Retained foreign objects after routine cataract surgery: a systematic review.

PURPOSE: Retained foreign objects (RFOs) can place patients undergoing cataract surgery at risk for significant vision-threatening complications. In this systematic review, we examine the characteristics, clinical outcomes, and management of RFOs originating from surgical instruments or the surgical field after routine cataract surgery. METHODS: Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we searched five databases in June 2023. The inclusion criteria were peer-reviewed, full-text, English-language articles describing RFOs after routine cataract surgery. Studies that described non-routine cataract surgeries, patients with a history of ocular trauma, or organic RFOs were excluded. Two investigators independently extracted data and appraised the methodological quality of each study using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Twenty-eight studies were included in our qualitative synthesis describing metal, fiber, and plastic RFOs. Typically, the RFOs were detected during surgery or slit-lamp examination. Presentations of patients with metal or fiber RFOs varied, with some being asymptomatic. Patients with plastic RFOs were usually symptomatic, often with decreased visual acuity and/or anterior chamber inflammation. Metal RFOs may have originated from metal fatigue from prolonged instrument usage and contact between surgical instruments, fiber RFOs from surgical wipes and gauzes, and plastic RFOs from instrument wrapping and intraocular lens defects. Factors such as location, biocompatibility, and secondary intraocular inflammation influenced the decision to surgically remove RFOs. Following surgical removal, the signs and symptoms resolved in most patients with RFOs. The studies' GRADE ratings indicated limitations in risk of bias and imprecision. CONCLUSION: The presentation and management of RFOs varied depending on the type of material. To prevent RFOs, clinicians should carefully inspect surgical instruments and packs and use fiber-free wipes, towels, and gauzes. Future studies should investigate the efficacy and cost-effectiveness of different RFO prevention strategies.

Interventions for acute non-arteritic central retinal artery occlusion.

BACKGROUND: Acute non-arteritic central retinal artery occlusion (CRAO) occurs as a sudden interruption of the blood supply to the retina and typically results in severe loss of vision in the affected eye. Although many therapeutic interventions have been proposed, there is no generally agreed upon treatment regimen. OBJECTIVES: To assess the effects of treatments for acute non-arteritic CRAO. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 15 February 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing any interventions with another treatment in participants with acute non-arteritic CRAO in one or both eyes.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and graded the certainty of the body of evidence for primary (mean change in best-corrected visual acuity [BCVA]) and secondary (quality of life and adverse events) outcomes using the GRADE classification. MAIN RESULTS: We included six RCTs with 223 total participants with acute non-arteritic CRAO; the studies ranged in size from 10 to 84 participants. The included studies varied geographically: one in Australia, one in Austria and Germany, two in China, one in Germany, and one in Italy. We were unable to conduct any meta-analyses due to study heterogeneity. None of the included studies compared the same pair of interventions: 1) tissue plasminogen activator (t-PA) versus intravenous saline; 2) t-PA versus isovolemic hemodilution, eyeball massage, intraocular pressure reduction, and anticoagulation; 3) nitroglycerin, methazolamide, mecobalamin tablets, vitamin B1 and B12 injections, puerarin and compound anisodine (also known as 654-2) along with oxygen inhalation, eyeball massage, tube expansion, and anticoagulation compared with and without intravenous recombinant tissue plasminogen activator (rt-PA); 4) transcorneal electrical stimulation (TES) with 0 mA versus with 66% of the participant's individual electrical phosphene threshold (EPT) at 20 Hz (66%) versus with 150% of the participant's individual EPT (150%) at 20 Hz; 5) ophthalmic artery branch retrograde thrombolysis versus superselective ophthalmic artery thrombolysis; and 6) pentoxifylline versus placebo. There was no evidence of an important difference in visual acuity between participants treated with t-PA versus intravenous saline (mean difference [MD] at 1 month -0.15 logMAR, 95% confidence interval [CI] -0.48 to 0.18; 1 study, 16 participants; low certainty evidence); t-PA versus isovolemic hemodilution, eyeball massage, intraocular pressure reduction, and anticoagulation (MD at 1 month -0.00 logMAR, 95% CI -0.24 to 0.23; 1 study, 82 participants; low certainty evidence); and TES with 0 mA versus TES with 66% of EPT at 20 Hz versus TES with 150% of EPT at 20 Hz. Participants treated with t-PA experienced higher rates of serious adverse effects. The other three comparisons did not report statistically significant differences. Other studies reported no data on secondary outcomes (quality of life or adverse events).  AUTHORS' CONCLUSIONS: The current research suggests that proposed interventions for acute non-arteritic CRAO may not be better than observation or treatments of any kind such as eyeball massage, oxygen inhalation, tube expansion, and anticoagulation, but the evidence is uncertain. Large, well-designed RCTs are necessary to determine the most effective treatment for acute non-arteritic CRAO.

Virtual supervision in ophthalmology: a scoping review.

PURPOSE: The published information on virtual supervision (VS) in ophthalmology is not well described. This scoping review describes the evidence and potential role for VS in ophthalmic practice and education. METHODS: A literature search strategy was developed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We included full-text articles published in an English-language peer-reviewed journal that involved physician-physician or physician-trainee VS in ophthalmology. We excluded studies with direct (in-person) supervision. Two investigators independently extracted from each article the year of publication and study location, design, participant characteristics, sample size, and outcomes. We appraised the methodological quality of the studies using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Seven articles were included in our qualitative synthesis. Supervisees ranged from physicians such as an ophthalmic surgeon and a general practitioner to medical trainees such as ophthalmology residents, vitreoretinal fellows, and emergency medicine residents. Study settings included emergency departments, operating rooms, eye clinics, and a rural hospital. All studies reported successful transmission of real-time images or videos of clinical examinations and surgical or in-office procedures. Various methods were used to ensure high image and video quality during VS, although some technical challenges remained. MMAT ratings revealed limitations in outcome measurement, statistical analysis, sampling strategy, and inclusion of confounding factors. CONCLUSION: Virtual supervision in ophthalmology is technologically feasible and permits synchronous communication and transmission of clinical data, which can be used to formulate diagnostic and management plans and learn new surgical skills. Future studies with larger sample sizes and robust study designs should investigate factors that make VS effective in ophthalmic practice and education.

Cheilectomy With Decompression Osteotomy for Treatment of Hallux Limitus and Rigidus: A Retrospective Study With 5-Year Outcomes.

We examined outcomes following metatarsophalangeal joint cheilectomy with decompression osteotomy to evaluate the efficacy of this technique for treatment of hallux limitus/rigidus. At a minimum follow-up of 5 years, we identified 94 patients who fit the inclusion criteria. Chart review was performed to obtain range of motion (ROM) of the first metatarsophalangeal joint (MTPJ) preoperatively and at 6 weeks, 6 months, and 5 years postoperatively. Additionally, time to traditional shoe gear return, need for revision arthrodesis, radiographic findings, and postoperative visual analog scale (VAS) pain scores were reviewed. Statistical analysis was conducted by 1-way analysis of variance with post-hoc analysis and independent sample t-test. At an average follow-up of 6.3 ± 0.9 years, 42.3% (33/78) of females and 25.0% (4/16) of males reported limited ROM of the first MTPJ with 5 patients requiring first MTPJ arthrodesis. MTPJ ROM improved on average from 11.0° to 36.3° by 5-year minimum follow-up after surgery (p < .001). Analysis of variance revealed a significant difference of the preoperative ROM when compared to all postoperative time points (F[3,368] = 69.4, p < .001). Mean postoperative VAS pain scores after decompression osteotomy of the 5 patients who required MTPJ fusion were higher when compared to the rest of the patient cohort at final follow-up (7.4 ± 0.6 vs 1.5 ± 1.3; p < .001). Cheilectomy with decompression osteotomy for treatment of hallux limitus/rigidus leads to satisfactory long-term outcomes.

Glaucoma Genetic Risk Scores in the Million Veteran Program.

PURPOSE: Primary open-angle glaucoma (POAG) is a degenerative eye disease for which early treatment is critical to mitigate visual impairment and irreversible blindness. POAG-associated loci individually confer incremental risk. Genetic risk score(s) (GRS) could enable POAG risk stratification. Despite significantly higher POAG burden among individuals of African ancestry (AFR), GRS are limited in this population. A recent large-scale, multi-ancestry meta-analysis identified 127 POAG-associated loci and calculated cross-ancestry and ancestry-specific effect estimates, including in European ancestry (EUR) and AFR individuals. We assessed the utility of the 127-variant GRS for POAG risk stratification in EUR and AFR Veterans in the Million Veteran Program (MVP). We also explored the association between GRS and documented invasive glaucoma surgery (IGS). DESIGN: Cross-sectional study. PARTICIPANTS: MVP Veterans with imputed genetic data, including 5830 POAG cases (445 with IGS documented in the electronic health record) and 64 476 controls. METHODS: We tested unweighted and weighted GRS of 127 published risk variants in EUR (3382 cases and 58 811 controls) and AFR (2448 cases and 5665 controls) Veterans in the MVP. Weighted GRS were calculated using effect estimates from the most recently published report of cross-ancestry and ancestry-specific meta-analyses. We also evaluated GRS in POAG cases with documented IGS. MAIN OUTCOME MEASURES: Performance of 127-variant GRS in EUR and AFR Veterans for POAG risk stratification and association with documented IGS. RESULTS: GRS were significantly associated with POAG (P < 5 × 10-5) in both groups; a higher proportion of EUR compared with AFR were consistently categorized in the top GRS decile (21.9%-23.6% and 12.9%-14.5%, respectively). Only GRS weighted by ancestry-specific effect estimates were associated with IGS documentation in AFR cases; all GRS types were associated with IGS in EUR cases. CONCLUSIONS: Varied performance of the GRS for POAG risk stratification and documented IGS association in EUR and AFR Veterans highlights (1) the complex risk architecture of POAG, (2) the importance of diverse representation in genomics studies that inform GRS construction and evaluation, and (3) the necessity of expanding diverse POAG-related genomic data so that GRS can equitably aid in screening individuals at high risk of POAG and who may require more aggressive treatment.

Assessing Physician Resident Contributions to Outpatient Clinical Workload.

BACKGROUND: Graduate medical education is centered in hospitals despite a care system where patients mostly receive their care in an outpatient setting. Such gaps may exist because of inadequate funding for residency positions in community and hospital-based clinics. OBJECTIVE: Determine if physician residents' contribution to outpatient workload offsets their costs for supervision, salary, and fringe benefits as residents acquire skills to become independent practitioners. RESEARCH DESIGN: VA's electronic patient records from 2005 through 2018 were analyzed using generalized linear mixed models to estimate resident and staff contributions to workload in relative value units. MEASURES: Resident participation rate is resident contributed workload net of supervision as a percent of total clinic workload. Productivity is per diem resident workload as a percent of per diem staff workload. Efficiency is per dollar resident workload as a percent of per dollar staff workload. Progressive independence is annual rate of change in resident productivity. RESULTS: Average participation rates varied by specialty from 6% to 22%, with 11% (primary care) and 13% (psychiatry). Productivity rates ranged from 21% to 94%, with 57% (primary care) and 61% (psychiatry). Efficiency rates varied from 0.63 to 3.81, with 1.69 (primary care), 1.89 (psychiatry). Progressive independence rates varied from 2.7%/year (psychiatry) to 39.7%/year (specialty care). CONCLUSIONS: Although residents rotating through most VA clinics generate revenue to cover their direct costs as they learn, some federal subsidies may be necessary to encourage hospital- and community-based clinics to accept residents from the less profitable primary care and mental health specialties.

Case Report: Ocular Manifestation of Mantle Cell Lymphoma.

SIGNIFICANCE: Mantle cell lymphoma (MCL) is a rare lymphoma that can present even more rarely in the orbit. Diagnosis, differentiation, and systemic treatment with the help of an oncologist are necessary for improved prognosis. Eye care providers must be vigilant when addressing ocular findings to determine next steps. PURPOSE: We present a case of presumed orbital fat prolapse confirmed as MCL found on routine eye examination. CASE REPORT: A 72-year-old White man presented for an annual comprehensive eye examination and was found to have conjunctival elevation in the superior and inferior fornices bilaterally. The patient had stable lymphadenopathy on positron emission tomography/computed tomography imaging 1 week before presentation. Coupled with the patient's recent diagnosis of systemic MCL, there was high suspicion that the conjunctival lesions were malignant. Biopsy of the conjunctival lesion confirmed MCL. A reevaluation of the previous imaging with a neuroradiologist confirmed the presence of orbital lesions consistent with MCL. The patient responded to treatment with low-dose focal radiation therapy. CONCLUSIONS: Primary eye care providers should be aware of limitations of orbital imaging during routine positron emission tomography and computed tomography scans in those with MCL, and consultation with neuroradiology for image review may be useful if the clinical findings are suspicious.

Virtual reality training for cataract surgery operating performance in ophthalmology trainees.

BACKGROUND: Cataract surgery is the most common incisional surgical procedure in ophthalmology and is important in ophthalmic graduate medical education. Although most ophthalmology training programs in the United States (US) include virtual reality (VR) training for cataract surgery, comprehensive reviews that detail the impact of VR training on ophthalmology trainee performance are lacking. OBJECTIVES: To assess the impact of VR training for cataract surgery on the operating performance of postgraduate ophthalmology trainees, measured by operating time, intraoperative complications, postoperative complications, supervising physician ratings, and VR simulator task ratings. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), Ovid MEDLINE, Embase.com, PubMed, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 14 June 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing VR training to any other method of training, including non-VR simulation training (e.g., wet laboratory training), didactics training, or no supplementary training in postgraduate ophthalmology trainees. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. Primary outcomes were operating times in the operating room and intraoperative complications. Secondary outcomes were operating times in simulated settings, simulator task ratings, and supervising physician ratings, either in the operating room or simulated settings. MAIN RESULTS: We included six RCTs with a total of 151 postgraduate ophthalmology trainees ranging from 12 to 60 participants in each study. The included studies varied widely in terms of geography: two in the US, and one study each in China, Germany, India, and Morocco. Three studies compared VR training for phacoemulsification cataract surgery on the Eyesi simulator (VRmagic, Mannheim, Germany) with wet laboratory training and two studies compared VR training with no supplementary training. One study compared trainees who received VR training with those who received conventional training for manual small incision cataract surgery on the HelpMeSee simulator (HelpMeSee, New York, NY). Industry financially supported two studies. All studies had at least three domains judged at high or unclear risks of bias. We did not conduct a meta-analysis due to insufficient data (i.e., lack of precision measurements, or studies reported only P values). All evidence was very low-certainty, meaning that any estimates were unreliable. The evidence for the benefits of VR training for trainees was very uncertain for primary outcomes. VR-trained trainees relative to those without supplementary training had shorter operating times (mean difference [MD] -17 minutes, 95% confidence interval [CI] -21.62 to -12.38; 1 study, n = 12; very low-certainty evidence). Results for operating time were inconsistent when comparing VR and wet laboratory training: one study found that VR relative to wet laboratory training was associated with longer operating times (P = 0.038); the other reported that two training groups had similar operating times (P = 0.14). One study reported that VR-trained trainees relative to those without supplementary training had fewer intraoperative complications (P < 0.001); in another study, VR and conventionally trained trainees had similar intraoperative complication rates (MD -8.31, 95% CI -22.78 to 6.16; 1 study, n = 19; very low-certainty evidence). For secondary outcomes, VR training may have similar impact on trainee performance compared to wet laboratory and greater impact compared to no supplementary training, but the evidence was very uncertain. One study reported VR-trained trainees relative to those without supplementary training had significantly reduced operating time in simulated settings (P = 0.0013). Another study reported that VR-trained relative to wet laboratory-trained trainees had shorter operating times in VR settings (MD -1.40 minutes, 95% CI -1.96 to -0.84; 1 study, n = 60) and similar times in wet laboratory settings (MD 0.16 minutes, 95% CI -0.50 to 0.82; 1 study, n = 60). This study also found the VR-trained trainees had higher VR simulator ratings (MD 5.17, 95% CI 0.61 to 9.73; 1 study, n = 60). Results for supervising physician ratings in the operating room were inconsistent: one study reported that VR- and wet laboratory-trained trainees received similar supervising physician ratings for cataract surgery (P = 0.608); another study reported that VR-trained trainees relative to those without supplementary training were less likely to receive poor ratings by supervising physicians for capsulorhexis construction (RR 0.29, 95% CI 0.15 to 0.57). In wet laboratory settings, VR-trained trainees received similar supervising physician ratings compared with wet laboratory-trained trainees (MD -1.50, 95% CI -6.77 to 3.77; n = 60) and higher supervising physician ratings compared with trainees without supplementary training (P < 0.0001). However, the results for all secondary outcomes should be interpreted with caution because of very low-certainty evidence.  AUTHORS' CONCLUSIONS: Current research suggests that VR training may be more effective than no supplementary training in improving trainee performance in the operating room and simulated settings for postgraduate ophthalmology trainees, but the evidence is uncertain. The evidence comparing VR with conventional or wet laboratory training was less consistent.

Characterising transnational ophthalmic surgical partnerships by engagement and training.

BACKGROUND: Transnational ophthalmic partnerships exist between high-income countries (HICs) and low- and middle-income countries (LMICs) in varying capacities. We analyzed partnership stakeholders to better understand and address disparities in ophthalmic surgical care. METHODS: An international Web search was conducted to identify surgeons, foundations or organisations participating in ophthalmic delivery and/or capacity building from 2010 to 2019. Partnerships were defined through clinical activities, education and training and/or research support. Descriptive data on current ophthalmic partnerships were collected from published reports, literature reviews and information on stakeholder webpages. Partnerships were classified by the extent of engagement and training: grade I 'engagement' represented documented partnerships of at least 1 year and grade I 'training' limited or poorly defined skills transfer programmes, while grade III 'engagement' represented partnerships with well-documented fiscal investment and/or research productivity and grade III 'training' established training programmes. Data were analysed using descriptive statistics and geospatially depicted on Tableau (Mountain View, CA) and ArcMap software (Redlands, CA). RESULTS: In total, 209 unique HIC-LMIC partnerships encompassing 92 unique countries were described. The most common HIC partners were from North America (123; 59%), followed by Europe (75; 36%). The most common LMIC partners were from Africa (102; 49%), followed by Asia-Pacific (54; 26%) and Latin America (44; 21%). Additionally, partnerships most frequently provided services in cataract (48%), glaucoma (25%) and diabetic retinopathy (25%). The most common 'engagement' classifications were grade I (36%) or II (40%); the most common 'training' classifications were grade I (61%) or II (23%). CONCLUSION: Transnational ophthalmic partnerships exist with varying degrees of both engagement and training. Partnerships are stronger in research collaboration and direct services, and weaker in LMIC-directed training programmes.

Case Report: Glaucoma-associated Peripapillary Retinoschisis with Corresponding Lamina Cribrosa Defect.

SIGNIFICANCE: Peripapillary retinoschisis is associated with primary and secondary glaucoma. It is important that clinicians are familiar with the presentation and management of peripapillary retinoschisis to understand its effects on the patient's glaucoma and to avoid unnecessary referral when the macula is not involved. PURPOSE: We present a case of peripapillary retinoschisis found incidentally on routine optical coherence tomographic (OCT) surveillance of primary open-angle glaucoma. CASE REPORT: A 70-year-old man presented for his annual diabetic eye examination. Surveillance with OCT revealed a splitting of the inner peripapillary retina corresponding to a previously noted notch in the right optic nerve. Further imaging of the right eye using enhanced depth imaging OCT revealed a defect in the lamina cribrosa that may have contributed to the formation and persistence of peripapillary retinoschisis. Retinal nerve fiber layer analysis showed a 5-year history of progressive temporal and inferotemporal thickening in the right eye. The patient was managed conservatively with instruction on regular Amsler grid testing. CONCLUSIONS: As seen in this case, peripapillary retinoschisis typically alters retinal nerve fiber layer thickness on OCT and can be mistakenly attributed to glaucomatous change. Glaucoma-associated peripapillary retinoschisis is usually not vision threatening and can be managed conservatively; in rare cases of progression to macular involvement, patients should be referred to a retina specialist.

Twelve tips for medical students to conduct a systematic review.

Background: Medical students engaged in research develop general skills that are instrumental to clinical practice. The systematic review, a cornerstone of evidence-based medicine, represents an ideal starting point for student researchers. Aim and methods: To outline twelve tips on conducting a systematic review for medical students with limited research experience. Results: The tips in this article are practical, comprehensive, and informed by the authors experience as medical students. Conclusion: The twelve tips can help medical students contribute to the literature and build a valuable skillset for future research and clinical practice.

Occupational styrene exposure and acquired dyschromatopsia: A systematic review and meta-analysis.

BACKGROUND: Styrene is a chemical used in the manufacture of plastic-based products worldwide. We systematically reviewed eligible studies of occupational styrene-induced dyschromatopsia, qualitatively synthesizing their findings and estimating the exposure effect through meta-analysis. METHODS: PubMed, EMBASE, and Web of Science databases were queried for eligible studies. Using a random effects model, we compared measures of dyschromatopsia between exposed and non-exposed workers to calculate the standardized mean difference (Hedges'g). We also assessed between-study heterogeneity and publication bias. RESULTS: Styrene-exposed subjects demonstrated poorer color vision than did the non-exposed (Hedges' g = 0.56; 95%CI: 0.37, 0.76; P < 0.0001). A non-significant Cochran's Q test result (Q = 23.2; P = 0.171) and an I2 of 32.2% (0.0%, 69.9%) indicated low-to-moderate between-study heterogeneity. Funnel plot and trim-and-fill analyses suggested publication bias. CONCLUSIONS: This review confirms the hypothesis of occupational styrene-induced dyschromatopsia, suggesting a modest effect size with mild heterogeneity between studies.

Can social media data lead to earlier detection of drug-related adverse events?

PURPOSE: To compare the patient characteristics and the inter-temporal reporting patterns of adverse events (AEs) for atorvastatin (Lipitor® ) and sibutramine (Meridia® ) in social media (AskaPatient.com) versus the FDA Adverse Event Reporting System (FAERS). METHODS: We identified clinically important AEs associated with atorvastatin (muscle pain) and sibutramine (cardiovascular AEs), compared their patterns in social media postings versus FAERS and used Granger causality tests to assess whether social media postings were useful in forecasting FAERS reports. RESULTS: We analyzed 998 and 270 social media postings between 2001 and 2014, 69 003 and 7383 FAERS reports between 1997 and 2014 for atorvastatin and sibutramine, respectively. Social media reporters were younger (atorvastatin: 53.9 vs. 64.0 years, p < 0.001; sibutramine: 36.8 vs. 43.8 years, p < 0.001). Social media reviews contained fewer serious AEs (atorvastatin, pain: 2.5% vs. 38.2%; sibutramine, cardiovascular issues: 7.9% vs. 63.0%; p < 0.001 for both) and concentrated on fewer types of AEs (proportion comprising the top 20 AEs: atorvastatin, 88.7% vs. 55.4%; sibutramine, 86.3% vs. 65.4%) compared with FAERS. While social media sibutramine reviews mentioning cardiac issues helped predict those in FAERS 11 months later (p < 0.001), social media atorvastatin reviews did not help predict FAERS reports. CONCLUSIONS: Social media AE reporters were younger and focused on less-serious and fewer types of AEs than FAERS reporters. The potential for social media to provide earlier indications of AEs compared with FAERS is uncertain. Our findings highlight some of the promises and limitations of online social media versus conventional pharmacovigilance sources and the need for careful interpretation of the results. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.