Incidence of disease after vasectomy: a record linkage retrospective cohort study.

OBJECTIVE--To determine whether vasectomy is associated with an increased risk of several diseases, and in particular testicular cancer, after operation. DESIGN--Retrospective cohort study using linked medical record abstracts. SETTING--Six health districts in Oxford region. SUBJECTS--13,246 men aged 25-49 years who had undergone vasectomy between 1970 and 1986, and 22,196 comparison subjects who had been admitted during the same period for one of three specified elective operations, appendicitis, or injuries. MAIN OUTCOME MEASURES--Hospital admission and death after vasectomy or comparison event. RESULTS--The mean durations of follow up were 6.6 years for men with a vasectomy and 7.5 years for men with a comparison condition. The relative risk of cancer of the testis in the vasectomy cohort (4 cases) compared with that in the other cohorts (17 cases) was 0.46 (95% confidence interval 0.1 to 1.4), that of cancer of the prostate (1 v 5 cases) 0.44 (0.1 to 4.0), and that of myocardial infarction (97 v 226 cases) 1.00 (0.8 to 1.3). There was no evidence of an increase associated with vasectomy in the incidence of a range of other diseases. CONCLUSIONS--Vasectomy was not associated with an increased risk of testicular cancer or the other diseases studied. With respect to prostatic cancer, while we found no cause for concern, longer periods of observation on large numbers of men are required.     

Post-acute health care burden after SARS-CoV-2 infection: a retrospective cohort study

Background:The post-acute burden of health care use after SARS-CoV-2 infection is unknown. We sought to quantify the post-acute burden of health care use after SARS-CoV-2 infection among community-dwelling adults in Ontario by comparing those with positive and negative polymerase chain reaction (PCR) test results for SARS-CoV-2 infection.Methods:We conducted a retrospective cohort study involving community-dwelling adults in Ontario who had a PCR test between Jan. 1, 2020, and Mar. 31, 2021. Follow-up began 56 days after PCR testing. We matched people 1:1 on a comprehensive propensity score. We compared per-person-year rates for health care encounters at the mean and 99th percentiles, and compared counts using negative binomial models, stratified by sex.Results:Among 531 702 matched people, mean age was 44 (standard deviation [SD] 17) years and 51% were female. Females who tested positive for SARS-CoV-2 had a mean of 1.98 (95% CI 1.63 to 2.29) more health care encounters overall per-person-year than those who had a negative test result, with 0.31 (95% CI 0.05 to 0.56) more home care encounters to 0.81 (95% CI 0.69 to 0.93) more long-term care days. At the 99th percentile per-person-year, females who tested positive had 6.48 more days of hospital admission and 28.37 more home care encounters. Males who tested positive for SARS-CoV-2 had 0.66 (95% CI 0.34 to 0.99) more overall health care encounters per-person-year than those who tested negative, with 0.14 (95% CI 0.06 to 0.21) more outpatient encounters and 0.48 (95% CI 0.36 to 0.60) long-term care days, and 0.43 (95% CI −0.67 to −0.21) fewer home care encounters. At the 99th percentile, they had 8.69 more days in hospital per-person-year, with fewer home care (−27.31) and outpatient (−0.87) encounters.Interpretation:We found significantly higher rates of health care use after a positive SARS-CoV-2 PCR test in an analysis that matched test-positive with test-negative people. Stakeholders can use these findings to prepare for health care demand associated with post-COVID-19 condition (long COVID).

The public health effects of the COVID-19 pandemic are difficult to overstate.¹ More than 600 million SARS-CoV-2 infections and 6.5 million deaths have been reported worldwide as of September 2022,² which are likely gross undercounts as many infections go undetected.³Long-term morbidity can be caused by SARS-CoV-2 infection.^4–9 In the first pandedmic wave, as many as 27% of people admitted to hospital died or were readmitted within 60 days, and as many as 70% of people who were not admitted to hospital reported at least 1 symptom 4 months after infection.^10,11 By the World Health Organization (WHO) definition, about 10%–20% of those infected acquire a post-COVID-19 condition (long COVID).^12,13Analysis of 10 prospective surveys and the medical records of 1.1 million patients with COVID-19 diagnosis codes before the emergence of the Omicron variant showed similar findings: 7.8%–17% had symptoms 12 weeks after self-reported COVID-19, with 1.2%–4.8% reporting debilitating symptoms.¹⁴ Estimates of long COVID vary by methodology (e.g., definitions of initial infection and timing of symptoms, timing of data collection), but risk is thought to be influenced by infection severity, type of variant, patient characteristics, vaccination¹⁵ and, potentially, previous infection.¹⁶ Because each new SARS-CoV-2 infection carries some risk of long COVID, everyone remains at risk for developing the condition.Health care funders, policy-makers and clinicians need a clear understanding of the impact of long COVID on use of health care resources to allocate resources equitably now and plan for future needs.¹⁷ We sought to quantify the post-acute burden of health care use after SARS-CoV-2 infection among community-dwelling adults in Ontario.     

Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study

The aim of the present study was to simultaneously assess several potential predictors of outcome (co-morbidity, previous and in-hospital treatment, radiologic Brixia score) in patients with COVID-19.This retrospective cohort study included 258 consecutive patients with confirmed COVID-19 admitted to a medical ward at Montichiari Hospital, Brescia, Italy from February 28th to April 30rd, 2020. Patients had SARS-CoV-2 related pneumonia with respiratory failure, and were treated with hydroxychloroquine and lopinavir plus ritonavir. In some patients, additional treatment with tocilizumab, dexamethasone and enoxaparin was adopted. Outcomes (death or recovery) were assessed at the end of the discharge period or at the end of the follow-up (August 2020).During hospitalization, 59 patients died, while 6 died after discharge. The following variables were demonstrated to be associated with a worse prognosis: Radiologic Brixia score higher than 8, presence at baseline of hypertension, diabetes, chronic obstructive pulmonary disease, heart disease, cancer, previous treatment with ACE-inhibitors or anti-platelet drugs. Anticoagulant treatment during hospital admission with enoxaparin at a dose higher than 4000 U once daily was associated with a better prognosis.In conclusion, our study demonstrates that some co-morbidities and cardiovascular risk factors may affect prognosis. The radiologic Brixia score may be a useful tool to stratify the risk of death at baseline. Anticoagulant treatment with enoxaparin might be associated to a clinical benefit in terms of survival in patients with COVID-19.     

Quantifying the impact of deprivation on preterm births: a retrospective cohort study

Background

Social deprivation is associated with higher rates of preterm birth and subsequent infant mortality. Our objective was to identify risk factors for preterm birth in the UK''s largest maternity unit, with a particular focus on social deprivation, and related factors.

Methodology/Principal Findings

Retrospective cohort study of 39,873 women in Liverpool, UK, from 2002–2008. Singleton pregnancies were stratified into uncomplicated low risk pregnancies and a high risk group complicated by medical problems. Multiple logistic regression, and generalized additive models were used to explore the effect of covariates including area deprivation, smoking status, BMI, parity and ethnicity on the risk of preterm birth (34⁺⁰ weeks). In the low risk group, preterm birth rates increased with deprivation, reaching 1.6% (CI₉₅ 1.4 to 1.8) in the most deprived quintile; the unadjusted odds ratio comparing an individual in the most deprived quintile, to one in the least deprived quintile was 1.5 (CI₉₅ 1.2 to 1.9). Being underweight and smoking were both independently associated with preterm birth in the low risk group, and adjusting for these factors explained the association between deprivation and preterm birth. Preterm birth was five times more likely in the high risk group (RR 4.8 CI₉₅ 4.3 to 5.4), and there was no significant relationship with deprivation.

Conclusions

Deprivation has significant impact on preterm birth rates in low risk women. The relationship between low socio-economic status and preterm births appears to be related to low maternal weight and smoking in more deprived groups.     

Effect of day 3 embryo morphometrics and morphokinetics on survival and implantation after slow freezing-thawing and after vitrification-warming: a retrospective cohort study

Background

Morphometric and morphokinetic evaluation of in vitro cultured human embryos allows evaluation without time restriction and reduces intra- and inter-observer variability. Even though these technologies have been reported to improve the quality of cleavage stage embryo evaluation during fresh culture, possible advantages in the evaluation of cryopreserved embryos have been scarcely explored. This study aims to compare morphometric and morphokinetic parameters between slow frozen and vitrified embryos and to determine their relationship to embryo survival and implantation rate (IR) after thawing/warming.

Methods

During fresh culture, morphometric characteristics (Total Cell Volume (TCV), symmetry, fragmentation and number of blastomeres) were measured in 286 thawed/warmed embryos. Likewise, after thawing/warming, similar morphometric characteristics were measured in 135 survived embryos. Moreover, morphokinetic parameters (time to mitosis resumption and time to compaction) were measured in 90 embryos after thawing/warming. Then, using linear regression, we investigated the differences between vitrified and slow frozen embryos and the relation of the measured characteristics to embryo survival and IR. Statistical corrections were applied to account for data clustering and for multiple testing.

Results

Vitrified embryos resume mitosis and start compaction significantly earlier than slow frozen embryos. Mitosis resumption rate was 82% for vitrified and 63% for slow frozen embryos and median time to mitosis resumption was 7.6 h and 13.1 h (p = 0.02), respectively. Compaction rate was 62% in vitrified and only 23% in slow frozen embryos. Median time to compaction was 18.1 h for vitrified embryos but, for slow frozen could not be computed since less than half of the slow frozen embryos reached compaction (p = 0.0001). Moreover, intact embryos resume mitosis significantly earlier than not intact ones regardless of the freezing method (rate: 79% vs. 66%, median time: 7.6 h vs 14.6 h, respectively, p = 0.03). Regarding morphometrics, slow frozen embryos showed lower TCV and higher blastomere symmetry after thawing than vitrified embryos despite having similar blastomere number. IR was related to blastomere number at cryopreservation in slow frozen embryos, but not in vitrified ones.

Conclusions

Interestingly, vitrified/warmed embryos undergo mitosis resumption and compaction significantly earlier than slow frozen/thawed embryos. However, the clinical use of this morphokinetic parameters still remains to be investigated in larger studies.

Trial registration

Retrospectively registered on December 15, 2015 NCT02639715.

     

Luteinizing hormone and androstendione are independent predictors of ovulation after laparoscopic ovarian drilling: a retrospective cohort study

Background  

Our objective was to investigate luteinizing hormone, follicle-stimulating hormone, testosterone, and androstenedione as predicitve markers for ovulation after laparoscopic ovarian drilling.     

Midline episiotomy and anal incontinence: retrospective cohort study

ObjectiveTo evaluate the relation between midline episiotomy and postpartum anal incontinence.DesignRetrospective cohort study with three study arms and six months of follow up.SettingUniversity teaching hospital.ParticipantsPrimiparous women who vaginally delivered a live full term, singleton baby between 1 August 1996 and 8 February 1997: 209 who received an episiotomy; 206 who did not receive an episiotomy but experienced a second, third, or fourth degree spontaneous perineal laceration; and 211 who experienced either no laceration or a first degree perineal laceration.ResultsWomen who had episiotomies had a higher risk of faecal incontinence at three (odds ratio 5.5, 95% confidence interval 1.8 to 16.2) and six (3.7, 0.9 to 15.6) months postpartum compared with women with an intact perineum. Compared with women with a spontaneous laceration, episiotomy tripled the risk of faecal incontinence at three months (95% confidence interval 1.3 to 7.9) and six months (0.7 to 11.2) postpartum, and doubled the risk of flatus incontinence at three months (1.3 to 3.4) and six months (1.2 to 3.7) postpartum. A non-extending episiotomy (that is, second degree surgical incision) tripled the risk of faecal incontinence (1.1 to 9.0) and nearly doubled the risk of flatus incontinence (1.0 to 3.0) at three months postpartum compared with women who had a second degree spontaneous tear. The effect of episiotomy was independent of maternal age, infant birth weight, duration of second stage of labour, use of obstetric instrumentation during delivery, and complications of labour. ConclusionsMidline episiotomy is not effective in protecting the perineum and sphincters during childbirth and may impair anal continence.     

Factors predicting patient use of the emergency department: a retrospective cohort study

Background:

Many studies have shown the tendency for people without a regular care provider or primary physician to make greater use of emergency departments. We sought to determine the effects of three aspects of care provided by primary physicians (physician specialty, continuity of care and comprehensiveness of care) on their patients’ use of the emergency department.

Methods:

Using provincial administrative databases, we created a cohort of 367 315 adults aged 18 years and older. Participants were residents of urban areas of Quebec. Affiliation with a primary physician, the specialty of this physician (i.e., family physician v. specialist), continuity of care (as measured using the Usual Provider Continuity index) and comprehensiveness of care (i.e., number of complete annual examinations) were measured among participants (n = 311 701) who had visited a physician three or more times during a two-year baseline period. We used multivariable negative binomial regression to investigate the relationships between measures of care and the number of visits to emergency departments during a 12-month follow-up period.

Results:

Among participants under 65 years of age, emergency department use was higher for those not affiliated than for those affiliated with a family physician (incidence rate ratio [IRR] 1.11, 95% confidence interval [CI] 1.05–1.16) or a specialist (IRR 1.10, 95% CI 1.04–1.17). Among patients aged 65 years and older, having a specialist primary physician, as opposed to a family physician, predicted increased use of the emergency department (IRR 1.13, 95% CI 1.09–1.17). Greater continuity of care with a family physician predicted less use of the emergency department only among participants who made 25 or more visits to a physician during the baseline period. Greater continuity of care with a specialist predicted less use of the emergency department overall, particularly among participants with intermediate numbers of multimorbidities and admissions to hospital. Greater comprehensiveness of care by family physicians predicted less use of the emergency department.

Interpretation:

Efforts to increase the proportion of adults affiliated with a family physician should target older adults, people who visit physicians more frequently and people with multiple comorbidities and admissions to hospital.Reforming primary care in Canada has been stimulated in part by increased crowding of emergency departments and evidence that their use, particularly for nonurgent care, may be related to inadequate primary care in the community.^1,2 Restructuring efforts, such as encouraging family physicians to work in multidisciplinary group practices with 24-hour access, are challenged by a relative shortage of family physicians.³ These issues are of particular importance in Quebec; despite relatively high numbers of family physicians per capita, in comparison with other provinces, residents of Quebec have the lowest rates of affiliation with a family physician and have one of the highest rates of seeing specialists.^4,5 In addition, residents of Quebec have among the highest rates of visits to emergency departments in international comparative studies.^6–8Research is needed into the effect that affiliation with a specialist rather than a family physician has on patients’ use of the emergency department, as is research into the continuity and comprehensiveness of care provided by the primary physician, regardless of specialty.Many studies have shown the tendency for people without a regular care provider to use the emergency department more often than people who have a primary physician.^1,9,10 Greater continuity of care with a primary physician has also been associated with fewer visits to the emergency department, but much of this research is cross-sectional, making causal interpretation difficult.¹¹ Furthermore, the distinction between continuity with a family physician versus a specialist primary physician has not been made, although one American study reported that having a specialist primary physician was associated with increased use of emergency departments.⁹We sought to determine whether certain factors predicted patients’ subsequent use of emergency departments, such as the specialty of their primary physician, the continuity of care with that physician and the comprehensiveness of care provided by that physician. To determine whether certain subgroups of the population may derive greater benefit from a particular type of care, we examined the potentially modifying effects of demographic factors, health status and previous use of health services. We restricted our study to residents of urban areas of Quebec for three reasons: rural residents visit the emergency department for primary care more often than residents of urban areas;¹² most specialist care is provided in urban areas; and primary care services in rural areas are more likely to be provided by salaried physicians, whose information is not available in the billing database.     

Following 411 Cochrane protocols to completion: a retrospective cohort study

Background

Cochrane reviews are regarded as being scientifically rigorous and are increasingly used by a variety of stakeholders. However, factors predicting the publication of Cochrane reviews have never been reported. This is important because if a higher proportion of Cochrane protocols with certain characteristics (e.g., funding) are being published, this may lead to inaccurate decisions. We examined the frequency of published and unpublished Cochrane reviews and protocol factors that predict the publication of Cochrane reviews.

Methodology/Principal Findings

Retrospective cohort study of Cochrane protocols published in 2000 (Issues 2 to 4) and 2001 (Issue 1). The publication status of these reviews was followed up to Issue 1, 2008 in The Cochrane Library. Survival analysis of the time from protocol publication to the first review publication and protocol factors predicting the time to publication was conducted. There were 411 new Cochrane protocols in the cohort. After excluding 39; 71/372 (19.1%) were unpublished and 301/372 (80.9%) were published as full Cochrane reviews at the time of study analysis (January 2008). The median time to publication was 2.4 years (range: 0.15 to 8.96). Multivariate analyses revealed that shorter time to publication was associated with the review subsequently being updated (hazard ratio, HR: 1.80 [95% confidence interval, CI: 1.39 to 2.33 years]) and longer time to publication was associated with the review having two published protocols, indicating changes to the review plan (HR: 0.33 [95% CI: 0.12 to 0.90 years]).

Conclusions/Significance

Only about 80% Cochrane protocols were published as full reviews after over 8 years of follow-up. The median time to publication was 2.4 years and some reviews took much longer. Strategies to decrease time to publication should be considered, such as streamlining the review process, increased support for authors when protocol amendments occur, and better infrastructure for updating Cochrane reviews.     

Enucleation and development of cluster headache: a retrospective study

Background  

Cluster headache (CH) is a neurovascular, primary headache disorder. There are, however, several case reports about patients whose CH started shortly after a structural brain disease or trauma. Motivated by a patient who developed CH 3 weeks after the removal of an eye and by similar case reports, we tested the hypothesis that the removal of an eye is a risk factor for CH.     

Mortality in young offenders: retrospective cohort study

Objectives To estimate overall and cause specific standardised mortality ratios in young offenders.Design Comparison of mortality data in cohort of young offenders.Settings State of Victoria, Australia.Subjects Cohort of young offenders aged 10-20 years with a first custodial sentence from 1 January 1988 to 31 December 1999.Main outcome measures Deaths ascertained by matching with the national death index, a database containing records of all deaths in Australia since 1980. Death rates in the reference Victorian population used to calculate standardised mortality ratios.Results The offender cohort comprised 2621 men and 228 women with 11 333 person years of observation. The median age of first detention was 17.9 years for men and 18.4 years for women. Median follow up was 3.3 years for men and 1.4 years for women. Overall standardised mortality ratio adjusted for age (expressed as a ratio) was 9.4 (95% confidence interval 7.4 to 11.9) for men and 41.3 (20.2 to 84.7) for women. Cause specific standardised mortality ratios for men were 25.7 (17.9 to 36.9) for drug related causes, 9.2 (5.8 to 15) for suicide, and 5.7 (3.6 to 9.2) for non-intentional injury. A quarter of drug related deaths in men aged 15-19 years were in offenders.Conclusions Social policies for young offenders should address both the prevalent drug and mental health problems as well the high levels of social disadvantage.     

Fracture risk among First Nations people: a retrospective matched cohort study

Background

Canadian First Nations people have unique cultural, socioeconomic and health-related factors that may affect fracture rates. We sought to determine the overall and site-specific fracture rates of First Nations people compared with non-First Nations people.

Methods

We studied fracture rates among First Nations people aged 20 years and older (n = 32 692) using the Manitoba administrative health database (1987–1999). We used federal and provincial sources to identify ethnicity, and we randomly matched each First Nations person with 3 people of the same sex and year of birth who did not meet this definition of First Nations ethnicity (n = 98 076). We used a provincial database of hospital separations and physician billing claims to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for each fracture type based on a 5-year age strata.

Results

First Nations people had significantly higher rates of any fracture (age- and sex-adjusted SIR 2.23, 95% CI 2.18–2.29). Hip fractures (SIR 1.88, 95% CI 1.61–2.14), wrist fractures (SIR 3.01, 95% CI 2.63–3.42) and spine fractures (SIR 1.93, 95% CI 1.79–2.20) occurred predominantly in older people and women. In contrast, craniofacial fractures (SIR 5.07, 95% CI 4.74–5.42) were predominant in men and younger adults.

Interpretation

First Nations people are a previously unidentified group at high risk for fracture.Most of the epidemiologic data describing fractures have been derived from white populations,¹ although it is known that there is ethnic variation in the epidemiology of fractures.^2,3,4 Canadian First Nations people are known to suffer from a heavy burden of medical and social problems that may affect fracture rates.⁵ To date, however, there have been no satisfactory studies of fracture rates among North American Aboriginal groups. We sought to determine the overall and site-specific fracture rates of First Nations people compared with non-First Nations people in Manitoba.     

Effects of propofol on the development of cancer in humans

Cancer is one of most the significant threats to human health worldwide, and the primary method of treating solid tumours is surgery. Propofol, one of the most widely used intravenous anaesthetics in surgery, was found to be involved in many cancer‐related pathophysiology processes, mainly including anti‐tumour and minor cancer‐promoting effects in various types of cancer. An increasing number of studies have identified that propofol plays a role in cancer by regulating the expression of multiple signalling pathways, downstream molecules, microRNAs and long non‐coding RNAs. Emerging evidence has indicated that propofol can enhance the anti‐tumour effect of chemotherapeutic drugs or some small molecular compounds. Additionally, in vivo animal models have shown that propofol inhibits tumour growth and metastasis. Furthermore, most clinical trials indicate that propofol is associated with better survival outcomes in cancer patients after surgery. Propofol use is encouraged in cancers that appear to have a better prognosis after its use during surgery. We hope that future large and prospective multicenter studies will provide more precise answers to guide the choice of anaesthetics during cancer surgery.     

Epidemiology of training injuries in amateur taekwondo athletes: a retrospective cohort study

The objectives of this study were to estimate the incidence and describe the pattern and severity of training injuries in taekwondo, and to compare pattern and severity of training injuries with competition injuries. One hundred and fifty-two active Australian amateur taekwondo athletes, aged 12 years or over, completed an online survey comprising questions on training exposure and injury history over the preceding 12 months. The main outcome measures were: overall injury incidence rate per athlete-year; training injury incidence rate per athlete-year, per 1000 athlete-training-sessions, and per 1000 athlete-hours of training; injury severity; and injury proportions by anatomical region and by type of injury. Injury incidence rates were calculated with 95% confidence intervals using standard methods, while injury proportions were compared using Fisher''s exact test. The vast majority (81.5%) of taekwondo injuries in an average athlete-year occurred during training. The training injury incidence rate was estimated to be 1.6 (95% CI: 1.4, 1.9) per athlete-year, 11.8 (95% CI: 10.4, 13.4) per 1000 athlete-training-sessions, and 7.0 (95% CI: 6.1, 7.9) per 1000 athlete-hours of training. Among athletes with five or fewer injuries, the severity and injury pattern of training injuries were, by and large, the same as for competition injuries. Approximately sixty percent (60.3%) of training injuries required treatment by a health professional. Considering the burden of training injuries exceeds that of competition injuries, taekwondo governing bodies and stakeholders are encouraged to devote more efforts towards the identification of risk factors for, and prevention of, training injuries in the sport of taekwondo.     

Assessment of risk factors for postoperative cognitive dysfunction after coronary artery bypass surgery: a single-center retrospective cohort study

Aim: To find out risk factors for postoperative cognitive dysfunction (POCD) after coronary artery bypass grafting (CABG), and to provide basis for clinical prevention of POCD. A total of 88 patients who underwent CABG were surveyed with Telephone Questionnaire (TICS-M) for their cognitive impairment after 3, 7, 21, 90, 180 days post-surgery. The occurrence of POCD was diagnosed by Neuropsychological Battery which included Vocabular Learning Test (VLT), Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) and Symbol Digit Modalities Test (SDMT). The preoperative, intraoperative and postoperative risk factors were assessed by the χ² or t test. Multivariate analysis was used to study the correlation between the risk factors and the occurrence of POCD. Age, aortic plaque, carotid artery stenosis, cerebrovascular disease, anesthesia time, the rate of decline in intraoperative hemoglobin concentration (ΔHb) and systemic inflammatory response syndrome (SIRS) score on postoperative day 2 had statistically significant (P<0.05) influence on the occurrence of POCD. Aortic plaque, carotid artery stenosis, anesthesia time and SIRS score (odds ratio (OR) value > 1, P<0.05) are the risk factors for POCD. The incidence of day-21 and -180 POCD was approximately 26.1 and 22.7%, respectively.     

Inflammatory ocular adverse events with the use of oral bisphosphonates: a retrospective cohort study

Background:

There have been several published reports of inflammatory ocular adverse events, mainly uveitis and scleritis, among patients taking oral bisphosphonates. We examined the risk of these adverse events in a pharmacoepidemiologic cohort study.

Methods:

We conducted a retrospective cohort study involving residents of British Columbia who had visited an ophthalmologist from 2000 to 2007. Within the cohort, we identified all people who were first-time users of oral bisphosphonates and who were followed to the first inflammatory ocular adverse event, death, termination of insurance or the end of the study period. We defined an inflammatory ocular adverse event as scleritis or uveitis. We used a Cox proportional hazard model to determine the adjusted rate ratios. As a sensitivity analysis, we performed a propensity-score–adjusted analysis.

Results:

The cohort comprised 934 147 people, including 10 827 first-time users of bisphosphonates and 923 320 nonusers. The incidence rate among first-time users was 29/10 000 person-years for uveitis and 63/10 000 person-years for scleritis. In contrast, the incidence among people who did not use oral bisphosphonates was 20/10 000 person-years for uveitis and 36/10 000 for scleritis (number needed to harm: 1100 and 370, respectively). First-time users had an elevated risk of uveitis (adjusted relative risk [RR] 1.45, 95% confidence interval [CI] 1.25–1.68) and scleritis (adjusted RR 1.51, 95% CI 1.34–1.68). The rate ratio for the propensity-score–adjusted analysis did not change the results (uveitis: RR 1.50, 95% CI 1.29–1.73; scleritis: RR 1.53, 95% CI 1.39–1.70).

Interpretation:

People using oral bisphosphonates for the first time may be at a higher risk of scleritis and uveitis compared to people with no bisphosphonate use. Patients taking bisphosphonates must be familiar with the signs and symptoms of these conditions, so that they can immediately seek assessment by an ophthalmologist.Oral bisphosphonates are the most frequently prescribed class of medications for the prevention of osteoporosis. Most literature about the safety of bisphosphonates has mainly focused on long-term adverse events, including atypical fractures,¹ atrial fibrillation,² and esophageal and colon cancer.³Uveitis and scleritis are ocular inflammatory diseases that are associated with major morbidity. Anterior uveitis is the most common type of uveitis with an estimated 11.4–100.0 cases/100 000 person-years.^4,5 Both diseases require immediate treatment to prevent further complications, which may include cataracts, glaucoma, macular edema and scleral perforation. Numerous case reports and case series have described an association between the use of oral bisphosphonates and anterior uveitis^6–8 and scleritis.^8,9 In most reported cases, severe eye pain was reported within days of taking an oral bisphosphonates, and the symptom resolved after stopping the agent.^6,9 Only one large epidemiologic study has examined the association between the use of bisphosphonates and ocular inflammatory diseases.¹⁰ This study did not find an association, but it was limited by a small number of events and a lack of power. Thus, the association between uveitis or scleritis and the use of oral bisphosphonates is not fully known. Given that early intervention may prevent complications, we performed a pharmacoepidemiologic study to assess the true risk of these potentially serious conditions.