Bilateral visual acuity decline in males with choroideremia: a pooled, cross-sectional meta-analysis

Background Choroideremia is a rare inherited retinal disease that leads to blindness. Visual acuity (VA) is a key outcome measure in choroideremia treatment studies, but VA decline rates change with age. An accurate understanding of the natural deterioration of VA in choroideremia is important to assess the treatment effect of new therapies in which VA is the primary outcome measure. We conducted a meta-analysis of data on individuals with choroideremia to determine the rate of VA deterioration between the better- and worse-seeing eye (BSE and WSE, respectively). Methods Data were collected from the prospective Natural History of the Progression of Choroideremia (NIGHT) study (613 eyes, baseline data only), studies included in a recent meta-analysis, and studies identified in a targeted literature search performed on March 25, 2020, including individual best-corrected VA (BCVA) and age data in male individuals with choroideremia. Best-corrected VA decline rates (measured by logMAR units) by age and trends in BCVA decline rates in the BSE and WSE were evaluated. Results Data from 1037 males (1602 eyes; mean age, 41.8 years) were included. Before and after an age cutoff of 33.8 years, BCVA decline rates for the WSE were 0.0086 and 0.0219 logMAR per year, respectively. Before and after an age cutoff of 39.1 years, BCVA decline rates for the BSE were 0.00001 and 0.0203 logMAR per year, respectively. Differences in absolute BCVA and decline rates increased between the 2 eyes until age ~ 40; thereafter, differences in absolute BCVA and decline rates were similar between eyes. Conclusions Using the largest choroideremia data set to date, this analysis demonstrates accelerated BCVA decline beginning between 30 and 40 years of age. Disparate interocular progression rates were observed before the transition age, with similar interocular progression rates after the transition age.

Hypokalemia Measurement and Management in Patients With Status Asthmaticus on Continuous Albuterol

OBJECTIVE: Status asthmaticus is commonly treated in pediatric patients by using continuous albuterol, which can cause hypokalemia. The primary aim of this study was to determine if serial potassium monitoring is necessary by examining treatment frequency of hypokalemia. METHODS: This retrospective analysis was performed in 185 pediatric patients admitted with status asthmaticus requiring continuous albuterol between 2017 and 2019. All patients were placed on intravenous fluids containing potassium. The primary outcome measure was the treatment of hypokalemia in relation to the number of laboratory draws for potassium levels. The secondary outcome measure was hypokalemia frequency and relation to the duration and initial dose of continuous albuterol. RESULTS: Included were 156 patients with 420 laboratory draws (average, 2.7 per patient) for potassium levels. The median lowest potassium level was 3.40 mmol/L (interquartile range, 3.2–3.7). No correlation was found between initial albuterol dose and lowest potassium level (P = .52). Patients with hypokalemia had a mean albuterol time of 12.32 (SD, 15.76) hours, whereas patients without hypokalemia had a mean albuterol time of 11.50 (SD, 12.53) hours (P = .29). Potassium levels were treated 13 separate times. CONCLUSIONS: The number of laboratory draws for potassium levels was high in our cohort, with few patients receiving treatment for hypokalemia beyond the potassium routinely added to maintenance fluids. Length of time on albuterol and dose of albuterol were not shown to increase the risk of hypokalemia. Serial laboratory measurements may be decreased to potentially reduce health care costs, pain, and anxiety surrounding needlesticks.

Hyaluronic acid injections for chronic tennis elbow

Background For most patients, tennis elbow (TE) resolves within 6 months of onset. For those with persistent and painful TE, nonsurgical treatment options are limited. Thousands of studies have tried to find effective treatments for TE but have usually failed. In this study, we tested the hypothesis that injections with hyaluronic acid (HA) would be effective at reducing pain from chronic TE. Methods Patients with a minimum of six months of pain from TE and with a pain level of 50 or greater (out of 100) were included in the study. They were randomized equally into one of two treatment groups: injection with HA or injection with saline control. Follow-up was conducted at 3, 6 and 12 months from the initial injection. Both the patient and the examiner at the follow-up visits were blinded to the treatment arm. The primary outcome measure was the visual analog scale (VAS pain) score at one year. Additional outcome measures included the shortened Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) and Patient Rated Tennis Elbow Evaluation (PRTEE) scores. Results Eighteen patients were randomized into the HA injection treatment arm, and 17 (94%) completed the study. The average age was 51.9 years, and 10 of the subjects were male. Patients had an average of 28.1 months of pain before entering the study. The VAS score in the HA group decreased from a baseline of 76.4–14.3 at 12 months. All 17 patients in the HA group showed VAS score reductions above the minimal clinically important difference (MCID) of at least 18. The PRTEE score improved from 67 to 28.1. The QuickDASH score improved from 53.7 to 22.5. Follow-up in the saline group was less than 50% and was therefore not used as a comparator. Conclusions HA injections yielded significant success in pain relief by three months. Patients continued to improve for the 12-month duration of the study. This study indicates that patients with chronic lateral epicondylitis may benefit from receiving injections of hyaluronic acid rather than having to undergo surgery.

Incidence of postoperative week 1 management changes after resident-performed phacoemulsification cataract surgery

Background The goal of this study was to investigate the incidence of departures from routine care at the postoperative week 1 (POW1) visit following uneventful resident-performed cataract surgery in asymptomatic patients who had a normal postoperative day 1 (POD1) examination. Methods A retrospective chart review of phacoemulsification surgeries performed by the senior resident class at Montefiore Medical Center between June 20, 2018 and April 1, 2019 was performed. The most recent preoperative visit note, operative report, POD1 visit note, and POW1 visit note were evaluated and variables were recorded. Exclusion criteria consisted of any complications that would have necessitated close follow-up and a POW1 visit, whether discovered preoperatively, intraoperatively, at the POD1 visit, or leading up to the POW1 visit. The primary outcome measure was the incidence of unanticipated management changes at the POW1 visit following resident-performed cataract surgery. Results The charts of 292 surgical cases of 234 patients that underwent phacoemulsification with intraocular lens implantation were reviewed. 226 cases (77%) had an uncomplicated pseudophakic fellow-eye history, with a routine surgery, and POD1 examination. 19 of these patients had symptomatic presentations at the POW1 timepoint, and an additional 30 had no POW1 visit at all. In total, 177 cases were included in the study, and only 4 of these cases (2.3%) had an unexpected management change at the POW1 visit. Conclusions Asymptomatic patients who underwent uncomplicated cataract surgeries performed by resident surgeons followed by a routine POD1 visit had a low incidence of unexpected management changes at the POW1 visit. These results suggest that regularly scheduled POW1 visits could potentially be omitted for patients deemed to be at low risk for complications, and instead performed on an as-needed basis.

A multi-center, international, randomized, 2-year, parallel-group study to assess the superiority of IVUS-guided PCI versus qualitative angio-guided PCI in unprotected left main coronary artery (ULMCA) disease: Study protocol for OPTIMAL trial

Background Percutaneous coronary intervention (PCI) is used increasingly for revascularization of unprotected left main coronary artery (LMCA) disease. Observational studies and subgroup analyses from clinical trials, have suggested a possible benefit from the use of intravascular ultrasound (IVUS) guidance when performing unprotected LMCA PCI. However, the value of imaging with IVUS has never been proven in an appropriately powered randomized clinical trial. The OPtimizaTIon of Left MAin PCI With IntravascuLar Ultrasound (OPTIMAL) trial has been designed to establish whether IVUS-guided PCI optimization on LMCA is associated with superior clinical outcomes when compared with standard qualitative angiography-guided PCI. Methods The OPTIMAL trial is a randomized, multicenter, international study designed to enroll a total of 800 patients undergoing PCI for unprotected LMCA disease. Patients will be randomized in a 1:1 fashion to IVUS-guided PCI versus angiogram-guided PCI. In patients allocated to the angiogram-guided arm, use of IVUS is discouraged, unless there are safety concerns. In patients allocated to the IVUS guidance arm, pre-procedural IVUS assessment is highly recommended, whilst post-procedural IVUS assessment is mandatory to confirm appropriate stenting result and/or to guide stent result optimization, according to predefined criteria. Patients will be followed up to 2 years after the index procedure. The primary outcome measure is the Academic Research Consortium (ARC) patient-oriented composite endpoint (PoCE) which includes all-cause death, any stroke, any myocardial infarction and any repeat revascularization at 2 years follow-up. Discussion The OPTIMAL trial aims to provide definitive evidence about the clinical impact of IVUS-guidance during PCI to an unprotected LMCA. It is anticipated by the investigators, that an IVUS-guided strategy will be associated with less clinical events compared to a strategy guided by angiogram alone. Trial registration ClinicalTrials.gov: NCT04111770. Registered on October 1, 2019.

Sample size and its evolution in research

Objective: Sample size is one of the crucial and basic steps involved in planning any study. This article aims to study the evolution of sample size across the years from hundreds to thousands to millions and to a trillion in the near future (H-K-M-B-T). It also aims to understand the importance of sampling in the era of big data. Study Design - Primary Outcome measure, Methods, Results, and Interpretation: A sample size which is too small will not be a true representation of the population whereas a large sample size will involve putting more individuals at risk. An optimum sample size needs to be employed to identify statistically significant differences if they exist and obtain scientifically valid results. The design of the study, the primary outcome, sampling method used, dropout rate, effect size, power, level of significance, and standard deviation are some of the multiple factors which affect the sample size. All these factors need to be taken into account while calculating the sample size. Many sources are available for calculating sample size. Discretion needs to be used while choosing the right source. The large volumes of data and the corresponding number of data points being analyzed is redefining many industries including healthcare. The larger the sample size, the more insightful information, identification of rare side effects, lesser margin of error, higher confidence level, and models with more accuracy. Advances in the digital era have ensured that we do not face most of the obstacles faced traditionally with regards to statistical sampling, yet it has its own set of challenges. Hence, considerable efforts and time should be invested in selecting sampling techniques which are appropriate and reducing sampling bias and errors. This will ensure the reliability and reproducibility in the results obtained. Along with a large sample size, the focus should be on getting to know the data better, the sample frame and the context in which it was collected. We need to focus on creation of good quality data and structured systems to capture the sample. Good data quality management makes sure that the data are structured appropriately.

Frontline thrombectomy strategy and outcome in acute basilar artery occlusion

BackgroundNovel thrombectomy strategies emanate expeditiously day-by-day counting on access system, clot retriever device, proximity to and integration with the thrombus, and microcatheter disengagement. Nonetheless, the relationship between native thrombectomy strategies and revascularization success remains to be evaluated in basilar artery occlusion (BAO).PurposeTo compare the safety and efficacy profile of key frontline thrombectomy strategies in BAO.MethodsRetrospective analyses of prospectively maintained stroke registries at two comprehensive stroke centers were performed between January 2015 and December 2019. Patients with BAO selected after MR imaging were categorized into three groups based on the frontline thrombectomy strategy (contact aspiration (CA), stent retriever (SR), or combined (SR+CA)). Patients who experienced failure of clot retrieval followed by an interchanging strategy were categorized as a fourth (switch) group. Clinicoradiological features and procedural variables were compared. The primary outcome measure was the rate of complete revascularization (modified Thrombolysis in Cerebral Infarction (mTICI) grade 2c–3). Favorable outcome was defined as a 90 day modified Rankin Scale score of 0–2.ResultsOf 1823 patients, we included 128 (33 underwent CA, 35 SR, 35 SR +CA, and 25 switch techniques). Complete revascularization was achieved in 83/140 (59%) primarily analyzed patients. SR +CA was associated with higher odds of complete revascularization (adjusted OR 3.04, 95% CI 1.077 to 8.593, p=0.04) which was an independent predictor of favorable outcome (adjusted OR 2.73. 95% CI 1.152 to 6.458, p=0.02). No significant differences were observed for symptomatic intracranial hemorrhage, functional outcome, or mortality rate.ConclusionAmong BAO patients, the combined technique effectively contributed to complete revascularization that showed a 90 day favorable outcome with an equivalent complication rate after thrombectomy.

Combining Lovastatin and Minocycline for the Treatment of Fragile X Syndrome: Results From the LovaMiX Clinical Trial

Background: Limited success of previous clinical trials for Fragile X syndrome (FXS) has led researchers to consider combining different drugs to correct the pleiotropic consequences caused by the absence of the Fragile X mental retardation protein (FMRP). Here, we report the results of the LovaMiX clinical trial, the first trial for FXS combining two disease-modifying drugs, lovastatin, and minocycline, which have both shown positive effects when used independently.Aim: The main goals of the study were to assess the safety and efficacy of a treatment combining lovastatin and minocycline for patients with FXS.Design: Pilot Phase II open-label clinical trial. Patients with a molecular diagnostic of FXS were first randomized to receive, in two-step titration either lovastatin or minocycline for 8 weeks, followed by dual treatment with lovastatin 40 mg and minocycline 100 mg for 2 weeks. Clinical assessments were performed at the beginning, after 8 weeks of monotherapy, and at week 20 (12 weeks of combined therapy).Outcome Measures: The primary outcome measure was the Aberrant Behavior Checklist-Community (ABC-C) global score. Secondary outcome measures included subscales of the FXS specific ABC-C (ABC-CFX), the Anxiety, Depression, and Mood Scale (ADAMS), the Social Responsiveness Scale (SRS), the Behavior Rating Inventory of Executive Functions (BRIEF), and the Vineland Adaptive Behavior Scale second edition (VABS-II).Results: Twenty-one individuals out of 22 completed the trial. There were no serious adverse events related to the use of either drugs alone or in combination, suggesting good tolerability and safety profile of the combined therapy. Significant improvement was noted on the primary outcome measure with a 40% decrease on ABC-C global score with the combined therapy. Several outcome measures also showed significance.Conclusion: The combination of lovastatin and minocycline is safe in patients for FXS individuals and appears to improve several elements of the behavior. These results set the stage for a larger, placebo-controlled double-blind clinical trial to confirm the beneficial effects of the combined therapy.

Is the French Paradox cementing philosophy superior to the standard cementing? A randomized controlled radiostereometric trial and comparative analysis

Aims Highly polished stems with force-closed design have shown satisfactory clinical results despite being related to relatively high early migration. It has been suggested that the minimal thickness of cement mantles surrounding the femoral stem should be 2 mm to 4 mm to avoid aseptic loosening. The line-to-line cementing technique of the femoral stem, designed to achieve stem press-fit, challenges this opinion. We compared the migration of a highly polished stem with force-closed design by standard and line-to-line cementing to investigate whether differences in early migration of the stems occur in a clinical study. Methods In this single-blind, randomized controlled, clinical radiostereometric analysis (RSA) study, the migration pattern of the cemented Corail hip stem was compared between line-to-line and standard cementing in 48 arthroplasties. The primary outcome measure was femoral stem migration in terms of rotation and translation around and along with the X-, Y-, and Z- axes measured using model-based RSA at three, 12, and 24 months. A linear mixed-effects model was used for statistical analysis. Results Results from mixed model analyses revealed a lower mean retroversion for line-to-line (0.72° (95% confidence interval (CI) 0.38° to 1.07°; p < 0.001), but no significant differences in subsidence between the techniques (-0.15 mm (95% CI -0.53 to 0.227; p = 0.429) at 24 months. Radiolucent lines measuring < 2 mm wide were found in three and five arthroplasties cemented by the standard and line-to-line method, respectively. Conclusion The cemented Corail stem with a force-closed design seems to settle earlier and better with the line-to-line cementing method, although for subsidence the difference was not significant. However, the lower rate of migration into retroversion may reduce the wear and cement deformation, contributing to good long-term fixation and implant survival. Cite this article: Bone Joint J 2022;104-B(1):19–26.

Real-world data from expanded access programmes in health technology assessments: a review of NICE technology appraisals

ObjectivesTo quantify and characterise the usage of expanded access (EA) data in National Institute for Health and Care Excellence (NICE) technology appraisals (TAs). EA offers patients who are ineligible for clinical trials or registered treatment options, access to investigational therapies. Although EA programmes are increasingly used to collect real-world data, it is unknown if and how these date are used in NICE health technology assessments.DesignCross-sectional study of NICE appraisals (2010–2020). We automatically downloaded and screened all available appraisal documentation on NICE website (over 8500 documents), searching for EA-related terms. Two reviewers independently labelled the EA usage by disease area, and whether it was used to inform safety, efficacy and/or resource use. We qualitatively describe the five appraisals with the most occurrences of EA-related terms.Primary outcome measureNumber of TAs that used EA data to inform safety, efficacy and/or resource use analyses.ResultsIn 54.2% (206/380 appraisals), at least one reference to EA was made. 21.1% (80/380) of the TAs used EA data to inform safety (n=43), efficacy (n=47) and/or resource use (n=52). The number of TAs that use EA data remained stable over time, and the extent of EA data utilisation varied by disease area (p=0.001).ConclusionNICE uses EA data in over one in five appraisals. In synthesis with evidence from well-controlled trials, data collected from EA programmes may meaningfully inform cost-effectiveness modelling.