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Background Conceptual and theoretical links between politics and public health are longstanding. Internationally comparative systematic review evidence has shown links between four key political exposures – the welfare state, political tradition, democracy and globalisation – on population health outcomes. However, the pathways through which these influences may operate have not been systematically appraised. Therefore, focusing on child and maternal health outcomes, we present a realist re-analysis of the dataset from a recent systematic review. Methods The database from a recent systematic review on the political determinants of health was used as the data source for this realist review. Included studies from the systematic review were re-evaluated and those relating to child and/or maternal health outcomes were included in the realist synthesis. Initial programme theories were generated through realist engagement with the prior systematic review. These programme theories were adjudicated and refined through detailed engagement with the evidence base using a realist re-synthesis involving two independent reviewers. The revised theories that best corresponded to the evidence base formed the final programme theories. Results Out of the 176 included studies from the systematic review, a total of 67 included child and/or maternal health outcomes and were included in the realist re-analysis. Sixty-three of these studies were ecological and data were collected between 1950 and 2014. Six initial programme theories were generated. Following theory adjudication, three theories in revised form were supported and formed the final programme theories. These related to a more generous welfare state leading to better child and maternal health especially in developed countries through progressive social welfare policies, left-of-centre political tradition leading to lower child mortality and low birth weight especially in developed countries through greater focus on welfare measures, and increased globalisation leading to greater child and infant mortality and youth smoking rates in LMECs through greater influence of multinational corporations and neoliberal trade organisations. Conclusion We present a realist re-analysis of a large systematically identified body of evidence on how four key political exposures – the welfare state, democracy, political tradition and globalisation – relate to child and maternal health outcomes. Three final programme theories were supported.

PURPOSE To evaluate the refractive outcomes of sutureless intrascleral fixation of intraocular lens with pars plana vitrectomy. METHOD A retrospective, consecutive cohort from multiple surgeons of a single center. Primary outcomes included spherical equivalent (SEQ) and change in SEQ (ΔSEQ) from preoperative intraocular lens power calculations. Secondary outcomes included refractive outcomes of fixation at 1.5 mm, 2 mm, and 2.5 mm posterior to the limbus. RESULTS In total, 84 eyes of 80 patients were included. Preoperative logarithm of the minimum angle of resolution visual acuity was 1.21 ± 0.68 (20/320). The mean follow-up time was 2.33 ± 1.36 years. At 3 months, SEQ was -0.50 ± 1.59 D and ΔSEQ was 0.58 ± 1.49 D. At 1 year, SEQ was -0.55 ± 1.32 D and ΔSEQ was 0.39 ± 1.42 D. At the last follow-up, logarithm of the minimum angle of resolution visual acuity was 0.34 ± 0.34 (20/40), SEQ was -0.51 ± 1.44 D, and ΔSEQ was 0.57 ± 1.27 D. There was no difference between SEQ or ΔSEQ throughout follow-up (P = 0.97 and P = 0.96, respectively). At fixation distances more posterior to the limbus, mean ΔSEQ was more hyperopic at 3 months, 1-year, and the last follow-up (P = 0.02, P = 0.01, and P = 0.006, respectively). CONCLUSION Refractive outcomes for sutureless intrascleral fixation of intraocular lens with pars plana vitrectomy were favorable and showed stability postoperatively. These results may aid surgeons achieve better desired refractive outcomes for this technique.

Background and purpose Factors influencing the outcome after the critical care unit (CCU) for patients with status epilepticus (SE) are poorly understood. Survival for these patients was examined to establish (i) whether the risk of mortality has changed over time and (ii) whether admission to different unit types affects mortality risk over and above other risk factors. Methods The Intensive Care National Audit and Research Centre database and the Case Mix Programme database (January 2001 to December 2016) were analysed. Units were defined as neuro-CCU (NCCU), general CCU with 24-h neurological support (GCCU-N) or general CCU with limited neurological support (GCCU-L). Results There were 35 595 CCU cases of SE with a 3-fold increase over time (4739 in 2001-2004 to 14 166 in 2013-2016). More recent admissions were older and were more often unsedated on admission. Mortality declined for all units although this was more marked for NCCUs (8.1% in 2001-2004 to 4.4% in 2013-2016 compared to 5.1% and 4.1% for GCCU-L). Acute hospital mortality was two to three times higher than CCU mortality although this has also declined with time. GCCU-L appeared to have lower mortality than NCCUs (odds ratio 0.84, 95% confidence interval 0.72, 0.98) but after post hoc adjustment for case mix there were no differences. Older age and markers of seriousness of morbidity were all associated with increased mortality risk. Conclusions The number of patients admitted to a CCU for SE is rising but critical care and acute hospital mortality is decreasing. Patients treated in an NCCU have higher mortality but this is explicable by more severe underlying disease.

PURPOSE: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that is classically associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterize MHEP macular hole associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes. DESIGN: Multi-center, interventional, retrospective case control study. SUBJECTS: Consecutive eyes that underwent surgery for FTMH with a minimum of 12-months follow-up. METHODS: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane peeling. Spectral domain optical coherence tomography imaging was obtained pre- and post-operatively. MAIN OUTCOME MEASURES: Improvement in visual acuity and single surgery hole closure rates in eyes with, versus without, MHEP at 12 months. RESULTS: 725 charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5%) had MHEP. Patients with FTMH and MHEP were older (P < 0.002), more often male (P = 0.001), and with more advanced macular hole stages than those without MHEP (P = 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P < 0.004). FTMH with MHEP had significantly less improvement in visual acuity 12-months postoperatively (P = 0.019) with higher rates of ellipsoid and external limiting membrane defects (P < 0.05) and with a higher rate of failure to close with one surgery compared to FTMH without MHEP (26.7% versus 4.8% [P = 0.002]). Peeling the internal limiting membrane was associated with improved rates of hole closure in FTMH with MHEP (P < 0.001). Multivariable testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P = 0.031), single-surgery non-closure (P = 0.009), and that ILM peeling improved single-surgery closure rates (P = 0.026). CONCLUSIONS: We found that FTMH with MHEP has poorer anatomic and visual outcomes after vitrectomy compared to FTMH without MHEP. ILM peeling was associated with improved closure rates and should be considered when MHEP is detected preoperatively.

BACKGROUND AND OBJECTIVE: To quantify vessel tortuosity among infants with retinopathy of prematurity (ROP). PATIENTS AND METHODS: This was a retrospective study including 61 RetCam images from 33 infants. The laser treatment (LT) group included 17 infants who underwent laser for ROP. The no-treatment (NT) group included 16 infants. The modified ROPtool was used to calculate mean vessel tortuosity (MVT) and highest vessel tortuosity (HVT) for the participants and for the standard plus disease photograph from the Early Treatment for Retinopathy of Prematurity (ETROP) study. RESULTS: The median MVT was 1.226 versus 1.056 for the LT and NT groups, respectively ( P < .001). The median HVT was 1.346 versus 1.088 ( P < .001). An MVT of 1.124 was 96.7% sensitive and 100% specific for identifying infants with treatment-requiring ROP. Both MVT and HVT cutoff values correctly captured plus disease in the standard ETROP trial photograph. CONCLUSION: The modified ROPtool can be used to identify infants who have treatment-requiring ROP with a high level of sensitivity and specificity. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:215–220.]

Chronic post traumatic infraorbital nerve (ION) hyperesthesia is a rare complication of orbital floor fractures. Surgical decompression of the ION has been reported to relieve chronic post traumatic infraorbital neuralgia. This case report describes a novel approach for ION decompression in a patient who suffered from chronic infraorbital neuralgia associated with a healed displaced orbital floor fracture. We used an intraoperative 3D image-guided navigation system to accurately localize the fracture site and employed piezoelectric surgery for nerve decompression. We further review the literature on the safety and efficacy of piezoelectric surgery on soft tissue and nerves.

BACKGROUND: Buprenorphine is a unique μ-opioid receptor partial agonist with avid receptor binding, nominal euphoric reward, and a ceiling effect on sedation and respiratory depression. Despite a pharmacologic profile that enhances safety, cases of fatal opioid overdose with buprenorphine on postmortem toxicology are reported, but details of these cases in the literature are limited. METHODS: A retrospective review of opioid-involved drug overdose fatalities in Rhode Island (RI) from 2016 to 2018 using the RI Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Deaths with buprenorphine on toxicology testing versus opioid-involved overdose deaths without buprenorphine were compared to assess the type and number of co-exposures. RESULTS: Of 534 opioid-involved deaths, 29 (5.4%) included buprenorphine and/or norbuprenorphine on toxicology. Most frequent co-exposures are as follows: fentanyl (75.9%), norfentanyl (72.4%), cocaine (41.4%), benzoylecgonine (41.4%), cannabinoids (31.0%), ethanol (31.0%), levamisole (31.0%), and free morphine (31.0%). An average number of co-exposures for fatalities with buprenorphine were 9.24 versus 6.68 in those without buprenorphine. In one case buprenorphine was the only drug listed to cause death; all other fatalities with buprenorphine on toxicology reported additional drugs contributing to death. CONCLUSION: Decedents with buprenorphine detected on toxicology testing commonly had documented polysubstance use. Although data are limited, buprenorphine may provide some risk mitigation against full agonist opioid overdose including fentanyl. Further work should explore the use of postmortem concentrations of buprenorphine, norbuprenorphine, and other opioid metabolites to determine the role of buprenorphine in fatal overdose pharmacology.

Subscapularis dysfunction and failure are the leading causes of complications of total shoulder arthroplasty (TSA). An approach to shoulder arthroplasty has been described that may improve exposure to the retroverted glenoid and spare the rotator cuff. This article details the 6-month clinical outcomes of the first 26 patients who underwent TSA using a posterior approach. Thirty-one patients who underwent TSA using a posterior approach between September 2016 and October 2017 were identified retrospectively. Patients were assessed for American Shoulder and Elbow Surgeons (ASES) scores, Simple Shoulder Test (SST) scores, range of motion, complications, radiographic outcomes, and patient satisfaction. Statistical models were used to compare the means for each outcome variable over time. Of the initial 31 patients, 26 patients were available for follow-up at a minimum of 6 months; the remaining 5 patients did not return for follow-up at 6 months. Significant improvement in each outcome variable from baseline was noted by 6 weeks postoperatively. Further improvement was observed at 3 months for SST and external rotation, and at 6 months for ASES function and forward flexion. All outcome variables demonstrated some improvement from one time point to the next. Posterior TSA is a safe and efficacious procedure at 6 months. Compared with traditional TSA, posterior cuff-sparing approaches may improve posterior joint access, posterior soft tissue balancing, and long-term rotator cuff issues. [ Orthopedics . 2020; 43(1):e15–e20.]

OBJECTIVE To determine asthma outcomes in children undergoing adenotonsillectomy (T&A) for treatment of sleep-disordered breathing (SDB). HYPOTHESIS Asthmatic children will demonstrate improvement in asthma control after T&A compared to asthmatic children not undergoing surgical treatment. STUDY DESIGN Prospective cohort. PATIENT-SUBJECT SELECTION 80 children with diagnosed asthma, aged 4-11, undergoing T&A and 62 controls matched to the T&A subjects by age, sex, and asthma severity classification. METHODOLOGY Parents and children completed the Childhood Asthma Control Test (C-ACT) and the Pediatric Sleep Questionnaire (PSQ). Parents were queried regarding the number of asthma exacerbations, the frequency of the use of systemic steroids, the number of emergency room visits and the number of hospitalizations in the prior 6 months. The identical questionnaires and interviews were completed 6 months after entry. RESULTS The adjusted mean (95% CI) C-ACT score was 21.86 (20.94-22.68) at entry and 25.15 (24.55-25.71) at follow-up for the T&A group compared with 22.42 (21.46-23.28) and 23.59 (22.77-24.33) for the control group. There was a significant group by time interaction (P

Purpose To describe surgical outcomes and structural characteristics of intraocular lenses (IOLs) implanted with transconjunctival sutureless intrascleral (SIS) fixation in human eyes. Design Retrospective interventional surgical case series involving live and cadaveric human eyes. Methods In this study, we investigated the surgical outcomes and structural anatomy of secondary IOLs implanted with the SIS technique in human eyes. All cases involving SIS IOL fixation performed at a single academic center from January 1, 2012, through July 30, 2016, were reviewed to describe the surgical technique, common indications, clinical outcomes, and the rate of common operative complications. To investigate the structure of SIS-fixated IOLs in vivo, slit-lamp biomicroscopy, ultrasound biomicroscopy, and intraoperative endoscopy were analyzed to describe anatomical outcomes. The primary anatomical outcomes were the optic pupillary centration and location of haptic externalization. Results were correlated with cadaveric human eyes that underwent the SIS-IOL technique. Cadaveric eyes were imaged and analyzed using high-resolution photography for centration, stress measurements at the haptic-optic junction, and qualitative descriptors of IOL optic and haptic position. Results A total of 122 consecutive patients who underwent IOL placement using SIS technique were included in the study with mean follow-up of 1.52 years (range, 0.4-4.5 years). The majority (75%) of patients received a new 3-piece IOL for primary aphakia or after IOL exchange. The other patients (25%) had a dislocated 3-piece IOL that was rescued using the SIS technique. Preoperative mean Snellen visual acuity was 20/633 (logarithm of the minimum angle of resolution = 1.501). At the final visit, the mean best-corrected visual acuity was 20/83 (logarithm of the minimum angle of resolution = 0.6243) and final mean spherical equivalent was -0.57 diopters. The most common complications were vitreous hemorrhage (22% of eyes), which resolved spontaneously in most cases, and cystoid macular edema. The rates of IOL dislocation, IOL decentration, haptic erosion, IOL tilting, iris capture, and endophthalmitis were low. Intraoperative endoscopy and ultrasound biomicroscopy demonstrated a securely fixated IOL and well-centered optic without iris or ciliary body touch. Structural study of cadaveric eyes confirmed IOL optic and haptic anatomy observed during live human surgery. The ab interno haptic insertion was the anterior pars plana, away from the iris, ciliary processes and ora serrata. The degree of haptic externalization was correlated with the degree of strain on the haptic-optic junction. The angle of the haptic-optic junction in SIS-fixated IOLs (33.97°) was not significantly different compared with overlaid native nonfixated IOL (32.93°) but increased slightly with degree of haptic tip externalization (36.26 and 39.16 for 2 and 3 mm haptic externalizations, respectively). Conclusion In this comprehensive study, we demonstrate the surgical outcomes achieved with SIS fixation of IOLs. Surgical and postoperative complications do occur, albeit at a low rate, and can effectively be managed with excellent anatomical and visual outcomes. The structural and anatomical data in this study may help guide SIS placement and optimize long-term surgical results.

ObjectiveIt is uncertain whether persons with chronic widespread pain (CWP) experience premature mortality. Using the largest study conducted, we determine whether such a relationship exists, estimate its magnitude and establish what factors mediate any relationship.MethodsUK Biobank, a cohort study of 0.5 million people aged 40–69 years, recruited throughout Great Britain in 2006–2010. Participants reporting ‘pain all over the body’ for >3 months were compared with persons without chronic pain. Information on death (with cause) was available until mid-2015. We incorporated these results in a meta-analysis with other published reports to calculate a pooled estimate of excess risk.Results7130 participants reported CWP and they experienced excess mortality (mortality risk ratio 2.43, 95%CI 2.17 to 2.72). Specific causes of death in excess were cancer (1.73adjusted age and sex, 95% CI 1.46 to 2.05), cardiovascular (3.24adjusted age and sex, 95% CI 2.55 to 4.11), respiratory (5.66adjusted age and sex, 95% CI 4.00 to 8.03) and other disease-related causes (4.04adjusted age and sex, 95% CI 3.05 to 5.34). Excess risk was substantially reduced after adjustment for low levels of physical activity, high body mass index, poor quality diet and smoking. In meta-analysis, all studies showed significant excess all-cause (combined estimate 1.59 (95% CI 1.05 to 2.42)), cardiovascular and cancer mortality.ConclusionsEvidence is now clear that persons with CWP experience excess mortality. UK Biobank results considerably reduce uncertainty around the magnitude of excess risk and are consistent with the excess being explained by adverse lifestyle factors, which could be targeted in the management of such patients.

Ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1) degrades the purines ATP and ADP that are key regulators of inflammation and clotting. We hypothesized that NTPDase1 polymorphisms exist and that they regulate this pathway. We sequenced the ENTPD1 gene (encoding NTPDase1) in 216 subjects then assessed genotypes in 2 cohorts comprising 2213 humans to identify ENTPD1 polymorphisms associated with venous thromboembolism (VTE). The G allele of the intron 1 polymorphism rs3176891 was more common in VTE vs. controls (odds ratio 1.26–1.9); it did not affect RNA splicing, but it was in strong linkage disequilibrium with the G allele of the promoter polymorphism rs3814159, which increased transcriptional activity by 8-fold. Oligonucleotides containing the G allele of this promoter region bound nuclear extracts more avidly. Carriers of rs3176891 G had endothelial cells with increased NTPDase1 activity and protein expression, and had platelets with enhanced aggregation. Thus, the G allele of rs3176891 marks a haplotype associated with increased clotting and platelet aggregation attributable to a promoter variant associated with increased transcription, expression, and activity of NTPDase1. We term this gain-of-function phenotype observed with rs3814159 G “CD39 Denver.”—Maloney, J. P., Branchford, B. R., Brodsky, G. L., Cosmic, M. S., Calabrese, D. W., Aquilante, C. L., Maloney, K. W., Gonzalez, J. R., Zhang, W., Moreau, K. L., Wiggins, K. L., Smith, N. L., Broeckel, U., Di Paola, J. The ENTPD1 promoter polymorphism −860 A > G (rs3814159) is associated with increased gene transcription, protein expression, CD39/NTPDase1 enzymatic activity, and thromboembolism risk.

Background From 2011 to 2016, the United States has experienced a 55% increase in overall overdose deaths and a 260% increase in fatal fentanyl-related overdoses. Increasing engagement in harm reduction practices is essential to reducing the rate of fentanyl-related overdoses. This study sought to examine the uptake of harm reduction practices among young adults who reported recent drug use and who were recruited for a study to assess the utility and acceptability of rapid fentanyl test strips. Methods Between May and October 2017, 93 young adults who reported drug use in the past 30 days were recruited through word of mouth, Internet advertising, and public canvasing. Participants completed an interviewer-administered survey that assessed participants’ sociodemographic and behavioral characteristics, suspected fentanyl exposure, and overdose history. We assessed harm reduction practices and other correlates associated with experiencing a suspected fentanyl-related overdose. Results Of 93 eligible participants, 36% ( n = 34) reported ever having experienced an overdose, among whom 53% ( n = 18) suspected having experienced a fentanyl-related overdose. Participants who had ever experienced a fentanyl-related overdose were more likely to keep naloxone nearby when using drugs compared with those who had never experienced an overdose and those who had experienced an overdose that they did not suspect was related to fentanyl ( P Conclusion Those who had experienced a suspected fentanyl-related overdose were more likely to carry and administer naloxone. Future overdose prevention interventions should involve persons who have experienced a suspected fentanyl overdose and/or responded to an overdose in order to develop harm reduction programs that meet the needs of those at risk of an overdose.

Colorectal cancer remains common, with the "80 per cent by 2018" initiative proposed by the National Colorectal Cancer Roundtable. This study was designed to examine obstacles for patients who did not receive their scheduled colonoscopy, focusing on the impact of insurance status. Retrospective chart review was carried out on patients who did not complete their colonoscopy as scheduled from January 2013 to June 2017. The control group consisted of patients who completed their scheduled colonoscopy. One hundred and seventy five patients missed 200 colonoscopies. The most common reasons for cancellation were patient illness (16%), no-show (14%), no prep carried out (13%), inadequate prep (10%), and no transportation (11%). The canceled patients were significantly more likely to have the combination of no insurance and no Primary Care Provider (PCP) (13%

Background In 2016, drug overdose deaths exceeded 64,000 in the United States, driven by a sixfold increase in deaths attributable to illicitly manufactured fentanyl. Rapid fentanyl test strips (FTS), used to detect fentanyl in illicit drugs, may help inform people who use drugs about their risk of fentanyl exposure prior to consumption. This qualitative study assessed perceptions of FTS among young adults. Methods From May to September 2017, we recruited a convenience sample of 93 young adults in Rhode Island (age 18–35 years) with self-reported drug use in the past 30 days to participate in a pilot study aimed at better understanding perspectives of using take-home FTS for personal use. Participants completed a baseline quantitative survey, then completed a training to learn how to use the FTS. Participants then received ten FTS for personal use and were asked to return 2–4 weeks later to complete a brief quantitative and structured qualitative interview. Interviews were transcribed, coded, and double coded in NVivo (Version 11). Results Of the 81 (87%) participants who returned for follow-up, the majority (n = 62, 77%) used at least one FTS, and of those, a majority found them to be useful and straightforward to use. Positive FTS results led some participants to alter their drug use behaviors, including discarding their drug supply, using with someone else, and keeping naloxone nearby. Participants also reported giving FTS to friends who they felt were at high risk for fentanyl exposure. Conclusion These findings provide important perspectives on the use of FTS among young adults who use drugs. Given the high level of acceptability and behavioral changes reported by study participants, FTS may be a useful harm reduction intervention to reduce fentanyl overdose risk among this population. Trial registration The study protocol is registered with the US National Library of Medicine, Identifier NCT03373825, 12/24/2017, registered retrospectively. https://clinicaltrials.gov/ct2/show/NCT03373825?id=NCT03373825&rank=1

PurposeTo quantify early neuroretinal alterations in patients with type 1 diabetes mellitus (T1DM) and to assess whether glycemic variability contributes to alterations in neuroretinal structure or function.MethodsThirty patients with T1DM and 51 controls underwent comprehensive ophthalmic examination and assessment of retinal function or structure with frequency doubling perimetry (FDP), contrast sensitivity, dark adaptation, fundus photography, and optical coherence tomography (OCT). Diabetic participants wore a subcutaneous continuous glucose monitor for 5 days, from which makers of glycemic variability including the low blood glucose index (LGBI) and area under the curve (AUC) for hypoglycemia were derived.ResultsSixteen patients had no diabetic retinopathy (DR), and 14 had mild or moderate DR. Log contrast sensitivity for the DM group was significantly reduced (mean±SD=1.63±0.06) compared with controls (1.77±0.13, P

The neuromuscular junction (NMJ) consists of a tripartite synapse with a presynaptic nerve terminal, Schwann cells that ensheathe the terminal bouton, and a highly specialized postsynaptic membrane. Synaptic structural integrity is crucial for efficient signal transmission. Congenital myasthenic syndromes (CMSs) are a heterogeneous group of inherited disorders that result from impaired neuromuscular transmission, caused by mutations in genes encoding proteins that are involved in synaptic transmission and in forming and maintaining the structural integrity of NMJs. To identify further causes of CMSs, we performed whole-exome sequencing (WES) in families without an identified mutation in known CMS-associated genes. In two families affected by a previously undefined CMS, we identified homozygous loss-of-function mutations in COL13A1, which encodes the alpha chain of an atypical non-fibrillar collagen with a single transmembrane domain. COL13A1 localized to the human muscle motor endplate. Using CRISPR-Cas9 genome editing, modeling of the COL13A1 c.1171delG (p.Leu392Sfs∗71) frameshift mutation in the C2C12 cell line reduced acetylcholine receptor (AChR) clustering during myotube differentiation. This highlights the crucial role of collagen XIII in the formation and maintenance of the NMJ. Our results therefore delineate a myasthenic disorder that is caused by loss-of-function mutations in COL13A1, encoding a protein involved in organization of the NMJ, and emphasize the importance of appropriate symptomatic treatment for these individuals.

To determine whether haptic flanging during 27-gauge sutureless intrascleral fixation of intraocular lenses (IOLs) increases IOL stability and to report the short-term clinical outcomes of sutureless intrascleral surgery using 27-gauge trocar cannulas with haptic flanging.Retrospective surgical case series using live and cadaveric human eyes.In the cadaveric experiment using five eyes, flanged haptics required more force to dislocate the IOL compared with unflanged haptics (14 ± 4 vs. 3 ± 1 g, P = 0.03). The clinical series included 52 eyes from 52 patients. The average age at the time of surgery was 73 ± 14 years, with a mean follow-up of 27 ± 19 weeks. The most common indication for surgery was IOL dislocation/subluxation (n = 43, 83%). Mean visual acuity improved from 20/140 preoperatively to 20/50 at postoperative Month 1 (P0.001). The most common postoperative issue was intraocular pressure elevation (n = 12, 23%). Two patients (4%) needed a reoperation for IOL dislocation.Haptic flanging during 27-gauge sutureless intrascleral surgery creates a more stable scleral-fixated IOL compared with the traditional unflanged technique based on a cadaveric human eye study. In addition, this variation of sutureless intrascleral surgery seems safe and effective for patients who require secondary IOLs.

PURPOSE: To determine the incidence of endophthalmitis following anti-vascular endothelial growth factor (VEGF) therapy at our institution and to identify potential risk factors for post-injection endophthalmitis DESIGN: Retrospective, single center cohort study PARTICIPANTS: All patients who received an intravitreal injection of an anti-VEGF medication between January 1, 2014 and March 31, 2017. METHODS: Current Procedural Terminology and International Classification of Diseases billing codes were used to identify instances of anti-VEGF administration and cases of endophthalmitis. Medical records and injection technique were carefully reviewed in each case. Multivariable logistic regression analysis was performed in a stepwise fashion to determine independent predictors of endophthalmitis based on injection protocol. MAIN OUTCOME MEASURES: Incidence of post-injection endophthalmitis and odds of endophthalmitis by injection technique with 95% confidence intervals (CI). RESULTS: A total of 154,198 anti-VEGF injections were performed during the time period of interest, resulting in 58 cases of endophthalmitis (0.038%, 1:2,659). After adjustment for confounders, both 2% lidocaine jelly (OR = 11.28, 95% CI: 3.39 – 37.46, p < 0.001) and 0.5% Tetravisc (OR = 3.95, 95% CI: 1.15 – 13.50, p = 0.03) use were independent risk factors for post-injection endophthalmitis. Lid speculum use, povidone iodine strength (5% vs. 10%), injection location (superior or inferior), conjunctival displacement, use of provider gloves, employment of a strict no-talking policy, use of subconjunctival lidocaine, and topical antibiotic use were not statistically significant predictors of post-injection endophthalmitis. There was no difference in endophthalmitis rate among the anti-VEGF agents (bevacizumab, ranbizumab 0.3 mg, ranibizumab 0.5 mg, and aflibercept). CONCLUSION: The incidence of endophthalmitis after anti-VEGF injections is low. Use of lidocaine jelly or Tetravisc may increase the risk of post-injection endophthalmitis.

BACKGROUND: The overdose epidemic has been exacerbated by a dramatic increase in deaths involving illicitly manufactured fentanyl (IMF). Drug checking is a novel strategy to identify IMF in illicit drugs. We examined the uptake and acceptability of rapid fentanyl test strips among young adults. METHODS: From May to September 2017, we recruited 93 young adults in Rhode Island who reported injecting drugs or using heroin, cocaine, or illicitly obtained prescription pills in the past 30 days. Participants were asked to test either their urine after drug use (post-consumption) or a drug sample prior to use (pre-consumption) using rapid fentanyl test strips. After a questionnaire and a brief training, participants received ten strips for their personal use and were asked to return for a one-month follow-up visit, which assessed the uptake and acceptability of the rapid strips tests, and behavioral outcomes associated with receipt of a positive test. RESULTS: Of the 81 (87%) participants who returned for follow-up and who had complete data, the mean age was 27, 45 (56%) were male, and 37 (46%) were non-white. A total of 62 participants (77%) reported using at least one test strip. Of these, 31 (50%) received at least one positive result. A positive result was associated with older age, homelessness, heroin use, injection drug use, ever witnessing an overdose, and concern about overdose or drugs being laced with fentanyl (all p < 0.05). Receiving a positive result was significantly associated with reporting a positive change in overdose risk behavior between baseline and follow-up (p ≤ 0.01). Among all participants, 79 (98%) reported confidence in their ability to use the test strips and 77 (95%) wanted to use them in the future. CONCLUSIONS: Young adults reported high uptake and acceptability of fentanyl test strips to detect IMF in illicit drugs.

Background U.S. opioid overdose deaths have increased five-fold since 1999. In 2014, two Rhode Island emergency departments (EDs) began providing take-home naloxone and peer recovery coach consultation to patients identified at risk of opioid overdose. Similar programs have been initiated throughout the country, but patient outcomes of ED naloxone distribution and recovery coach consultation have yet to be evaluated. Methods This is an observational, retrospective cohort study of ED patients discharged after a non-fatal opioid overdose in the six months after implementation of an ED naloxone distribution and recovery coach consultation program, September 2014 to February 2015. By provider and patient discretion, patients received either: usual care, take-home naloxone, or a recovery coach with take-home naloxone. Primary outcomes one year from index ED visit were initiation of medication for opioid use disorder (OUD), repeat ED visit for opioid overdose, and all-cause mortality. Results 151 adults met study inclusion criteria. Sixty (39.7%) received usual care, 26 (17.2%) received take-home naloxone alone, and 72 (47.7%) received take-home naloxone and a peer recovery coach. Less than a third (28.5% 48/151) initiated medication for OUD. Median time to new initiation of medication for OUD was shorter among those who got a recovery coach (81.5 days vs 139 days usual care). Thirty (19.9%) were treated in the ED for a repeat opioid overdose. Seven (4.6%) died within one year of initial ED visit. A smaller proportion of deaths occurred among those receiving services. Conclusion Preliminary patient outcomes demonstrate a high frequency of death and repeat overdose one-year following an ED visit for opioid overdose. A minority initiate medication for OUD. Among those who got a recovery coach and naloxone, median.

Background Synthetic opioid overdose mortality among young adults has risen more than 300% in the USA since 2013, primarily due to the contamination of heroin and other drugs with illicitly manufactured fentanyl. Rapid test strips, which can be used to detect the presence of fentanyl in drug samples (before use) or urine (after use), may help inform people about their exposure risk. The purpose of this study was to determine whether young adults who use drugs were willing to use rapid test strips as a harm reduction intervention to prevent overdose. We hypothesized that those who had ever overdosed would be more willing to use the test strips. Methods We recruited a convenience sample of young adults who use drugs in Rhode Island from May to September 2017. Eligible participants (aged 18 to 35 with past 30-day drug use) completed an interviewer-administered survey. The survey assessed participant’s socio-demographic and behavioral characteristics, overdose risk, as well as suspected fentanyl exposure, and willingness to use take-home rapid test strips to detect fentanyl contamination in drugs or urine. Participants were then trained to use the test strips and were given ten to take home. Results Among 93 eligible participants, the mean age was 27 years (SD = 4.8), 56% (n = 52) of participants were male, and 56% (n = 52) were white. Over one third (n = 34, 37%) had a prior overdose. The vast majority (n = 86, 92%) of participants wanted to know if there was fentanyl in their drug supply prior to their use. Sixty-five (70%) participants reported concern that their drugs were contaminated with fentanyl. After the brief training, nearly all participants (n = 88, 95%) reported that they planned to use the test strips. Conclusions More than 90% of participants reported willingness to use rapid test strips regardless of having ever overdosed, suggesting that rapid fentanyl testing is an acceptable harm reduction intervention among young people who use drugs in Rhode Island. Study follow-up is ongoing to determine whether, how, and under what circumstances participants used the rapid test strips and if a positive result contributed to changes in overdose risk behavior.

Bilateral lateral geniculate nucleus (LGN) injury is a rare cause of vision loss. We describe a patient with pre-eclampsia who developed profound but reversible bilateral vision loss, bilateral serous retinal detachments, and magnetic resonance imaging signs of a variant of posterior reversible encephalopathy syndrome (PRES) that affected both LGNs and spared the retrogeniculate pathways. We provide evidence that the visual loss was not from the chorioretinal lesions but from the LGN lesions. The concurrence of PRES and lesions attributed to choroidal hypoperfusion provides support for the notion that vasoconstriction also underlies the pathogenesis of PRES.

Objective To assess associations between cognitive status, intelligibility, acoustics and functional communication in PD. Design Cross-sectional exploratory study of functional communication, including a within-participants experimental design for listener assessment. Setting A major academic medical centre in the East of England, UK. Participants Questionnaire data were assessed for 45 people with Parkinson’s disease (PD), who had self-reported speech or communication difficulties and did not have clinical dementia. Acoustic and listener analyses were conducted on read and conversational speech for 20 people with PD and 20 familiar conversation partner controls without speech, language or cognitive difficulties. Main outcome measures Functional communication assessed by the Communicative Participation Item Bank (CPIB) and Communicative Effectiveness Survey (CES). Results People with PD had lower intelligibility than controls for both the read (mean difference 13.7%, p=0.009) and conversational (mean difference 16.2%, p=0.04) sentences. Intensity and pause were statistically significant predictors of intelligibility in read sentences. Listeners were less accurate identifying the intended emotion in the speech of people with PD (14.8% point difference across conditions, p=0.02) and this was associated with worse speaker cognitive status (16.7% point difference, p=0.04). Cognitive status was a significant predictor of functional communication using CPIB (F=8.99, p=0.005, η2 = 0.15) but not CES. Intelligibility in conversation sentences was a statistically significant predictor of CPIB (F=4.96, p=0.04, η2 = 0.19) and CES (F=13.65, p=0.002, η2 = 0.43). Read sentence intelligibility was not a significant predictor of either outcome. Conclusions Cognitive status was an important predictor of functional communication—the role of intelligibility was modest and limited to conversational and not read speech. Our results highlight the importance of focusing on functional communication as well as physical speech impairment in speech and language therapy (SLT) for PD. Our results could inform future trials of SLT techniques for PD.

PurposeTo analyse the clinical characteristics and treatment outcomes of choroidal neovascular membranes (CNVM) in paediatric subjects at three paediatric retina referral centres.MethodsMedical charts of patients aged 18 years or less with a diagnosis of CNVM were retrospectively reviewed. The demographic profile, laterality, presenting complaint, corrected vision, underlying pathology, fundus, fundus fluorescein angiogram and optical coherence tomogram (OCT) were analysed. CNVM type, frequency, treatment indications, recurrences and final visual acuity were noted.ResultsThere were a total of 35 subjects (43 eyes) with a mean age of 11.2 years. The CNVMs were mostly type 2 (90.0%), classic (90.9%), subfoveal (59.09%) and active (84.1%). Best vitelliform macular dystrophy was found to be the most common association (32.5%). Intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent was the initial therapy of choice in all. Eyes with CNVMs responsive to anti-VEGF alone required a mean of 2.11 injections. Patients with recurrent disease (21.21%) had an average of 1.14 episodes per eye. While 50% of recurrent CNVMs stabilised with repeat anti-VEGF treatment, the remaining patients required photodynamic therapy, laser or surgery.ConclusionPaediatric CNVMs in this series differed from those in the adult population with regard to aetiology, OCT and angiographic characteristics, treatment response and rate of recurrence.

Background We conducted an epidemiological investigation of fentanyl and non-fentanyl overdose deaths in Rhode Island to inform overdose prevention efforts. Methods All drug overdose deaths occurring in Rhode Island between January 1, 2014 and September 30, 2016 were included. Overdose circumstances and decedent characteristics were ascertained from medical examiner files. Toxicological reports provided quantification of fentanyl and metabolites. ArcGIS was used to map exact overdose locations. We compared fentanyl-associated with non-fentanyl overdose deaths using chi-square tests and Wilcoxon rank sum tests. To identify overdose clusters, we used the Getis-Ord Gi* statistic. Results A total of 778 overdose deaths were observed during the study period. In total, 358 (46.0%) were attributable to acute fentanyl intoxication, increasing from 84 (35.0%) in 2014 to 138 (55.6%) during the first nine months of 2016 (Mantel–Haenszel test for trend P

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P

Objective. To estimate the proportion of patients with axial spondyloarthritis (SpA) in a UK national biologics registry who met criteria for fibromyalgia (FM), and to delineate the characteristics of these patients. Methods. Two cohorts of patients are prospectively recruited from across 83 centers in the UK for the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS). All patients are required to meet Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA. Patients are either newly starting biologic therapy (biologics cohort) or are naive to treatment with biologic agents (non-biologics cohort) at the time of recruitment, and all patients are followed up prospectively. At recruitment and follow-up, clinical information and measurements are recorded while patients complete the 2011 research criteria for FM and assessments of the level of disease activity and work impact. Results. Of the patients registered in the BSRBR-AS, 1,504 (68% male) were eligible for the current analysis, of whom 311 (20.7%) met the 2011 research criteria for FM. Prevalence of FM was similar between patients who fulfilled the modified New York criteria for AS (19.7%) and those who fulfilled ASAS imaging criteria but not the modified New York criteria (25.2%); however, among those who fulfilled only the ASAS clinical criteria, the prevalence of FM was lower (9.5%). Patients who met FM criteria reported significantly worse disease activity, function, global severity scores, and quality of life, and were more likely to have moderate or severe levels of mood disorder and clinically important fatigue. Patients who met FM criteria reported experiencing work impairment around half their working time. Meeting FM criteria was not related to elevated C-reactive protein levels or most extraspinal manifestations, but was associated with a higher likelihood of having received biologic therapy. Conclusion. Developing management approaches that would address the significant unmet clinical needs of the 1 in 5 patients with axial SpA who meet criteria for FM should be a research priority.

Aim To examine the relationship between corneal nerve fiber length (CNFL) and diabetic neuropathy (DN) status in patients with type 1 or type 2 diabetes mellitus (DM). Methods In this cross-sectional study, we examined 25 diabetic patients without DN, 10 patients with mild DN, 8 patients with severe DN, and 9 controls without diabetes. DN status was assigned based on a combination of clinical symptoms, signs, and electrophysiological testing. Patients underwent corneal confocal microscopy (CCM) of the sub-basal nerve plexus. Post-hoc analysis of the CCM images was performed to quantify the average CNFL, and ANOVA was used to assess for differences in CNFL. Results All 25 subjects without DN had type 1 DM, and subjects with DN had type 2 DM. Participants with severe DN had significantly lower CNFL (12.5±6.1mm/mm 2 ) compared to controls (20.7±2.2mm/mm 2 ) (p=0.009). However, lower CNFL was also found in participants with type 1 DM who did not have DN (15.1±4.7mm/mm 2 ) relative to controls (p=0.033). Conclusions CCM of the sub-basal nerve plexus may be an indicator of early peripheral nerve degeneration in type 1 DM. Type of diabetes, in addition to degree of neuropathy, may influence the extent of corneal nerve damage.

To analyse mortality for spontaneous intracerebral haemorrhage (ICH), myasthenia gravis (MG) and Guillain–Barre syndrome (GBS) from 1996 to 2009 in UK intensive care units (ICUs). We used the Intensive Care National Audit & Research Centre (ICNARC) database. We identified specialised neurosciences critical care units (NCCUs) (n = 16), general ICUs with full neurological support (n = 48) and general ICUs with limited neurological support (n = 138) and undertook descriptive analyses for each condition. Poisson regression was used to identify trends in admission rates, median regression to identify trends in lengths of stay (LOS), and logistic regression (Wald test) to analyse interaction between unit type and time period; odds ratios were calculated for hospital mortality associated with unit types. For ICH (n = 10,313 cases), overall ICU mortality was 42.4 %, and acute hospital mortality 62.1 %. In NCCU, LOS was longer, but mortality lower, and over time, mortality from ICH decreased faster. For MG (n = 1,064 cases) and GBS (n = 1,906 cases), overall mortality was relatively high (MG: 8.7 % ICU mortality and 22 % acute hospital mortality; GBS: 7.7 and 16.7 %, respectively); overall mortality did not decrease over time. This first large-scale analysis of outcomes in acute neurological disease in the UK demonstrates real-life mortality higher than published series. NCCU care is associated with increased survival in conditions requiring highly specialised intensive care techniques, but high-quality step-down care is pivotal in others. Strategies that truly improve outcomes must integrate emergency department management, ICU admission criteria, NCCU treatment, high-quality step-down care and neurorehabilitation.

Childhood asthma is a common condition whose prevalence is changing. We hypothesized that the relationship between asthma and associated risk factors has changed over a 50-year period.An ecological study design was used. Children aged 8-13 attending schools in Aberdeen city were surveyed on seven occasions between 1964 and 2014. The following were determined: history of asthma, history of eczema, parental smoking, parental asthma, sex and socio-economic status. Analysis was by a structural change model with two knots. The outcome reported was the change in odds ratio between asthma and a given risk factor during a given period.There were 23,241 questionnaires distributed and 17,439 returned (75%). The odds ratio (OR) for a child with asthma to have eczema increased between 1989 and 1999 by 1.031 [95% CI 1.028, 1.035] and by 1.042 between 2004 and 2014 [1.038, 1.047]. The OR for a child with asthma to have a parent who smoked rose by 1.032 [1.028, 1.036] between 1989 and 1999 and by 1.043 [1.038, 1.047] between 2004 and 2014), and to have a parent with asthma (1.027 [1.022, 1.031] for 1994-99 and 1.042 [1.037, 1.048] for 2004-2014). The OR for a child with asthma being male, but not and being from the most deprived communities, rose between 1989-1999 and 2004-2014.The relationship between asthma prevalence and particular risk factors changed over the 50-year period of study, and this might reflect changes in children's environment and/or susceptibility.

IMPORTANCE: Neovascular age-related macular degeneration (nvAMD) is a leading cause of vision loss. The optimal screening protocol to detect choroidal neovascularization (CNV) in fellow eyes of patients undergoing treatment for unilateral CNV has not been determined. OBJECTIVE: To compare the visual outcomes of eyes with established, active nvAMD in index eyes with outcomes of fellow eyes that subsequently developed CNV during the management protocol. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective single-center case series conducted at a private vitreoretinal practice, data were collected for all patients treated for bilateral nvAMD between October 1, 2015, and October 1, 2016, for whom we could determine the date of index eye and fellow eye conversion to nvAMD (n = 1600). Per institutional protocol, patients were screened for new CNV in the fellow eye at every office visit. Patients were excluded if they had a condition that could result in marked asymmetric vision loss. EXPOSURES: Development of nvAMD. MAIN OUTCOMES AND MEASURES: Visual acuity (VA) at the time of diagnosis of nvAMD and at equivalent time points following conversion to nvAMD for both index eyes and fellow eyes. RESULTS: A total of 264 patients met the inclusion criteria; 197 (74.6%) were women and 253 (95.8%) were white, and the mean (SD) age was 79.1 (8.2) years at time of index eye conversion to nvAMD and 80.6 (8.2) years at time of fellow eye conversion to nvAMD. Fellow eyes presented with better VA (mean VA, 20/50 [0.40 logMAR]) compared with index eyes (mean VA, 20/90 [0.67 logMAR]) at the time of conversion (difference, 14 letters [0.27 logMAR]; 95% CI, 10-17 [0.20-0.34]; P

In order to investigate the potential involvement of mitochondrial electron transport chain (ETC) dysfunction in myotoxicity associated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) treatment, assessment was made of ETC activity and ubiquinone status in two patients experiencing myopathy following treatment with simvastatin (40 mg/day) and cyclosporin (patient 1) and simvastatin (40 mg/day) and itraconazole (patient 2). Analysis of skeletal muscle biopsies revealed a decreased ubiquinone status (77 and 132; reference range: 140-580 pmol/mg) and cytochrome oxidase (complex IV) activity (0.006 and 0.007 reference range: 0.014-0.034). To assess statin treatment in the absence of possible pharmacological interference from cyclosporin or itraconazole, primary astrocytes were cultured with lovastatin (100 microM). Lovastatin treatment resulted in a decrease in ubiquinone (97.9 +/- 14.9; control: 202.9 +/- 18.4 pmol/mg; p < 0.05), and complex IV activity (0.008 +/- 0.001; control: 0.011 +/- 0.001; p < 0.05) relative to control. These data, coupled with the patient findings, indicate a possible association between statin treatment, decreased ubiquinone status, and loss of complex IV activity.

Aim To assess how hemoglobin A 1c (HbA 1c ) values might change following the diagnosis of the first complication from diabetes mellitus (DM). Methods Using a nationwide, longitudinal managed care network claims database (2001–2011), we identified patients with DM who experienced an initial diabetes-related complication. A paired t-test was used to compare average HbA 1c levels before the initial complication was first diagnosed to average HbA 1c levels following the diagnosis of the complication. Results 518 enrollees met study inclusion criteria. Patients with suboptimally controlled DM (defined as HbA 1c >7% (53mmol/mol)) prior to the diagnosis of their first diabetic complication demonstrated a clinically significant reduction in average HbA 1c following the diagnosis of their first complication (mean pre-complication HbA 1c =8.5±1.5% (69±17mmol/mol) vs. mean post-complication HbA 1c =7.9±1.7% (63±18mmol/mol) (p Conclusion Enrollees with suboptimally controlled DM may achieve better glycemic control following the diagnosis of a complication from DM. The results from this study, if confirmed in prospective studies, may provide a rationale for the earlier detection of complications from DM to facilitate improved glycemic control among patients with DM.

North America has a diverse cicada fauna with multiple genera from all three Cicadidae subfamilies, yet molecular phylogenetic analyses have been completed only for the well-studied periodical cicadas (Magicicada Davis). The genus Tibicen Latreille, a large group of charismatic species, is in need of such work because morphological patterns suggest multiple groups with complicated relationships to other genera in the tribe Cryptotympanini. In this paper we present a molecular phylogenetic analysis, based on mitochondrial and nuclear DNA, of 35 of the 38 extant USA species and subspecies of the genus Tibicen together with their North American tribal allies (Cornuplura Davis, Cacama Davis), selected Tibicen species from Eurasia, and representatives of other Eurasian and Pacific cryptotympanine genera. This tree shows that Tibicen contains several well-supported clades, one predominating in eastern and central North America and related to Cryptotympana Stål and Raiateana Boulard, another in western North America related to Cacama and Cornuplura, and at least two clades in Eurasia. We also present a morphological cladistic analysis of Tibicen and its close allies based on 27 characters. Character states identified in the cladistic analysis define three new genera, two for North American taxa (Hadoa gen. n. and Neotibicen gen. n.) including several Mexican species, and one for Asian species (Subsolanus gen. n.). Using relaxed molecular clocks and literature-derived mtDNA rate estimates, we estimate the timeframe of diversification of Tibicen clades and find that intergeneric divergence has occurred since the late Eocene, with most extant species within the former Tibicen originating after the mid-Miocene. We review patterns of ecology, behavior, and geography among Tibicen clades in light of the phylogenetic results and note that the study of these insects is still in its early stages. Some Mexican species formerly placed in Tibicen are here transferred to Diceroprocta, following refinement of the definition of that genus.

A 41-year-old woman who underwent uncomplicated LASIK and two subsequent flap lifts for epithelial ingrowth of the right eye became progressively symptomatic with blurred vision, photophobia and foreign body sensation over the ensuing 5 years. Clinical examination of the right eye demonstrated extensive epithelial ingrowth around the flap periphery with overlying Salzmann nodules in the same distribution. Similar findings were not present in the left eye. Anterior segment optical coherence tomography demonstrated subclinical flap elevation in the areas of epithelial ingrowth, which may have predisposed to nodule development due to a dellen effect. The patient underwent superficial keratectomy with significant improvement of her symptoms.

Background: Management of lymphadenopathy caused by nontuberculous mycobacteria (NTM) is primarily surgical. Where this cannot achieve sufficient clearance of infected nodes, chemotherapy is often given. Aim: This study compared results of surgery alone with surgery followed by chemotherapy in instances where there was incomplete surgical removal of diseased tissue. Methods: Chemotherapy comprised azithromycin 10 mg/kg and rifabutin 6 mg/kg both given once daily for 6 mo. Ninety-eight children with NTM infection were seen in the period 1990-2004. Sixty-eight cases with adenopathy where "time to healing" (discharge stopped and inflammation settled) was known were available to compare response to treatment. Results : The median ( range) "time to healing" in weeks for 43 patients who had surgery alone was: incision and drainage (ID excision 3 (1-28) (n = 22); and from the last operation of multiple (repeat) surgery 3 (1-40) (n = 11). For 25 patients who required chemotherapy in addition to surgery, the median ( range) "time to healing" in weeks was I&D/curettage 10 (1-40) (n = 17), excision 14 (8-20) (n = 2) and multiple surgery 29 (2-88) (n = 6). Conclusion: In children with adenitis due to NTM, where surgical resection is followed by continued discharge and inflammation, chemotherapy should be considered before further surgery is undertaken.

Background— Therapeutic hypothermia can improve survival after cardiopulmonary resuscitation (CPR). Coenzyme Q10 (CoQ10) has shown a protective effect in neurodegenerative disorders. We investigated whether combining mild hypothermia with CoQ10 after out-of-hospital cardiac arrest provides additional benefit. Methods and Results— Forty-nine patients were randomly assigned to either hypothermia plus CoQ10 or hypothermia plus placebo after CPR. Hypothermia with a core temperature of 35°C was instituted for 24 hours. Liquid CoQ10 250 mg followed by 150 mg TID for 5 days or placebo was administered through nasogastric tube. Age, sex, premorbidity, cause of arrest, conditions of CPR, and degree of hypoxia were similar in both groups; no side effects of CoQ10 were identified. Three-month survival in the CoQ10 group was 68% (17 of 25) and 29% (7 of 24) in the placebo group ( P =0.0413). Nine CoQ10 patients versus 5 placebo patients survived with a Glasgow Outcome Scale of 4 or 5. Mean serum S100 protein 24 hours after CPR was significantly lower in the CoQ10 group (0.47 versus 3.5 ng/mL). Conclusions— Combining CoQ10 with mild hypothermia immediately after CPR appears to improve survival and may improve neurological outcome in survivors.

The point mutation at position 3243 of the tRNA- L e u ( U U R ) of the mitochondrial DNA is associated with mitochondrial encephalomyopathy, lactic acidosis and strokes (MELAS) as well as with mitochondrial diabetes anddeafness (MIDD). A defect in insulin secretion has been found in most of these patients. However, there have been controversial findings to which extent insulin resistance contributes to pathogenesis. The aim of the present investigation was to study the insulin sensitivity index (Sl), insulin secretion (AlR G l u c o s e ) and glucose effectiveness (Sg) in patients with the 3243-mutation. Material and Methods: 7 patients of a large pedigree (some of the members who were not investigated had MELAS) and 3 siblings of another family in whom the 3243-mutation had been detected, as well as 23 non-related, healthy control subjects underwent a modified intravenous glucose tolerance test (Bergman's minimal model). In addition, a screening of islet cell antibodies (ICA) was performed. Results: All patients except for one with known diabetes mellitus revealed normal glucose tolerance. There was no difference between patients and controls for SI, AlR G l u c o s e or Sg. However, when looking at the individual results, there were 4 closely related members of the large family with very poor insulin sensitivity. The other 2 patients of this pedigree were more distantly related and extremely insulin sensitive. The siblings of the other family revealed normal or even a very good insulin sensitivity. In one patient, ICA were detected. Conclusions: The 3243-mutation does not seem to be causative for insulin resistance in our patients. Whether nuclear genes are involved and indirectly influence the expression of the 3243-mutation or, more likely, directly lead to impaired insulin sensitivity in some of our patients cannot be answered by our data. It remains open whether there is a difference in the pathogenesis of diabetes between patients with MIDD and those with MELAS.

Importance The rate of endophthalmitis following dexamethasone intravitreal implant (DEX) has varied in large clinical trials. Furthermore, to our knowledge, the optimal management of eyes with endophthalmitis associated with DEX has not been established. Objective To report the incidence of culture-proven endophthalmitis in a single vitreoretinal practice over the course of 3 years and describe the clinical outcomes associated with each case of endophthalmitis. Design, Setting, and Participants All patients who received DEX between January 14, 2013, and August 31, 2016, were included in this retrospective single-center case series at a private vitreoretinal practice. The patients were identified during a search of the billing records over the period of interest. Cases of endophthalmitis associated with DEX were also identified. Exposures Treatment with DEX. Main Outcomes and Measures Development of endophthalmitis following DEX and the clinical management and outcomes of each case of endophthalmitis. Results Of the 1051 participants who collectively received 3593 injections of DEX, 4 patients developed endophthalmitis; all 4 patients were white, female, and 60 years or older (mean [SD] age, 75.6 [13] years). Two patients had culture-proven bacterial endophthalmitis after DEX monoinjections (0.06% of injections and 0.2% of patients). Three other cases of endophthalmitis developed after coinjection with bevacizumab (aggregate rate: 0.14% of injections and 0.38% of patients), of which 2 were culture positive. One patient developed endophthalmitis on 2 separate occasions. Vitrectomy was performed in 2 patients, and in 1 of these patients, the implant was removed. All 4 patients were treated with injection of intravitreous vancomycin and ceftazidime. Conclusions and Relevance These data suggest that endophthalmitis is a rare event following injection of DEX. However, given the rarity of endophthalmitis following DEX and the heterogeneity among our reported cases, it remains unclear whether the DEX endophthalmitis rate approximates that of intravitreous anti–vascular endothelial growth factor therapy. These data also suggest that vitrectomy with removal of DEX may not be necessary in all cases of DEX-associated endophthalmitis.

To identify changes in retinal function and structure in persons with proliferative diabetic retinopathy (PDR), including the effects of panretinal photocoagulation (PRP).Cross-sectional study.Thirty adults who underwent PRP for PDR, 15 adults with untreated PDR, and 15 age-matched controls.Contrast sensitivity, frequency doubling perimetry (FDP), Humphrey visual fields, photostress recovery, and dark adaptation were assessed. Fundus photography and macular spectral-domain optical coherence tomography (SD OCT) were performed. To quantify retinal layer thicknesses, SD OCT scans were segmented semiautomatically.Visual function measures were compared among patients with PDR and PRP, untreated patients with PDR, and controls. Mean retinal layer thicknesses were compared between groups. Correlation analyses were performed to evaluate associations between visual function measures and retinal layer thicknesses.A significant reduction of FDP mean deviation (MD) was exhibited in PRP-treated patients with PDR (MD ± standard deviation, -8.20±5.76 dB; P0.0001) and untreated patients (-5.48±4.48 dB; P0.0001) relative to controls (1.07±2.50 dB). Reduced log contrast sensitivity compared with controls (1.80±0.14) also was observed in both PRP-treated patients (1.42±0.17; P0.0001) and untreated patients (1.56±0.20; P = 0.001) with PDR. Compared with controls, patients treated with PRP demonstrated increased photostress recovery time (151.02±104.43 vs. 70.64±47.14 seconds; P = 0.001) and dark adaptation speed (12.80±5.15 vs. 9.74±2.56 minutes; P = 0.022). Patients who underwent PRP had diffusely thickened nerve fiber layers (P = 0.024) and diffusely thinned retinal pigment epithelium (RPE) layers (P = 0.009) versus controls. Untreated patients with PDR also had diffusely thinned RPE layers (P = 0.031) compared with controls.Patients with untreated PDR exhibited inner retinal dysfunction, as evidenced by reduced contrast sensitivity and FDP performance, accompanied by alterations in inner and outer retinal structure. Patients who underwent PRP had more profound changes in outer retinal structure and function. Distinguishing the effects of PDR and PRP may guide the development of restorative vision therapies for patients with advanced diabetic retinopathy.

To determine risk factors associated with development of a branch retinal vein occlusion (BRVO) among a large group of managed-care plan beneficiaries in the United States.Retrospective, longitudinal cohort study.All beneficiaries age ≥55 years continuously enrolled for ≥2 years in a managed care network from 2001-2009 who had ≥2 visits to an eye care provider.Multivariable Cox regression analyses identified sociodemographic factors, ocular and nonocular conditions associated with incident BRVO.Hazard of incident BRVO with 95% confidence interval (CI).Of the 492,488 enrollees who met inclusion criteria, 2283 (0.5%) developed incident BRVO. After adjustment for confounding factors, blacks (adjusted hazard ratio [aHR], 1.43; CI, 1.19-1.73; P = 0.0001) had a 43% increased hazard of BRVO relative to non-Hispanic whites. Enrollees with hypertension (HTN) alone (aHR, 1.78; CI, 1.36-2.32; P 0.0001) or HTN along with other metabolic syndrome components (diabetes mellitus [DM] and hyperlipidemia; aHR, 1.44; CI, 1.12-1.84; P = 0.005) had an increased hazard of developing a BRVO compared with those with none of these conditions. Disease severity was important; enrollees with end-organ damage caused by HTN had a 107% increased hazard of developing BRVO compared with enrollees without HTN (aHR, 2.07; CI, 1.75-2.45; P 0.0001). Although there was no association between DM without end-organ damage and BRVO (aHR, 0.92; CI, 0.81-1.04; P = 0.2), individuals with end-organ damage from DM had a 36% increased hazard of BRVO (aHR, 1.36; CI, 1.18-1.57; P0.0001) compared with those without DM. Although cerebrovascular accident was associated with an increased hazard of developing BRVO (aHR, 1.34; CI, 1.19-1.52; P 0.0001), other diseases of the vascular system (deep venous thrombosis/pulmonary embolism, peripheral vascular disease, hypercoagulable state, myocardial infarction) or anticoagulant use did not increase the risk of BRVO (P 0.10 for all comparisons).Both HTN and end-organ damage from DM contribute to arteriosclerosis, atherosclerosis, and endothelial dysfunction, which seem to be major risk factors for BRVO. Ophthalmologists should emphasize to patients and their primary physicians the importance of effectively managing systemic medical conditions associated with BRVO.

Introduction: Adenotonsillectomy usually cures obstructive sleep apnoea in otherwise healthy children. When children, with congenital cardiac pathology, suffer sleep hypoxaemia following their corrective cardiac surgery, they are referred to an otolaryngologist for adenotonsillectomy. Hardly any studies have been published to show how effective this operation is for these children. Objective: To determine whether adenotonsillectomy significantly improves hypoxaemia in children with congenital cardiac pathology following corrective cardiac surgery. Methods: Thirty children with sleep apnoea (aged 2–8 years) were recruited. Fifteen children with congenital cardiac pathology (Gp I) and 15 children who were otherwise healthy (Gp II). All children were assessed pre-operatively and at 1 and 3 months post-operatively with transcutaneous oxygen saturation monitoring. Tonsillar size, base oxygen saturation level, apnoeic episodes and snoring were recorded. Sleep apnoea and snoring was graded on a 5 point scale from I (no apnoea/snoring) to V (severe apnoea and snoring). Results: All children had an initial sleep grade of IV or V. Tonsillar size did not appear to be a significant factor on sleep grade in Gp I and Gp II. The median base line oxygen saturation was 88 and 93%, respectively in Gp I and II pre-operatively and improved to 90.1 and 99.2%, post-operatively. Following surgery, snoring and sleep apnoea disappeared in group II. In group I, there was significant reduction in the number of apnoeic episodes at 3 months, but the majority of children were still snoring with hypoxaemic episodes. Conclusion: This study shows that adenotonsillectomy significantly reduces the apnoeic episodes in children with cardiac pathology but does not abolish it. At 3 months after surgery there was significant overall improvement in the baseline oxygen saturation.

Eight carriers of the A3243G mutation of mitochondrial DNA without stroke-like episodes were monitored for up to 7 years in clinical and metabolic studies, by magnetic resonance imaging (MRI) and positron emission tomography (PET). None developed mitochondrial encephalopathy (MELAS), but 2 developed diabetes mellitus, 1 terminal kidney failure and 2 cardiomyopathy. One patient improved markedly under ubiquinone. Electroencephalography showed progressive slowing in 2 cases, but electrophysiological tests and MRI were otherwise noncontributary. PET showed widespread cortical and basal ganglion metabolic deficits in 6 cases. We conclude that internal medical complications are more common than MELAS in adult carriers of the mutation. PET findings, firstly reported in such patients, suggest that chronic subclinical encephalopathy is very frequent, and PET may play a role in monitoring in the future. Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Congenital myasthenic syndromes are a heterogeneous group of inherited disorders that arise from impaired signal transmission at the neuromuscular synapse. They are characterized by fatigable muscle weakness. We performed linkage analysis, whole-exome and whole-genome sequencing to determine the underlying defect in patients with an inherited limb-girdle pattern of myasthenic weakness. We identify ALG14 and ALG2 as novel genes in which mutations cause a congenital myasthenic syndrome. Through analogy with yeast, ALG14 is thought to form a multiglycosyltransferase complex with ALG13 and DPAGT1 that catalyses the first two committed steps of asparagine-linked protein glycosylation. We show that ALG14 is concentrated at the muscle motor endplates and small interfering RNA silencing of ALG14 results in reduced cell-surface expression of muscle acetylcholine receptor expressed in human embryonic kidney 293 cells. ALG2 is an alpha-1,3-mannosyltransferase that also catalyses early steps in the asparagine-linked glycosylation pathway. Mutations were identified in two kinships, with mutation ALG2p.Val68Gly found to severely reduce ALG2 expression both in patient muscle, and in cell cultures. Identification of DPAGT1, ALG14 and ALG2 mutations as a cause of congenital myasthenic syndrome underscores the importance of asparagine-linked protein glycosylation for proper functioning of the neuromuscular junction. These syndromes form part of the wider spectrum of congenital disorders of glycosylation caused by impaired asparagine-linked glycosylation. It is likely that further genes encoding components of this pathway will be associated with congenital myasthenic syndromes or impaired neuromuscular transmission as part of a more severe multisystem disorder. Our findings suggest that treatment with cholinesterase inhibitors may improve muscle function in many of the congenital disorders of glycosylation. © 2013 The Author (2013). Published by Oxford University Press on behalf of the Guarantors of Brain.

Amplification of an unstable CTG trinucleotide repeat sequence in a protein kinase gene on chromosome 19 has recently been recognised as the molecular basis of myotonic dystrophy (DM), a multisystem disorder with a wide spectrum of muscular and extramuscular manifestations. The CTG expansion of 40 patients was assessed by direct genotype analysis of the white blood cell DNA and correlated with MRI of the brain and muscles, and with functional clinical data. Cerebral pathology on MRI consisted of diffuse atrophy (68 %), subcortical white matter lesions (65 %), wide Virchow-Robin spaces (38 %) and thickening of the skull (35 %). Cerebral atrophy and extent of white matter disease correlated significantly with mental retardation, duration of disease and CTG fragment amplification. MRI of the muscular system showed fatty degeneration of different degrees in neighbouring muscles causing a mosaic pattern of the thigh in 38 % and the calf in 44 %. Muscular changes on MRI were strongly correlated with muscular impairment but less strongly with CTG expansion. Changes on MRI reflect the stage of development of tissue pathology in DM, modified by defect of the DM gene. Pathology on MRI is strongly correlated with functional deficits.

Spinocerebellar ataxia, type 3 (SCA3) and Machado-Joseph disease (MJD) are two clinically distinct representatives of the heterogeneous group of autosomal dominant cerebellar ataxias. Assignment of the disease genes to the same region of the long arm of chromosome 14 in both SCA3 and MJD suggested that these two disorders are genetically identical. The recent identification of a trinucleotide (CAG) repeat expansion in a gene underlying MJD facilitates assessment of this hypothesis. We analysed the MJD gene in members of a family with characteristic features of SCA3 and no symptoms typical of MJD. We found the same trinucleotide repeat expansion within the gene that was previously described in patients with MJD. The findings demonstrate that SCA3 and MJD are genetically identical in spite of their pronounced clinical differences. Furthermore, we demonstrate a striking variation in the copy number of the CAG repeat among affected members of the same family.

Purpose The pathophysiology of vision loss in persons with diabetic retinopathy (DR) is complex and incompletely defined. We hypothesized that retinal pigment epithelium (RPE) and rod and cone photoreceptor dysfunction, as measured by dark adaptometry, would increase with severity of DR, and that pan-retinal photocoagulation (PRP) would exacerbate this dysfunction. Methods Dark adaptation (DA) was measured in subjects with diabetes mellitus and healthy controls. Dark adaptation was measured at 5° superior to the fovea following a flash bleach, and the data were analyzed to yield cone and rod sensitivity curves. Retinal layer thicknesses were quantified using spectral-domain optical coherence tomography (OCT). Results The sample consisted of 23 controls and 73 diabetic subjects. Subjects with moderate nonproliferative diabetic retinopathy (NPDR) exhibited significant impairment of rod recovery rate compared with control subjects (P = 0.04). Cone sensitivity was impaired in subjects with proliferative diabetic retinopathy (PDR) (type 1 diabetes mellitus [T1DM]: P = 0.0047; type 2 diabetes mellitus [T2DM]: P < 0.001). Subjects with untreated PDR compared with subjects treated with PRP exhibited similar rod recovery rates and cone sensitivities. Thinner RPE as assessed by OCT was associated with slower rod recovery and lower cone sensitivity, and thinner photoreceptor inner segment/outer segment layer was associated with lower cone sensitivity. Conclusions The results suggest that RPE and photoreceptor cell dysfunction, as assessed by cone sensitivity level and rod- and RPE-mediated dark adaptation, progresses with worsening DR, and rod recovery dysfunction occurs earlier than cone dysfunction. Function was preserved following PRP. The findings suggest multiple defects in retinoid function and provide potential points to improve visual function in persons with PDR.

Purpose To identify risk factors associated with central retinal vein occlusion (CRVO) among a diverse group of patients throughout the United States. Design Longitudinal cohort study. Participants All beneficiaries aged ≥55 years who were continuously enrolled in a managed care network for at least 2 years and who had ≥2 visits to an eye care provider from 2001 to 2009. Methods Insurance billing codes were used to identify individuals with a newly diagnosed CRVO. Multivariable Cox regression was performed to determine the factors associated with CRVO development. Main Outcome Measures Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of being diagnosed with CRVO. Results Of the 494 165 enrollees who met the study inclusion criteria, 1302 (0.26%) were diagnosed with CRVO over 5.4 (±1.8) years. After adjustment for known confounders, blacks had a 58% increased risk of CRVO compared with whites (HR, 1.58; 95% CI, 1.25–1.99), and women had a 25% decreased risk of CRVO compared with men (HR, 0.75; 95% CI, 0.66–0.85). A diagnosis of stroke increased the hazard of CRVO by 44% (HR, 1.44; 95% CI, 1.23–1.68), and hypercoagulable state was associated with a 145% increased CRVO risk (HR, 2.45; 95% CI, 1.40–4.28). Individuals with end-organ damage from hypertension (HTN) or diabetes mellitus (DM) had a 92% (HR, 1.92; 95% CI, 1.52–2.42) and 53% (HR, 1.53; 95% CI, 1.28–1.84) increased risk of CRVO, respectively, relative to those without these conditions. Conclusions This study confirms that HTN and vascular diseases are important risk factors for CRVO. We also identify black race as being associated with CRVO, which was not well appreciated previously. Furthermore, we show that compared with patients without DM, individuals with end-organ damage from DM have a heightened risk of CRVO, whereas those with uncomplicated DM are not at increased risk of CRVO. This finding may provide a potential explanation for the conflicting reports in the literature on the association between CRVO and DM. Information from analyses such as this can be used to create a risk calculator to identify possible individuals at greatest risk for CRVO. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Background: Most of the previously described pathogenic mutations in desmin are located in highly conserved α-helical domains that play an important role in intermediate filament assembly. The role of the C-terminus non-α-helical ‘tail’ domain is much less investigated and until recently mutations in this domain have been implicated in only a few patients. The majority of reported desminopathy cases caused by the tail mutations were sporadic, creating a representation bias regarding the disease frequency and phenotypic characteristics. Methods: We performed detailed genotype-phenotype analysis of autosomal dominant desminopathy associated with tail domain mutations in a four-generation autosomal dominant family with 16 members affected by a progressive cardiac and/or skeletal myopathy caused by a c.1346A>C (p.Lys449Thr) mutation located in the tail domain of desmin. Results: Phenotypic features in patients with tail domain mutations are similar to those in patients with mutations localized in the 1B and 2B α-helical domains. Conclusion: We recommend that the tail domain is searched for mutations as intensely as desmin coil domains which until recently were considered to be more ‘functional’.