Patient characteristics, pain treatment patterns, and incidence of total joint replacement in a US population with osteoarthritis.

BACKGROUND: Currently available medications for chronic osteoarthritis pain are only moderately effective, and their use is limited in many patients because of serious adverse effects and contraindications. The primary surgical option for osteoarthritis is total joint replacement (TJR). The objectives of this study were to describe the treatment history of patients with osteoarthritis receiving prescription pain medications and/or intra-articular corticosteroid injections, and to estimate the incidence of TJR in these patients. METHODS: This retrospective, multicenter, cohort study utilized health plan administrative claims data (January 1, 2013, through December 31, 2019) of adult patients with osteoarthritis in the Innovation in Medical Evidence Development and Surveillance Distributed Database, a subset of the US FDA Sentinel Distributed Database. Patients were analyzed in two cohorts: those with prevalent use of "any pain medication" (prescription non-steroidal anti-inflammatory drugs [NSAIDs], opioids, and/or intra-articular corticosteroid injections) using only the first qualifying dispensing (index date); and those with prevalent use of "each specific pain medication class" with all qualifying treatment episodes identified. RESULTS: Among 1 992 670 prevalent users of "any pain medication", pain medications prescribed on the index date were NSAIDs (596 624 [29.9%] patients), opioids (1 161 806 [58.3%]), and intra-articular corticosteroids (323 459 [16.2%]). Further, 92 026 patients received multiple pain medications on the index date, including 71 632 (3.6%) receiving both NSAIDs and opioids. Altogether, 20.6% of patients used an NSAID at any time following an opioid index dispensing and 17.2% used an opioid following an NSAID index dispensing. The TJR incidence rates per 100 person-years (95% confidence interval [CI]) were 3.21 (95% CI: 3.20-3.23) in the "any pain medication" user cohort, and among those receiving "each specific pain medication class" were NSAIDs, 4.63 (95% CI: 4.58-4.67); opioids, 7.45 (95% CI: 7.40-7.49); and intra-articular corticosteroids, 8.05 (95% CI: 7.97-8.13). CONCLUSIONS: In patients treated with prescription medications for osteoarthritis pain, opioids were more commonly prescribed at index than NSAIDs and intra-articular corticosteroid injections. Of the pain medication classes examined, the incidence of TJR was highest in patients receiving intra-articular corticosteroids and lowest in patients receiving NSAIDs.

Outcomes in patients with lung cancer treated with crizotinib and erlotinib in routine clinical practice: A post-authorization safety cohort study conducted in Europe and in the United States.

PURPOSE: We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patients initiating crizotinib and erlotinib in routine clinical practice. METHODS: This descriptive cohort study used routinely collected health data in Denmark, Finland, Sweden, the Netherlands, and the United States (US) during 2011-2017, following crizotinib commercial availability in each country. Among crizotinib or erlotinib initiators, we reported baseline characteristics and incidence rates and cumulative incidences of the SOI - hepatotoxicity, pneumonitis/interstitial lung disease, QT interval prolongation-related events, bradycardia, vision disorders, renal cysts, edema, leukopenia, neuropathy, photosensitivity, malignant melanoma, gastrointestinal perforation, cardiac failure and OS. Results from the European Union (EU) countries were combined using meta-analysis; results from the US were reported separately. RESULTS: There were 456 patients in the crizotinib cohort and 2957 patients in the erlotinib cohort. Rates of the SOI per 1000 person-years in the crizotinib cohort ranged from 0 to 65 in the EU and from 0 to 374 in the US. Rates of the SOI per 1000 person-years in the erlotinib cohort ranged from 0 to 91 in the EU and from 3 to 394 in the US. In the crizotinib cohort, 2-year OS was ~50% in both EU and US. In the erlotinib cohort, 2-year OS was 21% in the EU and 35% in the US. CONCLUSIONS: This study describes clinical outcomes among lung cancer patients initiating crizotinib or erlotinib in routine clinical practice. Differences between SOI rates in EU and US may be partially attributable to differences in the underlying databases.

Risk of adverse birth outcomes after maternal varenicline use: A population-based observational study in Denmark and Sweden.

PURPOSE: To examine risks of adverse birth outcomes in women exposed to varenicline during pregnancy. METHODS: Population-based cohort study including live-born and stillborn infants from 1 May 2007 to 31 December 2012. Data from health and administrative registries in Denmark and Sweden, two Nordic countries with universal health care and routine registration of major life and health events. Infants were allocated to three cohorts on the basis of their in utero exposure: the exposed cohort consisting of infants whose mothers were dispensed varenicline during pregnancy; the unexposed cohort comprised infants unexposed to varenicline, but exposed to maternal smoking in utero; and the reference cohort of infants unexposed to varenicline and maternal smoking in utero. The primary outcome was major congenital malformations diagnosed from birth to the first year of life. Secondary outcomes included stillbirth, fetal growth restriction (measured as small for gestational age), preterm delivery, preterm premature rupture of membranes, and sudden infant death syndrome. We estimated the prevalence of the primary outcome and secondary outcomes in the exposed, unexposed, and reference cohorts. Prevalence odds ratios with 95% confidence intervals (CIs) were computed using logistic regression with propensity score adjustment to control for potential confounders. RESULTS: The combined cohort included 885 185 infants. Of these, 335 infants were exposed, 78 412 were unexposed, and the remaining 806 438 comprised the reference cohort. Major congenital malformations were detected among 3.6% of exposed infants, 4.3% of unexposed infants, and 4.2% of infants in the reference cohort. The propensity score-adjusted prevalence odds ratio for major congenital malformations was 0.80 (95% CI, 0.45-1.42) for exposed vs unexposed infants. All analyses of primary and secondary outcomes comparing exposed with unexposed infants yielded odds ratio estimates below or close to unity. Use of varenicline during pregnancy does not appear to increase the risk of major congenital malformations or other adverse birth outcomes.

The incidence of stroke among selected patients undergoing elective posterior lumbar fusion: a retrospective cohort study.

BACKGROUND: Although stroke is a rare complication among spinal surgery patients, the recognition of this adverse event is critical given the aging population undergoing surgical procedures. The objective of this study was to estimate the incidence of stroke among selected adults undergoing elective posterior lumbar fusion (PLF) during various post-operative risk windows and among different subgroups. METHODS: A retrospective cohort study using a longitudinal electronic healthcare record (EHR) database was conducted from January 1, 2007 to June 30, 2018. Elective PLF, stroke, and select clinical characteristics were defined based on International Classification of Disease codes. Patients aged 18 to 85 years with ≥183 days of enrollment in the database prior to undergoing elective PLF were followed from the index date until the occurrence of stroke, death, loss to follow-up, or end of study period, whichever occurred first. The incidence of stroke was estimated in the following risk windows: index hospitalization, ≤ 30 days, ≤ 90 days, ≤ 180 days, and ≤ 365 days post-operation. RESULTS: A total of 43,063 patients were eligible for the study. The incidence of stroke following elective PLF was 0.29% (95% confidence interval [CI]: 0.25, 0.35%) during index hospitalization, 0.44% (95% CI: 0.38, 0.50%) ≤ 30 days, 0.59% (95% CI: 0.52, 0.67%) ≤ 90 days, 0.76% (95% CI: 0.68, 0.85%) ≤ 180 days, and 1.12% (95% CI: 1.03, 1.23%) ≤ 365 days post-operation. Stratified analyses revealed that older patients had a higher incidence of stroke. Additionally, black patients had higher stroke incidences. Post-operative stroke incidence was higher among patients with a history of type 2 diabetes than among patients without such history; similarly, stroke incidence was higher among patients with a history of stroke compared to patients without such history. CONCLUSIONS: The incidence of stroke following elective PLF using an EHR database in this study is slightly higher than that reported in the literature. Our results suggest that stroke risk modification prior to PLF may be important for patients who are older, black, type 2 diabetic, and/or have a history of stroke.

Classification and characteristics of on-label and off-label apixaban use in Denmark and Sweden.

PURPOSE: To estimate the proportion of apixaban users who received the drug for on-label indications and characterise the patients using apixaban for on-label and off-label indications. METHODS: We report results from two independently conducted studies in Denmark and Sweden, with 19,709 Danish and 17,592 Swedish patients, who received at least one outpatient dispensing of apixaban as identified through nationwide prescription registries. Indications, inferred from inpatient and hospital diagnoses recorded at the initial apixaban dispensing, were classified as on-label, off-label, or unclassified according to the Summary of Product Characteristics. All diagnoses were retrieved using inpatient or outpatient hospital diagnoses at the first outpatient dispensing during the study period. RESULTS: Men comprised 52% of the users in both Denmark and Sweden. The median age was 76 years (interquartile range [IQR]: 68-83 years) among Danish patients and 74 years (IQR: 67-82 years) among Swedish patients. An on-label indication could be assigned to 82.6% (95% confidence interval [CI]: 82.1%-83.1%) of the Danish patients and 86.4% (95% CI: 85.9%-86.9%) of the Swedish patients. The main on-label indication for apixaban was non-valvular atrial fibrillation (NVAF), which accounted for 76.1% of the indications in Denmark and 69.1% of the indications in Sweden. Off-label indications were assigned to 10.8% (95% CI: 10.3-11.2) of the Danish patients (main indication possible mechanical heart valve) and 7.7% (95% CI: 7.3-8.1) of the Swedish patients (main indication off-label atrial fibrillation). CONCLUSION: The majority of apixaban initiators in Denmark and Sweden received apixaban for an on-label indication, primarily for NVAF.

Assessment of Risk Evaluation and Mitigation Strategies (REMS) for varenicline (Chantix): A multistage patient survey.

PURPOSE: To evaluate the Risk Evaluation and Mitigation Strategies (REMS) for varenicline by assessing patients' understanding of the varenicline medication guide (MG) at pre-specified time points: 18 months, 3 years, and 7 years after the REMS approval. METHODS: Self-administered surveys were mailed to people who received varenicline based on a pharmacy dispensing. Survey questions assessed understanding of potential risks outlined in the MG: neuropsychiatric symptoms, skin reactions, allergic reactions, and cardiovascular risks. Crude and weighted analyses were conducted. RESULTS: The response to the survey overall was between 18% and 19%. Among responders, approximately 90% recalled receiving the MG, and at least 80% read all or part of it. At least 88% correctly identified neuropsychiatric symptoms as potential medication effects, while 41% did so for skin reactions, 53% for allergic reactions, and 82% for cardiovascular risks. Patients who read the MG had a high proportion of correct responses to the risk comprehension questions. CONCLUSIONS: A large majority of patients who were dispensed varenicline recalled receiving the MG and were able to correctly recall neuropsychiatric and cardiovascular risks in all 3 surveys. The varenicline MG may be an effective tool for patient education.

Acute nonarteritic anterior ischemic optic neuropathy and exposure to phosphodiesterase type 5 inhibitors.

INTRODUCTION: Nonarteritic anterior ischemic optic neuropathy (NAION), a rare visual disorder, has been reported in men using phosphodiesterase type 5 inhibitors (PDE5i) for erectile dysfunction. AIM: We examined whether intermittent use of PDE5i is associated with acute NAION onset within approximately five half-lives following drug ingestion. METHODS: One hundred two ophthalmology centers in the United States and Europe identified potential cases of NAION. An expert adjudication committee conducted a blind review of the records of those with recent PDE5i use to classify cases as Definite, Possible, or not NAION. Subjects provided information on PDEi use via telephone interview. Each NAION case's PDE5i exposure immediately prior to onset was compared against his recent patterns of use in an observational case-crossover design. A sample size of 40 cases with intermittent PDE5i exposure in the 30 days prior to NAION onset was needed to detect an odds ratio (OR) of 3.0 with 80% power. MAIN OUTCOME MEASURES: The daily relative risk for acute NAION on days within five half-lives of PDE5i use vs. other days was estimated via an OR obtained from conditional logistic regression. RESULTS: Among 43 Definite NAION cases with PDE5i exposure in the prior 30 days, the OR was 2.15 (95% confidence interval [CI]: 1.06, 4.34). When 21 Possible NAION cases were included (n = 64), the OR was 2.36 (95% CI: 1.33, 4.19). CONCLUSIONS: We found an approximately twofold increased risk of acute NAION within five half-lives of PDE5i use compared with use in a more prior time period. Bias from inaccurate recall of exposure was unlikely to have substantially affected the results. Based on our results, we estimate that weekly use of PDE5i adds three NAION cases per 100,000 men 50 years and older annually.

Drug Utilization Studies in Pregnant Women for Newly Licensed Medicinal Products: A Contribution from IMI ConcePTION.

Purpose: Studies focusing on safety outcomes typically require large populations to comprehensively characterise the patient groups exposed to the medicines under investigation. However, there is often less information for subpopulations, such as pregnant or breastfeeding women, particularly when new medicines are considered. It is important to understand what information can be obtained from drug utilization studies (DUS) involving pregnant women in the early years postmarketing to provide supportive information for safety studies. The aims of this literature review are to (1) identify and review DUS for new medicines in pregnancy and breastfeeding and (2) list and summarise key information items to be reported in a DUS for new medicines in pregnancy. Methods: To identify postmarketing DUS of new prescription medicines or enantiomers in pregnancy, a systematic literature review was undertaken in PubMed and Embase between January 2015 and June 2022. In addition, the complete database of the ENCePP EU PAS Register was systematically searched to June 2022. Results: We identified 11 published DUS on new medicines in pregnancy from the ENCePP EU PAS Register and none from other sources. No studies on breastfeeding were identified. The 11 identified publications reported the medicine's use for the first 3 to 5 years after marketing approval. No reports assessed utilization in the first 3 years of approval. It was usual to issue interim reports annually (7 studies). All studies concerned conditions managed in ambulatory care (primary care and outpatient facilities) and included some primary care prescribing. Most (n = 8) only had prescribing/dispensing data available at individual level for ambulatory care; outpatient prescribing was included in three of these studies Three studies held a limited amount of in-hospital prescribing data. A DUS can confirm at an early stage whether there are sufficient exposed pregnancies in available data sources to ensure a safety study is powered to detect a difference in the prevalence of adverse pregnancy or infant outcomes or if additional data from other databases are needed. A DUS may also help address methodological considerations such as selection of comparators. DUS can be performed embedded in a DUS in the general population, in a cohort of women of childbearing age, or in a cohort of pregnant women. Conclusion: This review summarises key aspects of a DUS for new medicines in pregnancy. DUS for new medicines in pregnancy should be planned before marketing, scheduled for the first 3 to 5 years after release, with annual interim/progress reports, and reported in peer-reviewed journals. By offering detailed information on data sources, exposure timing, prevalence and location, coprescribing, comorbidities, coexposures, and demographics, a DUS will offer a firm foundation for safety studies and will help to contextualize spontaneous reporting of serious adverse events.

The effectiveness of varenicline medication guide for conveying safety information to patients: a REMS assessment survey.

PURPOSE: Risk Evaluation and Mitigation Strategies (REMS) include various mechanisms to enhance safe use of medications, including a patient medication guide (MG) that provides key information regarding the potential risks associated with the medication. To evaluate the effectiveness of the varenicline MG as a REMS tool for educating patients, we undertook a survey among patients who were dispensed varenicline. METHODS: Varenicline recipients within the Optum Research Database, a large U.S. administrative claims database, were invited to participate in a self-administered survey. Survey questions were general (receipt and reading of the MG) and specific regarding patient's understanding of the potential varenicline risks outlined in the MG (neuropsychiatric symptoms, skin reactions, and allergic reactions). RESULTS: From 3568 varenicline recipients invited, 640 (18%) responded, with 633 completing at least one of three risk-comprehension questions. The majority (93%) indicated receiving the MG, and 86% read all or part of it. Ninety-one percent, 41%, and 53% correctly answered at least one question on neuropsychiatric symptoms, skin reactions, and allergic reactions, respectively. A higher proportion who read the MG had correct responses to the risk-comprehension questions than those who did not read it. CONCLUSIONS: The varenicline MG was widely received and read among survey respondents, and the information conveyed was generally well understood regarding potential risk of neuropsychiatric symptoms. This study provides an assessment of the effectiveness of the varenicline MG in communicating information about potential risks associated with varenicline. This assessment method may apply to the evaluation of the effectiveness of other MGs.

The Structured Process to Identify Fit-For-Purpose Data: A Data Feasibility Assessment Framework.

To complement real-world evidence (RWE) guidelines, the 2019 Structured Preapproval and Postapproval Comparative study design framework to generate valid and transparent real-world Evidence (SPACE) framework elucidated a process for designing valid and transparent real-world studies. As an extension to SPACE, here, we provide a structured framework for conducting feasibility assessments-a step-by-step guide to identify decision grade, fit-for-purpose data, which complements the United States Food and Drug Administration (FDA)'s framework for a RWE program. The process was informed by our collective experience conducting systematic feasibility assessments of existing data sources for pharmacoepidemiology studies to support regulatory decisions. Used with the SPACE framework, the Structured Process to Identify Fit-For-Purpose Data (SPIFD) provides a systematic process for conducting feasibility assessments to determine if a data source is fit for decision making, helping ensure justification and transparency throughout study development, from articulation of a specific and meaningful research question to identification of fit-for-purpose data and study design.

The incidence of acute myocardial infarction after elective spinal fusions or joint replacement surgery in the United States: a large-scale retrospective observational cohort study in 322,585 patients : Post-surgical myocardial infarction data.

BACKGROUND: Acute myocardial infarction (AMI) is an uncommon but fatal complication among patients undergoing elective spinal fusion surgery (SF), total hip arthroplasty (THA), and total knee arthroplasty (TKA). Our objective was to estimate the incidence of AMI among adults undergoing elective SF, THA, and TKA in different post-operative risk windows and characterize high-risk sub-populations in the United States. METHODS: A retrospective cohort study was conducted using data from a longitudinal electronic healthcare record (EHR) database from January 1, 2007 to June 30, 2018. ICD codes were used to identify SF, THA, TKA, AMI, and selected clinical characteristics. Incidence proportions (IPs) and 95% confidence intervals were estimated in the following risk windows: index hospitalization, ≤ 30, ≤ 90, ≤ 180, and ≤ 365 days post-operation. RESULTS: A total of 67,533 SF patients, 87,572 THA patients, and 167,480 TKA patients were eligible for the study. The IP of AMI after SF, THA, and TKA ranged from 0.36, 0.28, and 0.25% during index hospitalization to 1.05, 0.93, and 0.85% ≤ 365 days post-operation, respectively. The IP of AMI was higher among patients who were older, male, with longer hospital stays, had a history of AMI, and had a history of diabetes. CONCLUSION: The IP of post-operative AMI was generally highest among the SF cohort compared to the THA and TKA cohorts. Additionally, potential high-risk populations were identified. Future studies in this area are warranted to confirm these findings via improved confounder control and to identify effect measure modifiers.

Effect of the patient information brochure in communicating the risks associated with crizotinib treatment to patients with non-small cell lung cancer (NSCLC) in Europe.

Crizotinib (XALKORI® ) is indicated for anaplastic lymphoma kinase-positive and ROS1-positive advanced non-small cell lung cancer. This study evaluated the distribution of the crizotinib patient information brochure (PIB) in Europe and patient knowledge of the key messages in the PIB. A cross-sectional survey was conducted in 10 European countries among patients who received crizotinib to ascertain whether each patient received and read the PIB, and his/her knowledge of its key messages on hepatotoxicity, interstitial lung disease/pneumonitis, QTc prolongation, bradycardia, and vision disorders. Of the 341 patients contacted, 40 responded (11.7%), and 39 patients were eligible. A total of 77% of respondents acknowledged receiving the PIB, of which, 93% reported reading it. Knowledge of the individual side effects ranged from 36% to 85%, and precautions for use ranged from 56% to 67%. Understanding the reasons for calling a physician ranged from 54% to 85%. Knowledge of each of the 6 key side effects was greater among readers of the PIB compared to non-readers or respondents who did not recall receiving the PIB. Approximately three-quarters of survey respondents recalled receiving the crizotinib PIB and respondents who read the PIB were more knowledgeable of the key side effects of crizotinib than those who did not read or receive. Caution should be taken in generalizing these results because of the potential for selection bias and small sample size. These survey results suggest that the crizotinib PIB may be an effective risk communication tool for crizotinib-treated patients in Europe.

Incidence rates of health outcomes of interest among Chinese children exposed to selected vaccines in Yinzhou Electronic Health Records: A population-based retrospective cohort study.

INTRODUCTION: Oral poliovirus vaccine (OPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP) are widely used in China while Haemophilus influenzae type b vaccines (Hib) and a DTaP, inactivated poliovirus (IPV) andHib polysaccharide conjugated to tetanus protein (PRP ~ T) combined vaccine (DTaP-IPV//PRP ~ T) have lower coverage. There are limited safety data on these vaccines in Chinese pediatric populations. METHODS: To estimate incidence rates (IRs) of health outcomes of interest (HOIs) among children exposed to OPV, DTaP, Hib, and DTaP-IPV//PRP ~ T, we conducted a retrospective cohort study using a population-based electronic health record (EHR) database in Yinzhou district, Ningbo City. Children 0-2 years of age receiving at least one dose of these vaccines between January 1, 2012 and March 31, 2017 were included in the study. Yinzhou EHR database consisted of immunization records and healthcare data of children from hospitals and community health centers in the district. Eight HOIs (i.e., anaphylaxis, febrile seizures, all seizures, asthma, apnea, Kawasaki disease [KD], urticaria/angioedema, Guillain-Barré syndrome [GBS]) were identified using ICD-10 codes. RESULTS: A total of 220,422 eligible children was identified. No cases of apnea, KD, and GBS were observed within 7 days post-vaccination. During 0-7 days post-vaccination for OPV, DTaP, Hib, and DTaP-IPV//PRP ~ T, the IRs of anaphylaxis, febrile seizures, all seizures, urticaria/angioedema and asthma ranged from 0.0 to 50.0, 0.0 to 99.9, 29.1 to 249.8, 297.8 to 949.1, and 992.7 to 2298.2 per 100,000 person-years, respectively, and 0.0 to 0.9, 0.0 to 1.9, 0.6 to 4.6, 5.6 to 17.5, and 18.7 to 42.3 per 100,000 doses, respectively. CONCLUSION: IRs of some HOIs in our study were comparable with those in the literature while IRs of other HOIs were not due to differences in study design, post-vaccination risk periods assessed, and vaccine types. Future studies should consider medical chart review for validating HOIs obtained in the EHR.

Metabolic syndrome clusters and the risk of incident stroke: the atherosclerosis risk in communities (ARIC) study.

BACKGROUND AND PURPOSE: Little is known about the metabolic syndrome (MetS) and the risk of incident stroke. This study is designed to identify particular clusters of MetS components that carry the highest risk of incident stroke. METHODS: We analyzed the public use data from the population-based Atherosclerosis Risk in Communities study. At baseline, 14 993 stroke-free middle-aged individuals were followed-up over 9 years for incident stroke. MetS components were defined according to the National Heart, Lung, and Blood Institute/American Heart Association criteria. Incident stroke was identified using a standardized incident events identification and classification protocol. Proportional hazard models were used to assess the RRs and 95% CIs of ischemic stroke associated with MetS and its different clusters. RESULTS: At baseline, the prevalence of MetS was 39%. The mean age was 54, with 26% blacks and 55% females. The hazard ratio of incident ischemic stroke associated with MetS among women (hazard ratio, 2.41; 95% CI, 1.69 to 3.49) and men (hazard ratio, 2.11; 95% CI, 1.56-2.85) was similar. There was a dose-response relationship between the numbers of MetS components and the risk of incidence stroke. Persons with either elevated blood pressure or elevated fasting glucose in the clusters to form a MetS had the highest risk for incident stroke (hazard ratio, 2.74-4.16 comparing to the reference group) than MetS without these 2 components (hazard ratio,

Age-related macular degeneration is associated with incident myocardial infarction among elderly Americans.

OBJECTIVE: To investigate whether age-related macular degeneration (AMD) is associated with the development of myocardial infarction (MI) among elderly Americans. DESIGN: Population-based cross-sectional and cohort study. PARTICIPANTS: Five percent random sample of 2000 to 2003 Medicare enrollees. METHODS: The cross-sectional study included the first 2-year (2000 and 2001) enrollees who were aged > or =65 years (n = 1,519,086). The cohort study included only baseline MI-free enrollees (n = 1445677). MAIN OUTCOME MEASURES: Chronic conditions (AMD and type, history of MI, hypertension, and diabetes) were defined based on any occurrence of relevant International Classification of Diseases 9 codes in relevant diagnosis fields of the baseline Medicare claim files. A total of 56611 incident MI cases were identified from the follow-up data (2002 and 2003). RESULTS: Baseline mean age was 76 years, with 60% women and 88% whites. The prevalence of neovascular AMD was 2.2% (2.3% in women vs. 1.7% in men and 2.3% in whites vs. 1.2% in blacks; P<0.01 for both gender and race differences). The prevalence of nonneovascular AMD was 8.8% (9.9% in women vs. 7.3% in men and 9.5% in whites vs. 4.3% in blacks; P<0.01 for both gender and race differences). Baseline age-, gender-, and race-adjusted prevalences of hypertension, diabetes, and history of MI were 75%, 33%, and 5.00%, respectively, in the neovascular AMD group. In contrast, they were 73%, 27%, and 4.68% in the nonneovascular AMD group, and 65%, 25%, and 4.54% in the non-AMD group (P<0.01 for comparing the prevalence in neovascular and nonneovascular AMD vs. non-AMD groups). Prospectively, baseline age-, gender-, race-, hypertension-, and diabetes-adjusted 2-year incident odds ratios and 95% confidence intervals of MI associated with AMD are 1.19 (1.16-1.22) for all persons with AMD, 1.26 (1.20-1.33) for neovascular AMD, and 1.18 (1.14-1.21) for nonneovascular AMD. CONCLUSIONS: AMD is associated with older age, female gender, being white, and having a history of MI, hypertension, and diabetes. Furthermore, presence of AMD, especially neovascular AMD, is prospectively associated with a higher risk of incident MI. These findings, if confirmed by other studies that control for smoking and other lifestyle covariables, suggest the possibility of shared common antecedents between MI and AMD.

Diabetes and the risk of lung cancer.

OBJECTIVE: The incidence of some cancers has been reported to be higher in diabetic patients than in the general population. We estimated the incidence of lung cancer in diabetic patients and investigated the hypothesis that the rate of lung cancer is different in diabetic compared with nondiabetic patients. RESEARCH DESIGN AND METHODS: Diabetic patients and age-, sex-, and general practice-matched nondiabetic control subjects were identified from U.K. computerized general practice records (General Practice Research Database), and these records searched for any incident lung cancer, demographic details, and smoking status. Primary lung cancer incidence was calculated and rates compared between diabetic patients and nondiabetic control subjects using multivariate Cox regression, adjusting for age, sex, and smoking. The comparison was repeated for incident diabetic patients followed from diagnosis and after stratifying by diabetic treatment. RESULTS: The incidence of primary lung cancer in all 66,848 diabetic patients was 1.63 per 1,000 patient-years (95% CI 1.48-1.79) and 2.05 per 1,000 patient-years (1.76-2.38) among diabetic patients followed from diagnosis. When compared with nondiabetic control subjects, the hazard ratio was 0.88 (0.79-0.97) for all diabetic patients and 1.12 (0.95-1.34) for those followed from diagnosis. When observation was truncated to allow for shorter life expectancy, the hazard ratio for the total cohort was 0.98 (0.84-1.13), and no association was found with any treatment group. CONCLUSIONS: No increased risk of lung cancer in diabetes was found. We hypothesize that the lower incidence may be partly due to shorter life expectancy.

Practice patterns of ophthalmologists administering intravitreal injections in Europe: a longitudinal survey.

PURPOSE: This study was performed to understand the practice patterns of ophthalmologists administering intravitreal (IVT) injections in Europe after the procedure became routine. METHODS: As part of a prospective, multinational, non-interventional cohort study in 13 countries in Europe between 2006 and 2012, ophthalmologists completed the Baseline Questionnaire and the Follow-up Questionnaire 1 year after baseline. RESULTS AND DISCUSSION: Of the 125 ophthalmologists who participated in the study, 113 (90.4%) completed the Baseline Questionnaire. Most of these ophthalmologists were medical retina specialists (43.0%). The median number of IVT injections that the ophthalmologists performed per month during the year prior to completing the Baseline Questionnaire was 20.0. The majority of the ophthalmologists had performed their last IVT injection prior to completing the questionnaire in an operating room or theater (68.4%). When performing IVT injections, a majority of the ophthalmologists reported applying povidone-iodine (90.4%) before IVT injections and topical antibiotics right after IVT injections (89.5%). In addition, 81.6% of the ophthalmologists reported using a sterile adhesive eye drape and 80.7% reported using an eyelid speculum. In all, 95 ophthalmologists (76%) completed the Follow-up Questionnaire. The median number of IVT injections performed per month during the year prior to completing the Follow-up Questionnaire by these ophthalmologists was increased to 35. The results of the Follow-up Questionnaire on administering IVT injections were similar to those of the Baseline Questionnaire. A majority of the ophthalmologists reported applying povidone-iodine (87.4%) before IVT injections, topical antibiotics right after IVT injections (89.5%), and an eyelid speculum (85.3%). CONCLUSION: The results of this study indicated a good adherence to all aspects of the guidelines on IVT injections. It seemed that ophthalmologists were more experienced in IVT injections after they became a routine treatment procedure.

Serum total and lipoprotein cholesterol levels and awareness, treatment, and control of hypercholesterolemia in China.

BACKGROUND: Cardiovascular disease has become the leading cause of death in China. We examined the levels of serum total and lipoprotein cholesterol and status of awareness, treatment, and control of hypercholesterolemia in China. METHODS AND RESULTS: A cross-sectional survey in a nationally representative sample of 15,540 Chinese adults 35 to 74 years of age was conducted during 2000 to 2001. Serum cholesterol was measured by use of standard methods, and information on treatment of hyperlipidemia was obtained by use of a standard questionnaire. Age-standardized mean levels of total, HDL, and LDL cholesterol and triglycerides were 186.1, 51.7, 109.5, and 128.1 mg/dL, respectively. Of the Chinese population 35 to 74 years of age, 23.8% (112,500000 persons) had borderline high total cholesterol (200 to 239 mg/dL), and 9.0% (42,540000 persons) had high total cholesterol (> or =240 mg/dL). The population estimates for borderline high (130 to 159 mg/dL), high (160 to 189 mg/dL), and very high (> or =190 mg/dL) LDL cholesterol were 17.0% (80,122000 persons), 5.1% (24,329000 persons), and 2.7% (12,822000 persons), respectively. In addition, 19.2%, or 90 803 000 persons, had a low HDL cholesterol (<40 mg/dL). Among those who had a total cholesterol > or =200 mg/dL or who were on cholesterol-lowering medications, the proportion of men and women who were aware, treated, and controlled was only 8.8% and 7.5%, 3.5% and 3.4%, and 1.9% and 1.5%, respectively. CONCLUSIONS: The prevalence of hypercholesterolemia was relatively high and the percentage of adults with controlled blood cholesterol was low in China. Prevention and treatment of hypercholesterolemia should be an important component of a national strategy to reduce the substantial and increasing burden of cardiovascular disease in China.

Cardiovascular disease in patients with schizophrenia in Saskatchewan, Canada.

BACKGROUND: Studies have shown that patients with schizophrenia have higher rates of cardiovascular disease and mortality compared with the general population. However, population-based data on the prevalence, incidence, and mortality of cardiovascular disease are needed. METHOD: In this retrospective cohort study, the Saskatchewan Health databases were searched for all patients diagnosed with schizophrenia (ICD-9 code 295) in 1994 or 1995. 3022 subjects were identified. For each subject, 4 age- and sex-matched comparison individuals were selected randomly among residents of the province who had no diagnosis of schizophrenia or any other mental disorders and who received no prescriptions for antipsychotic medications. Prevalence of cardiovascular morbidity during 1994 and 1995 and incidence of cardiovascular morbidity and mortality during the follow-up period of January 1996 through March 1999 were analyzed. RESULTS: Concerning prevalence of morbidity in schizophrenia patients, significantly increased risk-adjusted odds ratios were as follows: arrhythmia, 1.5 (95% CI = 1.2 to 1.8); syncope, 4.0 (95% CI = 2.0 to 7.9); heart failure, 1.7 (95% CI = 1.4 to 2.2); stroke, 2.1 (95% CI = 1.6 to 2.7); transient cerebral ischemia, 2.6 (95% CI = 1.7 to 3.7); and diabetes, 2.1 (95% CI = 1.8 to 2.4). Odds of acute myocardial infarction, ischemic heart disease, and ventricular arrhythmias were not significantly different from those for the comparison group. Concerning incidence of morbidity and mortality in the patients, adjusted relative risk was significantly increased for ventricular arrhythmia, 2.3 (95% CI = 1.2 to 4.3); heart failure, 1.6 (95% CI = 1.2 to 2.0); stroke, 1.5 (95% CI = 1.2 to 2.0); diabetes, 1.8 (95% CI = 1.2 to 2.6); all-cause mortality, 2.8 (95% CI = 2.3 to 3.4); and cardiovascular mortality, 2.2 (95% CI = 1.7 to 2.8). CONCLUSIONS: Persons with schizophrenia appear to be at greater risk for cardiovascular morbidity and mortality than those in the general population.