UNASSIGNED: For the past five years, our annual reports have been tracking the clinical development of new drug-based therapies for the neurodegenerative condition of Parkinson\'s disease (PD). These reviews have followed the progress both of \"symptomatic treatments\" (ST - improves/reduces symptoms of the condition) and \"disease-modifying treatments\" (DMT - attempts to delay/slow progression by addressing the underlying biology of PD). Efforts have also been made to further categorize these experimental treatments based on their mechanisms of action and class of drug.
UNASSIGNED: A dataset of clinical trials for drug therapies in PD using trial data downloaded from the ClinicalTrials.gov online registry was generated. A breakdown analysis of all the studies that were active as of January 31st, 2024, was conducted. This analysis involved categorizing the trials based on both the mechanism of action (MOA) and the drug target.
UNASSIGNED: There were 136 active Phase 1-3 trials evaluating drug therapies for PD registered on ClinicalTrials.gov, as of January 31, 2024. Of these trials, 76 (56%) were classified as ST trials and 60 (44%) were designated DMT. More than half (58%) of the trials were in Phase 2 testing stage, followed by Phase 1 (30%) and Phase 3 (12%). 35 of the trials were registered since our last report, with the remaining 101 trials appearing in at least one earlier report.
UNASSIGNED: The drug development pipeline for PD remains in a robust state with a wide variety of approaches being developed and evaluated in Phase 1 and 2. Yet again, however, only a limited number of DMTs are transitioning to Phase 3.
The development of new medical therapies, particularly for neurodegenerative conditions, is a long process that involves multiple phases of testing before a treatment is approved for use in a doctor’s clinic. The first phase assesses the short-term safety of a drug – most often in healthy volunteers but sometimes in people affected by the disease. The second phase explores the short-term safety and preliminary efficacy of the agent in people affected by the disease of interest, and the third phase investigates long-term safety and efficacy in a large group of people affected by the disease. For a disease like Parkinson’s disease, where the causes of the condition are not well understood, drugs targeting different biological pathways need to be tested to determine which ones may be useful in treating the symptoms, and which could be administered to slow down or stop the progression of the condition. Here, we provide an annual report on the current landscape of both these clinical testing efforts. In total, we reviewed 136 active studies evaluating therapies for Parkinson’s disease registered on a clinical trial database called ‘ClinicalTrials.gov’. Of these trials, approximately 55% were testing experimental symptomatic treatments, while the rest were focused on slowing down disease progression. More than half (58%) of the studies were in the second phase of clinical testing (short-term safety and preliminary efficacy), but only three studies were found to be testing treatments to stop the progression of Parkinson’s in the Phase 3 testing. We concluded that the drug development pipeline for Parkinson’s is robust, but more progress needs to be made with late-stage testing of treatments to slow the disease.

UNASSIGNED: One approach to promoting healthy lifestyle behaviors is to target students with digital interventions. One of these is the digital intervention Buddy. This study aimed to understand why college and university students\' chose to participate in a digital multiple lifestyle behavior intervention trial (Buddy), and their subsequent experiences of the behavior-change process.
UNASSIGNED: College and university students taking part in a trial of the Buddy intervention were individually interviewed after completing the 4-month intervention. Participants were guided to narrate their experiences and actions that followed signing up. Altogether, 50 interviews were conducted via telephone. The verbatim transcribed texts were analyzed qualitatively.
UNASSIGNED: The analysis generated seven personas, which illustrated the students\' different levels of engagement with the intervention and the behavior-change process. These were: the Occupied, the Kickstarter, the Aimless, the Reflective, the Goal-oriented, the Compliant, and the Personally developed. Buddy worked best for students who had clear ideas about what they wanted to change and why, and who were aware of their needs, and those who could translate information and reflection into action and had the mental and physical energy needed to make changes.
UNASSIGNED: The progress of behavior change depends on the interaction between the digital mode of delivery, the intervention materials of Buddy, the individual\'s expectations, needs, and skills, and their current life situation. This suggests that designing lifestyle interventions could benefit from more often considering the various personas\' different intentions, knowledge, and contexts. By doing so, interventions are likely to emerge that can better match different needs in the target population.

Lung cancer, a multifaceted disease, demands tailored therapeutic approaches due to its diverse subtypes and stages. This comprehensive review explores the intricate landscape of lung cancer research, delving into recent breakthroughs and their implications for diagnosis, therapy, and prevention. Genomic profiling and biomarker identification have ushered in the era of personalised medicine, enabling targeted therapies that minimise harm to healthy tissues while effectively combating cancer cells. The relationship between pulmonary tuberculosis and lung cancer is examined, shedding light on potential mechanisms linking these two conditions. Early detection methods, notably low-dose computed tomography scans, have significantly improved patient outcomes, emphasising the importance of timely interventions. There has been a growing interest in segmentectomy as a surgical intervention for early-stage lung cancer in recent years. Immunotherapy has emerged as a transformative approach, harnessing the body\'s immune system to recognise and eliminate cancer cells. Combining immunotherapy with traditional treatments, such as chemotherapy and targeted therapies, has shown enhanced efficacy, addressing the disease\'s heterogeneity and overcoming drug resistance. Precision medicine, guided by genomic profiling, has enabled the development of targeted therapies like tyrosine kinase inhibitors, offering personalised treatments tailored to individual patients. Challenges such as drug resistance and limited accessibility to advanced therapies persist, emphasising the need for collaborative efforts and innovative technologies like artificial intelligence. Despite challenges, ongoing interdisciplinary collaborations and technological advancements offer hope for a future where lung cancer is treatable and preventable, reducing the burden on patients and healthcare systems worldwide.

The goal was to review mobile apps with COVID-19 digital vaccination certificates between November 2022 and March 2023 and evaluate: (a) compliance with the WHO Proof of Vaccination Scenario requirements, (b) risk levels of app permissions using a Permission Accumulated Risk Score (PARS), and (c) readability and transparency of the app\'s privacy policies using a Privacy Transparency Index (PTI) score. We found 49 mobile apps with COVID-19 digital vaccination certificates from across 32 countries. Most apps were developed by governments (37/49, 75.51%). We discovered a high positive correlation between the country-wide app total installs and the people vaccinated with at least one dose in the country (r = 0.93, P = <.001). Most apps (97.96%) had sources of information available for compliance with WHO Proof of Vaccination Scenario requirements. Only two apps included all the required data items, while most apps (75%) included five or more data out of nine items. We found that most (97.96%) apps had a Google Play link to generate the Exodus platform permission report, and most (95.92%) apps had an associated privacy policy available. We identified 80 unique permissions; some (23.75%) were dangerous or special. We also found 28 types of trackers. The average PARS was 28.58 (IQR 23.25, range 15-38.25). Most of the apps\' privacy policies documents were difficult or very difficult to read (median grade level 14, IQR 2.6, range 13-15.6). The average PTI was 50.43 (SD 14.73; range 22.5-75). In conclusion, higher compliance with the WHO Proof of Vaccination Scenario requirements is desirable to support interoperability. Developers should limit the number of permissions for essential needs and disclose their purpose. Developers should write privacy policies that a wider audience can understand.

UNASSIGNED: Clinical management of ventilator-assisted individuals (VAIs) was challenged by social distancing rules during the COVID-19 pandemic. In May 2020, the Long-Term In-Home Ventilator Engagement (LIVE) Program was launched in Ontario, Canada to provide intensive digital care case management to VAIs. The purpose of this qualitative study was to explore the acceptability of the LIVE Program hosted via a digital platform during the COVID-19 pandemic from diverse perspectives.
UNASSIGNED: We conducted a qualitative descriptive study (May 2020-April 2021) comprising semi-structured interviews with participants from eight home ventilation specialty centers in Ontario, Canada. We purposively recruited patients, family caregivers, and providers enrolled in LIVE. Content analysis and the theoretical concepts of acceptability, feasibility, and appropriateness were used to interpret findings.
UNASSIGNED: A total of 40 individuals (2 VAIs, 18 family caregivers, 20 healthcare providers) participated. Participants described LIVE as acceptable as it addressed a longstanding imperative to improve care access, ease of use, and training provided; feasible for triaging problems and sharing information; and appropriate for timeliness of provider responses, workflows, and perceived value. Negative perceptions of acceptability among healthcare providers concerned digital workload and fit with existing clinical workflows. Perceived benefits accorded to LIVE included enhanced physical and psychological safety in the home, patient-provider relations, and VAI engagement in their own care.
UNASSIGNED: Study findings identify factors influencing the LIVE Program\'s acceptability by patients, family caregivers, and healthcare providers during pandemic conditions including enhanced access to care, ease of case management triage, and VAI safety. Findings may inform the implementation of digital health services to VAIs in non-pandemic circumstances.

OBJECTIVE: Under the Food and Drug Administration Amendments Act of 2007 (FDAAA), the FDA has the authority to require applicants to conduct postmarketing studies or clinical trials. These postmarketing requirements (PMRs) provide additional data on the safety of the drug product. The purpose of the study was to conduct a descriptive analysis of FDAAA PMRs and the resulting regulatory actions.
METHODS: This study evaluated FDAAA PMRs established between 2013 and 2019. We used the Medical Dictionary for Regulatory Activities (MedDRA) to map preferred terms (PTs) for serious risks associated with the PMRs. Relevant documents available in the FDA\'s document archiving, reporting, and regulatory tracking system (DARRTS), including but not limited to internal letters and reviews, documents submitted by applicants, and publicly available data sources were assessed for data collection of study elements.
RESULTS: Of the 1079 new FDAAA PMRs established between January 01, 2013, and December 31, 2019, 82% (n = 884) were associated with new drug applications (NDAs) and 18% (n = 195) with biologic license applications (BLAs). Most PMRs were established at the time of drug approval (73%, n = 789) compared to post-approval (27%, n = 290). The majority of PMRs had an open status (59%, n = 639) and 41% (n = 440) were closed. The median time from the PMR establishment date to submission of the results to the FDA was 690 days (interquartile range [IQR]: 748 days) for 167 completed clinical trials and 483 days (IQR: 603 days) for 241 completed studies. Approximately 53% (180/339) of fulfilled FDAAA PMRs resulted in labeling changes.
CONCLUSIONS: FDAAA PMRs are useful in informing postmarket safety of drugs. Most FDAAA PMRs were established at the time of drug approval, reflecting safety signals identified during the review of the marketing application, and over half of fulfilled FDAAA PMRs resulted in regulatory action.

UNASSIGNED: This paper aims to report our experience of developing, implementing, and evaluating myHealthE (MHE), a digital innovation for Child and Adolescents Mental Health Services (CAMHS), which automates the remote collection and reporting of Patient-Reported Outcome Measures (PROMs) into National Health Services (NHS) electronic healthcare records.
UNASSIGNED: We describe the logistical and governance issues encountered in developing the MHE interface with patient-identifiable information, and the steps taken to overcome these development barriers. We describe the application\'s architecture and hosting environment to enable its operability within the NHS, as well as the capabilities needed within the technical team to bridge the gap between academic development and NHS operational teams.
UNASSIGNED: We present evidence on the feasibility and acceptability of this system within clinical services and the process of iterative development, highlighting additional functions that were incorporated to increase system utility.
UNASSIGNED: This article provides a framework with which to plan, develop, and implement automated PROM collection from remote devices back to NHS infrastructure. The challenges and solutions described in this paper will be pertinent to other digital health innovation researchers aspiring to deploy interoperable systems within NHS clinical systems.

BACKGROUND: Fabry disease is a rare, progressive X-linked lysosomal storage disorder. It is caused by mutations in the GLA gene resulting in deficiency of α-galactosidase A (α-Gal A), leading to peripheral neuropathy, cardiovascular disease, stroke, end-stage renal disease, gastrointestinal disorders and premature death. Given the long-term nature of disease progression, trials in Fabry disease are often not powered to capture these clinical events. Clinical measures such as estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMI) are often captured instead. eGFR and LVMI are believed to be associated with long-term Fabry disease clinical events of interest, but the precise relationships are unclear.
OBJECTIVE: We aimed to identify published literature exploring the link between eGFR/LVMI and long-term clinical events in Fabry disease.
METHODS: A comprehensive literature search was conducted in Embase® and MEDLINE® (using Embase.com), and a targeted literature review was conducted. Studies reporting a quantitative relationship between eGFR and/or LVMI and clinical events in Fabry disease were extracted, and narrative synthesis was conducted to understand these predictive relationships.
RESULTS: Eight studies, consisting of seven patient-level retrospective analyses plus one prospective cohort study, met the inclusion criteria. Seven of these studies reported eGFR and six reported LVMI, with five reporting both. All studies presented results for either a composite measure including a range of key Fabry disease clinical events, or a composite outcome that included at least one key Fabry disease clinical event. All studies employed Cox proportional hazards survival modelling. The studies consistently reported that eGFR and LVMI are predictors of key clinical events in Fabry disease, with the findings remaining consistent regardless of the therapy received by patients in the studies.
CONCLUSIONS: The evidence identified suggests that eGFR and LVMI outcomes may be appropriate indicators for long-term clinical events in Fabry disease, and all identified papers implied the same directional relationship. However, additional research is needed to further understand the specific details of these relationships and to quantify them.

UNASSIGNED: In 2011, only 18% of the population in Galician knew the COPD. Since then, activities have been carried out to publicize this disease. The objective of this study was to evaluate the current situation regarding the knowledge of COPD in the Galician population.
UNASSIGNED: Cross-sectional study, through telephone surveys. Variables included in the questionnaire, related to knowledge of the disease, were analyzed.
UNASSIGNED: 872 respondents, 53% women, mean age 54 years. 63% with secondary/university studies. 40% has knowledge of COPD. In contrast, more than 90% of respondents know other high-frequency diseases (diabetes, stroke, asthma). The factors most associated with knowledge of COPD were female gender, having secondary/university studies, and having previously performed spirometry.
UNASSIGNED: The knowledge of COPD in the Galician population is 40% now, higher than in 2011, but it is far from that of other prevalent diseases.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a frequent cause of heart failure and sudden cardiac death. Our understanding of the genetic bases and pathogenic mechanisms underlying HCM has improved significantly in the recent past, but the combined effect of various pathogenic gene variants and the influence of genetic modifiers in disease manifestation are very poorly understood. Here, we set out to investigate genotype-phenotype relationships in 2 siblings with an extensive family history of HCM, both carrying a pathogenic truncating variant in the MYBPC3 gene (p.Lys600Asnfs*2), but who exhibited highly divergent clinical manifestations.
We used a combination of induced pluripotent stem cell (iPSC)-based disease modeling and CRISPR (clustered regularly interspersed short palindromic repeats)/Cas9 (CRISPR-associated protein 9)-mediated genome editing to generate patient-specific cardiomyocytes (iPSC-CMs) and isogenic controls lacking the pathogenic MYBPC3 variant.
Mutant iPSC-CMs developed impaired mitochondrial bioenergetics, which was dependent on the presence of the mutation. Moreover, we could detect altered excitation-contraction coupling in iPSC-CMs from the severely affected individual. The pathogenic MYBPC3 variant was found to be necessary, but not sufficient, to induce iPSC-CM hyperexcitability, suggesting the presence of additional genetic modifiers. Whole-exome sequencing of the mutant carriers identified a variant of unknown significance in the MYH7 gene (p.Ile1927Phe) uniquely present in the individual with severe HCM. We finally assessed the pathogenicity of this variant of unknown significance by functionally evaluating iPSC-CMs after editing the variant.
Our results indicate that the p.Ile1927Phe variant of unknown significance in MYH7 can be considered as a modifier of HCM expressivity when found in combination with truncating variants in MYBPC3. Overall, our studies show that iPSC-based modeling of clinically discordant subjects provides a unique platform to functionally assess the effect of genetic modifiers.