Long-term Users Research Articles

Examining Use Behavior of a Goal-Supporting mHealth App in Primary Care Among Patients With Multiple Chronic Conditions: Qualitative Descriptive Study.

Although mobile health (mHealth) apps are increasingly being used to support patients with multiple chronic conditions (multimorbidity), most mHealth apps experience low interaction and eventual abandonment. To tackle this engagement issue, when developing an mHealth program, it is important to understand the social-behavioral factors that affect patients' use behavior. The aim of this study was to explore the social and behavioral factors contributing to patients' use behavior of an mHealth app called the electronic Patient-Reported Outcome (ePRO). The ePRO app supports goal-oriented care delivery in interdisciplinary primary care models. A descriptive qualitative study was used to analyze interview data collected for a larger mixed methods pragmatic trial. The original 15-month trial was conducted in 6 primary care teams across Ontario, Canada, between 2018 and 2019. The eligibility criteria for patients were being aged ≥60 years with ≥10 visits within the previous 12 months of study enrollment. For this analysis, patients were classified as long-term or short-term users based on their length of use of the ePRO app during the trial. The Social Cognitive Theory by Bandura was used to categorize social-behavioral factors that contributed to patients' decision to continue or discontinue using the app. The patient-provider relationship emerged as a key factor that shaped patients' experiences with the app and subsequent decision to continue using the app. Other factors that contributed to patients' decision to continue using the app were personal and social circumstances, perceived usefulness, patients' previous experience with goal-related behaviors, and confidence in one's capability. There was an overlap of experience between long- and short-term app users but, in general, long-term users perceived the app to be more useful and their goals to be more meaningful than short-term app users. This observation was complicated by the fact that patient health-related goals were dynamic and changed over time. Complex patients' use behavior of a goal-supporting mHealth app is shaped by an array of sociobehavioral factors that can evolve. To tackle this dynamism, there should be an emphasis on creating adaptable health technologies that are easily customizable by patients and able to respond to their changing contexts and needs. ClinicalTrials.gov NCT02917954; https://clinicaltrials.gov/ct2/show/NCT02917954.

Recognition and treatment of anabolic androgenic steroid use: literature review

Viktorija Antonova-Šiaudvytė1 1Vilnius University, Faculty of Medicine, Vilnius, Lithuania Abstract Introduction. Anabolic androgenic steroids are used by athletes to improve performance and/or gain muscle mass. The most common adverse effects are acne and reproductive problems (testicular atrophy, impotence, azoospermia, male infertility, hypogonadism). Abuse increases the risk of cardiovascular and liver damage. Long-term users develop mental […]

Cost-effectiveness analysis of hydrophilic-coated catheters in long-term intermittent catheter users in the UK

Objective To estimate the cost-effectiveness of single-use hydrophilic-coated intermittent catheters (HCICs) versus single-use uncoated intermittent catheters (UICs) for urinary catheterization. Methods The evaluation took a UK national health service (NHS) perspective. The population of interest were people using intermittent catheters, with either a spinal cord injury or multiple sclerosis. A Markov model was developed that estimated costs and clinical evidence over the lifetime of a hypothetical cohort and applied health-related quality of life estimates. Model inputs were sourced from published evidence, including a network meta-analysis to inform the treatment effect (reduction in catheter-associated urinary tract infections [CAUTIs]), and were supported by expert opinion. The model outputs included per-patient lifetime costs, quality-adjusted life years (QALYs) and the incremental cost effectiveness ratio (ICER). Event counts were also produced. Results Using HCICs instead of UICs could prevent seven CAUTI events per patient over a lifetime horizon (1.8 requiring secondary care). Overall, lifetime use of HCICs is £3,183 more expensive than use of UICs per patient. However, for these additional costs, 0.55 QALYs are gained. The ICER is £5,755 per additional QALY gained. Key drivers of the model results were identified and subject to sensitivity analyses. The results were found to be robust to parameter uncertainty. Conclusion HCICs are likely to be a cost-effective alternative to UICs, a result driven by substantial reductions in the number of CAUTIs. Their adoption across clinical practice could avoid a substantial number of infections, freeing up resources in the NHS and reducing antibiotic use in urinary catheter users.

The Effects of Proton Pump Inhibitors in Acid Hypersecretion-Induced Vitamin B12 Deficiency: A Systematic Review (2022).

Gastroesophageal reflux disease (GERD) is the most common disease, for which proton pump inhibitors (PPIs) are a widely used class of drugs. Due to their efficacy and relative safety profile, PPIs are used chronically by GERD patients. Although it is a safe drug, particular attention focuses on the long-term adverse effects of PPI. The association with vitamin deficiencies has received additional focus since chronic PPI treatment increases the incidence of vitamin B12 deficiency, especially in the elderly. However, numerous studies regarding the establishment of an association between PPI and vitamin B12 status revealed conflicting results. In this systematic review, we systematically examined observational studies that focused on the impact of chronic PPI effects on vitamin B12 absorption and diagnostic biomarkers of vitamin B12 deficiency. Our review showed significant changes in diagnostic biomarkers of vitamin B12 status in long-term PPI users, including elevated homocysteine and methylmalonic acid (MMA) concentration levels defining cellular vitamin B12 deficiency. Although there is uncertainty regarding the exact mechanism, it supports the concept that long-term intake of PPI can have clinical implications for vitamins.

A nationwide survey of hydroxychloroquine retinopathy presenting to the hospital eye service in the United Kingdom

BackgroundThe risk of developing hydroxychloroquine retinopathy is considered sufficient to justify national monitoring programmes. There are an estimated 71,144–77,170 long-term hydroxychloroquine users in the UK. However, the number of patients diagnosed with retinopathy is unknown. This study aimed to identify the number of cases and clinical characteristics of hydroxychloroquine retinopathy diagnosed annually in hospital eye services across the UK.MethodsA nationwide, prospective case ascertainment study was undertaken using the British Ophthalmological Surveillance Unit, which sends approximately 1420 reporting cards to UK Ophthalmologists monthly. The case definition was two abnormal tests suggestive of hydroxychloroquine retinopathy. Demographic and clinical data relating to hydroxychloroquine use and retinopathy were collected from identified cases using a standardised questionnaire over a 1-year period (2018–2019).ResultsSixty-six cases of hydroxychloroquine retinopathy were reported, and 46 questionnaires were received (73% response rate). Twenty-four incident cases of hydroxychloroquine retinopathy were identified (24-43 cases following adjustment). The median duration of drug therapy was 19 years (range: 4–50 years, IQR: 14.5–23 years). Fourteen patients were asymptomatic, and 9 symptomatic at diagnosis. A trend towards a lower mean deviation on visual field testing was observed in the symptomatic group (−11.55 dB versus −6.9 dB; P = 0.15).ConclusionBetween 1 in 1655 and 3215 (0.03–0.06%) long-term hydroxychloroquine users were diagnosed with retinopathy over the study period. We estimate that monitoring was available for 1.9–3.8% of long-term users, accounting for a lower than expected incidence. The high proportion of symptomatic retinopathy at diagnosis underlines the importance of monitoring to detect pre-symptomatic disease.

Metformin Use and the Risk of Myeloproliferative Neoplasms in a Danish Population Based Cohort

INTRODUCTION The peroral antidiabetic drug metformin (MT) is primarily prescribed for hyperglycaemia due to insulin-resistance in type-2 diabetes mellitus or metabolic syndrome and is a widely used drug worldwide. Use of MT has been associated with reduced cancer risk and mortality in meta-analyses (Gandini et al, 2014). Constitutive activation of the JAK-STAT pathway by the recurrent gain-of-function mutation JAK2V617F is a hallmark of MPN and has been related to the formation of bone marrow fibrosis by altering the bone marrow microenvironment. Preclinical studies of MT have shown antileukemic activity in myeloid neoplasms by activating the AMPK-mTOR-pathway, downregulating JAK2/STAT signaling, and mitochondrial activity suggesting MT as a possible treatment option in MPN (Biondani & Peyron, 2018; MacHado-Neto et al, 2018; Kawashima & Kirito, 2016). Recently, the phase II study Fibromet failed to demonstrate effect of MT in reversing bone marrow fibrosis in myelofibrosis. However, significant down regulation of the JAK-STAT-pathway and cytokine production were demonstrated (Campos et al, 2021). Currently, the association between MT use and the risk of MPNs remains to be elucidated. METHODS We conducted a nationwide population-based nested case-control study to compare MT use among patients diagnosed with MPN between 2010 and 2018 and a matched population without MPN in the Danish general population to estimate odds ratios (ORs) for MPN associated with MT use. We utilized five large nationwide Danish health registries to obtain data on exposure, outcome, and covariates for adjustment. The index date was defined as the date of MPN diagnosis and cases were identified using the National Chronic Myeloid Neoplasia Registry covering >90% of MPN cases in Denmark (Bak et al, 2016). Controls were selected by incidence density sampling (five to one) from the Danish general population matched on age, gender, and calendar year. Data on MT exposure were collected from the Danish National Prescription Registry. "Ever-use” was defined as a minimum of one prescription before the index date and "Long-term use” as >5 years of MT use (assuming an intake of the WHOs defined daily dose for MT at 2000 mg plus 25% to account for minor prescription variations and incompliances). Exposure to MT, comorbidity, and concomitant drug use were disregarded 12 months prior to the index date to avoid reverse causation. By conditional logistic regression analysis, we obtained ORs and 95% confidence intervals (95% CIs) adjusted for study design (age, gender, and index date) and fully adjusted ORs (aORs) (see footnote in Table 2 for adjusted variables). RESULTS The study population included a total of 3,816 cases and 19,080 matched controls (Table 1). Exposure assessment categorized 7.0% of cases and 8.2% of controls as "Ever-users” of MT resulting in an aOR for MPN of 0.70 (95% CI, 0.61-0.81). Long-term users were rare and comprised 1.1% of cases and 2.0% of controls resulting in an aOR for MPN 0.45 (0.33-0.63). When assessing the duration of MT exposure, we found a trend towards a dose-response relationship (<1 year: aOR 0.79 [0.62-1.00]; 1-4.99 years: 0.78 [0.64-0.95]; 5-9.99 years: 0.42 [0.29-0.61]; >10 years: 0.56 [0.30-1.03]); however, this was not statistically significant for the >10 years category, most likely due to small numbers. In stratified analyses the protective effect of long-term MT use was consistent according to gender with aOR of 0.37 (0.23-0.60) and 0.56 (0.36-0.89) for males and females, respectively, compared to males and females without MT use. In a subgroup analysis the effect was consistent across all age groups and MPN-subtypes. However, aORs did not reach statistical significance for age <60 years, myelofibrosis, and MPN unclassifiable (Table 2). CONCLUSION In this study we found an inverse association between MT use and risk of MPNs indicating a potential protective effect of MT on the development of MPNs. The protective effect was most pronounced for long-term use, older age (≥60 years) and for polycythemia vera and essential thrombocythemia. Whether this effect is causal should be determined interventional studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effects of concomitant benzodiazepines and antidepressants long-term use on perspective-taking

Background: Benzodiazepines and antidepressants are known to alter responses to empathic pain when used alone, however the effects of their combined use on the perspective-taking facet of empathy are unknown. In order to examine the effects of concomitant benzodiazepines and antidepressants long-term use on perspective-taking, we analyzed behavioral and neural changes on perspective-taking ability using event-related potentials. Methods: To this purpose, 13 long-term concomitant benzodiazepines and antidepressants users and 13 healthy controls performed a task designed to assess affective perspective-taking with simultaneous EEG recording. Results: The behavioral results revealed similar performance between groups. The neural results showed no significant differences between groups for the N170 and late positive potential (LPP) components. These results seem to suggest that long-term use of benzodiazepines and antidepressants together does not affect perspective-taking abilities nor the processing of related information. Conclusions: The concomitant benzodiazepines and antidepressants long-term use seem to preserve the perspective-taking ability of social cognition.

Prophylactic action of ayahuasca in a non-human primate model of depressive-like behavior.

Observational studies of long-term users of ayahuasca, an Amazonian psychedelic brew, suggest an increase in resilience via improvements in emotion and cognition. Ayahuasca has also demonstrated clinical antidepressant effects in human and animal studies; however, its potential prophylactic action in depression has not been previously studied. Therefore, this experimental study sought to evaluate the potential prophylactic effects of repeated and long-term ayahuasca use, via the modulation of resilience, in a non-human primate animal model, Callithrix jacchus, subjected to a protocol for induction of depressive-like behavior. For the formation of the study groups, some juvenile marmosets were kept in their family groups (GF = 7), while for the two experimental groups, the animals were removed from the family and kept socially isolated. Then, part of the isolated animals made up the group in which ayahuasca was administered (AG, n = 6), while for others, no intervention was made (IG, n = 5). AG animals took ayahuasca (1.67 mL/300g body weight) at weeks 4 (before isolation), 8, and 12 (during isolation) of the study. More adaptive stress response was observed for the AG when compared to the IG. The AG showed higher cortisol reactivity and fecal cortisol levels than IG, while both measures were similar to FG. Moreover, AG animals showed no signs of anhedonia and no increase in chronic stress-related behaviors, which were expressed by the IG. Thus, ayahuasca seems to promote the expression of resilient responses, indicating a prophylactic action, buffering the emergence of depressive-like behaviors and cortisol alterations associated with major depression. These results are encouraging for further research on the prophylactic use of psychedelics to prevent psychopathologies associated with chronic stress.

Risk Factors for QT Prolongation in Patients with Chronic Hydroxychloroquine Use.

Hydroxychloroquine is used as an antimalarial and immunomodulator, however it can induce QT prolongation that could potentially lead to fatal arrhythmia. We investigated changes in QT interval in long-term hydroxychloroquine users, and identified possible risk factors associated with significant QTc prolongation. We retrospectively enrolled 3603 patients who received long-term hydroxychloroquine treatment from 2009 to 2019, of whom 167 had electrocardiography (ECG) results before and during hydroxychloroquine therapy. Baseline characteristics, laboratory data, comorbidities, concurrent medications, and related clinical outcomes were reviewed. Overall, 225 patients (6.2%) died within the study period, with 50 patients (1.4%) continuously receiving hydroxychloroquine treatment until death. Three patients had fatal ventricular arrhythmia. No significant change in corrected QT interval (QTc) was noted before and during hydroxychloroquine treatment (451.1 ± 39.9 ms vs. 456.0 ± 37.3 ms, P = 0.140) in the ECG cohort. Multivariable logistic regression showed that diabetes mellitus [odds ratio (OR): 9.55, 95% confidence interval (CI): 2.02-45.22; P = 0.005] and use of additional QT-prolonging drugs (OR: 2.89, 95% CI: 1.40-5.94; P = 0.004) were independent risk factors for significant QTc prolongation. Multiple linear regression, with the number of QT-prolonging drugs and comorbidities including diabetes mellitus, hypertension, and atrial fibrillation as explanatory variables, predicted QTc response (adjusted R2 = 0.385) in the long-term hydroxychloroquine users. In the long-term users of hydroxychloroquine, those with diabetes mellitus and concurrent use of additional QT-prolonging drugs were at a higher risk of significant QTc prolongation. Baseline QTc interval, concurrent medications, and comorbidities predicted QTc response.

Linking a Survey of Clinician Benzodiazepine-Related Beliefs to Risk of Benzodiazepine Prescription Fills Among Patients in Medicare.

In this pilot study, we used a Medicare sample to identify primary care clinicians who prescribed a benzodiazepine (BZD) in 2017 and surveyed a random sample (n = 100) about BZD prescribing. Among 61 respondents, 11.5% (SD 5.9) of their patient panels filled a BZD prescription. Patients of primary care clinicians who agreed that potential harms to long-term BZD users were low had a greater BZD fill risk relative to patients of disagreeing primary care clinicians (adjusted risk ratio 1.31; 95% CI, 1.01-1.7). We highlight the potential of using Medicare claims to sample clinicians. Using claims-based objective measures presents a new method to inform the development of behavior-change interventions.

Polysubstance Use Plays a Key Role in Midlife Structural Brain Alterations in Long-term Cannabis Users

Approximately 147 million people across the world consume cannabis annually, making it the most commonly used illicit drug globally ( 1 World Health Organization Alcohol, Drugs, and Addictive Behaviours Unit. Cannabis.. https://www.who.int/teams/mental-health-and-substance-use/alcohol-drugs-and-addictive-behaviours/drugs-psychoactive/cannabisDate accessed: August 8, 2022 Google Scholar ). Although the use of cannabis has generally become more accepted and perceptions of harm have been decreasing in recent years ( 2 Patrick M.E. Schulenberg J.E. Miech R.A. Johnston L.D. O’Malley P.M. Bachman J.G. Monitoring the Future Panel Study annual report: National data on substance use among adults ages 19 to 60, 1976-2021. Monitoring the Future Monograph Series. University of Michigan Institue for Social Research, Ann Arbor, MI2022 Google Scholar ), negative effects of cannabis use on health and well-being have been identified. Cannabis use has been found to be associated with neurocognitive deficits in memory, learning, and attention and to contribute to alterations to both brain function and structure [see Volkow et al. ( 3 Volkow N.D. Swanson J.M. Evins A.E. DeLisi L.E. Meier M.H. Gonzalez R. et al. Effects of cannabis use on human behavior, including cognition, motivation, and psychosis: A review. JAMA Psychiatry. 2016; 73: 292-297 Crossref PubMed Scopus (480) Google Scholar ) for review]. However, existing studies examining the neural correlates of cannabis use have produced mixed findings in relation to cannabis-specific effects. The question of whether—and to what extent—cannabis use produces unique neural detriments compared with other psychoactive substances remains largely unknown. A possible reason for this knowledge gap is that there are likely other variables at play, variables that are often unaccounted for, that confound direct associations between cannabis use and neural outcomes. Pulling from literature at the intersection of developmental science, addiction research, and neuroscience, two likely targets are age and polysubstance use. SEE CORRESPONDING ARTICLE ON PAGE 861 Diminished Structural Brain Integrity in Long-term Cannabis Users Reflects a History of Polysubstance UseBiological PsychiatryVol. 92Issue 11PreviewCannabis legalization and use are outpacing our understanding of its long-term effects on brain and behavior, which is fundamental for effective policy and health practices. Existing studies are limited by small samples, cross-sectional measures, failure to separate long-term from recreational use, and inadequate control for other substance use. Here, we address these limitations by determining the structural brain integrity of long-term cannabis users in the Dunedin Study, a longitudinal investigation of a population-representative birth cohort followed to midlife. Full-Text PDF

Frequency of Worsening Clinical Test Values Related to Supplement Use: Estimation by Using Nationwide Online Survey

This study examined the frequency of worsening clinical test values related to supplement use using a nationwide online survey, with a focus on liver function markers, and clarified the differences between outcome indices of diarrhea or skin manifestations. A nationwide online survey was conducted with 73,010 supplement users from the previous year. Of these, 221 individuals with worsening clinical test values responded to the full-scale survey. To compare surveys with different outcome indices, we used previously reported data from similar surveys.Only 0.5% of individuals who self-reported worsening of clinical test values caused by supplement use recognized an almost certain causal relationship. Among the test items, blood lipids were the most frequently reported. The frequency of worsening liver function markers was 0.2% in supplement users. Among those who experienced worsening clinical test values, 56.1% received no treatment and 82.4% did not report the incidence of worsening clinical test values anywhere. The ingredient-based classification of products revealed more "Peptides or animal by-products" and "Combination products/not classifiable products" than those associated with other categories. Compared to the results of the survey about the experience of diarrhea or skin manifestations, those who experienced worsening clinical test values were predominantly men, frequent and long-term users, and individuals whose products could not be identified.Few supplement users experience worsening of liver function markers, which does not seem serious. However, it is difficult for supplement users to recognize abnormal changes by themselves. Thus, it is important to record product information, usage, and changes in physical condition.

Exploring of cardiac autonomic activity with heart rate variability in long-term kratom (Mitragyna speciosa Korth.) users: a preliminary study.

BackgroundKratom is a psychoactive plant used to enhance productivity among laborers in Southeast Asian countries. Previous findings from in vitro research of mitragynine, a major component of kratom, suggested a possible risk of heart function abnormality. However, the cardiac autonomic function in long-term kratom users with chewing forms has never been studied. This study aimed to investigate heart rate variability (HRV) indices of cardiac autonomic function in long-term kratom chewers (LKC), compared to the control levels, and also to examine the correlation between HRV indices and relevant kratom use factors.MethodA total number of 50 participants consisted of LKC (n = 31) who regularly chewed fresh kratom leaves for at least 2 years and demographically matched control subjects (n = 19). Resting electrocardiogram (ECG) signals were recorded from subjects for 3 min to analyze the ultrashort HRV in the frequency domain. The normalized low frequency (LFn) and high frequency (HFn) were chosen to be the HRV indices to evaluate cardiac autonomic function. The comparison of HRV indices between groups and the correlation between HRV indices and duration and quantity of kratom use was further conducted in statistical analysis.ResultsThe LKC significantly increased LFn together with enhanced HFn compared to the control group tested, indicating that LKC changed cardiac autonomic function with parasympathetic dominance. Furthermore, no significant correlation between the HRV indices and the duration and quantity of kratom use was found, suggesting that the HRV indices were not relevant to these factors. The present study provided scientific-based evidence of cardiac autonomic modulation in long-term kratom chewers. LFn and HFn may be promising cardiac autonomic indicators for monitoring health outcomes in LKC.

Risk of gastric and oesophageal adenocarcinoma following discontinuation of long-term proton-pump inhibitor therapy

BackgroundThere is uncertainty whether long-term use of proton-pump inhibitors can cause gastric adenocarcinoma (GAC) and oesophageal adenocarcinoma (OAC). This study aimed to determine how discontinuation of long-term PPI therapy influences the risk of GAC and OAC.MethodsThis population-based cohort study included all long-term users of PPI therapy in Sweden in 2005–2018 was based on Swedish nationwide health registry data. The exposure was discontinuation of long-term PPI therapy, defined as no dispensation of PPI following inclusion and used as a time-varying variable, compared to remaining on PPI. Main outcomes were GAC and OAC, while oesophageal squamous cell carcinoma (OSCC) was included as a comparison outcome. Incidence rate ratios (IRR) with 95% CI adjusted for age, sex, comorbidity, obesity, diabetes, hyperlipidaemia, NSAIDs/aspirin, and statins were calculated with Poisson regression.ResultsAmong 730,176 long-term PPI users (mean age 65.6 years, 58.4% females) with 4,210,925 person-years at risk (median 5.5 person-years), 439,390 (60.2%) discontinued PPIs. In total, 495 developed GAC, 598 OAC, and 188 developed OSCC. PPI discontinuation was associated with decreased risk of GAC (IRR 0.81, 95% CI 0.67–0.98) and OAC (IRR 0.80, 95% CI 0.68–0.96), but not OSCC (IRR 1.10, 95% CI 0.82–1.49) compared to continued PPI use. Stratified analyses showed decreased point estimates across most age categories and both sexes for GAC and OAC risk among participants discontinuing PPI therapy.ConclusionDiscontinuation of long-term PPI therapy may decrease the risk of GAC and OAC, suggesting that physicians should consider ceasing prescribing long-term PPI in patients without continued indication for its use.

Mindfulness-induced endogenous theta stimulation occasions self-transcendence and inhibits addictive behavior.

Self-regulation is instantiated by theta oscillations (4 to 8 Hz) in neurons of frontal midline brain regions. Frontal midline theta (FMΘ) is inversely associated with default mode network (DMN) activation, which subserves self-referential processing. Addiction involves impaired self-regulation and DMN dysfunction. Mindfulness is an efficacious self-regulatory practice for treating addiction, but little is known about the mechanisms by which mindfulness reduces addictive behavior. In this mechanistic study of long-term opioid users (N = 165), we assessed meditation-induced FMΘ as a mediator of changes in opioid misuse. Relative to a supportive psychotherapy control, participants treated with Mindfulness-Oriented Recovery Enhancement (MORE) exhibited increased FMΘ during a laboratory-based meditation session. FMΘ during meditation was associated with self-transcendent experiences characterized by ego dissolution, nondual awareness, and bliss. MORE’s effects on decreasing opioid misuse were mediated by increased FMΘ. Given the role of aberrant self-referential processing in addiction, mindfulness-induced endogenous theta stimulation might “reset” DMN dysfunction to inhibit addictive behavior.

Characteristics and Potential Risk Factors of Hydroxychloroquine Retinopathy in Patients with Systemic Lupus Erythematosus: Focusing on Asian Population.

Purpose: Hydroxychloroquine (HCQ) would cause irreversible retinal damage, despite its pivotal role in treatment of systemic lupus erythematosus (SLE). This study aims to reassess the characteristics and risk factors of HCQ retinopathy. Methods: This study included patients with SLE who had used HCQ for >5 years and received ophthalmologic examinations during November 2017 to December 2020 in a tertiary hospital in Taiwan. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) were performed in all patients. Visual field assessment and/or multifocal electroretinography were done if suspicious findings were noted by SD-OCT or FAF. Clinical features and dosing details of HCQ were recorded by chart review. Results: Ninety-two patients were included, with the median duration of drug exposure of 11.2 years [interquartile range (IQR) 9.4-12.7 years], median daily dose of 6.9 mg/kg (IQR 6.1-7.7 mg/kg), and cumulative dose of 1,503.6 g (IQR 1,257.7-1,805.9 g). HCQ retinopathy was diagnosed in 10.9% of patients (10 of 92), and in 20.8% of patients (5 of 24) who complained about blurred vision. High myopia [odds ratio (OR) 5.03; 95% confidence interval (CI) 1.29-24.79; P = 0.03] and lower body weight (OR 0.88; 95% CI 0.78-0.97; P = 0.03) were significantly associated with HCQ retinopathy. Conclusions: Long-term HCQ users may suffer from retinal toxicity. Since there is no optimal substitute for HCQ, careful retinal evaluation is needed to avoid unnecessary drug discontinuation. In addition, an association between high myopia and HCQ retinopathy was noted. More investigation is needed to clarify this association.

A Blockchain-based Trust and Reputation Model with Dynamic Evaluation Mechanism for IoT

The rapid development of the Internet of Things (IoT) has dramatically increased the number of distributed IoT devices and users. Trust and Reputation Model (TRM) is a well-known technique for improving the security of IoT, which detects malicious attacks by evaluating user behavior. Since traditional distributed TRMs lack secure and reliable data sharing mechanisms, some works have integrated the TRMs into the trusted blockchains. Nevertheless, they have not realized the security requirements of the comprehensive assessment of user behavior and dynamic evaluation of reputation. Therefore, this paper introduces a Blockchain-based Trust and Reputation Model (BTRM), which evaluates user reputation from many aspects and can resist multiple malicious attacks in the distributed network. Second, we propose a novel Dynamic Evaluation Mechanism (DEM), which reduces the number of reputation evaluations without degrading network security and builds a trusting foundation between long-term inactive users and the network. Eventually, we deploy the proposed model DEM-BTRM in a prototype system of Hyperledger Fabric and compare it with existing reputation evaluation methods. The results show that the DEM-BTRM can comprehensively evaluate user behavior and dynamically detect malicious attacks.

FORMULATION OF CREAM CONTAINING IBUPROFEN 5%

Background: Non-steroidal anti-inflammatory drug (NSAID) is a group of drugs commonly used to treat musculoskeletal diseases. However, according to statistics, up to 25% of long-term NSAID users had peptic ulcer disease, and 2-4% had gastrointestinal bleeding or perforation. Therefore, it is necessary to study preparations for external use to minimize these undesirable effects. Objectives: The cream containing ibuprofen 5% has been formulated with good physical characteristics and high bioavailability in the in vitro test based on the support of design and optimization software. Methods: According to the D–Optimal model, the formula models of cream containing ibuprofen 5% were designed with the different concentrations of oil phase, water phase, and emulsifier. The formulas of medicinal cream were prepared by direct emulsification method, then evaluated and compared to the criteria consisting of the phase separation, spreadability, and release of the active ingredient through cellulose nitrate membrane with a 0.45 µm pore size. Results: The formulation of the cream containing ibuprofen 5% with various components consisting of ibuprofen (5 g), cetyl alcohol (3.85 g), stearyl alcohol (1.54 g), beeswax (3.85 g), paraffin oil (10.77 g), span 80 (11.70 g), sodium lauryl sulfate (3.30 g), propylene glycol (59.90 g), and nipagin M (0.10 g). The results also showed that the product had good physical characteristics with no separation between the oil and the water phases, a spread area of 618 mm2, and the release of the active ingredient through the cellulose nitrate membrane at 0.209 mg/mL. Conclusion: The cream containing ibuprofen 5% was researched based on excipients of oil and water, making an emulsion structure stable and helping meet the foundational criteria according to the medicinal cream regulations.

Preparedness for healthy ageing and polysubstance use in long-term cannabis users: a population-representative longitudinal study

SummaryBackgroundCannabis is often characterised as a young person’s drug. However, people who began consuming cannabis in the 1970s and 1980s are no longer young and some have consumed it for many years. This study tested the preregistered hypothesis that long-term cannabis users show accelerated biological ageing in midlife and poorer health preparedness, financial preparedness, and social preparedness for old age.MethodsIn this longitudinal study, participants comprised a population-representative cohort of 1037 individuals born in Dunedin, New Zealand, between April, 1972, and March, 1973, and followed to age 45 years. Cannabis, tobacco, and alcohol use and dependence were assessed at ages 18 years, 21 years, 26 years, 32 years, 38 years, and 45 years. Biological ageing and health, financial, and social preparedness for old age were assessed at age 45 years. Long-term cannabis users were compared using independent samples t tests with five groups: lifelong cannabis non-users, long-term tobacco users, long-term alcohol users, midlife recreational cannabis users, and cannabis quitters. In addition, regression analyses tested dose–response associations for continuously measured persistence of cannabis dependence from age 18 years to 45 years, with associations adjusted for sex, childhood socioeconomic status, childhood IQ, low childhood self-control, family substance dependence history, and persistence of alcohol, tobacco, and other illicit drug dependence.FindingsOf 997 cohort members still alive at age 45 years, 938 (94%) were assessed at age 45 years. Long-term cannabis users showed statistically significant accelerated biological ageing and were less equipped to manage a range of later-life health, financial, and social demands than non-users. Standardised mean differences between long-term cannabis users and non-users were large: 0·70 (95% CI 0·46 to 0·94; p<0·0001) for biological ageing, −0·72 (−0·96 to −0·49, p<0·0001) for health preparedness, −1·08 (−1·31 to −0·85; p<0·0001) for financial preparedness, and −0·59 (−0·84 to −0·34, p<0·0001) for social preparedness. Long-term cannabis users did not fare better than long-term tobacco or alcohol users. Tests of dose–response associations suggested that cannabis associations could not be explained by the socioeconomic origins, childhood IQ, childhood self-control, and family substance-dependence history of long-term cannabis users. Statistical adjustment for long-term tobacco, alcohol, and other illicit drug dependence suggested that long-term cannabis users’ tendency toward polysubstance dependence accounted for their accelerated biological ageing and poor financial and health preparedness, although not for their poor social preparedness (β −0·10, 95% CI −0·18 to −0·02; p=0·017).InterpretationLong-term cannabis users are underprepared for the demands of old age. Although long-term cannabis use appears detrimental, the greatest challenge to healthy ageing is not use of any specific substance, but rather the long-term polysubstance use that characterises many long-term cannabis users. Substance-use interventions should include practical strategies for improving health and building financial and social capital for healthy longevity.

The Medical Needs and Characteristics of Cancer and Progressive Neurologic Disease Patients Who Use Home-Based Medical Care in Korea: A Retrospective Study for 2011-2020.

To investigate the needs and characteristics of patients with cancer and neurologic disorders requiring home-based medical care (HBMC). Retrospective observational study. Patients receiving HBMC on discharge from a tertiary hospital in Korea during 2011-2020. Patients were classified into 3 disease groups: cancer, progressive neurologic disorders (NR), and others. Characteristics and medical needs were assessed in each disease group. Medical needs were categorized based on functional items requiring support or management at the time of registration: respiratory, feeding, urinary system, drain tube, central catheter, wound, medication, and other. Patients with multiple medical needs were assigned to multiple categories. Patients who used HBMC for more than 3months were defined as long-term users; their characteristics were evaluated in the same way. Of the total 655 patients, 47.0% (308) had cancer and 17.3% (113) were NR patients. Among all patients, 78.8% were partially dependent (44.0%) or completely dependent (34.8%) in daily activities, and there were more dependent patients in the NR group (80.5%) than cancer (26.6%). Patients with cancer needed central catheter management the most (43.5%), followed by wound care (36.7%), feeding support (35.1%), and drain tube management (22.1%). NR patients required feeding support the most (80.5%), followed by respiratory support (43.4%), wound care (41.6%), and urinary system support (19.5%). Of all patients, 30.2% (198) were long-term users (NR, 37.9%; cancer, 35.4%). Long-term users were common among patients who needed respiratory support (59.4%), feeding support (48.75), and urinary system support (34.6%). Homebound patients with cancer and progressive neurologic disorders need medical services at home after discharge. Patients who need feeding and respiratory support usually use HBMC for more than 3months. Further studies are needed to design an optimal HBMC that continuously provides medical services to patients with serious illnesses living at home.