Long-term Users Research Articles

Association between the Use of Statins and Brain Tumors.

This study aimed to investigate the effects of statin use on the incidence of brain tumors. The Korean National Health Insurance Service-National Sample Cohort from 2005 to 2019 was used. The 1893 patients who were diagnosed with brain tumors were matched with 7572 control patients for demographic variables. The history of dyslipidemia was collected, and their history of prescription of statins before diagnosis of brain tumor was examined. The participants without dyslipidemia were set as a reference population. Then, the odds for brain tumors were analyzed in dyslipidemia patients without statin use, dyslipidemia patients who were prescribed statins for less than 365 days, and dyslipidemia patients who were prescribed statins for 365 days or more. Propensity score overlap weighted multivariable logistic regression analysis was used and adjusted for demographics and comorbidities. Secondary analyses were conducted according to types of statins, malignancy of brain tumors, and histories of demographics or comorbidities. A total of 11.78% of brain tumor patients and 10.95% of control participants had histories of statin use for 365 days or more. Dyslipidemia patients with 365 days or more duration of statin use demonstrated 1.22 times higher odds for brain tumors than normal participants (95% confidence intervals [CI] = 1.06-1.14, p = 0.007). Dyslipidemia patients with less than 365 days of statin use had higher odds of brain tumors than other groups (odds ratio = 1.60, 95% CI = 1.36-1.87, p < 0.001). The higher odds for brain tumors in short-term statin users (<365 days) than in long-term statin users (≥365 days) were consistent in secondary analyses according to types of statins, malignancy of brain tumors, and histories of demographics or comorbidities. Long-term statin use in dyslipidemia patients was related to a lower risk of brain tumors than short-term statin use in patients with dyslipidemia.

It's like an uncontrollable demon in your body: The lived experiences of youth using crystal meth during the COVID-19 pandemic in Witbank, Mpumalanga

Crystal methamphetamine (meth) is quickly becoming one of the most used synthetic drugs worldwide, adding to the growing pandemic of substance abuse worldwide. Crystal meth may cause serious health effects including infertility, cancer and even DNA damage, especially among long-term users. Crystal meth users are often not aware of the serious health implications caused by crystal meth until it’s too late. This qualitative research paper employed the phenomenological research design to explore and describe lived experiences of crystal meth users. A total of 11 crystal meth users in the Witbank hotspots were identified through purposive convenience and key informants sampling. Data was collected through semi-structured interviews and the thematic content analysis was used for analysis. The study's findings reveal that crystal meth users have an uncontrollable urge to use the substance which results in them being stigmatized in society and negatively affecting their family functioning. The findings also show that some crystal meth users engage in criminal activities. There is a need for further studies on lived experiences across all types of drugs. Policymakers in South Africa should work towards an Instant-admission policy for people who use substances, through the capacity of social workers.

Towards a Guideline for UAV-Based Data Acquisition for Geomorphic Applications

Recent years have seen a rapid rise in the generation of high-resolution topographic data using custom-built or commercial-grade Unmanned Aerial Vehicles (UAVs). Though several studies have demonstrated the application potential of UAV data, significant knowledge gaps still exist in terms of proper documentation of protocols for data acquisition, post-flight data processing, error assessments, and their mitigation. This work documents and provides guidelines for UAV data acquisition and processing from several years of field experience in diverse geomorphic settings across India, including undulating topography (~17 km2), alluvial plains (~142 km2), lowland-river basin (~66 km2), and a highly urbanized area (~5 km2). A total of 37,065 images with 16 and 20 Megapixels and 604 ground control points (GCPs) were captured with multiple UAV systems and processed to generate point clouds for a total area of ~230 km2. The Root Mean Square Error (RMSE) for each GCP for all sites ranged from 6.41 cm to 36.54 cm. This manuscript documents a comprehensive guideline for (a) pre-field flight planning and data acquisition, (b) generation and removal of noise and errors of the point cloud, and (c) generation of orthoimages and digital elevation models. We demonstrate that a well-distributed and not necessarily uniformly distributed GCP placement can significantly reduce doming error and other artifacts. We emphasize the need for using separate camera calibration parameters for each flight and demonstrate that errors in camera calibration can significantly impact the accuracy of the point cloud. Accordingly, we have evaluated the stability of lens calibration parameters between consumer-grade and professional cameras and have suggested measures for noise removal in the point cloud data. We have also identified and analyzed various errors during point cloud processing. These include systematic doming errors, errors during orthoimage and DEM generation, and errors related to water bodies. Mitigation strategies for various errors have also been discussed. Finally, we have assessed the accuracy of our point cloud data for different geomorphic settings. We concluded that the accuracy is influenced by Ground Sampling Distance (GSD), topographic features, and the placement, density, and distribution of GCPs. This guideline presented in this paper can be extremely beneficial to both experienced long-term users and newcomers for planning the UAV-based topographic survey and processing the data acquired.

Use of statins and risk of myeloproliferative neoplasms: a Danish nationwide case-control study.

Previous studies have indicated a possible cancer-protective effect of statins in solid cancers; however, this has never been investigated in myeloproliferative neoplasms (MPNs). We aimed to investigate the association between statin use and the risk of MPNs in a nested nationwide case-control study, using Danish national population registries. Information on statin use was obtained from the Danish National Prescription Registry, and patients diagnosed with MPNs between 2010 and 2018 were identified from the Danish National Chronic Myeloid Neoplasia Registry. The association between statin use and MPNs was estimated using age- and sex-adjusted odds ratios (ORs) and fully adjusted ORs (aORs), adjusting for prespecified confounders. The study population included 3816 cases with MPNs and 19 080 population controls (5:1) matched for age and sex using incidence density sampling. Overall, 34.9% of the cases and 33.5% of the controls ever used statins, resulting in an OR for MPN of 1.07 (95% confidence interval [CI], 0.99-1.16) and an aOR of 0.87 (95%CI, 0.80-0.96), respectively. 17.2% were categorized as long-term users (≥5 years) among the cases compared with 19.0% among controls, yielding an OR for MPN of 0.90 (95%CI, 0.81-1.00) and an aOR of 0.72 (95%CI, 0.64-0.81). Analysis of the effect of the cumulative duration of statin use revealed a dose-dependent response, and the association was consistent for sex, age, and MPN subgroups and across different statin types. Statin users were associated with significantly lower odds of being diagnosed with an MPN, indicating a possible cancer-preventive effect of statins. The retrospective of this study precludes causal inferences.

Cognitive dysfunction and impaired neuroplasticity following repeated exposure to the synthetic cannabinoid JWH-018 in male mice.

Psychotic disorders have been reported in long-term users of synthetic cannabinoids. This study aims at investigating the long-lasting effects of repeated JWH-018 exposure. Male CD-1 mice were injected with vehicle, JWH-018 (6mg·kg-1 ), the CB1 -antagonist NESS-0327 (1mg·kg-1 ) or co-administration of NESS-0327 and JWH-018, every day for 7days. After 15 or 16 days washout, we investigated the effects of JWH-018 on motor function, memory, social dominance and prepulse inhibition (PPI). We also evaluated glutamate levels in dialysates from dorsal striatum, striatal dopamine content and striatal/hippocampal neuroplasticity focusing on the NMDA receptor complex and the neurotrophin BDNF. These measurements were accompanied by in vitro electrophysiological evaluations in hippocampal preparations. Finally, we investigated the density of CB1 receptors and levels of the endocannabinoid anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and their main synthetic and degrading enzymes in the striatum and hippocampus. The repeated treatment with JWH-018 induced psychomotor agitation while reducing social dominance, recognition memory and PPI in mice. JWH-018 disrupted hippocampal LTP and decreased BDNF expression, reduced the synaptic levels of NMDA receptor subunits and decreased the expression of PSD95. Repeated exposure to JWH-018, reduced hippocampal CB1 receptor density and induced a long-term alteration in AEA and 2-AG levels and their degrading enzymes, FAAH and MAGL, in the striatum. Our findings suggest that repeated administration of a high dose of JWH-018 leads to the manifestation of psychotic-like symptoms accompanied by alterations in neuroplasticity and change in the endocannabinoid system.

Switching patterns of immediate-release forms of generic mixed amphetamine salts products among privately and publicly insured individuals aged 15-64 years in the United States, 2013-2019.

Immediate-release forms of generic mixed amphetamine salts (MAS) have been the subject of passive surveillance reports signaling lack of effectiveness. We examined switching patterns that might suggest whether long-term users of specific MAS are more likely to switch away or switch back after use of the MAS of interest in the FDA's Sentinel Distributed Database. We required at least 60-day continuous supply of selected MAS grouped by Abbreviated New Drug Application (ANDA) to describe patterns of switching away from and to generics approved under the ANDAs of interest among individuals ages 15-64 years with attention deficit hyperactivity disorder or narcolepsy during 2013-2019. We observed the greatest number of treatment episodes for ANDA 040422 (n = 525 771), followed by ANDA 202424 (n = 181 693), ANDA 040439 (n = 62 363), ANDA 040440 (n = 21 143), and ANDA 040480 (n = 8792). Of those with switches away from their original ANDA, episodes initiated on generic products under ANDA 040422 (48.6%) and ANDA 202424 (43.0%) were most likely to switch back, while those initiated on generic product under ANDA 040480 were least likely (24.1%). Of those episodes with switches to a generic under an ANDA of interest, about one-third (range 27.1% to 37.0%) switched back to the same product. These switches back had a median time to switch of about 30 days. These descriptive analyses, although subject to limitations, did not suggest increased switching away or switching back after use of the generics of interest. Continued post-marketing surveillance is warranted.

Use of optical coherence tomography retinal thickness deviation map for hydroxychloroquine retinopathy screening

Background: Hydroxychloroquine (HCQS) is widely used to treat several rheumatic and skin diseases and can cause damage to the outer retina, known as HCQS retinopathy, and is common among long-term users of the drug with higher daily dose by weight. The goal of screening for retinopathy is to recognize signs of toxicity at an early enough stage to prevent the loss of visual acuity. Aims and Objectives: This study aimed to evaluate the diagnostic performance of a commercially available retinal thickness deviation map obtained by spectral-domain (SD) optical coherence tomography (OCT) for screening of HCQS retinopathy. Materials and Methods: This study was a prospective comparative study between unaffected (patients who did not develop retina toxicity) and affected (who developed toxicity) of 50 patients of the age group of 14–60 years taking HCQS medication for several dermatological and rheumatologic disorders. The patients who fulfilled the inclusion criteria were screened for HCQS retinal toxicity using SD-OCT, standard automated perimetry, fundus autofluorescence, and comprehensive ophthalmic examinations. Results: In this study, in group 2 patients, 60% were having parafoveal, 30% having perifoveal, and 10% having a mixed pattern (P&lt;0.001) of HCQS retinopathy, and the mean deviation and pattern standard deviation increase as the severity of disease increases (P&lt;0.005). Conclusion: This study concluded that HCQS is a safer drug and can be used safely in these patients with proper HCQS retinal toxicity monitoring with an SD-OCT-generated retinal thickness deviation map and with regular follow-up to monitor reduced thickness in the parafoveal region.

The Effect of Hormonal Contraception Use on Ovarian Reserve Markers and the Uptake of Assisted Reproductive Technology in Individuals Seeking an Infertility Evaluation.

Background and objective The effects of hormonal contraception (HC) use on ovarian reserve (OR) markers in individuals seeking an infertility evaluation and the success of assisted reproductive technology (ART) warrantfurther investigation. Therefore, the aim of this study was to determine if women seeking an evaluation for unexplained infertility who used long-term (≥2 years) HC have lower ovarian reserve (OR) markers and higher uptake of ART compared to short-term (<2 years) or never HC users. Methods We performed a cross-sectional patient survey involving a retrospective medical chart review of patients seeking an evaluation for unexplained infertility at the University of Colorado Advanced Reproductive Medicine (CU ARM) clinic. Results Most participants (87%; 107/123) reported a history of HC use with 98 (79.7%) reporting long-term continuous use for two or more years. Median OR markers were similar between long-term and short-term/never HC users [anti-Müllerian hormone (AMH): 2.4 vs. 3.2, p=0.20; antral follicle count (AFC): 18 vs. 26, p=0.10; follicle-stimulating hormone (FSH): 7.6 vs. 6.3, p=0.26] and remained so after adjusting for age and diagnosis of polycystic ovarian syndrome (PCOS) or primary ovarian insufficiency (POI) in linear regression models. However, amongHC users aged less than 30 years(n=9), those who had discontinued HC between two and three years prior to the assessment of their OR markers had a 6.20 ng/mL increase in AMH level compared to those whohad discontinued HCless than two years prior to the assessment (p=0.02). Additionally, there was a marginally increased use of ART overall among long-term HC users compared to short-term/never HC users (64.3% vs. 44.0%, p=0.06), specifically in the use of in vitro fertilization (IVF) (58.7% vs. 18.2%, p=0.01). Among long-term HC users, ovulation induction was less likely to result in live birth compared to short-term/never HC users (8.9% vs. 62.5%, p<0.001); however, after adjusting for age, PCOS, POI, and type of ART used, there was no difference in the odds of live birth after ART between long-term HC users and short-term/never users. Conclusion While long-term HC users report increased use of ART, in particular IVF, the overall conception rates and live birth outcomes among ART users do not appear to be significantly affected by a history of long-term HC use.

653-P: Associations between Anxiety and Depression Levels and Hypoglycemia Awareness and Beliefs in Long-Term Advanced Diabetes Technology Users with Type 1 Diabetes (T1D)

The information characterizing anxiety and depression levels and associated factors in long-term T1D advanced diabetes technology users is sparse. A cross-sectional observational study in T1D adults using continuous glucose monitors (CGMs) ≥1 year was conducted in a tertiary academic medical center. The Hospital Anxiety and Depression Scale was used to evaluate anxiety levels (HADS-A) and depression levels (HADS-D). CGM % of time with glucose &amp;lt;70 mg/dL, hypoglycemia awareness (measured with Gold questionnaire), hypoglycemia beliefs (with Attitude to Awareness of Hypoglycemia questionnaire) and demographic information were collected. Multivariable linear regression was used to identify factors associated with higher HADS-A and HADS-D. Among 196 participants (63% female; mean±SD age 47±16; 91% non-Hispanic Caucasian; 80% using insulin pumps with 55% closed-loop pump users), mean±SD HADS-A was 6.5±4.0 (40% scores≥8), HADS-D was 4.1±3.1 (15% score≥8), and % of CGM time &amp;lt;70 mg/dL was 2.0±3.0%; 34% had impaired hypoglycemia awareness. Higher HADS-A was independently associated with less time with glucose &amp;lt;70 mg/dL, female sex, younger age, lower hypoglycemia awareness, weaker hypoglycemia concern minimization, and stronger hyperglycemia avoidance prioritization (P&amp;lt;0.05). Higher HADS-D was independently associated with less time with glucose &amp;lt;70 mg/dL, lower hypoglycemia awareness, and stronger hyperglycemia avoidance prioritization (P&amp;lt;0.05). In summary, clinically significant anxiety and depression presented in 40% and 15% of T1D patients using advanced diabetes technologies, respectively. Hypoglycemia awareness and hypoglycemia beliefs, rather than time spent in hypoglycemia, were associated with greater anxiety and depression levels. Attention to hypoglycemia awareness, hypoglycemia beliefs and mental health are needed to improve overall outcomes in T1D advanced technology users. Disclosure Y. Lin: None. J.E. Aikens: None. W. Ye: None. G. Piatt: None. S. Fisher: None. R. Busui: Board Member; American Diabetes Association. Consultant; Averitas Pharma, Inc., Lexicon Pharmaceuticals, Inc., Nevro Corp. Research Support; Novo Nordisk. Consultant; Novo Nordisk, Roche Diagnostics. Research Support; Medtronic, National Institutes of Health. Consultant; Procter &amp; Gamble. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K23DK129724); Michigan Center for Clinical and Translational Research (P30DK092926)

Biomechanics of wheelchair turning manoeuvres: novel insights into wheelchair propulsion.

Wheelchair turning biomechanics is an under researched area despite its obvious relevance to functional mobility of wheelchair users. Wheelchair turns might be linked to a higher risk of upper limb injuries due to the increased forces and torques potentially associated with asymmetric movement. Our aim was to obtain a better theoretical understanding of wheelchair turning by biomechanically analyzing turns compared to steady-state straightforward propulsion (SSSFP). Ten able-bodied men received 12-min familiarization and 10 trials (in a random order) of SSSFP and multiple left and right turns around a rectangular course. A Smartwheel was mounted at the right wheel of a standard wheelchair to measure kinetic parameters during SSSFP and of the inner hand during right turns and the outer hand during left turns. A repeated measures ANOVA was used to detect differences across tasks. Two strategies were identified: 3% demonstrated roll turns and 97% spin turns. Spin turns consisted of three phases: approach, turning and depart phase. The turning phase was accomplished by increasing peak force (72.9 ± 25.1 N vs. 43.38 ± 15.9 N in SSSFP) of the inner hand, while maintaining high push frequency of the outer hand (1.09 ± 0.20 push/s vs. 0.95 ± 0.13 push/s in SSSFP). Peak negative force and force impulse during the turning phase were much higher than SSSFP, 15.3 ± 15.7 and 4.5 ± 1.7 times higher, respectively. The spin turn strategy might carry an increased risk of upper limb injuries due to higher braking force and requires particular attention by rehabilitation professionals to preserve upper limb function of long-term wheelchair users.

Understanding the properties of intermittent catheters to inform future development.

Despite the extensive use of intermittent catheters (ICs) in healthcare, various issues persist for long-term IC users, such as pain, discomfort, infection, and tissue damage, including strictures, scarring and micro-abrasions. A lubricous IC surface is considered necessary to reduce patient pain and trauma, and therefore is a primary focus of IC development to improve patient comfort. While an important consideration, other factors should be routinely investigated to inform future IC development. An array of in vitro tests should be employed to assess IC's lubricity, biocompatibility and the risk of urinary tract infection development associated with their use. Herein, we highlight the importance of current in vitro characterisation techniques, the demand for optimisation and an unmet need to develop a universal 'toolkit' to assess IC properties.

Cortical thickness is inversely associated with transcranial magnetic stimulation-evoked N45 potential among young adults whose heavy drinking began in adolescence.

Adolescence is a particularly vulnerable stage of development in terms of the deleterious effects of alcohol. Both lower gray matter (GM) volume and greater GABAergic activity have been associated with chronic alcohol consumption during adolescence. However, the association between these measures has not been investigated. In this exploratory study, we compared 26 young adults with a 10year history of heavy alcohol consumptionwith 21 controls who used little or no alcohol. Simultaneous transcranial magnetic stimulation and electroencephalography were used to assess transcranial magnetic stimulation-evoked N45 potentials, reflecting a balance between GABAergic inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated glutaminergic excitation in the brain. GM thickness was measured from magnetic resonance images and GM and N45 potentials were then correlated. Cortical thickness was significantly lower in several brain regions in the heavy-drinking group than the light-drinking group. The N45 amplitude was significantly larger frontally in the heavy-drinking group. Among heavy drinkers, there were several statistically significant correlations between thinner GM and larger frontal N45 amplitudes that were not detectable in the light-drinking group. The strongest correlations were detected in the frontal and parietal lobes, especially in the left superior frontal gyrus and the left supramarginal gyrus, and in both hemispheres in the superior parietal lobes. These findings show that a thinner cortex and greater inhibitory neurotransmission are correlated in certain brain regions among young, long-term heavy alcohol users. Studies are needed to explore the possible causal mechanisms underlying these effects.

The Association of Long-Term Opioid Use With Health Care and Home Care Service Use Among Aged Home Care Clients.

To compare health care and home care service utilization, mortality, and long-term care admissions between long-term opioid users and nonusers among aged home care clients. A retrospective cohort study based on the Resident Assessment Instrument-Home Care (RAI-HC) assessments and electronic medical records. The study sample included all regular home care clients aged ≥65years (n= 2475), of whom 220 were long-term opioid users, in one city in Finland (population base 222,000 inhabitants). Health care utilization, mortality, and long-term care admissions over a 1-year follow-up were recorded from electronic medical records, and home care service use from the RAI-HC. Negative binomial and multivariable logistic regression, adjusted for several socioeconomic and health characteristics, were used to analyze the associations between opioid use and health and home care service use. Compared with nonusers, long-term opioid users had more outpatient consultations (incidence rate ratio 1.26; 95% CI 1.08-1.48), home visits (1.23; 1.01-1.49), phone contacts (1.38; 1.13-1.68), and consultations without a patient attending a practice (1.22; 1.04-1.43) after adjustments. A greater proportion of long-term opioid users than nonusers had at least 1 hospitalization (49% vs 41%) but the number of inpatient days did not differ after adjustments. The home care nurses' median work hours per week were 4.3 (Q1-Q3 1.5-7.7) among opioid users and 2.8 (1.0-6.1) among nonusers. Mortality and long-term care admissions were not associated with opioid use. Long-term opioid use in home care clients is associated with increased health care utilization regardless of the severity of pain and other sociodemographic and health characteristics. This may indicate the inability of health care organizations to produce alternative treatment strategies for pain management when opioids do not meet patients' needs. The exact reasons for opioid users' greater health care utilization should be examined in future.

RWD25 Usage and Costs Profile of Long-Term Contraception Users at a Health Plan Operator in the Brazil

To evaluate the profile of health resource utilization and costs linked to contraception in users of Etonogestrel Contraceptive Implant (ETN-IMP) and Levonorgestrel Intrauterine System (LNG-IUS).

Endocrinological Changes after Anamorelin Administration in Patients with Gastrointestinal Cancer.

Changes in hormone levels in patients with cancer cachexia after anamorelin administration have not been fully investigated. This study aimed to determine how anamorelin affects the endocrine system in patients with gastrointestinal cancer and cachexia. We prospectively enrolled 13 patients and comprehensively investigated their body weight and levels of serum albumin, hemoglobin A1c (HbA1c), and hormones before (week 0) and 3 and 12 weeks after anamorelin administration. The variables were evaluated at week 3 in 9 patients and at week 12 in 5 patients. At week 3, anamorelin administration resulted in body weight gain and increased the levels of growth hormone and HbA1c, as well as insulin-like growth factor-1 standard deviation scores (IGF-1 SD scores). At the same time, negative correlations were observed between ΔIGF-1 SD score and Δthyroidstimulating hormone (TSH) and between ΔIGF-1 SD score and Δfree testosterone. ΔBody weight and ΔIGF-1 SD score correlated positively at week 12. These results suggest that TSH and free testosterone levels can be affected 3 weeks after anamorelin administration; however, those variables tend to return to a state of equilibrium, and anabolic effects of anamorelin appear in long-term (≥ 12 weeks) users.

ID: 207123 When to Evaluate for Catheter Revision/Replacement in Long-Term Intrathecal Baclofen Pump Users: A Case Series

Baclofen withdrawal is a life-threatening issue that has been demonstrated in patients with intrathecal baclofen use with catheter-related dysfunction. Prior to 2012, Medtronic baclofen pumps used traditional silicone catheters. In 2012, Medtronic introduced a new coated catheter designed to increase catheter strength and reduce kinking and occlusions. According to a 2016 review comparing traditional silicone catheters vs the coated catheter in children, 18% compared with 1.1% had catheter-related complications in the traditional and coated catheter groups respectively1. According to a 2020 Product Performance Report, there were 700 catheter-related events out of 5475 catheters (12.79%) and 277 events out of 2779 catheters (9.97%) in the old and new catheter models, respectively2.

Embracing Challenges for Population Aging in China: Building Scientific Evidence to Inform Long-Term Care Policymaking and Practice

ABSTRACT In China, rapid aging of the population is driving up demand for healthcare and long-term care services for older adults. This special issue of the Journal of Aging & Social Policy features a collection of studies that provided timely analyses and fresh insights into a wide range of policy relevant topics concerning long-term care for older adults in China. In this introductory article, we orient readers to these studies organized under four themes: migration, caregiving, and elder care challenges; long-term care service users, frontline workers, and workforce challenges; unmet needs across the care span in healthcare, long-term care, and end of life care; and long-term care financing. We highlight major findings and contributions of each study and provide perspectives on key issues within China’s evolving healthcare and social policy contexts. Collectively, these studies contribute to building scientific evidence where it is lacking and supporting evidence-based long-term care policymaking and practice to meet the mounting challenges of population aging in China.

Hydroxychloroquine-induced Retinal Toxicity.

Long-term use of hydroxychloroquine can cause retinopathy, which may result in severe and progressive visual loss. In the past decade, hydroxychloroquine use has markedly increased and modern retinal imaging techniques have enabled the detection of early, pre-symptomatic disease. As a consequence, the prevalence of retinal toxicity in long-term hydroxychloroquine users is known to be higher than was previously estimated. The pathophysiology of the retinopathy is incompletely characterised, although significant advances have been made in understanding the disease from clinical imaging studies. Hydroxychloroquine retinopathy elicits sufficient public health concern to justify the implementation of retinopathy screening programs for patients at risk. Here, we describe the historical background of hydroxychloroquine retinopathy and summarize its current understanding. We review the utility and limitations of each of the mainstream diagnostic tests used to detect hydroxychloroquine retinopathy. The key considerations towards a consensus on the definition of hydroxychloroquine retinopathy are outlined in the context of what is known of the natural history of the disease. We compare the current screening recommendations for hydroxychloroquine retinopathy, identifying where additional evidence is required, and the management of proven cases of toxicity. Finally, we highlight the areas for further investigation, which may further reduce the risk of visual loss in hydroxychloroquine users.

Association of oral bisphosphonates with cardioembolic ischemic stroke: a nested case-control study.

Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants. Methods: We performed a case-control study nested in a cohort of patients aged 40-99years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered. Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01-1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10-1.66) and 1.03 (95% CI: 0.88-1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1year = 1.10; 95% CI:0.82-1.49; AOR>1-3years = 1.41; 95% CI:1.01-1.97; AOR>3years = 1.81; 95% CI:1.25-2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1year = 0.59; 0.30-1.16). An interaction between oral bisphosphonates and calcium supplements was suggested. Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.

Physical activity levels and statin therapy: differences between symptomatic and asymptomatic statin users

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Combining statin treatment and physical activity is highly effective to reduce cardiovascular diseases. Statin use may exacerbate statin-associated muscle symptoms (SAMS), making an active lifestyle more difficult for statin users. It is, however, unknown whether daily activity patterns differ between symptomatic and asymptomatic statin users. Purpose To objectively assess physical activity levels and sedentary time and compare these between long-term statin users with or without muscle complaints. Methods Ninety-seven symptomatic (66±9 years, 74% male) and 97 asymptomatic statin users, matched for age and gender in a 1:1 ratio, were recruited from general practitioners offices. Physical activity patterns were measured using the activPAL3 micro monitor, which was attached to the upper right thigh. Participants wore the activity monitor 24 hours per day during 7 consecutive days and were asked to maintain normal daily activities. Results Symptomatic statin users performed less physical activity of moderate to vigorous intensity per day (61.1 min, IQR: 43.1-77.0 min) compared to asymptomatic statin users (69.1 min, IQR: 50.7-94.6 min; P=0.02). There were no differences in physical activity levels of light intensity or sedentary time between the statin groups. Symptomatic statin users took less steps per day (7560 steps, IQR: 5649-9692 steps) compared to asymptomatic statins users (8721 steps, IQR 6306-11791 steps; P=0.02). Conclusion Symptomatic statin users have reduced levels of physical activity compared to asymptomatic statin users. These findings highlight the clinical relevance to explore possibilities for symptomatic statin users to increase physical activity levels and the associated health benefits.