Prevalent Users Research Articles

Association of Antihypertensives and Cognitive Impairment in Long-Term Care Residents.

Certain classes of antihypertensive medication may have different associations with cognitive impairment. To examine the association between prevalent use of antihypertensive medications that stimulate (thiazides, dihydropyridine calcium channel blockers, angiotensin type I receptor blockers) versus inhibit (angiotensin-converting enzyme inhibitors, beta-blockers, non-dihydropyridine calcium channel blockers) type 2 and 4 angiotensin II receptors on cognitive impairment among older adults residing in Veterans Affairs (VA) nursing homes for long-term care. Retrospective cohort study. Long-term care residents aged 65 + years admitted to a VA nursing home from 2012 to 2019 using blood pressure medication and without cognitive impairment at admission. Main exposure was prevalent use of angiotensin II receptor type 2 and 4-'stimulating' (N = 589), 'inhibiting' (N = 3,219), or 'mixed' (N = 1,715) antihypertensive medication regimens at admission. Primary outcome was any cognitive impairment (Cognitive Function Scale). Over an average of 5.4 months of follow-up, prevalent use of regimens containing exclusively 'stimulating' antihypertensives was associated with a lower risk of any incident cognitive impairment as compared to prevalent use of regimens containing exclusively 'inhibiting' antihypertensives (HR 0.83, 95% CI 0.74-0.93). Results for the comparison between 'mixed' versus 'inhibiting' regimens were in the same direction but not statistically significant (HR 0.96, 95% CI 0.88-1.06). For residents without cognitive impairment at baseline, prevalent users of regimens containing exclusively antihypertensives that stimulate type 2 and 4 angiotensin II receptors had lower rates of cognitive impairment as compared to prevalent users of regimens containing exclusively antihypertensives that inhibit these receptors. Residual confounding cannot be ruled out.

Incidence of Antiseizure Medication-Induced Severe Cutaneous Adverse Reactions in Malaysia.

Antiseizure medication can potentially cause severe cutaneous adverse reactions, and certain antiseizure medication-induced severe cutaneous adverse reactions are associated with specific human leukocyte antigen alleles. This caused a change in antiseizure medication prescribing patterns, which may influence the incidence of antiseizure medication-induced severe cutaneous adverse reactions. Thus, we aimed to determine the incidence of antiseizure medication-induced severe cutaneous adverse reactions and its change over 15 years (2006-2019) in Malaysia. This retrospective analysis combined antiseizure medication-induced SCAR cases from the national adverse drug reaction database in the National Pharmaceutical Regulatory Agency, antiseizure medication usage data from the Malaysian Statistics of Medicine, and prescribing data from University Malaya Medical Centre, a national-level tertiary hospital to calculate antiseizure medication-induced SCAR incidence in Malaysia. We observed an upward trend in reported antiseizure medication-induced SCAR cases from 28 cases in 2006 to 92 in 2016. The incidence of carbamazepine (CBZ)-induced severe cutaneous adverse reactions increased from 7.5 per 1000 person-years (2006) to 17.8 per 1000 person-years (2016) but dropped to 7.2 per 1000 person-years subsequently (2019). Concurrently, there was an increase in the incidence of severe cutaneous adverse reactions secondary to phenytoin and lamotrigine. The prevalent users of CBZ had reduced from 22.8% (2006) to 14.1% (2016), whereas the levetiracetam and sodium valproate users increased by 5.5% and 4.8%, respectively. The incidence of CBZ-induced severe cutaneous adverse reactions had reduced since 2016, probably related to the implementation of human leukocyte antigen-B*1502 screening in Malaysia or substitution of CBZ with other antiseizure medications. However, this was accompanied by an increase in SCAR incidence related to phenytoin and lamotrigine.

Predictors of new persistent opioid use after benign hysterectomy in the United States

Despite substantial reductions in the past decade, prescription opioids continue to cause widespread morbidity and mortality in the United States. Little is known regarding patterns and predictors of opioid use among women undergoing benign hysterectomy. This study aimed to identify the incidence and predictors of new persistent opioid use after benign hysterectomy among opioid-naïve women from a set of demographic, operative, and opioid prescription characteristics of patients. In this retrospective cohort study, we identified women undergoing benign hysterectomy from 2011 to 2016 using a validated national insurance claims database (IBM MarketScan Commercial Database). After excluding women with prevalent opioid use (from 365 to 31 days preoperatively), we identified patients who received a perioperative opioid prescription (30 days before to 14 days after hysterectomy) and evaluated them for new persistent opioid use, defined as at least 1 prescription from 15 to 90 days and at least 1 prescription from 91 to 365 days postoperatively. Multivariate logistic regression was used to examine demographic, clinical, operative, and opioid prescription-related factors associated with new persistent use. International Classification of Diseases, Ninth and Tenth Revisions, and Clinical Classification Software codes were used to identify hysterectomies, preoperative pain and psychiatric diagnoses, surgical indications, and surgical complications included as covariates. We identified 114,260 women who underwent benign hysterectomy and were not prevalent opioid users, of which 93,906 (82.2%) received at least 1 perioperative opioid prescription. Of 93,906 women, 4334 (4.6%) developed new persistent opioid use. Logistic regression demonstrated that new persistent use odds is significantly increased by younger age (18-34 years; adjusted odds ratio, 1.97; 95% confidence interval, 1.69-2.30), southern geographic location (adjusted odds ratio, 2.03; 95% confidence interval, 1.79-2.27), preoperative psychiatric and pain disorders (anxiety: adjusted odds ratio, 1.20 [95% confidence interval, 1.09-1.33]; arthritis: adjusted odds ratio, 1.30 [95% confidence interval, 1.21-1.40]), >1 perioperative prescription (adjusted odds ratio, 1.53; 95% confidence interval, 1.24-1.88), mood disorder medication use (adjusted odds ratio, 1.51; 95% confidence interval, 1.40-1.64), tobacco smoking (adjusted odds ratio, 1.65; 95% confidence interval, 1.45-1.89), and surgical complications (adjusted odds ratio, 1.84; 95% confidence interval, 1.69-2.00). Although statistically nonsignificant, total morphine milligram equivalent of ≥300 in the first perioperative prescription increased persistent use likelihood by 9% (95% confidence interval, 1.01-1.17). Dispensing of a first perioperative prescription before the surgery, as opposed to after, increased new persistent use odds by 61% (95% confidence interval, 1.50-1.72). Each additional perioperative day covered by a prescription increased the likelihood of persistent use by 2% (95% confidence interval, 1.02-1.03). In contrast, minimally invasive hysterectomy (laparoscopic: adjusted odds ratio, 0.89 [95% confidence interval, 0.71-0.88]; vaginal: adjusted odds ratio, 0.82 [95% confidence interval, 0.72-0.93]) and a more recent surgery year (2016 vs reference 2011: adjusted odds ratio 0.58; 95% confidence interval, 0.51-0.65) significantly decreased its likelihood. New persistent opioid use after hysterectomy was associated with several patient, operative, and opioid prescription-related factors. Considering these factors may be beneficial in counseling patients and shared decision-making about perioperative prescription to decrease the risk of persistent opioid use.

FACTORS ASSOCIATED WITH SWITCHING FROM INJECTABLE TO ORAL DISEASE MODIFYING AGENTS AMONG PATIENTS WITH MULTIPLE SCLEROSIS

BackgroundSince the introduction of oral disease-modifying agents (DMA) in 2010, the treatment options for multiple sclerosis (MS) have changed significantly. There is limited information regarding the factors associated with switching to oral DMA among prevalent injectable DMA users. ObjectiveThis study evaluated the factors associated with switching to oral DMAs among prevalent injectable DMA users with MS. MethodsA retrospective observational cohort study using the TriNetX electronic medical records (EMR) data was conducted among patients with MS. The study included prevalent injectable DMA users with at least two injectable DMA (interferon beta-1a, interferon beta-1b, peginterferon beta-1a, or glatiramer acetate) prescription records within 6 months between September 2010 and May 2018. The second injectable DMA prescription date was considered as the index date. Switching was defined as any oral DMA prescription record (fingolimod, dimethyl fumarate, or teriflunomide) within 12 months after the index date. Patients with any infusion DMA prescription after the first injectable DMA prescription, and those less than 18 years of age were excluded from the study. The Andersen Behavioral Model was used as the conceptual framework to identify predisposing, enabling, and need factors measured during the 1-year baseline period before the index date. A multivariable logistic regression model was used to examine the predisposing (age, sex, race, and ethnicity), enabling (time-period), and need factors (comorbidities, MS symptoms, MS-related medication, and healthcare utilization) associated with switching from injectable to oral DMAs. ResultsAmong 2,943 prevalent injectable users included in this study, 8.09% (n=238) patients switched to oral DMAs. Patients who switched to oral DMAs were primarily younger adults aged 18-44 years (64.29%), females (82.77%), had sensory and visual symptoms, and had corticosteroid utilization during the one-year look-back period compared to non-switchers. Results from multivariable logistic regression model revealed that middle-aged adults (45-64 years, adjusted odds ratio [aOR]: 0.43, 95% Confidence Interval [CI]: 0.32-0.58), old adults (≥65 years, aOR: 0.30, 95% CI: 0.13-0.66) and men (aOR: 0.67, 95% CI: 0.47-0.96) were associated with decreased odds of switching to oral DMAs. Presence of MS-related sensory symptoms (aOR: 1.52, 95% CI: 1.07-2.16), visual symptoms (aOR: 1.59, 95% CI: 1.10-2.31), and corticosteroids usage (aOR: 1.44, 95% CI: 1.04-1.98) were associated with increased odds of switching to oral DMAs. ConclusionThe study found that about one in twelve prevalent injectable DMA users switched to oral DMA. Both demographic and clinical factors were associated with switching to oral DMAs. Further research is needed to evaluate the outcomes of switching to inform treatment decisions for MS management.

Do Informational and Emotional Elements Differ between Online Psychological and Physiological Disease Communities in China? A Comparative Study of Depression and Diabetes.

Disease-specific online health communities provide a convenient and common platform for patients to share experiences, change information, provide and receive social support. This study aimed to compare differences between online psychological and physiological disease communities in topics, sentiment, participation, and emotional contagion patterns using multiple methods as well as to discuss how to satisfy the users’ different informational and emotional needs. We chose the online depression and diabetes communities on the Baidu Tieba platform as the data source. Topic modeling and theme coding were employed to analyze discussion preferences for various topic categories. Sentiment analysis was used to identify the sentiment polarity of each post and comment. The social network was used to represent the users’ interaction and emotional flows to discover the differences in participation and emotional contagion patterns between psychological and physiological disease communities. The results revealed that people affected by depression focused more on their symptoms and social relationships, while people affected by diabetes were more likely to discuss treatment and self-management behavior. In the depression community, there were obvious interveners spreading positive emotions and more core users in the negative emotional contagion network. In the diabetes community, emotional contagion was less prevalent and core users in positive and negative emotional contagion networks were basically the same. The study reveals insights into the differences between online psychological and physiological disease communities, providing a greater understanding of the users’ informational and emotional needs expressed online. These results are helpful for society to provide actual medical assistance and deploy health interventions based on disease types.

Association of Antihypertensives That Stimulate vs Inhibit Types 2 and 4 Angiotensin II Receptors With Cognitive Impairment

Use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, has been associated with a lower risk of dementia. However, this association with cognitive outcomes in hypertension trials, with blood pressure levels in the range of current guidelines, has not been evaluated. To examine the association between use of exclusively antihypertensive medication regimens that stimulate vs inhibit type 2 and 4 angiotensin II receptors on mild cognitive impairment (MCI) or dementia. This cohort study is a secondary analysis (April 2011 to July 2018) of participants in the randomized Systolic Blood Pressure Intervention Trial (SPRINT), which recruited individuals 50 years or older with hypertension and increased cardiovascular risk but without a history of diabetes, stroke, or dementia. Data analysis was conducted from March 16 to July 6, 2021. Prevalent use of angiotensin II receptor type 2 and 4-stimulating or -inhibiting antihypertensive medication regimens at the 6-month study visit. The primary outcome was a composite of adjudicated amnestic MCI or probable dementia. Of the 8685 SPRINT participants who were prevalent users of antihypertensive medication regimens at the 6-month study visit (mean [SD] age, 67.7 [11.2] years; 5586 [64.3%] male; and 935 [10.8%] Hispanic, 2605 [30.0%] non-Hispanic Black, 4983 [57.4%] non-Hispanic White, and 162 [1.9%] who responded as other race or ethnicity), 2644 (30.4%) were users of exclusively stimulating, 1536 (17.7%) inhibiting, and 4505 (51.9%) mixed antihypertensive medication regimens. During a median of 4.8 years of follow-up (95% CI, 4.7-4.8 years), there were 45 vs 59 cases per 1000 person-years of amnestic MCI or probable dementia among prevalent users of regimens that contained exclusively stimulating vs inhibiting antihypertensive medications (hazard ratio [HR], 0.76; 95% CI, 0.66-0.87). When comparing stimulating-only vs inhibiting-only users, amnestic MCI occurred at rates of 40 vs 54 cases per 1000 person-years (HR, 0.74; 95% CI, 0.64-0.87) and probable dementia at rates of 8 vs 10 cases per 1000 person-years (HR, 0.80; 95% CI, 0.57-1.14). Negative control outcome analyses suggested the presence of residual confounding. In this secondary analysis of SPRINT, prevalent users of regimens that contain exclusively antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors had lower rates of incident cognitive impairment. Residual confounding cannot be ruled out. If these results are replicated in randomized clinical trials, certain antihypertensive medications could be prioritized to prevent cognitive decline.

Medication adherence among persons with coronary heart disease and associations with blood pressure and low-density-lipoprotein-cholesterol

PurposeTo describe medication adherence to lipid-lowering drugs (LLDs), antihypertensive drugs, and acetylsalicylic acid (ASA) among persons with coronary heart disease (CHD) and explore its association with low-density-lipoprotein (LDL)-cholesterol, and systolic and diastolic blood pressure.MethodsBased on record linkage between the seventh wave of the Tromsø Study and the Norwegian Prescription Database, medication adherence was calculated as the proportion of days covered (PDC) for persistent prevalent users in the period of 365 days before the attendance date. Multivariable linear regression models were used to assess the association between systolic and diastolic blood pressure and medication nonadherence to antihypertensive drugs, age, sex, lifestyle, body mass index (BMI), current and previous diabetes, and between LDL-cholesterol and medication nonadherence to LLDs, age, sex, lifestyle, BMI, and current and previous diabetes.ResultsMean PDC was 0.94 for LLDs and antihypertensive drugs and 0.97 for ASA. Among persons with PDC ≥ 0.80 for LLDs, 12.0% had an LDL-cholesterol < 1.8 mmol/L. Blood pressure < 140/90 mmHg (< 140/80 mmHg if diabetes patient) was reached by 55.1% of those with a PDC ≥ 0.80 for antihypertensive drugs. Adherence to LLDs was associated with lower LDL-cholesterol, while neither systolic nor diastolic blood pressure was associated with adherence to antihypertensive drugs.ConclusionAdherence to antihypertensive drugs, LLDs, and ASA among persons with CHD were high despite low achievement of treatment goals for blood pressure and LDL-cholesterol. There was a statistically significant association between adherence to LLDs and LDL-cholesterol, but not between adherence to antihypertensive drugs and blood pressure.

Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population-based cohort study.

AimTo investigate the association between proton pump inhibitors (PPIs) and risk of incident diabetes in a follow‐up study and to investigate its potential mechanisms.MethodsA total of 9531 individuals without type 2 diabetes (T2DM) at baseline were included from the Rotterdam Study, a prospective population‐based cohort of 14 926 individuals aged 45 years or older. During the study period (1 April 1997 to 1 January 2012) all incident cases of T2DM were enrolled. We used multivariable linear regression analysis to investigate the associations of baseline PPI use and various serum biomarkers (eg, serum magnesium, insulin‐like growth factor 1) which might modify the association. Thereafter, we excluded prevalent PPI users and performed a Cox proportional hazard regression analysis to explore the time‐varying effect of incident PPI use on T2DM during follow‐up.ResultsBaseline use of a PPI was associated with increased serum levels of fasting insulin (0.091 pmoL/L, 95% confidence interval [CI] 0.049, 0.133), homeostasis model assessment‐insulin resistance (0.100, 95% CI 0.056, 0.145) and C‐reactive protein (0.29 mg/L, 95% CI 0.198, 0.384), but decreased levels of magnesium (−0.009 mmol/L, 95% CI −0.014, −0.004) and IGF‐1 (−0.805 nmoL/L, 95% CI −1.015, −0.595). After adjustment for risk factors such as physical activity and body mass index/waist‐to‐hip ratio, current use of PPI was associated with an increased risk of incident T2DM (hazard ratio [HR] 1.69, 95% CI 1.36‐2.10). The effect was dose‐dependent with the highest risk (HR 1.88, 95% CI 1.29‐2.75) in those on more than one defined daily dose.ConclusionNew users of PPIs during follow‐up had a significantly higher dose‐dependent risk of incident diabetes. We suggest vigilance regarding their potential adverse effect on glucose homeostasis.

Worldwide trends in oral anticoagulant use in patients with atrial fibrillation from 2010 to 2018: a systematic review and meta-analysis.

Non-vitamin K antagonist oral anticoagulants (NOACs) are effective and safe alternatives compared with vitamin K antagonists (VKAs) for thromboembolic prevention in atrial fibrillation (AF), while antiplatelets are no longer recommended. However, to which extent NOAC introduction and guideline updates have increased OAC use in AF, is unclear. Therefore, worldwide trends in real-life prescribing of OACs, NOACs, VKAs, and antiplatelet monotherapy in AF patients were investigated. Using PubMed and Embase, observational nationwide cohort studies on annual prevalent and/or incident OAC use in non-selected AF patients since 2010 were included. A meta-analysis of single proportions was performed. Twenty-one studies were included assessing prevalent and incident use among 9 758 637 and 197 483 OAC-eligible AF patients, respectively. Worldwide prevalence and incidence of OAC users increased from 0.42 [95% confidence interval (CI) 0.22-0.65] and 0.43 (95% CI 0.37-0.49) in 2010 to 0.78 (95% CI 0.77-0.78) and 0.75 (95% CI 0.74-0.76) in 2018, respectively. Prevalent and incident NOAC users increased globally from 0 in 2010 to 0.45 (95% CI 0.45-0.46) and 0.68 (95% CI 0.67-0.69) in 2018, respectively, whereas prevalent and incident VKA use decreased from 0.42 (95% CI 0.22-0.65) and 0.42 (95% CI 0.36-0.49) in 2010 to 0.32 (95% CI 0.32-0.32) and 0.06 (95% CI 0.06-0.07) in 2018, respectively. Prevalent antiplatelet monotherapy use decreased from 0.37 (95% CI 0.32-0.42) in 2010 to 0.09 (95% CI 0.09-0.10) in 2018. The proportion of OAC users worldwide almost doubled following NOAC introduction. As one-quarter of OAC-eligible AF subjects were not anticoagulated and 9% were only treated with antiplatelets in 2018, there is still room for improvement.

The association of antidiabetic medications and Mini-Mental State Examination scores in patients with diabetes and dementia

BackgroundThe effect of antidiabetic medication on cognitive function is unclear. We analyzed the association between five antidiabetic drugs and change in Mini-Mental State Examination (MMSE) scores in patients with diabetes and dementia.MethodsUsing the Swedish Dementia Registry and four supplementary Swedish registers/databases, we identified 1873 patients (4732 observations) with diagnosis of type 2 diabetes (diabetes) and Alzheimer’s disease or mixed-pathology dementia who were followed up at least once after dementia diagnosis. Use of metformin, insulin, sulfonylurea, thiazolidinediones (TZD), and dipeptidyl-peptidase-4 inhibitors (DPP-4i) was identified at baseline. Prevalent-user, incident-user, and drug-drug cohorts were sampled, and propensity-score matching was used to analyze comparable subjects. Beta coefficients with 95% confidence intervals (CI) from the random intercept and slope linear mixed-effects models determined the association between the use of antidiabetic medications and decline in MMSE score points between the follow-ups. Inverse-probability weighting was used to account for patient dropout.ResultsCompared to non-users, prevalent users of metformin (beta 0.89, 95% CI 0.44; 1.33) and DPP-4i (0.72, 0.06; 1.37) experienced a slower cognitive decline with time. Secondly, compared to DPP-4i, the use of insulin (−1.00, −1.95; −0.04) and sulfonylureas (−1.19; −2.33; −0.04) was associated with larger point-wise decrements in MMSE with annual intervals.ConclusionsIn this large cohort of patients with diabetes and dementia, the use of metformin and DPP-4i was associated with a slower decline in MMSE scores. Further examination of the cognitive effects of metformin and incretin-based medications is warranted.

Utilisation of disease modifying treatment and diversity of treatment pathways in relapsing remitting multiple sclerosis

BackgroundThere is minimal information on the utilisation of Disease Modifying Treatment (DMTs) for multiple sclerosis. The appropriate and safe use of medicines is informed by utilisation studies. Outcomes can inform health interventions to improve appropriate use of medicines and post marketing surveillance activities to improve safety. ObjectiveTo evaluate utilisation and treatment patterns of disease modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS). MethodsA representative sample of the Australian pharmaceutical benefits scheme data were analysed (2006–2016). Demographics of incident users and trends in incident and prevalent users were determined. Individual patient treatment pathways were determined by sequential initiation of medicines in two different periods (2006–2013 and 2014–2019). ResultsThere were 20,660 patients with at least one dispensing of a DMT for RRMS during the study period (median age 41 years, 75% female). Incident and prevalent use increased by 20% and 88%, respectively. The market was responsive to 13 new listings of DMTs over the study period. Sequential treatment was found for 66% of initiators in 2006–2013 and 28.5% of initiators in 2014–2019. Diverse treatment pathways were found, with 278 and 93 unique sequences in 2006–2013 and 2014–2019, respectively. ConclusionThe availability of new DMTs has influenced both initial treatment choice and prevalence of users. Individualised treatment patterns and exposure to multiple medicines over time will challenge traditional pharmacovigilance systems.

Use of antidepressants and risk of repeat self-harm in older adults 75+ with nonfatal self-harm: A 1-year prospective national study.

To assess exposure to antidepressants (AD) before and after nonfatal self-harm (SH) in older adults and to examine 1-year rates and risk factors for subsequent SH. Longitudinal national register-based retrospective cohort study of Swedish residents aged 75+ (N=2775) with treatment at hospital or specialist outpatient clinic in connection with SH between January 1, 2006, and December 31, 2013. The cohort was followed for 1 year after the index episode. Exposure to AD was assessed at index and at subsequent SH. Cox regression analysis was used to assess factors associated with 1-year repeat SH. At the index episode, 51% were prevalent AD users; 23% started AD during the following year. Overall 12% of prevalent AD users, 8% of AD nonusers, and 6% of AD new users repeated SH or died by suicide. About two-thirds of these subsequent behaviors occurred within 3 months after the index episode. Men had increased risk of subsequent SH (Hazard ratio [HR] 1.38, 95% CI: 1.09-1.74); older age (>85 years) was associated with a lower risk (HR 0.72, CI 95% 0.55-0.93). Users of AD did not have an increased risk of repeat SH. Half of older adults who self-harmed were prevalent AD users and a further one fourth started an AD within 1 year after the index SH. Antidepressant use was not associated with increased risk of subsequent SH in this high-risk cohort of older adults.

Use of antidepressants during COVID19 outbreak: a real-world drug-utilization study

BackgroundLockdown measures implementation (LMI) to prevent COVID19 disease diffusion was associated to increased depression and anxiety cases. The main aim was to evaluate whether LMI affected prevalence and incidence of antidepressants (ADs) use, and ADs treatment interruption (TI) in the general population.MethodsAdults (≥18 years) with at least 1 dispensing of ADs between 01/01/2019-26/09/2020 were selected from a regional Italian healthcare administrative database. Patients presenting an AD dispensing in the year preceding the first observation were considered as prevalent otherwise as incident users. We divided the studied period into 3 parts: pre-lockdown (01/01/2019-08/03/2020), lockdown (09/03/2020-14/06/2020) and post-lockdown (15/06/2020-27/09/2020). The weekly prevalence (WP) and incidence (WI) per 10,000 inhabitants were compared among periods. Incidence of TI (no dispensing refill within 30 days of the end of its validity) was computed among prevalent AD users.ResultsThe WP (mean of 552.3 per 10,000 pre-lockdown vs 505.5 lockdown phase; relative change: -9%) and WI (5.2 vs 3.7; -29%) of ADs use decreased after LMI. During the post-lockdown phase WP (505.5 vs 495.9; -2%) decreased whereas the WI (3.7 vs 4.3; 16%) slightly increased in relation to the lockdown period, although differences were not statistically significant. Conversely, the incidence of TI increased during lockdown (344.7 vs 384.3; 12%) and post-lockdown (384.3 vs 394.2; 3%) periods, even not always statistically significant.ConclusionsOur analysis showed a reduction of ADs use during the early phase of lockdown. Several factors might have impacted on the observed phenomenon (i.e, patient reluctance to start new AD treatment). Considering the mutation of the virus and the potential waves that might occur in the next months, a continuous monitoring of the impact of COVID19 on mental diseases onset and treatment adherence are suggested.Key messages In Italy, the implementation of lockdown measures was followed by a reduction in antidepressants use, even though evidences are that diagnoses of psychiatric disorders increased.Future studies should monitor if these phenomena led to an increase in adverse events potentially correlated with inappropriate treatment of depression.

Comparing Continuous and Binary Group-based Trajectory Modeling Using Statin Medication Adherence Data.

Of 58 medication adherence group-based trajectory modeling (GBTM) published studies, 74% used binary and 26% used continuous GBTM. Few studies provided a rationale for this choice. No medication adherence studies have compared continuous and binary GBTM. The objective of this study was to assess whether continuous versus binary GBTM: (1) impacts adherence trajectory shapes; and (2) results in the differential classification of patients into adherence groups. Patients were prevalent statin users with myocardial infarction hospitalization, 66+ years old, and continuously enrolled in fee-for-service Medicare. Statin medication adherence was measured 6 months prehospitalization using administrative claims. Final GBTM specifications beyond default settings were selected using a previously defined standardized procedure and applied separately to continuous and binary (proportion of days covered ≥0.80) medication adherence measures. Assignment to adherence groups was compared between continuous and binary models using percent agreement of patient classification and the κ coefficient. Among 113,296 prevalent statin users, 4 adherence groups were identified in both models. Three groups were consistent: persistently adherent, progressively nonadherent, and persistently nonadherent. The fourth continuous group was moderately adherent (progressively adherent in the binary model). When comparing patient assignment into adherence groups between continuous and binary trajectory models, only 78.4% of patients were categorized into comparable groups (κ=0.641; 95% confidence interval: 0.638-0.645). The agreement was highest in the persistently adherent group (∼94%). Continuous and binary trajectory models are conceptually different measures of medication adherence. The choice between these approaches should be guided by study objectives and the role of medication adherence within the study-exposure, outcome, or confounder.

Current and recommended practices for evaluating adverse drug events using electronic health records: A systematic review

AbstractElectronic health records (EHR) are widely used sources of real‐world data in pharmacoepidemiologic research. As there is no end‐to‐end guidance for generating medication safety evidence with EHR, this study conducted a systematic review to determine the current and recommended practices in the literature. PubMed, Scopus, and CINAHL were searched for English articles published between 1 January 2010 and 11 June 2020. Selected articles were published in peer‐reviewed journals, conducted in the United States, analyzed structured EHR data, and defined drug exposure and adverse drug events (ADEs). The study evaluated methodological quality with a modified Newcastle‐Ottawa Scale (NOS) score ranging from 0 to 9 points. Data synthesis was performed with thematic analysis. Twenty‐six from 3885 articles were selected. The majority were cohort studies (85%). The studies were well designed, with a median NOS score of 9. Drug exposure was defined with dispensing (58%) and prescribing (31%) records. ADEs were defined across five categories: diagnosis codes (77%), validated outcome algorithms (35%), objective measures (35%), treatment procedures (19%), and antidotes (2%). Common covariates were age (89%), gender (85%), comorbidities (81%), and medication‐co‐medication use (73%). Four studies (15%) empirically defined covariates in a data‐driven manner. Twenty‐two (85%) analyzed covariates as confounders or effect modifiers in their analyses. Results were analyzed with either intention‐to‐treat (73%) or as‐treated (39%) approaches. Key recommendations include selecting dispensing rather than prescribing records, considering a proxy date of dispensation where applicable, selecting new instead of prevalent drug users, improving adoption of validated outcome algorithms, and not utilizing objective measures as the primary indicator of ADEs.

Anti-dementia drugs: A descriptive study of prescription pattern in Italy

More than one million people in Italy have dementia and nearly 900 thousand people are affected by Mild cognitive impairment (MCI). No effective treatments are yet to be approved and acetylcholinesterase inhibitors (AChEi) and memantine are currently used to reduce cognitive decline related symptoms. Aim of the study is to provide a comprehensive analysis of anti-dementia drugs consumption in Italy between 2014 and 2020 with an analysis of demographic characteristics of the prevalent and incident users. The association between AChEI and memantine or anti-dementia and antipsychotic drugs will be also considered.

Non-Time Varying and Cumulative Effects of Long-Term Use of Renin-Angiotensin System Inhibitor on All-Site Cancers and Mortality in the Hong Kong Diabetes Surveillance Database (2002-2019)

Background: In many countries, cancer is replacing cardiovascular disease as a leading causes of death. Type 2 diabetes (T2D) is associated with increased risk of cancer. Patients with T2D have activated renin-angiotensin-system (RAS) although the association of RAS inhibitors (RASi) and cancer risk remains inconclusive in T2D. Methods: We conducted a prospective cohort study with new-user design in 253,491 Chinese patients with T2D in 2002-2019. We used longitudinal real-world-data from a territory-wide electronic medical record system and evaluated the associations of time-varying RASi use (angiotensin-converting-enzyme-inhibitor [ACEi] and angiotensin-receptor-blocker [ARBs]) with all-site cancer, diabetes-related cancers, and cancer-specific mortality with or without comparison with new-users of calcium-channel-blockers (CCBs). Findings: After excluding prevalent RASi users, amongst the eligible patients (n=253,491), 133,730 (52·8%) were new-RASi and 119,761 (47·2%) were non-RASi users during 6·5 years follow-up period. Time-varying RASi use was associated with lower risk of all-site cancer (HR=0·76, 95%CI: 0·74-0·79), diabetes-related cancer (HR=0·79, 0·75-0·84), cancer-specific mortality (HR=0·50, 0·47-0·53), and diabetes-related cancer mortality (HR=0·49, 0·45-0·54) versus non-RASi. ARBs use was associated with lower risk of cancer-specific mortality versus ACEi (HR=0·77, 0·66-0·91). Use of RASi was non-time-varying with an estimated prevention of 2·6 (95% CI: 2·3-3·0) all-site cancer events per-1000-person-years and 2·2 (95%CI: 2·0-2·5) cancer-related mortality per-1000-person-years. The reduced risk associations of RASi with all-cause and cancer-specific mortality were most evident in young adults versus new-CCBs users. Interpretation: Long-term RASi use was independently associated with lower cancer risk in T2D, including diabetes-related cancers and cancer-specific mortality, with stronger associations in users of ARBs than ACEi. Funding Information: Dr. Aimin Yang was supported by a CUHK Impact-Research-Fellowship Scheme. Declaration of Interests: JCNC has received research grants and/or honoraria for consultancy or giving lectures, from AstraZeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, Hua Medicine, Lee Powder, Merck Serono, Merck Sharp & Dohme, Pfizer and Sanofi. APSK has received research grants and/or speaker honoraria from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, Merck Serono, Nestle, Novo Nordisk, Pfizer and Sanofi. AOYL has served as a member of advisory panel for Amgen, AstraZeneca, Boehringer Ingelheim and Sanofi and received research support from Amgen, Asia Diabetes Foundation, Bayer, Boehringer Ingelheim, Lee’s Pharmaceutical, MSD, Novo Nordisk, Roche, Sanofi, Sugardown Ltd, Takeda. None of these relationships had any influence on the content of the present manuscript. RCWM has received research funding from AstraZeneca, Bayer, Merck Sharp & Dohme, Novo Nordisk, Pfizer and Tricida Inc. for carrying out clinical trials, and has received speaker honorarium or consultancy in advisory boards from AstraZeneca, Bayer and Boehringer Ingelheim. All proceeds have been donated to the Chinese University of Hong Kong to support diabetes research. Other authors have no conflicts of interest to disclose. Ethics Approval Statement: Ethical approval was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee for analysis and reporting of anonymized data.

Does administration of vaginal estrogens increase the risk of venous thromboembolism: A case-control study.

Does administration of vaginal estrogens increase the risk of venous thromboembolism: A case-control study.

Treatment Persistence of Renin-Angiotensin-Aldosterone-System Inhibitors Over Time in Heart Failure with Reduced Ejection Fraction

Clinical practice guidelines support sustained use of renin-angiotensin-aldosterone-system (RAAS) inhibitors over time in heart failure with reduced ejection fraction, yet few data are available regarding the frequency, timing or predictors of early treatment discontinuation in clinical practice. Among prevalent or new users of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs) in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, we estimated the frequency and independent predictors of treatment discontinuation during follow-up. Among sites with > 5 users of a given RAAS inhibitor, we evaluated practice variation in the proportion of patients with treatment discontinuation. Over median follow-up of 18 months, frequency of drug discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.7% (444 of 3509 users), 10.4% (140 of 1352 users), and 20.4% (435 of 2129 users), respectively. An additional, 149 (11.0%) of ARNI users were switched to ACEis/ARBs, and 447 (12.7%) of ACEi/ARB users were switched to ARNIs during follow-up. Across sites, the median proportion of discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.5% (25th-75th percentiles 6.9%-18.9%), 18.8% (25th-75th percentiles 12.5%-28.6%), and 19.6% (25th-75th percentiles 10.7%-27.0%), respectively. Chronic kidney disease was the only independent predictor of increased risk of discontinuation of each of the RAAS inhibitor classes (P < 0.02 for all). Higher Kansas City Cardiomyopathy Questionnaire overall summary scores independently predicted lower risk of discontinuation of ACEis/ARBs and ARNIs (both P < 0.001) but not of MRAs. Investigator clinical experience was predictive of lower risks of discontinuation of ACEis/ARBs and MRAs (P < 0.02) but not of ARNIs. All other independent predictors of discontinuation were unique to individual therapeutic classes. One in 10 patients discontinue ACEis/ARBs or ARNIs, and 1 in 5 discontinue MRAs in routine clinical practice of heart failure with reduced ejection fraction. Unique patient-level and clinician/practice-level factors are associated with premature discontinuation of individual RAAS inhibitors, which may help to guide structured efforts to promote treatment persistence in clinical care.

Evaluation of Adjuvant Chemotherapy-Associated Steatosis (CAS) in Colorectal Cancer.

Chemotherapy-associated steatosis is poorly understood in the context of colorectal cancer. In this study, Stage II–III colorectal cancer patients were retrospectively selected to evaluate the frequency of chemotherapy-associated steatosis and to determine whether patients on statins throughout adjuvant chemotherapy develop chemotherapy-associated steatosis at a lower frequency. Baseline and incident steatosis for up to one year from chemotherapy start date was assessed based on radiology. Of 269 patients, 76 (28.3%) had steatosis at baseline. Of the remaining 193 cases, patients receiving adjuvant chemotherapy (n = 135) had 1.57 (95% confidence interval [CI], 0.89 to 2.79) times the adjusted risk of developing steatosis compared to patients not receiving chemotherapy (n = 58). Among patients who underwent chemotherapy, those using statins for pre-existing hyperlipidemia (n = 37) had 0.71 (95% CI, 0.10 to 2.75) times the risk of developing steatosis compared to patients who were not prevalent users of statins (n = 98). Chemotherapeutic treatment of Stage II–III colorectal cancer appears to be consistent with a moderately increased risk of steatosis, although larger studies are necessary to assess the significance of this observation. Prospective trials should be considered to further explore the potential for protective use of statins in this curative patient population.