Preventative Medicine

Disease risk prediction tools are used for population screening and to guide clinical care. They identify which individuals have particularly elevated risk of disease. The development of a new risk prediction tool involves several methodological components including: selection of a general modelling framework and specific functional form for the new tool, making decisions about the inclusion of risk factors, dealing with missing data in those risk factors, and performing validation checks of a new tool’s performance. There have been many methodological developments of relevance to these issues in recent years. Developments of importance for disease detection in humans were reviewed and their uptake in risk prediction tool development illustrated. This review leads to guidance on appropriate methodology for future risk prediction development activities.

Background: Patients with Inflammatory bowel disease (IBD) often seek alternative therapies for symptom management. This study investigates the perceptions, consumption patterns, and reported outcomes of cannabis and cannabidiol (CBD) oil use among IBD patients and controls. Methods: A 37-question survey was administered to 139 participants (IBD patients, n = 93; control/non-IBD participants, n = 33) to assess usage frequency and beliefs regarding cannabis and CBD oil as treatment for IBD. The survey also evaluated the impact of these substances on IBD symptoms, quality of life, and opioid use. Results: Cannabis consumption was higher in IBD patients (57, 53.8%) than controls (15, 45.5%) with both groups strongly supporting medical cannabis use (IBD; 92,86.8% vs. controls; 29, 84.9%). Most IBD patients believed cannabis (67, 63.2%), CBD oil (60, 56.6%), corticosteroids (77, 73.3%), and biologics/immunosuppressants (85, 81.0%) had a somewhat-extremely beneficial effect in relieving IBD symptoms. Over 50% of IBD cannabis users reported relief from abdominal pain, other pain, stress, anxiety, depression, and nausea/vomiting, with Crohn’s disease patients experiencing significantly more relief than ulcerative colitis patients for certain symptoms (p < 0.05). Notably, 19.4% of IBD patients reported decreased opioid use, and 14.5% reported induced remission with cannabis or CBD oil. Conclusions: Consumption of cannabis and CBD oil was perceived as beneficial for relieving IBD, with many reporting significant symptom relief from usingthese substances. The strong support of cannabis and CBD oil as medical treatments and therapeutic effects highlights the potential for cannabis and CBD oil as treatments in IBD.

Preventative Care in the Preindustrial World: Comparative and Cross-Cultural Perspectives
12-14 June 2025
India International Centre, New Delhi and Zoom

This conference explores the contours for a global history of preventative care before the development of the modern, industrialized world, with a view to recover ‘public’ health practices across different civilizations; and to look at inter-connections and comparative perspectives. For too long now, discussions on public health have focused on the modern, urban and western world, leading to a lopsided, Eurocentric understanding. In order to redress the imbalance, this conference showcases papers that deal with non-European world(s), in particular, South Asia, the Persianate world, and the Indian Ocean network in the pre-colonial period. Given the relative dearth of research on preindustrial public health, we solicited papers that enriched our empirical base and provided fresh insights and perspectives from unexplored medical treatises and historical and religious texts, epigraphs, images, architecture and archaeological sites and reports. Moreover, we accepted papers that invite cross-cultural comparisons, and that bring out affinities and divergences in health practices across regions and cultures.

The assessment of offenders' risk of reoffending, particularly sexual reoffending, is a core activity of forensic mental health practitioners. The purpose of these assessments is to reduce the risk of harm to the public, but they are controversial and become more contentious when Australian practitioners who want to undertake such assessments in an ethically responsible way must use reliable validated instruments, disclose the limitations of their assessment methods, instruments and data to judicial decision-makers and must understand how decision-makers might use their reports. The purpose of this systematic literature review was to explore the practices of Australian practitioners and courts in respect of the assessment of Australian Indigenous male sexual offenders' risk of reoffending. We could not identify an instrument that has been developed for the assessment of this population group. Australian courts differ in whether they admit and give weight to practitioners' evidence and opinions based on data obtained with non-validated instruments. We could only identify three possible predictor variables with enough quantitative support to justify including them in an instrument that could be used to assess Indigenous sexual offenders. There is a need for research regarding the validity of the instruments practitioners use.

Background Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis. We assessed the eff ects of discontinuation of topiramate after a treatment period of 6 months. 818 patients who have migraines were enrolled from 88 clinics in 21 countries. After a 4-8-week lead-in period, patients received topiramate in a 26-week open-label phase. Daily dose was increased from 25 mg to 100 mg in steps of 25 mg every week; the dose could be adjusted further in the range 50-200 mg/day, but was stable for the fi nal 4 weeks. Patients were randomly assigned to continue this dose or switch to placebo for a 26-week double-blind phase. The primary endpoint was the diff erence in number of days with migraine during the last 4 weeks of the double-blind phase compared with the last 4 weeks of the open-label phase. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-000321-29. Findings 559 patients (68•3%) completed the open-label phase; 514 entered the double-blind phase and were assigned to topiramate (n=255) or placebo (n=259). The mean increase in number of migraine days was greater in the placebo group (1•19 days in 4 weeks, 95% CI 0•71 to 1•66; p<0•0001) than in the topiramate group (0•10, -0•36 to 0•56; p=0•5756; mean diff erence between groups -1•09, -1•75 to -0•43). Patients in the placebo group had a greater number of days on acute medication than did those in the topiramate group (mean diff erence between groups -0•95, -1•49 to -0•41; p=0•0007). Quality of life, as assessed by the MIDAS questionnaire, fell in the placebo group but remained stable in the topiramate group. Patients were more satisfi ed with the effi cacy of topiramate than with that of placebo, whereas satisfaction with tolerability was similar in both treatment groups. Interpretation Sustained benefi t was reported after discontinuation of topiramate, although number of migraine days did increase. These fi ndings suggest that patients should be treated for 6 months, with the option to continue to 12 months in some patients.

The search for effective anti-aging interventions has led to intense investigation into rapamycin, a macrolide antibiotic originally used for its immunosuppressive properties. By inhibiting the mechanistic target of rapamycin (mTOR) pathway, rapamycin has emerged as a promising agent in extending lifespan and improving healthspan in multiple model organisms. This article reviews the molecular mechanisms behind rapamycin’seffects on aging, examines the preclinical evidence supporting its use, discusses the translational challenges for human application, and outlines future research directions.

Background: Primary care is the initial contact point for most patients with opioid use disorder (OUD) but lacks tools for guiding treatment. Only a small fraction of patients access evidence-based care. Long-acting injectable buprenorphine has potential to improve medication adherence and program retention in low-barrier primary care treatment settings. We present the first clinical decision support algorithm incorporating long-acting buprenorphine (LAIB) in primary care. We include a protocol for a future evaluation of the algorithm's implementation process, "Medication for Opioid Use Disorder (MOUD) 2.0," at a housing and integrated care clinic at a Federally Qualified Health Center.
Methods: Literature review and expert consensus informed creation of the algorithm, which underwent iterative development with feedback from clinicians, staff, and patients. Patients are categorized by adherence to therapy and retention in the program, with recommendations for each category. Adherence is determined by urine screen supplemented by self-report. To ensure all patients in this high morbidity and mortality risk population are treated, we will treat patients as their own controls in the evaluation, with potential for multisite comparisons. We will present descriptive statistics for adherence proportion before and after MOUD 2.0 implementation, testing for differences using McNemar's test. We will then present pre-and post-implementation unadjusted six-month survival curves for retention.
Discussion: LAIB is incorporated as an alternative or adjunctive treatment for patients refractory to sublingual buprenorphine and as an initial treatment for selected patients. We developed an algorithm with 4-, 8-, and 12-week decision points to guide treatment for patients with varying levels of response to sublingual buprenorphine and LAIB. This clinical decision tool incorporates LAIB among treatment options for OUD in primary care settings. The protocol will evaluate the algorithm's implementation, presenting a replicable method for assessing adherence and retention among high-risk patients in similar settings.

Can you instinctively tell if you are healthy by the way you feel, or do you need routine medical exams and tests to know?

Current medical practice promotes routine exams with medical tests and disease screening for healthy individuals, as a method for early detection and treatment of disease.

However, this sows doubt in the minds of individuals being examined. This paper explores the impact of creating doubt about one’s health in the minds of healthy individuals, including medical gaslighting through the promotion of “silent” diseases, the loss of and the profit motive behind it all.

It will show that when we subordinate our instincts to the technology, tests, and theories of experts, we undermine ourselves. We lose power over our lives, and come to rely on paid experts who profit from our confusion and doubts.

In addition, many of the treatments and recommendations made by these experts can cause more harm than good. Modern theories are not as reliable as time-tested intuition. And many treatments prescribed cause more problems than they solve.

The use of family history as a predictive tool in medicine is widely accepted, yet its significance is overstated for non-genetic diseases. While a small percentage of diseases are caused by inheritable genetic mutations, the vast majority—estimated at 90–95%—are driven by lifestyle and environmental factors. This article critically examines the assumption that familial disease history indicates individual risk, arguing that cultural, environmental, and technological changes across generations render many such comparisons misleading and inaccurate. It highlights how inherited behaviors, such as diet or clothing habits, may masquerade as genetic inheritance. The role of negative expectation and belief in shaping health outcomes is also considered, as fear induced by medical predictions and testing for familial diseases can itself be detrimental. The article questions the commercial motivations that often accompany tests and the resulting preventive treatments, which can last a lifetime. Ultimately, it calls for a shift away from genetic fatalism and toward individual agency, cultural context, and personal responsibility in health.

Background Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis. We assessed the eff ects of discontinuation of topiramate after a treatment period of 6 months. Methods 818 patients who have migraines were enrolled from 88 clinics in 21 countries. After a 4-8-week lead-in period, patients received topiramate in a 26-week open-label phase. Daily dose was increased from 25 mg to 100 mg in steps of 25 mg every week; the dose could be adjusted further in the range 50-200 mg/day, but was stable for the fi nal 4 weeks. Patients were randomly assigned to continue this dose or switch to placebo for a 26-week double-blind phase. The primary endpoint was the diff erence in number of days with migraine during the last 4 weeks of the double-blind phase compared with the last 4 weeks of the open-label phase. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-000321-29. Findings 559 patients (68•3%) completed the open-label phase; 514 entered the double-blind phase and were assigned to topiramate (n=255) or placebo (n=259). The mean increase in number of migraine days was greater in the placebo group (1•19 days in 4 weeks, 95% CI 0•71 to 1•66; p<0•0001) than in the topiramate group (0•10,-0•36 to 0•56; p=0•5756; mean diff erence between groups-1•09,-1•75 to-0•43). Patients in the placebo group had a greater number of days on acute medication than did those in the topiramate group (mean diff erence between groups-0•95,-1•49 to-0•41; p=0•0007). Quality of life, as assessed by the MIDAS questionnaire, fell in the placebo group but remained stable in the topiramate group. Patients were more satisfi ed with the effi cacy of topiramate than with that of placebo, whereas satisfaction with tolerability was similar in both treatment groups. Interpretation Sustained benefi t was reported after discontinuation of topiramate, although number of migraine days did increase. These fi ndings suggest that patients should be treated for 6 months, with the option to continue to 12 months in some patients.

Mental health in schools has attracted a lot of attention in recent years. Positive Psychology Interventions (PPIs) in secondary schools have been shown to improve mental health outcomes for students. Previous PPIs have tended to be delivered by trained Psychology specialists or have tended to focus on a single aspect of Positive Psychology such as Mindfulness. The current study involved 2 phases. Phase 1 was a pilot PPI, delivered by current university students in Psychology, which educated secondary school students (N = 90) in a variety of Positive Psychology concepts. Phase 2 involved delivering the PPI to secondary school students (N = 1,054). This PPI, the Hummingbird Project, led to improvements in student well-being, as measured by the World Health Organization Well-Being Index (WHO-5). The intervention also led to improvements in student resilience, as measured by the Bolton Uni-Stride Scale (BUSS), and hope, as measured by the Children's Hope Scale (CHS). Results are discussed in the context of their implications for the future of psychological intervention in secondary school settings.

Background: An Infectious Disease vaccine specialist joined our institution's Cochlear Implant Team in 2010 in order to address the high percentage of non-compliance to immunization prior to surgery identified previously from an internal review. The purpose of this study was to (1) review the immunization status of cochlear implant recipients in 2010-2014, (2) assess if introducing a vaccine specialist made a significant change in vaccination compliance and (3) elucidate any barriers to vaccination compliance. Methods: Retrospective chart review and a telephone survey. Medical records of 116 cochlear implant recipients between 2010 and 2014 were reviewed. A telephone survey was conducted to obtain the current vaccination status in children who required post-operative vaccinations with incomplete records on chart review and, if applicable, the reason for non-compliance. Results: Between 2010 and 2014, 98% of children were up-to-date at the time of surgery, compared to 67% up-todate at the time of surgery between 2002 and 2007. 27 children were included in our post-operative immunization analysis. 29.6% (8/27) failed to receive necessary vaccinations post-surgery. Pneumovax-23, a vaccine for high-risk patients (such as cochlear implant candidates) was missed in all cases. Conclusion: Pre-operative vaccination for cochlear implant recipients improved dramatically with the addition of a vaccine specialist. However, a significant proportion of patients requiring vaccinations post-surgery did not receive them. The main reason for non-compliance was due to parents being unaware that their children required this vaccine postoperatively by being "high-risk". Although improvement was demonstrated, a communication gap continued to impede the adequacy of vaccination uptake in pediatric cochlear implant recipients following surgery at age 2 when the high-risk vaccine was due.

Healthcare worker burnout has far-reaching consequences, impacting individual well-being, healthcare system efficiency, and patient outcomes. This paper identifies the root causes of burnout, examines its impact, and proposes evidence-based strategies to mitigate its effects. The analysis emphasizes unique challenges in low-resource settings, such as limited staffing, inadequate infrastructure, and restricted access to mental health support. Key recommendations include redistributing workloads, enhancing mental health resources, implementing supportive organizational practices, and fostering resilience through tailored interventions. By addressing these systemic and individual challenges, healthcare systems can promote workforce sustainability and improve care delivery.

ImportanceAn increasing number of emergency departments (EDs) are initiating buprenorphine for opioid use disorder (OUD) and linking patients to ongoing community-based treatment, yet community-based clinician and staff perspectives regarding this practice have not been characterized.ObjectiveTo explore perspectives and experiences regarding ED-initiated buprenorphine among community-based clinicians and staff in geographically distinct regions.Design, Setting, and ParticipantsThis qualitative study reports findings from Project ED Health, a hybrid type 3 effectiveness-implementation study designed to evaluate the impact of implementation facilitation on ED-initiated buprenorphine with referral to ongoing medication treatment. Clinicians and staff from community-based treatment programs were identified by urban academic EDs as potential referral sites for ongoing OUD treatment in 4 cities across the US in a formative evaluation as having the capability to continue medication treatme...

Applied to health, literacy enhances the capacity to make the decisions that are necessary for autonomous health management. With this position paper, we intend to defend the thesis that the conditions for creating a national strategy for health literacy in Portugal along the life course are strengthened by the modernization of the National Health Service (SNS). First, we conducted a scope review on health literacy, and then we collected data on the National Strategy for Health Literacy and the different actions around it. The Literacy Program in Health and Care Integration, aligned with the modernization program of the National Health Service “SNS + Proximidade,” has been developed based on a life course approach. On the other hand, the National Strategy for Health Literacy, in addition to encompassing different dimensions of health literacy, from the individual and community level to the health systems, also presents strategic opportunities for intervention in contexts associated ...

Background: In a recent randomized, double-blind, placebo-controlled study, we observed a nonsignificant reduction of attack frequency in cluster headache after pulse administration of psilocybin (10 mg/70 kg, 3 doses, 5 days apart each). We carried out a blinded extension phase to consider the safety and efficacy of repeating the pulse regimen. Methods: Eligible participants returned to receive a psilocybin pulse at least 6 months after their first round of study participation. Participants kept headache diaries starting two weeks before and continuing through eight weeks after the first drug session. Ten participants completed the extension phase and all ten were included in the final analysis. Results: In the three weeks after the start of the pulse, cluster attack frequency was significantly reduced from baseline (18.4 [95% confidence interval 8.4 to 28.4] to 9.8 [4.3 to 15.2] attacks/week; p = 0.013, d' = 0.97). A reduction of approximately 50% was seen regardless of individual response to psilocybin in the first round. Psilocybin was well-tolerated without any unexpected or serious adverse events. Discussion: This study shows a significant reduction in cluster attack frequency in a repeat round of pulse psilocybin administration and suggests that prior response may not predict the effect of repeated treatment. To gauge the full potential of psilocybin as a viable medicine in cluster headache, future work should investigate the safety and therapeutic efficacy in larger, more representative samples over a longer time period, including repeating the treatment.

Introduction: In 2007 wildfires ravaged Southern California resulting in the largest evacuation due to a wildfire in American history. We report how these wildfires affected emergency department (ED) visits for respiratory illness. Methods: We extracted data from a Kaiser Permanente database for a single metropolitan community ED. We compared the number of visits due to respiratory illness at time intervals of 2 weeks before and during the time when the fires were burning. We counted the total number of patients with chief complaint of dyspnea, cough, and asthma and final international classification of disease 9 coding diagnosis of asthma, bronchitis, chronic obstructive pulmonary disease and respiratory syndrome, and analyzed data for both total number and proportion of ED visits. We evaluated the data using Early Aberration Reporting System software to determine significant single-visit increases compared to expected counts. We also analyzed the average length of ED stay. Data on air quality were extracted from the http:// www.airnow.gov site. Results: There were significant differences between pre-fire and fire period average visit counts for the chief complaints of dyspnea and asthma. Dypnea complaints increased by 3.2 visits per day. During the fire the diagnoses of asthma increased significantly by 2.6 patients per day. Air quality reached air quality index values of 300, indicating very unhealthy conditions. Average ED length of stay times remained unchanged during the fire period compared to the pre-fire period. Conclusion: The 2007 Southern California wildfires caused significant surges in the volume of ED patients seeking treatment for respiratory illness. Disaster plans should prepare for these surges when future wildfires occur. [

In 2007 wildfires ravaged Southern California resulting in the largest evacuation due to a wildfire in American history. We report how these wildfires affected emergency department (ED) visits for respiratory illness. We extracted data from a Kaiser Permanente database for a single metropolitan community ED. We compared the number of visits due to respiratory illness at time intervals of 2 weeks before and during the time when the fires were burning. We counted the total number of patients with chief complaint of dyspnea, cough, and asthma and final international classification of disease 9 coding diagnosis of asthma, bronchitis, chronic obstructive pulmonary disease and respiratory syndrome, and analyzed data for both total number and proportion of ED visits. We evaluated the data using Early Aberration Reporting System software to determine significant single-visit increases compared to expected counts. We also analyzed the average length of ED stay. Data on air quality were extra...

Background: In order to streamline the emergency department (ED) referral process in a multi-network automated opioid treatment referral program, we performed a needs assessment of community providers for Medication for Opioid Use Disorder (MOUD) in the EMergency department-initiated BuprenorphinE for opioid use Disorder (EMBED) trial network. Methods: A needs assessment was conducted in two phases: (1) key stakeholder meetings and (2) a survey of community sites offering MOUD. Stakeholder meetings were conducted with five key stakeholder groups: 1) ED clinicians and staff, 2) community sites offering MOUD, 3) the investigative team, 4) health system IT staff, and 5) medical ethics experts. Meetings continued until each stakeholder group stated that their priorities and needs were understood. Major categories of needs were extracted pragmatically based on recurrence across stakeholder groups. Informed by needs expressed by IT and MOUD site stakeholders, nineteen MOUD sites were surveyed to better characterize information needs of community sites offering MOUD when receiving an ED referral. Results: Three major categories of needs for referral system were identified: 1) The system to be automated, flexible and allow multiple channels of referral, 2) Referral metrics are retrievable in a HIPAA compliant manner, 3) Patients are scheduled into community sites offering MOUD as urgently as possible. Of the MOUD sites surveyed, 68.4% (13/19) responded. Based on the responses, specific patient identifiers were required for most MOUD site referrals, and encrypted emails and EHR were the preferred methods of communication for the handoff. 53.8% (7/13) of the sites were able to accept patients within 3 days with only 1 site requiring > 7 days. Conclusion: These findings can inform IT solutions to address the discordant priorities of the ED (rapid and flexible referral process) and the community sites offering (referrals minimize variability and overbooking). To prevent drop-out in the referral cascade, our findings emphasize the need for increased availability and accessibility to MOUD on demand and protected communication channels between EDs and community providers of MOUD. 1. Background Medication for opioid use disorder (MOUD) is a safe and effective method for treating opioid addiction (Mattick, Breen, Kimber, & Davoli, 2014). Buprenorphine (BUP), a partial opioid agonist often combined with the antagonist naloxone, and methadone, a full opioid agonist, are MOUDs that are highly effective in decreasing the rates of non-fatal and fatal overdose, withdrawal symptoms, craving, opioid use, risks of infectious-disease transmission, and criminal activity engagement as well as increasing addiction treatment retention (

On 5 May 2023, the World Health Organization declared that
COVID-19 no longer constituted a public health emergency of
international concern. Medical science must now consider how
it ought to recalibrate its imagination and idealism in a post-
COVID-19 pandemic world. The fact that advanced age was the
largest risk factor for COVID-19 mortality and serious illness,
as well as for the most prevalent chronic diseases, reveals the
urgency and significance of shifting the focus from mitigating
each specific pathology risk, one at a time, to targeting
biological ageing itself. In his 1910 JAMA Address entitled
‘Imagination and Idealism in the Medical Sciences’, Christian
Herter made an important distinction between two ways
imagination and idealism can be invoked in the medical
sciences: (i) humanitarian medicine, which emphasizes the
obvious and direct paths of ameliorating human suffering; and
(ii) a curiosity-oriented approach which explores pure science
and the experimental laboratory. The latter examines the
indirect ways of winning, in Herter’s words, ‘the citadel’ of
health promotion. Herter’s reflections on these two contrasting
approaches to medicine have significance for both the COVID-
19 pandemic and the aspiration to promote the ideal of healthy
ageing in the post-COVID-19 pandemic era.

Background: In the United States, the high dropout rate (75%) in opioid use disorder (OUD) treatment among women and racial/ethnic minorities calls for understanding factors that contribute to making progress in treatment. Whereas counseling and medication for OUD (MOUD, e.g. methadone, buprenorphine, naltrexone) is considered the gold standard of care in substance use disorder (SUD) treatment, many individuals with OUD receive either counseling or methadone-only services. This study evaluates gender disparities in treatment plan progress in methadone-compared to counseling-based programs in one of the largest SUD treatment systems in the United States. Methods: Multi-year and multi-level (treatment program and client-level) data were analyzed using the Integrated Substance Abuse Treatment to Eliminate Disparities (iSATed) dataset collected in Los Angeles County, California. The sample consisted of 4 waves: 2011 (66 SUD programs, 1035 clients), 2013 (77 SUD programs, 3686 clients), 2015 (75 SUD programs, 4626 clients), and 2017 (69 SUD programs, 4106 clients). We conducted two multi-level negative binomial regressions, one per each outcome (1) making progress towards completing treatment plan, and (2) completing treatment plan. We included outpatient clients discharged on each of the years of the study (over 95% of all clients) and accounted for demographics, wave, homelessness and prior treatment episodes, as well as clients clustered within programs. Results: We detected gender differences in two treatment outcomes (progress and completion) considering two outpatient program service types (MOUD-methadone vs. counseling). Clients who received methadone vs. counseling had lower odds of completing their treatment plan (OR = 0.366; 95% CI = 0.163, 0.821). Female clients receiving methadone had lower odds of both making progress (OR = 0.668; 95% CI = 0.481, 0.929) and completing their treatment plan (OR = 0.666; 95% CI = 0.485, 0.916) compared to male clients and receiving counseling. Latina clients had lower odds of completing their treatment plan (OR = 0.617; 95% CI = 0.408, 0.934) compared with non-Latina clients. Conclusions: Clients receiving methadone, the most common and highly effective MOUD in reducing opioid use, were less likely to make progress towards or complete their treatment plan than those receiving counseling. Women, and in particular those identified as Latinas, were least likely to benefit from methadone-based programs. These findings have implications for health policy and program design that consider the need for comprehensive and culturally responsive services in methadone-based programs to improve outpatient treatment outcomes among women.

Disease risk prediction tools are used for population screening and to guide clinical care. They identify which individuals have particularly elevated risk of disease. The development of a new risk prediction tool involves several methodological components including: selection of a general modelling framework and specific functional form for the new tool, making decisions about the inclusion of risk factors, dealing with missing data in those risk factors, and performing validation checks of a new tool’s performance. There have been many methodological developments of relevance to these issues in recent years. Developments of importance for disease detection in humans were reviewed and their uptake in risk prediction tool development illustrated. This review leads to guidance on appropriate methodology for future risk prediction development activities.

The subject technology relates, in part, to a method of treating Alzheimer\u27s Disease (AD), early-stage AD, elevated risk of AD, mild cognitive impairment (MCI), or other forms of age-related cognitive decline in a subject in need thereof by administering to the subject a molecule that promotes calcium-release stabilization in ryanodine receptors (RyRs) and/or inosital triphosphate receptors (InsP3Rs) in brain cells. Diagnostic methods using calcium-release stabilizing immunophilins, junctophilins or calmodulin are also disclosed

The subject technology relates, in part, to a method of treating Alzheimer's Disease (AD), early-stage AD, elevated risk of AD, mild cognitive impairment (MCI), or other forms of age-related cognitive decline in a subject in need thereof by administering to the subject a molecule that promotes calcium-release stabilization in ryanodine receptors (RyRs) and/or inosital triphosphate receptors (InsP3Rs) in brain cells. Diagnostic methods using calcium-release stabilizing immunophilins, junctophilins or calmodulin are also disclosed. 10 Claims, 4 Drawing Sheets US 9,464,322 B2 Page 2 (56) References Cited OTHER PUBLICATIONS Skolnick eta!. "From genes to protein structure and function: novel applications of computational approaches in the genomic era."

The subject technology relates, in part, to a method of treating Alzheimer's Disease (AD), early-stage AD, elevated risk of AD, mild cognitive impairment (MCI), or other forms of age-related cognitive decline in a subject in need thereof by administering to the subject a molecule that promotes calcium-release stabilization in ryanodine receptors (RyRs) and/or inosital triphosphate receptors (InsP3Rs) in brain cells. Diagnostic methods using calcium-release stabilizing immunophilins, junctophilins or calmodulin are also disclosed. 10 Claims, 4 Drawing Sheets US 9,464,322 B2 Page 2 (56) References Cited OTHER PUBLICATIONS Skolnick eta!. "From genes to protein structure and function: novel applications of computational approaches in the genomic era."

Around the world, about 15 to 40% of individuals with inflammatory bowel disease (IBD) rely on cannabis and cannabinoids to reduce the need for other medications, as well as increase appetite and reduce pain. Whereas more and more patients continue to report benefits accruing from cannabis and cannabinoid usage in IBD, agreement relative to the use of cannabis and its derivatives in IBD remains unclear. This paper reviewed the interplay between cannabinoid use and IBD disease treatment, remission, or symptom relief. The study was conducted from a systematic review perspective. It involved consulting literature from published original research articles, noting outcomes, and performing a meta-analysis to identify trends and draw conclusions. The selected articles were those that had been published in a 10-year period ranging between 2012 and 2022. The motivation was to ensure recency and also relevance to contemporary scientific research and clinical environment practices. Indeed, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework helped in answering the focal question of the investigation, which revolved around whether cannabinoids are beneficial to IBD treatment and to what extent. The aim of using this protocol was to ensure the satisfaction of the article exclusion and inclusion criteria, as well as ensure the utilization of articles directly contributing to the central subject under investigation. In the findings, it was established that on the one hand, cannabinoid usage in IBD treatment comes with promising results as reported in the majority of the selected studies which reported reduced clinical complications which were assessed using Mayo scores, Crohn's Disease Activity Index (CDAI) score, weight gain, enhanced patient health perception, Lichtiger Index and Harvey-Bradshaw Index or general wellbeing. On the other hand, cannabinoid use remains questionable because evidence of high quality is yet to surface vividly, especially in terms of the mode of administration and the appropriate dose. It is also notable that the findings were characterized by a state of high heterogeneity in terms of the study designs of the studies that were selected, disease activity indices, the duration of treatment by different scholarly researchers, the difference in the modes of administration of cannabinoid and cannabis by different researchers, variations in cannabis dosage, differences in the selected studies' inclusion criteria, and variations in their case definitions. The implication is that whereas the efficacy of cannabinoid use in IBD treatment was reported in most studies, outcome generalizability from the review was highly likely to be restricted. In the future, it is recommended that randomized controlled trials center, set universal parameters for IBD treatment using cannabis and cannabinoids to determine intervention safety and effectiveness as well as having homogenous outcomes that can be compared between different studies. In so doing, the appropriate dose and ideal mode of administration of cannabis and its derivatives might be discerned, ensuring relevance based on patient characteristics such as gender and age, as well as the appropriate administration mode and dose as per IBD symptom severity.

Introduction Preexposure prophylaxis (PrEP) dosing options such as event-driven PrEP hold promise to increase PrEP uptake among gay, bisexual, and queer men (GBQM), but their impacts have not yet been realized and uptake by GBQM suitable for PrEP remains slow in countries where it is only considered an alternative option to daily PrEP. Methods We conducted semi-structured interviews between June 2020 and February 2021 with 40 GBQM in Australia to understand PrEP dosing behaviors, knowledge, and preferences. Results All participants commenced PrEP daily; 35% had ever switched to non-daily PrEP, mostly taking it event-driven. GBQM who preferred non-daily PrEP had infrequent or predictable sex, were concerned about cost given infrequency of sex, and/or wanted to minimize unnecessary drug exposure. Accurate knowledge of event-driven PrEP was poor. However, reflecting concepts underpinning critical pedagogy, having accurate knowledge was supported by access to consistent messaging across...

Background Buprenorphine-naloxone is an evidence-based treatment for Opioid Use Disorder. However, despite its efficacy, nearly half of participants are unsuccessful in achieving stabilization (i.e., period of time following medication induction in which medication dose is adjusted to be effective in reducing cravings/withdrawal, minimize potential side effects, and eliminate illicit substance use). This paper presents the study design and protocol for a digital health intervention designed to promote engagement in and adherence to buprenorphine treatment, offered through an outpatient addiction treatment center, through motivational enhancement and distress tolerance skills training. Personalized feedback interventions represent a promising method to effectively motivate engagement in and adherence to buprenorphine treatment. These interventions are generally brief, individually tailored, and have the potential to be delivered via mobile platforms. Distress tolerance, a transdiagno...

Long-acting buprenorphine formulations have been recently marketed for the Opioid Agonist Treatment (OAT) of opioid use disorder (OUD) associated with medical, social, and psychological support. Their duration of action ranges from one week up to 6 months. The non-medical use of opioids is increasing with a parallel rise in lethal overdoses. Methadone and buprenorphine are the standard treatment for opioid dependence. Methadone Maintenance Treatment (MMT) is widely recognized as one of the most effective ways of reducing the risks of overdose, crime, and transmission of HIV (Human Immunodeficiency Virus) in people who use opioids; however, its effectiveness has been hindered by low rates of uptake and retention in treatment. Furthermore, both methadone and buprenorphine are widely diverted and misused. Thus, a crucial aspect of treating OUD is facilitating patients’ access to treatment while minimizing substance-related harm and improving quality of life. The newly developed long-ac...

COVID-19 restrictions and increased risk of overdose for street-based people with opioid dependence in South Africa To the Editor: The placement of street-based people in temporary shelters as part of South Africa (SA)'s lockdown efforts to mitigate the COVID-19 epidemic increases the risk of overdose among people who are dependent on heroin. The number of street-based heroindependent people is unknown, [1] but many of the country's estimated 75 000 people who inject drugs live on the street and inject heroin, [2] and many more smoke it (known locally as nyaope, whoonga and unga). [3] People with opioid dependence develop tolerance after repeated use, and an increased dose is essential to maintain a required effect. Tolerance reverses within several days of abstinence, and the opioid system up-regulates and resensitises to pre-use levels. [4] Failure to moderate dosing to accommodate reduced tolerance after periods of abstinence is a significant cause of overdose following release from prison or inpatient rehabilitation and after periods of drug supply interruption. [5] Globally, opioid overdoses are the leading cause of drug-related deaths, inducing respiratory depression and hypoxia that can be fatal. [6] Opioid substitution therapy (OST), using methadone or buprenorphine at a correct dose as long-term maintenance, is the gold standard for managing opioid dependence. [7] OST improves health and reduces overdose mortality. Overdose is also mitigated through community awareness and training, and wide distribution of naloxone. [8] Apart from efforts across Pretoria to provide access to OST as maintenance and one shelter in Durban providing methadone as part of managed withdrawal, the majority of the heroin-dependent population who remain in shelters will have an extended, involuntary period of abstinence. Heroin is a potent physical and psychological analgesic and helps many people to endure the adverse conditions, hopelessness and stigma of living on the street. [9] Furthermore, there is a strong relationship between heroin dependence and adverse childhood events and trauma. [10] Without OST as maintenance, most heroindependent people are likely to re-initiate heroin use once they return to their communities. [11] After the lockdown in SA, the overdose risk will be elevated due to reduced tolerance and the concurrent use of other central nervous system depressants (e.g. alcohol and benzodiazepines). [12] The trauma of leaving a 'formal' safe shelter and ongoing drug criminalisation further increase overdose vulnerability. [13] The potential for poisoning from potent synthetic opioids, such as fentanyl and its analogues, in light of the changed drug market is unknown. [14] To mitigate the risk of overdose in the time of COVID-19, we recommend: • That government funds the scaling up and access to OST at all shelters in locations where the capacity for OST initiation exists through partnership with civil society and academic institutions. People initiated onto OST during lockdown should be linked to ongoing maintenance therapy with access to psychosocial services once released. • That government enables civil society and academic institutions to establish opioid overdose prevention programmes before the lockdown period ends, that focus on education and skillsbased training of people who use opioids. Additionally, increased community-based access to naloxone in health and substance use treatment centres and the provision of naloxone to OST clients, paired with appropriate administration training, is needed.

Primary care presentations of dry eye disease (DED) are common and pose a diagnostic challenge due to the variety of symptoms and the absence of certainty for family practitioners. While there are many published articles on the topic, the 2017 Tear Film and Ocular Surface Society Dry Eye Workshop was a landmark report in distinguishing multifactorial differences. Redefined terms clarified the DED disorder. The ocular surface-the tear/air interfaceis the primary refractive component of the eye, which is why DED is so significant and impacts vision. There is a high prevalence of DED in the community, ranging from 5% to 30% of people across multiple studies. Elderly patients have up to 75% increased risk of DED and receive more intensive treatment than younger age groups. DED is also more common in women than men, Electronic supplementary material The online version of this article (

Inflammatory bowel diseases (IBDs) are chronic conditions of unknown cause or cure. Treatment seeks to reduce symptoms and induce and maintain remission. Many patients have turned to alternatives, such as cannabis, to alleviate living with IBD. This study reports the demographics, prevalence, and perception on cannabis use of patients attending an IBD clinic. Patients agreed to participate and completed an anonymous survey during their visit or online. Descriptive analysis, Fisher’s exact test, and Wilcoxon-Mann-Whitney rank-sum test were used. One hundred and sixty-two adults (85 males, 77 with CD) completed the survey. Sixty (37%) reported use of cannabis, of which 38 (63%) used it to relieve their IBD. A value of 77% reported low to moderate knowledge about cannabis, and 15% reported little to no knowledge. Among cannabis users, 48% had discussed use with their physician, but 88% said they would feel comfortable discussing medical cannabis for IBD. Most saw improvement of their s...

• Relapses occurred in 54% of rural patients at an opioid use disorder clinic. • Almost half of all participants reported four or more adverse childhood events. • ACE score was related to an increase in the odds of relapse. • Each treatment visit reduced the odds of opioid relapse. • The highest relapse rate was on the first clinic visit.

Aims: Prospective data collection, using interactive voice response (IVR) and text-messaging (SMS) systems, provide an exciting new research methodology for examination of substance use and other risk behaviors. This paper presents data from an experimental study of a high risk sample of emerging adults to examine compliance under different data collection methods (IVR, SMS) and assessment schedules (daily, weekly). Methods: Emerging adults (18-28) who agreed to be recontacted (n = 279) from the FYI study completed a baseline assessment and were randomized into one of four groups: either weekly (12 weeks) or daily (90 days) surveys by IVR or by SMS. In addition, the amount of the incentive for completion changed by cohort. Cohort 1 (n = 87) was paid $1 per daily survey or $7 per weekly survey. Cohort 2 (n = 192) were paid $4 per daily survey and $28 per weekly survey. Results: The mean time for weekly survey was 35.2 min for SMS and 7.4 min for IVR and for daily was 16.9 min for SMS and 2.2 min for IVR. Overall, ANOVA analysis shows that the main effect of assessment schedule was significant (p < .05), with post-hoc tests indicating that IVR weekly reported significantly greater compliance (mean = 67.0) than IVR daily (mean = 48.0); SMS weekly (mean = 55.3) did not differ from SMS daily (mean = 55.3). Overall, Cohort 2 showed significantly greater compliance (mean = 61.0) than cohort 1 (mean = 45.1) (p < .001). When examining cohort differences by experimental groups, Cohort 2 had significantly better compliance than cohort 1 for the IVR-weekly (p < .01) and the SMS daily (p < .05), but not for the other groups. Conclusions: Rates of compliance varied by frequency and method of data collection. Although support was found for increasing incentives on improving compliance rates, these effects varied by method of data collection. Future analyses will examine the effects of assessment schedule and data collection methods on reliability and validity of self-reports of substance use and other high risk behaviors. Financial support: NIDA# RO1 DA 035183.

Aims: Despite the increase in cannabis treatment seeking there has been no assessment of changes in treatment seeking behaviour for cannabis problems associated with the introduction of these clinics. This study aims to (1) describe the characteristics of clients attending cannabis clinics and compares, (2) treatment seeking history, and (3) treatment completion rates between specialist and non-specialist counselling clinics. Methods: An observational study of administrative information from 209,012 drug and alcohol treatment episodes from services reporting to the NSW Alcohol and Other Drug Treatment Services Minimum Dataset, July 2003-June 2008 Results: Across all episodes, cannabis was the second most prevalent primary drug of concern (17.8%, n = 37242) after alcohol across all treatment types. The majority of clients seeking treatment for cannabis as a primary concern were male (69.4%, 26,088), with a mean age of 29 years. Counselling was the most common cannabis treatment (34.1%, n = 12713) with 11.6% (n = 1476) of those receiving counselling having done so at a cannabis clinic. Those treated in specialist cannabis clinics were older (30.12 years vs. 27.95 years; p < 0.0001); had shorter episode durations (10.95 weeks vs. 12.71 weeks; p < 0.0001); and were more likely to be naïve to treatment (53.7% vs. 47.7%; p < 0.0001), than those in non-specialist clinics. Conclusions: Cannabis clinics have attracted groups traditionally difficult to attract and retain in treatment. As the cohort of daily cannabis users age, it is important such dedicated services are attractive to older clients who have not previously sought treatment. Rigorous, prospective research examining client treatment outcomes is now warranted.

2023 Update. Summarizes and references compelling evidence for a relationship between Vitamin D deficiency, “Flu Season,” and COVID vulnerability. A five page document suitable for sharing and printing.

The opening page has a flyer with a simple summary for visual impact, the next four pages summarize the scientific research, including links to source material for easy verification, that highlights some of the most compelling evidence of a causal relationship between Vitamin D deficiency, “Flu Season” and COVID vulnerability. Page 4 features a chart showing the seasonal pattern of Covid-19 deaths in 2020, the same pattern we see every year for flu deaths. The chart on page 4 shows the results of a large study (over 190,000 patients) showing the relationship between Vitamin D blood levels and the likelihood of testing positive for Covid-19.

Approximately 15% of hospitalized patients have an active substance use disorder (SUD). Starting treatment for SUD, including medications, during acute hospitalizations can engage patients in addiction care. In July 2015, the Boston Medical Center Addiction Consult Service (ACS), began providing inpatient diagnostic, management, and discharge linkage consultations. We describe this implementation. The ACS staff recorded SUDs diagnoses and medication recommendations and tracked follow-up data for affiliated outpatient office-based addiction clinics and methadone maintenance programs. We assessed the number of consults, SUDs diagnoses, medications recommended and initiated, and outpatient addiction clinic follow-up. Over 26weeks, the BMC ACS completed 337 consults: 78% had an opioid use disorder (UD), 37% an alcohol UD, 28% a cocaine UD, 9% a benzodiazepine UD, 3% a cannabinoid (including K2) UD, and &lt;1% a methamphetamine UD. Methadone was initiated in 70 inpatients and buprenorphi...

With the advent and acceptance of biological medicine, now called as modern biomedicine (or allopathy), the older regional medical systems were categorized as complementary and alternative medicine (CAM). Recently, the term CAM has been replaced with ''integrative medicine.'' This viewpoint manuscript focuses on the essential connotation of such terms and clarifies the debates on the several confusing terminologies hampering its actual conceptualization and leading to the ''othering'' phenomenon in health care approaches. Integrative medicine, in its essence, is a form of holistic and evidence-based health care approach that includes but is not limited to medical treatment. A closer look at the current management protocols of most noncommunicable diseases, such as diabetes mellitus, hypertension, obesity, pain syndromes, and psychiatric illnesses reveals that it incorporates relevant evidence-based management of all health care domains, along with mainstream pharmacologic and surgical treatment options. These management approaches point toward an already existing integration in the mainstream medical practice. Simultaneous management of all the dimensions of health and illness by expanding the current sphere of integration will ultimately result in comprehensive patient care. Therefore, we conclude that integrative medicine is essentially an application of different ''culturally sensitive'' health care approaches, optimally tailored to a given patient's needs and difficulties. Efforts are needed at the clinical, research, and administrative levels to reduce the ''othering'' phenomenon seen in health care approaches that are often detrimental to efficient patient care. There is a need to promote collaboration between different disciplines and generate evidence base to optimize integrative medical practice further. Establishing interdisciplinary departments of integrative medicine at mainstream medical institutions may be the first step in this direction.

Background Morbidity and mortality related to opioid use disorder (OUD) in the U.S. is at an all-time high. Innovative approaches are needed to address gaps in retention in treatment with medications for opioid use disorder (MOUD). Mobile health (mHealth) approaches have shown improvement in engagement in care and associated clinical outcomes for a variety of chronic diseases, but mHealth tools designed specifically to support patients treated with MOUD are limited. Methods Following user-centered development and testing phases, a multi-feature smartphone application called HOPE (Heal. Overcome. Persist. Endure) was piloted in a small cohort of patients receiving MOUD and at high risk of disengagement in care at an office-based opioid treatment (OBOT) clinic in Central Virginia. Outcomes were tracked over a six-month period following patient enrollment. They included retention in care at the OBOT clinic, usage of various features of the application, and self-rated measures of mental...

The EXIT-CJS (N = 1005) multisite open-label randomized controlled trial will compare retention and effectiveness of extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR NTX) to treat opioid use disorder (OUD) among criminal justice system (CJS)-involved adults in six U.S. locales (New Jersey, New York City, Delaware, Oregon, Connecticut, and New Hampshire). With a pragmatic, noninferiority design, this study hypothesizes that XR-B (n = 335) will be noninferior to XR-NTX (n = 335) in retention-in-study-medication treatment (the primary outcome), self-reported opioid use, opioid-positive urine samples, opioid overdose events, and CJS recidivism. In addition, persons with OUD not eligible or interested in the RCT will be *

We describe a case of Crohn's disease occurring in a young Tanzanian female. Crohn's disease is rare in Africa and not encountered normally. The presentation of Crohn's disease overlaps with many other abdominal disorders that are common in an African setting, such as tuberculosis and schistosomiasis. The disease is probably underdiagnosed in Africa due to limitations in diagnostic testing and rarity.

Objectives To explore the independent association between cannabis abuse and subsequent hospitalizations for acute pancreatitis (AP) and delineate the demographic differences among AP in patients with and without persistent cannabis abuse. Methods We conducted a retrospective cross-sectional study using the nationwide inpatient sample and included 50,444,133 patients (age 18-50 years) with a primary discharge diagnosis for medical illnesses and further grouped by presence of AP (N = 666,248). We used the logistic regression model to measure the odds ratio (OR) of the association between cannabis abuse and hospitalization for AP and adjusted it for demographic confounders and comorbid risk factors. Results Cannabis abuse significantly increases the odds for AP-related hospitalization (OR 2.12, P &lt;0.001). When the regression model was controlled for potential risk factors (gall stones, cystic fibrosis, hypertriglyceridemia, hypercalcemia, hyperparathyroidism, abdominal surgeries, t...

Background: Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed. Purpose: To synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain.