Risk of maculopathy with pentosan polysulfate sodium use.

AIMS: Recent epidemiologic studies have examined the risk of maculopathy with pentosan polysulfate sodium (PPS), a drug indicated for the treatment of interstitial cystitis. However, results have been contradictory. Thus, we quantified the risk of maculopathy with PPS with a focus on risk with duration of use. METHODS: We used a new user, retrospective cohort study with an active comparator. We created a cohort of mutually exclusive 6221 PPS users and 89 744 amitriptyline users, a tricyclic antidepressant also used for the treatment of pain secondary to interstitial cystitis. Subjects were selected from the PharMetrics Plus database (IQVIA, Durham, NC) from 2006 to 2020. Cohort members were followed to the first event of the study outcome (maculopathy) or end of enrolment. A Cox regression model was constructed to adjust for potential confounders. RESULTS: The mean follow-up was 3.0 years for PPS users and amitriptyline users. The adjusted hazard ratio (HR) for maculopathy in PPS users was 2.64 (95% confidence interval [CI]: 1.90-3.68). The HR for the sensitivity analysis that combined maculopathy and age-related macular degeneration (AMD) was 1.38 (95% CI: 1.16-1.65). A cumulative duration-response pattern was observed, with use greater than 3 years having a 9.5-fold risk of maculopathy (HR = 9.56, 95% CI: 3.60-25.37) compared to a 2.3-fold risk of maculopathy with use for 1 year or less (HR = 2.27, 95% CI: 1.50-3.43). The number needed to harm for the first 4 years of use was 250. CONCLUSIONS: The results of this study suggest an increased risk of maculopathy with PPS use, particularly with longer duration of use.

The association between hormonal contraceptive use and glaucoma in women of reproductive age.

AIMS: We aimed to investigate the association between hormonal contraceptive (HC) use and the incidence of glaucoma in females of reproductive age with a focus on duration and type of HCs used. METHODS: A retrospective cohort study with a case-control analysis (nested case-control) was undertaken using data from IQVIA's electronic medical record (IQVIA, USA) from 2008 to 2018. Within a cohort of 4 871 504 women, cases of glaucoma or ocular hypertension were identified. Subjects were followed to the first diagnosis of glaucoma. Each glaucoma case was matched to four controls by age, body mass index and follow up time. The main outcome measure was the first diagnosis of glaucoma defined by the first ICD-9/10 code for glaucoma or ocular hypertension. RESULTS: Among 4 871 504 women identified, there were 2366 cases of glaucoma and 9464 controls. Regular users of hormonal contraceptives had an elevated risk of glaucoma compared to non-users with an adjusted incident rate ratio (aIRR) of 1.57 (95% CI: 1.29-1.92). Current users were of greatest risk (aIRR of 2.38, 95% CI: 1.81-3.13), whereas the aIRR among past users was 1.08 (95% CI: 0.82-1.43). The aIRR for glaucoma increased from 0.82 (95% CI: 0.70-0.95) among those with one or two prescriptions in the 2 years prior to the first diagnosis of glaucoma to 1.54 (95% CI: 1.32-1.81) among those with greater than four prescriptions. CONCLUSIONS: This nested case-control study demonstrated an elevated risk, albeit low, of glaucoma in females of reproductive age who use regular hormonal contraception. Future studies are needed to confirm these findings.

Short and long-term barriers and facilitators of skin self-examination among individuals diagnosed with melanoma.

BACKGROUND: Melanoma can be lethal if not detected early and treated. Early detection can be facilitated via skin self-examination (SSE) and as such, SSE is part of melanoma follow-up care for individuals with a prior history, who face a life-long risk of reoccurrence. The objective of the current study was to identify short- and long-term predictors of SSE among melanoma survivors to inform future prevention interventions in high-risk groups. METHOD: This is an observational study with longitudinal assessments conducted with adult melanoma patients in active follow-up care. PRIMARY OUTCOME MEASURES: Behavioral outcomes, comprehensive SSE (checking up to 5 body areas in the last 3 months) and optimal SSE (checking the entire body at least monthly in the last 3 months) were assessed at 3, 12, and 24 months post a dermatological educational session on skin cancer prevention. T tests and chi square analyses were used to examine changes in outcomes from 3 to 12 and 24 months. Linear and logistic regression models were used to examine the association between predictors and the primary outcomes. RESULTS: Comprehensive SSE did not decrease significantly from 3 (M = 2.7, SD = 1.1) to 12 (M = 2.6, SD = 1.2) and 24 months (M = 2.4, SD = 1.2) post the education session, with the stronger predictor at all timepoints being intentions to perform SSE. Optimal SSE was higher at 3 months (59%) compared to 12 (46%) and 24 months (34%), with key predictors including self-efficacy and intentions to perform SSE and male sex at 3 months post; self-efficacy and reliance on medical advice at 12 months; and (lower) education and self-efficacy at 24 months. CONCLUSIONS: The key findings of this study are that 1) survivors maintain SSE behaviour over time, but rates of SSE performed in agreement with medical recommendations are higher immediately post standard dermatological education (i.e. usual care) and decrease somewhat over a 24-month period; and 2) the strongest psycho-social predictors of SSE are intentions and self-efficacy to perform the behavior, which are highly modifiable, for example via motivational interviewing and goal setting health interventions.

Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma.

The majority of diffuse large B-cell lymphoma (DLBCL) tumors contain mutations in histone-modifying enzymes (HMEs), indicating a potential therapeutic benefit of histone deacetylase inhibitors (HDIs), and preclinical data suggest that HDIs augment the effect of rituximab. In this randomized phase 2 study, we evaluated the response rate and toxicity of panobinostat, a pan-HDI administered 30 mg orally 3 times weekly, with or without rituximab, in 40 patients with relapsed or refractory de novo (n = 27) or transformed (n = 13) DLBCL. Candidate genes and whole exomes were sequenced in relapse tumor biopsies to search for molecular correlates, and these data were used to quantify circulating tumor DNA (ctDNA) in serial plasma samples. Eleven of 40 patients (28%) responded to panobinostat (95% confidence interval [CI] 14.6-43.9) and rituximab did not increase responses. The median duration of response was 14.5 months (95% CI 9.4 to "not reached"). At time of data censoring, 6 of 11 patients had not progressed. Of the genes tested for mutations, only those in MEF2B were significantly associated with response. We detected ctDNA in at least 1 plasma sample from 96% of tested patients. A significant increase in ctDNA at day 15 relative to baseline was strongly associated with lack of response (sensitivity 71.4%, specificity 100%). We conclude that panobinostat induces very durable responses in some patients with relapsed DLBCL, and early responses can be predicted by mutations in MEF2B or a significant change in ctDNA level at 15 days after treatment initiation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT01238692).

Association of Antidepressant Use With Drug-Related Extrapyramidal Symptoms: A Pharmacoepidemiological Study.

BACKGROUND: Antidepressants are one of the most prescribed classes of medications. A number of case reports have linked these drugs to extrapyramidal symptoms (EPSs), but no large epidemiologic study to date has examined this association. We sought to quantify the association of EPSs with different antidepressants by undertaking a large pharmacoepidemiologic study. METHODS: A nested case-control study was conducted using a large health claims database in the United States from June 2006 to December 2015. Subjects with a diagnosis of primary Parkinson disease and those who received prescriptions of levodopa, ropinirole, pramipexole, domperidone, metoclopramide, entacapone, benztropine, selegiline, rasagiline, diphenhydramine, trihexyphenidyl, typical and atypical antipsychotics, and tricyclic antidepressants were excluded. Cases were followed to the first billing code for an extrapyramidal event or last date of enrollment in the cohort. For each case, 10 control subjects were matched by follow-up time, calendar time, and age through density-based sampling. Rate ratios were computed using conditional logistic regression adjusting for other covariates. RESULTS: We identified 3,838 subjects with EPSs compared with 38,380 age-matched control subjects. Rate ratios with respect to EPSs were as follows: duloxetine, 5.68 (95% confidence interval [CI], 4.29-7.53); mirtazapine, 3.78 (95% CI, 1.71-8.32); citalopram, 3.47 (95% CI, 2.68-4.50); escitalopram, 3.23 (95% CI, 2.44-4.26); paroxetine, 3.07 (95% CI, 2.15-4.40); sertraline, 2.57 (95% CI, 2.02-3.28); venlafaxine, 2.37 (95% CI, 1.71-3.29); bupropion, 2.31 (95% CI, 1.67-3.21); and fluoxetine, 2.03 (95% CI, 1.48-2.78). CONCLUSIONS: This observational study demonstrates a harmful association between the incidence of Parkinson disease or associated EPSs and use of the antidepressants duloxetine, mirtazapine, citalopram, escitalopram, paroxetine, sertraline, venlafaxine, bupropion, and fluoxetine.

Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss.

This database study examines the association between glucagon-like peptide 1 agonists (eg, semaglutide, liraglutide) used for weight loss and reports of gastrointestinal adverse events.

Association Between Sublingual Buprenorphine-Naloxone Exposure and Dental Disease.

This study examines the association of sublingual buprenorphine/naloxone and dental adverse events using the IQVIA health claims database.

Inflammatory bowel disease and risk of mortality in COPD.

Patients with chronic obstructive pulmonary disease (COPD) have higher incidence and prevalence of other chronic inflammatory diseases, including inflammatory bowel disease (IBD). We assessed whether IBD onset increases mortality risk in patients with COPD or asthma-associated COPD.Two population-based cohorts of COPD and asthma-COPD subjects were identified using the administrative health databases in Québec, Canada, 1990-2007. Death records were retrieved from the death certificate registry. Cox proportional hazards models were used to assess the impact of newly developed IBD on mortality risk.The COPD and asthma-COPD cohorts included 273 208 and 26 575 patients, respectively, of which 697 and 119 developed IBD. IBD increased the risk of all-cause mortality in both COPD (hazard ratio 1.23, 95% CI 1.09-1.4) and asthma-COPD (hazard ratio 1.65, 95% CI 1.23-2.22). In asthma-COPD patients, IBD increased the risk of mortality from respiratory conditions (hazard ratio 2.18, 95% CI 1.31-3.64); in COPD patients, IBD increased the risk of death from digestive conditions (hazard ratio 4.45, 95% CI 2.39-8.30).IBD is a risk factor for mortality in patients with pre-existing COPD or asthma-COPD. IBD increased mortality by respiratory and digestive conditions in patients with asthma-COPD and COPD, respectively.

Incidence and causes of maternal mortality in the USA.

AIM: To characterize the most common causes and risk factors of maternal mortality in the USA and observe trends over the past 9 years. METHODS: We carried out a population-based retrospective cohort study using data from the Health Care Cost and Utilization Project, Nationwide Inpatient Sample. Women who were pregnant between 2003 and 2011 were identified. Baseline characteristics of pregnant women who died and those who lived were measured. ICD-9 codes for each cause of death were examined by up to three independent reviewers. Causes of death were categorized into the nine most common subgroups and trends were examined by tertiles of the period 2003-2011. RESULTS: During this 9-year period, there were approximately 7 million births and 1102 maternal deaths, for an overall incidence of 14.2 per 100 000 births. Primary causes of maternal death included sepsis (20.6%), cardiac disease (17.8%), hemorrhage (16.2%), venous thromboembolism (15.2%), and hypertensive disorders (9.4%). During the study period, there was a significant decrease in the frequency of sepsis from 33.2% to 10.0% and a non-significant decrease in venous thromboembolism from 19.1% to 12.9%. There were increases noted in all other groups, notably in terms of hemorrhage from 8.2% to 22.0% and hypertensive disorders from 2.1% to 16.4%. CONCLUSION: Maternal mortality remains a rare event. Although sepsis was the overall predominant cause of mortality during the study period, frequency declined over time and it was surpassed by hemorrhage and hypertensive disorders as the leading causes of maternal mortality.

Incidence and risk factors of sepsis mortality in labor, delivery and after birth: population-based study in the USA.

AIM: Maternal sepsis is one of the leading causes of maternal mortality around the world. The aim of this study was to estimate the incidence and mortality rate of sepsis, and the associated risk factors for their development during pregnancy, labor, delivery and the post-partum period. METHODS: We conducted a population-based cohort study consisting of 5 million births that occurred in the USA. Data were obtained from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database from 1998 to 2008. Logistic regression was used to calculate the adjusted odds ratio and corresponding 95% confidence intervals (95%CI) for sepsis development and sepsis-related death during admission for delivery. RESULTS: The overall incidence of maternal sepsis was 29.4 per 100 000 births (95%CI: 28.0-30.9) with a sepsis case fatality rate of 4.4 per 100 births (95%CI: 3.5-5.6). Both the incidence of maternal sepsis and sepsis-related death rate have increased over the last decade. Women who are black, older than 35 years and who smoke were more likely to experience maternal sepsis. An association was also found between maternal sepsis and diabetes mellitus, cardiovascular disease, eclampsia, preterm birth, hysterectomy, puerperal infection, post-partum hemorrhage, transfusion and chorioamnionitis. CONCLUSIONS: Mortality from maternal sepsis during labor and delivery is an increasing and important problem in westernized countries. Initiatives aimed at improving early recognition and effective management may help reduce the occurrence and outcomes of maternal sepsis at time of labor and delivery.

Antihypertensive agents acting on the renin-angiotensin system and the risk of sepsis.

AIMS: In response to safety concerns from two large randomized controlled trials, we investigated whether the use of telmisartan, an angiotensin receptor blocker (ARB), ARBs as a class and angiotensin-converting enzyme inhibitors (ACEIs) increase the risk of sepsis, sepsis-associated mortality and renal failure in hypertensive patients. METHODS: We performed a nested case-control study from a retrospective cohort of adults with hypertension from the UK General Practice Research Database diagnosed between 1 January 2000 and 30 June 2009. All subjects hospitalized with sepsis during follow-up were matched for age, sex, practice and duration of follow-up with 10 control subjects. Exposure was defined as current use of antihypertensive drugs. RESULTS: From the cohort of 550 436 hypertensive patients, 1965 were hospitalized with sepsis during follow-up (rate 6.9 per 10 000 per year), of whom 824 died and 346 developed acute renal failure within 30 days. Compared with use of ß-blockers, calcium-channel blockers or diuretics, use of ARBs, including telmisartan, was not associated with an elevated risk of sepsis (relative risk 1.09; 95% confidence interval 0.83-1.43); but use ACEIs was (relative risk 1.65; 95% confidence interval 1.42-1.93). Users of ARBs, ß-blockers, calcium-channel blockers or diuretics, but not users of ACEIs, had lower rates of hospitalization for sepsis compared with untreated hypertensive patients. Findings were similar for sepsis-related 30 day mortality and renal failure. CONCLUSIONS: Hypertensive patients treated with ARBs, including telmisartan, do not appear to be at increased risk of sepsis or sepsis-related 30 day mortality or renal failure. On the contrary, users of ACEIs may have an increased risk.

Sickle cell disease and pregnancy outcomes: population-based study on 8.8 million births.

OBJECTIVE: To estimate the prevalence of sickle cell disease (SCD) in pregnancy, and to measure risk factors, morbidity, and mortality among women with SCD with and without crisis at the time of birth. METHODS: We conducted a population-based, retrospective cohort study on all births in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) from 1999 to 2008. Births to SCD with and without crisis were identified using ICD-9 codes. Adjusted effects of risk factors and outcomes were estimated using logistic regression analyses. Effect of hemoglobin variants among women with SCD was analyzed as a predictor of crisis. RESULTS: There were 4262 births to women with SCD for an overall prevalence of 4.83 per 10,000 deliveries. 28.5% of women with SCD developed crisis at the time of delivery. The maternal mortality rate was 1.6 per 1000 deliveries in women with SCD, compared to 0.1 per 1000 in women without SCD. Pregnant women with SCD had a higher risk of developing preeclampsia, eclampsia, venous thromboembolism, cardiomyopathy, intrauterine fetal demise, and intrauterine growth restriction. Cesarean delivery rates were higher in women with SCD. Among the 1898 SCD women with identified hemoglobin variants, homozygous SS was the greatest risk factor for sickle cell crisis, accounting for 89.8% of all women who developed crisis. CONCLUSION: Pregnant women with SCD have a high risk of morbidity and mortality. Developing acute sickle cell crisis worsened perinatal outcomes.

Trends, risk factors and mortality among women with venous thromboembolism during labour and delivery: a population-based study of 8 million births.

OBJECTIVE: Venous thromboembolism (VTE) is amongst the main causes of maternal death in the developed world. The objective of this study is to elucidate risk factors of VTE and specifically, predictors of fatal thromboembolic disease during the delivery. STUDY DESIGN: We conducted a population-based cohort study on 8 million birth records using the Healthcare Cost and Utilisation Project-Nationwide Inpatient Sample from 1999 to 2008 to estimate the incidence and case fatality of VTE's during labour admission. Logistic regression was used to calculate the odds ratio (OR) and corresponding 95 % confidence intervals (CIs) of demographic and obstetrical determinants of VTEs and fatal VTEs. RESULTS: The overall incidence of VTE was 167.7/100,000 births, increasing over the 10-year period, with an average case fatality rate of 0.41 %. VTE was associated with maternal age above 25, elderly primigravida, multigravida, black race, smoking, thrombophilia, cardiovascular disease, hypertension, obesity, postpartum haemorrhage and blood transfusion. Predictors of VTE fatalities included black race, hypertension, caesarean section and transfusion. CONCLUSION: VTE is a rare but serious condition that is increasing in incidence and is associated with a significant degree of maternal morbidity and mortality. Further research targeting prevention among high-risk groups is warranted.

The use of inhaled corticosteroids and the risk of adrenal insufficiency.

Adrenal insufficiency is a potential complication of therapy with an inhaled corticosteroid (ICS). Although prior studies found the highest risk of adrenal insufficiency with fluticasone, a more potent ICS, these results might be explained by a channelling bias and concomitant exposure to oral corticosteroids. We re-examined the relationship between the use of ICSs and adrenal insufficiency by using a cohort of patients treated for respiratory conditions during 1990-2005, identified in the healthcare databases from the province of Quebec, Canada, with follow-up until 2007. A nested case-control analysis was performed within this cohort. Cases of adrenal insufficiency were matched with up to 10 controls. 392 cases were identified (incidence rate 1.1 per 10 000 person-years). Although the rate of adrenal insufficiency was not significantly higher among all current users of ICSs, patients receiving the highest dosages showed a greater risk (OR 1.84, 95% CI 1.16-2.90). Consistently, an increased risk was estimated for the highest tertile of ICS dose (OR 1.90, 95% CI 1.07-3.37) cumulated in the year before the event. ICS at high doses appear to be a significant independent risk factor for adrenal insufficiency. Physicians prescribing ICS at such dosages should be sensitive to the signs and symptoms of adrenal insufficiency in their patients.

Incidence and obstetrical outcomes of cervical intraepithelial neoplasia and cervical cancer in pregnancy: a population-based study on 8.8 million births.

OBJECTIVE: To estimate the incidence and outcomes of cervical intraepithelial neoplasia (CIN) and cervical cancer in pregnancy. METHODS: We conducted a population-based cohort study using the United States Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 1999 to 2008. The incidence of CIN and cervical cancer was measured and logistic regression analysis used to estimate the adjusted effect of CIN and cervical cancer on obstetrical outcomes. RESULTS: There were 8,826,137 births over a 10-year period of which 11,755 were among women with CIN and 294 among women with cervical cancer. Compared with controls, women with CIN were younger, had lower annual incomes, and more likely to be on Medicaid while women with cancer were more likely to be older. Women with CIN had lower rates of cesarean delivery but higher rates of transfusions and cesarean hysterectomies, while women with cancer had higher rates of cesarean deliveries, transfusions and cesarean hysterectomies. There were no significant increase of thrombosis; maternal death, instrumental delivery, IUGR, PPROM or intrauterine death was found. CONCLUSION: CIN and cervical cancer are rare in pregnancy. Although there is a greater risk of transfusion/hysterectomy, overall major maternal and neonatal morbidity does not appear to be increased.

Fluoroquinolones and the risk of serious arrhythmia: a population-based study.

BACKGROUND: Fluoroquinolones have been suspected to cause cardiac arrhythmia but data are lacking, particularly for the individual fluoroquinolones. We assessed the risk of serious arrhythmia, defined as ventricular arrhythmia or sudden/unattended death identified in hospital discharge diagnoses, related to fluoroquinolones as a class as well as for each individual molecule. METHODS: We used a cohort of patients treated for respiratory conditions from 1 January 1990 to 31 December 2005, identified using the healthcare databases from the province of Quebec (Canada), with follow-up until 31 March 2007. A nested case-control analysis was performed within this cohort, with all cases of serious arrhythmia occurring during follow-up identified from hospitalization records. These cases were matched with up to 20 controls. Conditional logistic regression was used to compute adjusted rate ratios (RRs) of serious arrhythmia associated with fluoroquinolone use. RESULTS: Within the cohort of 605127 subjects, 1838 cases were identified (incidence rate=4.7/10000 person-years). The rate of serious arrhythmia was elevated with current fluoroquinolone use (RR=1.76; 95% confidence interval [CI], 1.19-2.59), in particular with new current use (RR=2.23; 95% CI, 1.31-3.80). Gatifloxacin use was associated with the highest rate (RR=7.38; 95% CI, 2.30-23.70); moxifloxacin and ciprofloxacin were also associated with elevated rates of serious arrhythmia (RR=3.30; 95% CI, 1.47-7.37 and RR=2.15; 95% CI, 1.34-3.46, respectively). CONCLUSIONS: The use fluoroquinolones is associated with an elevated risk of serious arrhythmia, with some differences among molecules. Given that the individual fluoroquinolones share various indications, the relative risks of serious arrhythmia could inform the choice of different molecules in high-risk patients.

Inhaled corticosteroids and risk of tuberculosis in patients with respiratory diseases.

RATIONALE: Treatment with substantial doses of oral corticosteroids (OCS) for prolonged periods increases the risk of tuberculosis (TB). However, little is known about the effect of inhaled corticosteroids (ICS) in this respect. OBJECTIVES: We quantified the independent contribution of ICS to the risk of TB in a population of patients with airway diseases. METHODS: A population-based cohort design with a nested case-control analysis was used. A cohort of patients with airways disease was formed using the Quebec databases. TB cases were identified and age-matched control subjects were selected from all subjects who entered the cohort in the same month as the cases. TB incidence among the cohort was compared with the general population of Quebec using the standardized incidence ratio. MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 427,648 subjects. There were 564 cases of TB identified between 1990 and 2005. The standardized incidence ratio was 3.9 (95% confidence interval [CI], 2.6-5.4). Any and current users of ICS are at an increased risk of TB (rate ratio [RR], 1.27; 95% CI, 1.05-1.53; and RR, 1.33; 95% CI, 1.04-1.71, respectively). Among users of OCS, no significant relationship could be demonstrated. Among subjects without OCS exposure, adjusted RRs were significant for any ICS use (RR, 1.26; 95% CI, 1.02-1.56) and current use (RR, 1.48; 95% CI, 1.11-1.97) and at the current high dose exposure level (RR, 1.97; 95% CI, 1.18-3.3). CONCLUSIONS: Exposure to ICS is not associated with risk of TB in the presence of OCS but is associated with increased TB risk in nonusers of OCS.

Effects of hormonal contraceptives on dry eye disease: a population-based study.

BACKGROUND: Hormonal contraceptives (HCs) are a known risk factor for dry eye disease (DED), yet the relationship between HCs use and DED in women of child-bearing age remains debatable. The aim of this study was to determine the association between HCs and DED in females of reproductive age. METHODS: This was a retrospective cohort study using data from IQVIA's electronic medical record (IQVIA, USA). 4,871,504 women (age 15-45) between 2008 and 2018 were followed to the first diagnosis of DED as defined by an ICD-9/10 code. DED cases also required at least two prescriptions of cyclosporine or lifitegrast topical drops within 60 days of the first code. The date of the first code was designated as the index date. Regular HCs users needed to have at least two prescriptions in both the first year and second year prior to the index date. For each case, five controls were selected and matched to cases by age and follow-up time. A conditional logistic regression model was used to adjust for confounders of DED and to calculate odds ratios (ORs). RESULTS: HCs users were at a higher risk for DED than non-users. Regular users of HCs were more likely to develop DED (ORs = 2.73, 95% CI [2.21-3.73]) than irregular users. Those who used a greater number of HCs were at a higher risk for DED. CONCLUSIONS: This study indicates an increased risk of DED with HCs use in women of child-bearing age.

The Incidence of Sympathetic Ophthalmia After Trauma: A Meta-analysis.

PURPOSE: Sympathetic ophthalmia (SO) is a rare, bilateral panuveitis that occurs following open globe injury (OGI), with a variable incidence reported in the literature. Our objective was to determine the incidence proportion and incidence rate of SO following OGI to help guide shared physician-patient decision making. DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was performed using the MEDLINE, EMBASE, and Cochrane databases from inception to November 2020 for population-based studies on OGI and SO in adults and children. Two reviewers independently screened search results. Random-effects meta-analyses were performed to calculate the incidence proportion and incidence rate. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. The study was registered on PROSPERO CRD42020198920. RESULTS: A total of 24 studies were utilized in the meta-analyses. After OGI, the estimated overall incidence proportion of SO was 0.19% (95% CI 0.14%-0.24%) and the incidence rate of SO was 33 per 100,000 person-years, (95% CI 19.61-56.64) with I2 of 13% and 72%, respectively. CONCLUSIONS: SO after OGI is rare. The estimated incidence proportion and incidence rate are useful when counselling patients regarding management options after OGI. Further studies are needed to examine the influence of age, the extent and location of trauma, timing of repair, and prophylactic eye removal on the incidence of SO.

Acetylcholinesterase inhibitors and risk of bleeding and acute ischemic events in non-hypertensive Alzheimer's patients.

INTRODUCTION: Acetylcholinesterase inhibitors (AChEIs) are commonly used to treat mild to moderate cases of Alzheimer disease (AD). To the best of our knowledge, there has been no study estimating the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Therefore, this study aimed to estimate the association between AChEIs and the risk of bleeding and cardiovascular ischemic events in patients with non-hypertensive AD. METHODS: A nested case-control study was conducted to estimate the risk of bleeding and ischemic events (angina, myocardial infarction [MI], and stroke) in patients with AD. This study was conducted using the UK Clinical Practice Research Datalink and Hospital Episode Statistics (HES) databases. The study cohort consisted of AD patients ≥65 years of age. The case groups included all AD subjects in the database who had a bleeding or ischemic event during the cohort follow-up. Four controls were selected for each case. Patients were classified as current users or past users based on a 60-day threshold of consuming the drug. Simple and multivariable conditional logistic regression analyses were used to calculate the adjusted odds ratio for bleeding events and cardiovascular events. RESULTS: We identified 507 cases and selected 2028 controls for the bleeding event cohort and 555 cases and 2220 controls for the ischemic event cohort. The adjusted odds ratio (OR) (95% confidence interval [CI]) for the association of AChEI use was 0.93 (0.75 to 1.16) for bleeding events, 2.58 (1.01 to 6.59) for angina, and 1.89 (1.07 to 3.33) for MI. Past users of AChEIs were also at increased risk of stroke (1.51 [1.00 to 2.27]). DISCUSSION: This is the first study assessing the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Our findings could be of great interest for clinicians and researchers working on AD.