806
DOI: 10.1186/s12889-024-18132-6 -
Trials Feb 2024The ProMPT-2 trial (Propofol for Myocardial Protection Trial #2) aims to compare the safety and efficacy of low- and high-dose propofol supplementation of the...
Efficacy of propofol-supplemented cardioplegia on biomarkers of organ injury in patients having cardiac surgery using cardiopulmonary bypass: a statistical analysis plan for the ProMPT-2 randomised controlled trial.
BACKGROUND
The ProMPT-2 trial (Propofol for Myocardial Protection Trial #2) aims to compare the safety and efficacy of low- and high-dose propofol supplementation of the cardioplegia solution during adult cardiac surgery versus sham supplementation. This update presents the statistical analysis plan, detailing how the trial data will be analysed and presented. Outlined analyses are in line with the Consolidated Standards of Reporting Trials and the statistical analysis plan has been written prior to database lock and the final analysis of trial data to avoid reporting bias (following recommendations from the International Conference on Harmonisation of Good Clinical Practice).
METHODS/DESIGN
ProMPT-2 is a multi-centre, blinded, parallel three-group randomised controlled trial aiming to recruit 240 participants from UK cardiac surgery centres to either sham cardioplegia supplementation, low dose (6 µg/ml) or high dose (12 µg/ml) propofol cardioplegia supplementation. The primary outcome is cardiac-specific troponin T levels (a biomarker of cardiac injury) measured during the first 48 h following surgery. The statistical analysis plan describes the planned analyses of the trial primary and secondary outcomes in detail, including approaches to deal with missing data, multiple testing, violation of model assumptions, withdrawals from the trial, non-adherence with the treatment and other protocol deviations. It also outlines the planned sensitivity analyses and exploratory analyses to be performed.
DISCUSSION
This manuscript prospectively describes, prior to the completion of data collection and database lock, the analyses to be undertaken for the ProMPT-2 trial to reduce risk of reporting and data-driven analyses.
TRIAL REGISTRATION
ISRCTN ISRCTN15255199. Registered on 26 March 2019.
Topics: Adult; Humans; Biomarkers; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Heart Arrest, Induced; Multicenter Studies as Topic; Propofol; Randomized Controlled Trials as Topic; Treatment Outcome; Troponin T
PubMed: 38424570
DOI: 10.1186/s13063-024-08016-w -
Vaccine Mar 2024COVID-19 seriously impacted routine immunization (RI) in Iraq. Coverage declined to a 6-year low in 2021, and COVID-19 vaccination uptake was slow. In response,...
INTRODUCTION
COVID-19 seriously impacted routine immunization (RI) in Iraq. Coverage declined to a 6-year low in 2021, and COVID-19 vaccination uptake was slow. In response, government implemented intensification of integrated immunization services (3IS), a nationwide approach comprising regular outreach sessions of COVID-19 vaccination and RI for children who had either missed doses or never commenced scheduled vaccination (zero-dose children). We describe the 3IS and its impact on vaccination coverage in Iraq.
METHODS
3IS comprised new outreach sessions for urban and rural communities where administrative data suggested there were gaps in coverage. Groups of six personnel from each of 1,321 primary healthcare centres implemented six outreach sessions per month during February-November 2022. Community engagement was an integral component. We compared RI administrative data (2019-2022) and data reported during 3IS activities to assess its impact.
RESULTS
In total 4,189,859 vaccine doses were administered during 72,495 3IS outreach sessions, over one-fifth of 19,106,849 vaccine doses administered in Iraq over these 10 months. Among them, 957,874 (22.9 %) were COVID-19 vaccines, adding slightly to national coverage, and 3,231,985 (77.1 %) were RI vaccines, dramatically reducing zero-dose children, adding 18 %, 25 %, 21 %, and 31 % to 2022 penta1, penta3, measles first-dose and MMR1 vaccine coverage, and contributing to national coverage of 102.2 %, 94.5 %, 91.8 % and 96.3 % for these vaccines during February-November, respectively. Moreover, 3IS sessions delivered 133,528 doses of tetanus toxoid, 16,353 doses of adult HepB vaccine, and 315,032 vitamin A doses to eligible individuals.
CONCLUSION
In the context of global encouragement to integrate vaccination services, Iraq's 3IS approach enabled dramatic improvements in RI coverage, virtual elimination of zero-dose status among children born during the pandemic, and small improvements in COVID-19 and adult vaccination. Our findings provide lessons for future integrated primary care towards universal health coverage in Iraq, and for other countries yet to undertake integration.
Topics: Child; Adult; Humans; Infant; COVID-19 Vaccines; Vaccination Coverage; Iraq; COVID-19; Vaccination; Immunization; Immunization Programs; Tetanus Toxoid
PubMed: 38418341
DOI: 10.1016/j.vaccine.2024.02.038 -
PLOS Global Public Health 2024Adolescents account for an estimated 800,000 incident tuberculosis (TB) cases annually and are at risk for suboptimal adherence to TB treatment. Most studies of...
Adolescents account for an estimated 800,000 incident tuberculosis (TB) cases annually and are at risk for suboptimal adherence to TB treatment. Most studies of adolescent TB treatment adherence have used surveillance data with limited psychosocial information. This prospective cohort study aimed to identify risk factors for suboptimal adherence to rifampicin-susceptible TB treatment among adolescents (10-19 years old) in Lima, Peru. We collected psychosocial data using self-administered surveys and clinical data via medical record abstraction. Applying k-means cluster analysis, we grouped participants by psychosocial characteristics hypothesized to impact adherence. Then, we conducted mixed effects regression to compare suboptimal adherence-defined as <90% (missing >10% of doses)-between clusters. Treatment setting (facility vs. home) and drug formulation (single drug vs. fixed dose combination) were interaction terms. Of 249 participants, 90 (36.1%) were female. Median age was 17 (IQR: 15, 16.6) years. We identified three clusters-A, B, and C-of participants based on psychosocial characteristics. Cluster C had the lowest support from caregivers, other family members, and friends; had the weakest motivation to complete TB treatment; were least likely to live with their mothers; and had experienced the most childhood adversity. Among the 118 (47.4%) participants who received facility-based treatment with single drug formulations, adherence did not differ between Clusters A and B, but Cluster C had six-fold odds of suboptimal adherence compared to Cluster A. In Clusters B and C, adherence worsened over time, but only in Cluster C did mean adherence fall below 90% within six months. Our findings have implications for the care of adolescents with TB. When caring for adolescents with low social support and other risk factors, clinicians should take extra measures to reinforce adherence, such as identifying a community health worker or peer to provide treatment support. Implementing newly recommended shorter regimens also may facilitate adherence.
PubMed: 38412160
DOI: 10.1371/journal.pgph.0002918 -
Vaccines Feb 2024Zero-dose (ZD) children is a critical objective in global health, and it is at the heart of the Immunization Agenda 2030 (IA2030) strategy. Coverage for the first dose...
Zero-dose (ZD) children is a critical objective in global health, and it is at the heart of the Immunization Agenda 2030 (IA2030) strategy. Coverage for the first dose of diphtheria-tetanus-pertussis (DTP1)-containing vaccine is the global operational indicator used to estimate ZD children. When surveys are used, DTP1 coverage estimates usually rely on information reported from caregivers of children aged 12-23 months. It is important to have a global definition of ZD children, but learning and operational needs at a country level may require different ZD measurement approaches. This article summarizes a recent workshop discussion on ZD measurement for targeted surveys at local levels related to flexibilities in age cohorts of inclusion from the ZD learning Hub (ZDLH) initiative-a learning initiative involving 5 consortia of 14 different organizations across 4 countries-Bangladesh, Mali, Nigeria, and Uganda-and a global learning partner. Those considerations may include the need to generate insights on immunization timeliness and on catch-up activities, made particularly relevant in the post-pandemic context; the need to compare results across different age cohort years to better identify systematically missed communities and validate programmatic priorities, and also generate insights on changes under dynamic contexts such as the introduction of a new ZD intervention or for recovering from the impact of health system shocks. Some practical considerations such as the potential need for a larger sample size when including comparisons across multiple cohort years but a potential reduction in the need for household visits to find eligible children, an increase in recall bias when older age groups are included and a reduction in recall bias for the first year of life, and a potential reduction in sample size needs and time needed to detect impact when the first year of life is included. Finally, the inclusion of the first year of life cohort in the survey may be particularly relevant and improve the utility of evidence for decision-making and enable its use in rapid learning cycles, as insights will be generated for the population being currently targeted by the program. For some of those reasons, the ZDLH initiative decided to align on a recommendation to include the age cohort from 18 weeks to 23 months, with enough power to enable disaggregation of key results across the two different cohort years. We argue that flexibilities with the age cohort for inclusion in targeted surveys at the local level may be an important principle to be considered. More research is needed to better understand in which contexts improvements in timeliness of DTP1 in the first year of life will translate to improvements in ZD results in the age cohort of 12-23 months as defined by the global DTP1 indicator.
PubMed: 38400178
DOI: 10.3390/vaccines12020195 -
Healthcare (Basel, Switzerland) Feb 2024Fookkun is a pill dispenser in which single doses of several medications intended to be taken simultaneously are sealed in single film bags rolled onto a medication...
Fookkun is a pill dispenser in which single doses of several medications intended to be taken simultaneously are sealed in single film bags rolled onto a medication rotating drum. The system makes musical alert sounds when it is time for the patient to take the medications. If the patient misses a dose, a designated contact, such as the patient's child, is alerted. We conducted an experiment monitoring the use of a pill dispenser (Fookkun) by an older patient. The participant was a 71-year-old woman with diabetes living in a dwelling home. The experiment lasted approximately 6 months. Fookkun and the prototype data transmitter were installed at the patient's home. Fookkun's medication history data are displayed on the electronic medication record book (E-MRB) and the patient's pharmacist checks the patient's medication history on the E-MRB. The Fookkun was effective in facilitating medication adherence. The pharmacist and the patient's daughter did not need to check the E-MRB because Fookkun alerted them when the patient missed her medication. We believe that if the medication history data linked between a pill dispenser and an E-MRB can be shared among medical staff, this will contribute to a medical digital transformation in Japan in the future.
PubMed: 38391874
DOI: 10.3390/healthcare12040499 -
Clinical Trials (London, England) Jun 2024The Patient-Centered Dosing Initiative, a patient-led effort advocating for a paradigm shift in determining cancer drug dosing strategies, pioneers a departure from...
The Patient-Centered Dosing Initiative, a patient-led effort advocating for a paradigm shift in determining cancer drug dosing strategies, pioneers a departure from traditional oncology drug dosing practices. Historically, oncology drug dosing relies on identifying the maximum tolerated dose through phase 1 dose escalation methodology, favoring higher dosing for greater efficacy, often leading to higher toxicity. However, this approach is not universally applicable, especially for newer treatments like targeted therapies and immunotherapies. Patient-Centered Dosing Initiative challenges this "more is better" ethos, particularly as metastatic breast cancer patients themselves, as they not only seek longevity but also a high quality of life since most metastatic breast cancer patients stay on treatment for the rest of their lives. Surveying 1221 metastatic breast cancer patients and 119 oncologists revealed an evident need for flexible dosing strategies, advocating personalized care discussions based on patient attributes. The survey results also demonstrated an openness toward flexible dosing and a willingness from both patients and clinicians to discuss dosing as part of their care. Patient-centered dosing emphasizes dialogue between clinicians and patients, delving into treatment efficacy-toxicity trade-offs. Similarly, clinical trial advocacy for multiple dosing regimens encourages adaptive strategies, moving away from strict adherence to maximum tolerated dose, supported by recent research in optimizing drug dosages. Recognizing the efficacy-effectiveness gap between clinical trials and real-world practice, Patient-Centered Dosing Initiative underscores the necessity for patient-centered dosing strategies. A focus on individual patient attributes aligns with initiatives like Project Optimus and Project Renewal, aiming to optimize drug dosages for improved treatment outcomes at both the pre- and post-approval phases. Patient-Centered Dosing Initiative's efforts extend to patient education, providing tools to initiate dosage-related conversations with physicians. In addition, it emphasizes physician-patient dialogues and post-marketing studies as essential in determining optimal dosing and refining drug regimens. A dose-finding paradigm prioritizing drug safety, tolerability, and efficacy benefits all stakeholders, reducing emergency care needs and missed treatments for patients, aligning with oncologists' and patients' shared goals. Importantly, it represents a win-win scenario across healthcare sectors. In summary, the Patient-Centered Dosing Initiative drives transformative changes in cancer drug dosing, emphasizing patient well-being and personalized care, aiming to enhance treatment outcomes and optimize oncology drug delivery.
Topics: Humans; Antineoplastic Agents; Patient-Centered Care; Female; Breast Neoplasms; Dose-Response Relationship, Drug; Maximum Tolerated Dose; Surveys and Questionnaires; Quality of Life; Neoplasms
PubMed: 38385314
DOI: 10.1177/17407745241232428 -
Journal of Applied Clinical Medical... Jun 2024A workflow/planning strategy delivering low-dose radiation therapy (LDRT) (1 Gy) to all polymetastatic diseases using conventional planning/delivery...
PURPOSE
A workflow/planning strategy delivering low-dose radiation therapy (LDRT) (1 Gy) to all polymetastatic diseases using conventional planning/delivery (Raystation/Halcyon = "conventional") and the AI-based Ethos online adaptive RT (oART) platform is developed/evaluated.
METHODS
Using retrospective data for ten polymetastatic non-small cell lung cancer patients (5-52 lesions each) with PET/CTs, gross tumor volumes (GTVs) were delineated using PET standardized-uptake-value (SUV) thresholding. A 1 cm uniform expansion of GTVs to account for setup/contour uncertainty and organ motion-generated planning target volumes (PTVs). Dose optimization/calculation used the diagnostic CT from PET/CT. Dosimetric objectives were: D ≥ 95% (acceptable variation (Δ) ≥ 90%), V ≥ 95% (Δ ≥ 90%), and D ≤ 120% (Δ ≤ 125%). Additionally, online adaptation was simulated. When available, subsequent diagnostic CT was used to represent on-treatment CBCT. Otherwise, the CT from PET/CT used for initial planning was deformed to simulate clinically representative changes.
RESULTS
All initial plans generated, both for Raystation and Ethos, achieved clinical goals within acceptable variation. For all patients, D ≥ 95%, V ≥ 95%, and D ≤ 120% goals were achieved for 84.8%/99.5%, 97.7%/98.7%, 97.4%/92.3%, in conventional/Ethos plans, respectively. The ratio of 50% isodose volume to PTV volume (R), maximum dose at 2 cm from PTV (D), and the ratio of the 100% isodose volume to PTV volume (conformity index) in Raystation/Ethos plans were 7.9/5.9; 102.3%/88.44%; and 0.99/1.01, respectively. In Ethos, online adapted plans maintained PTV coverage whereas scheduled plans often resulted in geographic misses due to changes in tumor size, patient position, and body habitus. The average total duration of the oART workflow was 26:15 (min:sec) ranging from 6:43 to 57:30. The duration of each oART workflow step as a function of a number of targets showed a low correlation coefficient for influencer generation and editing (R= 0.04 and 0.02, respectively) and high correlation coefficient for target generation, target editing and plan generation (R= 0.68, 0.63 and 0.69, respectively).
CONCLUSIONS
This study demonstrates feasibility of conventional planning/treatment with Raystation/Halcyon and highlights efficiency gains when utilizing semi-automated planning/online-adaptive treatment with Ethos for immunostimulatory LDRT conformally delivered to all sites of polymetastatic disease.
Topics: Humans; Radiotherapy Planning, Computer-Assisted; Radiotherapy Dosage; Retrospective Studies; Carcinoma, Non-Small-Cell Lung; Cone-Beam Computed Tomography; Positron Emission Tomography Computed Tomography; Lung Neoplasms; Feasibility Studies; Radiotherapy, Intensity-Modulated; Organs at Risk; Image Processing, Computer-Assisted; Radiotherapy, Image-Guided; Prognosis; Male
PubMed: 38377378
DOI: 10.1002/acm2.14303