Endogenous DNA 3' Blocks Are Vulnerabilities for BRCA1 and BRCA2 Deficiency and Are Reversed by the APE2 Nuclease.

The APEX2 gene encodes APE2, a nuclease related to APE1, the apurinic/apyrimidinic endonuclease acting in base excision repair. Loss of APE2 is lethal in cells with mutated BRCA1 or BRCA2, making APE2 a prime target for homologous recombination-defective cancers. However, because the function of APE2 in DNA repair is poorly understood, it is unclear why BRCA-deficient cells require APE2 for viability. Here we present the genetic interaction profiles of APE2, APE1, and TDP1 deficiency coupled to biochemical and structural dissection of APE2. We conclude that the main role of APE2 is to reverse blocked 3' DNA ends, problematic lesions that preclude DNA synthesis. Our work also suggests that TOP1 processing of genomic ribonucleotides is the main source of 3'-blocking lesions relevant to APEX2-BRCA1/2 synthetic lethality. The exquisite sensitivity of BRCA-deficient cells to 3' blocks indicates that they represent a tractable vulnerability in homologous recombination-deficient tumor cells.

SGLT2 inhibitors reduce adverse renal and CV outcomes in patients with or without diabetes.

SOURCE CITATION: Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022;400:1788-801. 36351458.

Comparison of radiation exposure associated with transradial and transfemoral access: An updated meta-analysis.

OBJECTIVES: To assess differences in radiation exposure between transradial access (TRA) and transfemoral access (TFA) for coronary procedures. BACKGROUND: TRA is associated with increased radiation exposure as compared to TFA. We compared radiation exposure between the two access sites. METHODS: Databases were searched from June 2014 to August 2021 for randomized controlled trials (RCTs) reporting coprimary outcomes of fluoroscopy time (FT) and/or dose area product (DAP) comparing TRA with TFA. Meta-regression was performed to assess the behavior of weighted mean difference (WMD) in FT from 1995 to 2021. Observational study data was used for corroborative evidence. RESULTS: Data from 8 RCTs (11,611 patients) showed the WMD of FT was 0.62 min (37 s) (95% confidence interval [CI]: [0.08-1.17], p = 0.023) in favor of TFA, WMD in DAP (9169 patients) was 1.94 Gy.cm2 (95% CI: [-2.1 to 5.9], p = 0.35) showing no significant difference. Pooled data from OBS and RCTs (83,990 patients) showed a similar trend. Studies from outside US between 1995 and 2021 showed WMD of FT between TRA and TFA of 0.88 min (52 s) (95% CI: [0.67-1.09], p = 0.005) versus 2.1 min (126 s) (95% CI: [1.38-2.8], p = 0.005) for US in favor of TFA. Meta-regression showed a declining WMD of FT between TRA and TFA from 1.6 min (96 s) in 1996 to 0.5 min (30 s) in 2020 with the lower limit of CI crossing the zero line in 2019. CONCLUSION: Radiation exposure between TRA and TFA continues to decrease overtime and is becoming clinically nonsignificant.

Impact of suspected adverse drug reactions on mortality and length of hospital stay in the hospitalised patients: a meta-analysis.

PURPOSE: To estimate the risk of mortality and length of stay in hospitalised patients who have experienced suspected adverse drug reactions (ADRs) as compared to patients who did not experience suspected ADRs. METHODS: A systematic literature search was conducted on databases for observational and randomised controlled studies conducted in any inpatient setting that reported deaths and/or length of hospital stay in patients who had suspected ADRs and did not have suspected ADRs during hospitalisation. PRISMA guidelines were strictly followed during the review. The methodological quality of included studies was assessed using a tool designed by Smyth et al. for the studies of adverse drug reactions. The meta-analytic summary of all-cause mortality was estimated using odds ratio-OR (95% CI) and length of stay using mean difference-MD (95% CI). Both outcomes were pooled using a random effect model (DerSimonian and Laird method). Subgroup and meta-regression were performed based on study variables: study design, age group, study ward, study region, types of suspected ADRs (ADRAd-suspected ADRs that lead to hospitalisation and ADRIn-suspected ADRs that occur following hospitalisation), study duration, sample size and study period. The statistical analysis was conducted through the 'Review manager software version 5.4.1 and JASP (Version 0.14.1)'. RESULTS: After screening 475 relevant articles, 55 studies were included in this meta-analysis. Patients having suspected ADRs had reported significantly higher odds of all-cause mortality [OR: 1.50 (95% CI: 1.21-1.86; I2 = 100%) than those patients who did not have suspected ADRs during hospitalisation. Study wards, types of suspected ADRs and sample size were observed as significant predictors of all-cause mortality (p < 0.05). Patients having suspected ADRs had reported significantly higher mean difference in hospital stay [MD: 3.98 (95% CI: 2.91, 5.05; I2 = 99%) than those patients who did not have suspected ADRs during hospitalisation. Types of suspected ADRs and study periods were observed as significant predictors of length of stay (p < 0.05). CONCLUSION: Suspected ADRs significantly increase the risk of mortality and length of stay in hospitalised patients. SYSTEMATIC REVIEW REGISTRATION: CRD42020176320.

Clinical Diagnosis of the Infantile Shoulder Subluxation in Residual Brachial Plexus Birth Injury and Its Correlation With Ultrasound Diagnosis.

INTRODUCTION AND AIMS OF STUDY: Timely detection of shoulder subluxation in infants with brachial plexus birth injury (BPBI) is essential to prevent the progression of glenohumeral deformity. Shoulder ultrasonography (USG) is routinely used to detect an infantile subluxation/dislocation, but its use is limited because of the paucity of expert radiologists in developing countries. The aim of this study was to determine the clinical examination predictors to determine shoulder subluxation in patients with BPBI correlating with ultrasound confirmation. METHODS: We prospectively studied children who presented to our hospital between 2017 and 2021 diagnosed as brachial plexus birth injury. In patients developing internal rotation contracture of the shoulder, we looked for 3 standard clinical signs: reduced passive external rotation <60 degrees, deep anterior crease (DAC) and relatively short arm segment. Shoulder subluxation was defined as USG measurement of alpha angle>30 degrees and ossific nuclei of the humerus lying behind the dorsal scapular line. Sensitivity and specificity were used to assess their efficacy in clinical diagnosis of shoulder subluxation in different groups. The predicted probability of shoulder subluxation from each prediction rule was compared with actual distributions based on USG confirmation. RESULTS: Of the 58 BPBI infants who developed PER<60 degrees at the shoulder, 41 had USG confirmed shoulder subluxation. The 2 independent predictors of shoulder subluxation (PER<45 degrees and DAC) were identified in the current patient population based on data analysis. The presence of short arm segment is a very specific marker of shoulder subluxation but not sensitive. The predicted probability of shoulder subluxation from the prediction rule combining all the 3 markers were similar to the actual distributions in the current patient population. CONCLUSIONS: PER<45 degrees and presence of deep anterior crease are clinical markers indicating shoulder dislocation in patients with BPBI developing reduced external rotation at the shoulder. On the basis of the proposed clinical diagnosis algorithm, the above markers along with the selective use of USG can help in early detection and treatment of infantile shoulder dislocation.

Evaluation of the incidence of radial artery occlusion using different introducer sheaths and hemostasis techniques.

BACKGROUND: Radial artery occlusion (RAO) remains one of the most important complications of transradial access (TRA). Despite the identification of multiple predictors, the interaction between these predictors on the occurrence of RAO has not been evaluated. METHODS: Consecutive patients undergoing TRA coronary angiography (CA) or percutaneous coronary intervention (PCI), were retrospectively analyzed to compare the effect of standard patent hemostasis using a one-bladder band versus two-bladder band with simultaneous ipsilateral ulnar artery compression and two introducer sizes on the primary endpoint of RAO. Access was obtained using 6-Fr slender introducer sheath or 7-Fr slender introducer sheath and hemostasis with either a one-bladder band or a two-bladder band. The radial artery was evaluated using ultrasound. RESULTS: Total of 2019 patients undergoing CA or PCI were included in the analysis. In the one-bladder band group, the incidence of RAO with a 6-Fr slender introducer sheath was 4.2%. In those receiving hemostasis with a two-bladder band, RAO occurred in 1% of patients receiving a 6-Fr slender introducer sheath versus 0.9% in those receiving a 7-Fr slender introducer sheath (p = 0.68). Larger radial artery diameter, larger body weight, and a two-bladder hemostasis band with ipsilateral ulnar compression were independently associated with a lower incidence of RAO. CONCLUSION: A two-bladder band with simultaneous ipsilateral ulnar artery compression when used for radial artery hemostasis, is associated with a lower incidence of RAO, and can mitigate the penalty for a larger catheter with reassuring implications for use of a 7-Fr capable system for complex transradial PCI.

Drug-related deaths among inpatients: a meta-analysis.

PURPOSE: To estimate the prevalence of drug-related deaths with regard to total hospital mortality and to explore the heterogeneity in its estimation through subgroup analysis, univariate and multivariate analysis. METHODS: Two investigators independently searched the PubMed and Google Scholar databases with appropriate key terms to identify observational and randomised studies assessing drug-related problems. The prevalence of drug-related deaths was estimated using a double arcsine method. The heterogeneity was explored through subgroup and univariate analysis for the following study characteristics: study design, age group, study ward, study region, types of drug-related problems, study duration, sample size and study period. The study variables showing significant effects were further explored through a multivariable regression model. The percentage of preventable drug-related deaths was explored as a secondary objective. RESULTS: Of the 480 full-text articles assessed, 23 studies satisfying the selection criteria were included. The mean percentage of drug-related deaths was 5.6% (95% CI: 3.8-7.6%; I2 = 96%). The univariable analysis showed study design (regression coefficient: 4.31) and study wards (regression coefficient: - 6.37) as heterogeneity modifiers. In the multivariable model, only the study ward was considered a significant predictor of drug-related deaths (regression coefficient: - 5.78; p = 0.04). The mean percentage of preventable drug-related deaths was 45.2% (95% CI: 33.6-57.0%; I2 = 60%). CONCLUSION: Drug-related problems are an important cause of mortality. The variability in its estimation could be explained by admission wards.

Efficacy and safety of intranasal ketamine compared with intranasal dexmedetomidine as a premedication before general anesthesia in pediatric patients: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To compare the efficacy and safety of intranasal ketamine with intranasal dexmedetomidine as a premedication in pediatric patients undergoing general anesthesia for elective surgery or other procedures. SOURCE: We conducted a systematic literature search in PubMed, PubMed Central, Scopus, LILACS, Google Scholar, the Cochrane Database of Systematic Reviews, and trial registries for randomized controlled trials (RCTs) comparing intranasal ketamine with intranasal dexmedetomidine as preanesthetic medication in elective surgery or other procedures in pediatric patients. We used Review Manager software version 5.4.1 for statistical analysis and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed the methodological quality of the included studies with the RoB 2 risk of bias tool. All outcomes were pooled using the Mantle-Haenszel method and a random-effects model. The quality of evidence was assessed using the GRADE approach. PRINCIPAL FINDINGS: Out of 2,445 full texts assessed, we included ten RCTs in the analysis. The efficacy outcomes did not fulfill the comparability criteria between intranasal ketamine and intranasal dexmedetomidine for sedation at parental separation (risk ratio [RR], 0.90; 95% confidence interval [CI], 0.79 to 1.04; I2 = 89%; GRADE evidence, low), mask acceptance (RR, 0.86; 95% CI, 0.66 to 1.13; I2 = 50%; GRADE evidence, low), and iv canulation (RR, 1.16; 95% CI, 0.79 to 1.69; I2 = 69%; GRADE evidence, very low). Intranasal ketamine-treated patients showed a higher incidence of nausea and vomiting (RR, 2.47; 95% CI, 1.24 to 4.91; I2 = 0; GRADE evidence, moderate). Significantly more bradycardia was observed in the intranasal dexmedetomidine group (RR, 0.16; 95% CI, 0.04 to 0.70; I2 = 40%; GRADE evidence, moderate) than in the ketamine group. CONCLUSION: The low to very low-quality evidence in this systematic review and meta-analysis of RCTs neither confirmed nor refuted comparable premedication efficacy of intranasal ketamine and dexmedetomidine in terms of parental separation, mask acceptance, and iv cannulation in a pediatric population. Clinical decision-making is likely to be influenced by differences in gastrointestinal and cardiovascular safety profiles. STUDY REGISTRATION: PROSPERO (CRD42021262516); registered 22 July 2021.

RéSUMé: OBJECTIF: Comparer l'efficacité et l'innocuité de la kétamine intranasale à la dexmédétomidine intranasale comme prémédication chez les patients pédiatriques bénéficiant d'une anesthésie générale pour une chirurgie élective ou d'autres interventions. SOURCES: Nous avons réalisé une recherche documentaire systématique dans les bases de données PubMed, PubMed Central, Scopus, LILACS, Google Scholar, ainsi que dans la base de données Cochrane des revues systématiques et dans les registres d'études pour en tirer les études randomisées contrôlées (ERC) comparant la kétamine intranasale à la dexmédétomidine intranasale comme médicament préanesthésique en chirurgie élective ou pour d'autres interventions chez les patients pédiatriques. Nous avons utilisé la version 5.4.1 du logiciel Review Manager pour l'analyse statistique et nous nous sommes conformés aux lignes directrices PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Nous avons évalué la qualité méthodologique des études incluses à l'aide de l'outil d'évaluation du risque de biais RoB 2. Tous les résultats ont été regroupés à l'aide de la méthode Mantle-Haenszel et d'un modèle à effets aléatoires. La qualité des données probantes a été évaluée à l'aide de l'approche GRADE. CONSTATATIONS PRINCIPALES: Sur les 2445 textes intégraux évalués, nous avons inclus dix ERC dans l'analyse. Les critères d'efficacité ne remplissaient pas les critères de comparabilité entre la kétamine intranasale et la dexmédétomidine intranasale pour la sédation lors de la séparation des parents (risque relatif [RR], 0,90; intervalle de confiance [IC] à 95 %, 0,79 à 1,04; I2 = 89 %; qualité des données probantes selon GRADE, faible), acceptation du masque (RR, 0,86; IC 95 %, 0,66 à 1,13; I2 = 50 %; qualité des données probantes selon GRADE, faible) et canulation IV (RR, 1,16; IC 95 %, 0,79 à 1,69; I2 = 69 %; qualité des données probantes selon GRADE, très faible). Les patients traités par kétamine intranasale ont montré une incidence plus élevée de nausées et vomissements (RR, 2,47; IC 95%, 1,24 à 4,91; I2 = 0; qualité des données probantes selon GRADE, modérée). Une proportion significativement plus élevée de cas de bradycardie a été observée dans le groupe dexmédétomidine intranasale (RR, 0,16; IC 95%, 0,04 à 0,70; I2 = 40 %; qualité des données probantes selon GRADE, modérée) comparativement au groupe kétamine. CONCLUSION: Les données probantes de qualité faible à très faible de cette revue systématique et méta-analyse des ERC n'ont ni confirmé ni infirmé l'efficacité comparable de la prémédication par kétamine ou dexmédétomidine intranasale, que ce soit en termes de séparation parentale, d'acceptation du masque ou de canulation IV dans une population pédiatrique. La prise de décision clinique est susceptible d'être influencée par les différences dans les profils d'innocuité gastro-intestinale et cardiovasculaire. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021262516); enregistrée le 22 juillet 2021.

Safety and Efficacy of Robotic-Assisted PCI.

PURPOSE OF REVIEW: Robotics has been used in multiple areas of procedural medical intervention. Robotic percutaneous coronary intervention (PCI) has been available since 2004. Its adoption has been slow with initial application in simple cases. RECENT FINDINGS: With increasing adoption, robotic PCI has been applied to a broader variety of coronary substrates with demonstration of safety and efficacy. Improvements in the robotic console with future generation devices should add to the utility of this platform. Robotic PCI advances the innovations in endovascular space into a different dimension, removing the dependence of the procedure on patient-operator ergonomics and likely operator skill.

Conversion of pyrolytic non-condensable gases from polypropylene co-polymer into bamboo-type carbon nanotubes and high-quality oil using biochar as catalyst.

The conversion of low-value plastic waste into high-value products such as carbon nanomaterial is of recent interest. In the current study, the non-condensable pyrolysis gases, produced from Polypropylene Copolymer (PPC) feedstock, was converted into bamboo-type carbon nanotubes (BCNTs) through catalytic chemical vapour deposition using biochar. Experiments were conducted in a three-zone furnace fixed bed reactor, where PPC was pyrolysed in the second zone and carbon nanotubes (CNTs) growth was eventuated in the third zone. The effects of different growth temperatures (500, 700, 900 °C) and biochar particle sizes (nanoparticle as well as 0-100 and 100-300 µm) were investigated to optimise the production of hydrogen and the yield of carbon nanotubes on the biochar surface. Biochar samples used in the synthesis of CNTs were obtained from the pyrolysis of saw dust at 700 °C in a muffle furnace. Analyses performed by using Scanning electron microscopy, Transmission electron microscopy, X-ray diffraction, and Raman spectroscopy techniques suggested that the best crystalline structure of CNTs were obtained at 900 °C with nano-sized biochar as a catalyst. The strong gas-solid contact and void fraction of nano-sized particles enhances the diffusion-precipitation mechanism, leading to the growth of CNTs. The nano-sized biochar increased hydrogen production at 900 °C and reduced the polycyclic aromatic hydrocarbons content in oil to only 1%, which is advantageous for further utilisation. Therefore, the production of high-value CNTs from waste plastic using low-cost biochar catalyst can be a sustainable approach in the management of waste plastic while participating in the circular economy.

Multiple unplanned readmissions after discharge for an admission with percutaneous coronary intervention.

OBJECTIVE: This study aims to describe temporal trends, characteristics, and clinical outcomes of patients with more than one unplanned readmission within 30 and 180 days after admission with percutaneous coronary intervention (PCI). BACKGROUND: There is limited understanding of multiple readmissions after PCI. METHODS: Patients undergoing PCI between 2010 and 2014 in the U.S. Nationwide Readmission Database were evaluated for unplanned readmissions at 30 and 180 days after discharge. Trends in multiple readmissions, characteristics of patients, and causes of first readmissions are described. RESULTS: A total of 2,324,194 patients were included in the analysis of 30-day unplanned readmissions and 1,327,799 patients in the analysis of 180-day unplanned readmission. The proportions of patients with a single readmission and multiple readmissions within 30 days were 8.5 and 1.0% and at 180 days were 15.4 and 9.1%, respectively. Common reasons for first readmission among patients with multiple readmissions were coronary artery disease, including angina, heart failure, and acute myocardial infarction. Factors associated with multiple readmissions were discharge against medical advice, discharge to care home, renal failure, and liver failure. The total cost of multiple readmissions is significant, with an increase from ~$20,000 for no readmission to over $60,000 at 30-day follow up and $86,000 at 180-day follow up. CONCLUSIONS: Multiple readmissions are rare within 30 days after PCI but increase to nearly 1 in 10 patients at 180 days, and 20-25% of patients who have multiple readmissions are readmitted for the same cause as for the first and second readmissions.

Association between distance from the radiation source and radiation exposure: A phantom-based study.

OBJECTIVES: The study evaluated the association between distance from radiation source and radiation exposure. BACKGROUND: Radiation exposure during medical procedures is associated with increased risk of cancer and other adverse effects. METHODS: An American National Standards Institute phantom was used to study the relationship between measured entrance surface exposure (MESE) and distance from the X-ray source in postero-anterior, left anterior oblique, and right anterior oblique projections. Three distance settings for table height were evaluated with "low" defined as 52 cm, "mid" 66 cm, and "high" 80 cm from the focal point of the X-ray source. Air-kerma and dose-area product measurements were recorded. Operator exposure with each of these conditions was measured, in a short operator (150 cm) as well as in a tall operator (190 cm). RESULTS: Aggregate results for the three projections were as follows. MESE (µGy/frame) significantly decreased as table-height increases (median, interquartile range, p-value) (low table-height 192.5 [122.4-201.2], mid table-height 105.8 [82.7-115.8], and high table-height 71.7 [58.4-75], p < .0005). The operator exposure (µGy/frame), significantly increased as the table-height increased (low table-height 0.0943 [0.0598-0.1157], medium table-height 0.1128 [0.0919-0.1397], and high table-height 0.158 [0.1339-0.2165], p < .0005). A shorter operator received higher radiation exposure compared to a taller operator (short operator 0.1405 [0.1155-0.1758] and tall operator 0.0995 [0.0798-0.1212], p < .0005). CONCLUSIONS: Increasing table-height is associated with a significant decrease in MESE. Operator radiation exposure increases with increasing table-height and shorter operators receive greater radiation exposure compared to taller operators.

Trends of repeat revascularization choice in patients with prior coronary artery bypass surgery.

OBJECTIVE: To examine rates and predictors repeat revascularization strategies (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]) in patients with prior CABG. METHODS: Using the National Inpatient Sample, patients with a history of CABG hospitalized for revascularization by PCI or CABG from January 2004 to September 2015 were included. Regression analyses were performed to examine predictors of receipt of either revascularization strategy as well as in-hospital outcomes. RESULTS: The rate of redo CABG doubled between 2004 (5.3%) and 2015 (10.3%). Patients who underwent redo CABG were more comorbid and experienced significantly worse major adverse cardiovascular and cerebrovascular events (odds ratio [OR]: 5.36 95% CI 5.11-5.61), mortality (OR 2.84 95% CI 2.60,-3.11), bleeding (OR 5.97 95% CI 5.44-6.55) and stroke (OR 2.15 95% CI 1.92-2.41), but there was no difference in cardiac complications between groups. Thoracic complications were high in patients undergoing redo CABG (8%), especially in females. Factors favoring receipt of redo CABG compared to PCI included male sex, age < 80 years, and absence of diabetes and renal failure. CONCLUSION: Reoperation in patients with prior CABG has doubled in the United States over a 12-year period. Patients undergoing redo CABG are more complex and associated with worse clinical outcomes than those receiving PCI.

A structured mentorship program for medical college faculty on health research.

BACKGROUND: A paradigm shift is required in faculty development programs on research skills, from theory-driven to hands-on practical approach. The objective of this study was to develop and implement a structured mentorship model for training of medical faculties in research skills. METHODS: An interventional study using functional mentorship and experiential learning based on a research project was conducted over a period of one year through two prevalidated modules: protocol and manuscript writing. We included early and mid-career medical faculty as mentees (mentor:mentee ratio-1:2). Module 1 consisted of eight days of active learning and 25 days of refinement period-the end point being submission of research proposal to the ethics committee. Module 2 consisted of six days of active learning and 15 days of refinement period with the end point being manuscript submission to a peer-reviewed journal. Context, Input, Process and Product model of evaluation was used for this program. RESULTS: All eight faculty who participated as mentees in this program completed the first module, developed protocols under this program and processed them through the ethics committee. Six of the eight participants of this original cohort attended the second module and five could submit their manuscript to a peer-reviewed journal within the stipulated date. Participants expressed improvement in their self-rating of research skills, satisfaction with the program and an overall favourable change in attitude towards research. CONCLUSION: Structured mentorship program with the help of local mentors could enhance research skills of medical faculty.

Minimally Invasive Subscapularis Release: A Novel Technique and Results.

BACKGROUND: Shoulder imbalance secondary to residual brachial plexus birth palsy requires release of internal rotation contracture and tendon transfer. Subscapularis is considered as the prime element of internal rotation contracture and various methods have been described for subscapularis lengthening. It includes open subscapularis slide or lengthening and arthroscopic release. We hypothesized that subscapularis can be released through minimally invasive approach from the medial border of scapula and thus avoiding formal open procedures and risk of weakening the internal rotation strength. METHODS: Safety zones to avoid injury to important neurovascular structures while performing minimally invasive subscapularis release (MISR) were determined through cadaveric dissection. Between 2014 and 2016, 45 patients underwent MISR. A concomitant conjoined Latissimus Dorsi and Teres Major transfer was performed. Twenty patients with minimum 2-year follow-up were included in this study. Average age of patients was 6.4 years. A 5-point modified Mallet Score, degrees of active and passive rotations and abduction were used as outcome measures. Axial MRI imaging were available to classify the gleno-humeral deformity. RESULTS: Mean improvement in passive external rotation was 80 degrees and in active external rotation was 43 degrees (P <0.001) at 3 months, which was maintained at final follow-up. Average shoulder abduction improved from preoperative-101 degrees to postoperative-142 degrees. Aggregate 5-point Mallet Score improved from 12.8 points (range, 11 to 16) preoperatively to 18.5 points (range, 16 to 21) postoperatively. None of the patients developed external rotation contracture. The results were comparable with other existing techniques of subscapularis release with conjoint tendon transfer. CONCLUSIONS: MISR with conjoined tendon transfer is an effective way of treating internal rotation contracture in children with congruent glenohumeral joints. This procedure has shown beneficial outcomes even in patients with noncongruous glenohumeral joints, when performed in children younger than 4 years. Advantages of MISR include less risk to neurovascular structures, minimal soft tissue trauma, directly addressing the medial tight subscapularis fibers, significantly less surgical time and minimum learning curve. LEVELS OF EVIDENCE: Level III-retrospective comparative study.

The Role of Far Cortical Endosteal Fixation for the Treatment of Medial Malleolus Fractures: A Biomechanical Study.

The traditional method for fixation of medial malleolus fractures has been with partially threaded (PT) lag screws extending beyond the physeal scar. The purpose of this study was to evaluate the biomechanical strength of an innovative method of fixation for medial malleolus fractures using a fully threaded (FT) lag screw that extends to the far endosteal cortex. Medial malleolus fractures were simulated in 12 matched cadaver pairs. A single PT 4.0-mm cancellous lag screw was placed in 1 ankle. The contralateral ankle of the same matched pair received an FT 3.5-mm cortical lag screw that extended to the far lateral tibial cortex and achieved endosteal purchase. Final torque of both screw configurations was recorded, and radiographs were taken to confirm appropriate screw placement. Average torque for the PT cancellous screws was 5.02 ± 2.34 in-lb. Average torque for the FT cortical screw was 7.63 ± 3.86 in-lb (p = .002). Visual and radiographic inspections revealed no displacement of the fracture site with use of the FT endosteal lag screw. Our results indicate superior biomechanical torque with far endosteal fixation with use of an FT cortical lag screw versus a traditional PT cancellous lag screw in a cadaver model. Far endosteal fixation is an alternative surgical option for medial malleolus fractures that provides added strength compared with PT lag screws and may obviate downsides associated with bicortical fixation.

Contemporary transradial access practices: Results of the second international survey.

OBJECTIVES: To gain insight into current practice of transradial angiography and intervention in the United States and around the world. BACKGROUND: Transradial access (TRA) has grown worldwide. In a prior survey, there was significant practice variation and there was minimal US participation which limited the generalizability to US operators. METHODS: We used an internet-based survey software program to solicit input from practicing interventional cardiologists from the United States and around the world. US operators were compared with outside the United States (OUS) operators and respondent-level comparisons were made with the prior survey to assess for temporal changes in practice. RESULTS: Between August 2016 and January 1, 2017, 125 interventional cardiologists completed the survey representing 91 countries with the United States having 449 (39.9%) respondents. Preprocedure, noninvasive testing for collateral circulation is used more commonly in the United States (54.1%) than around the world (26.6%) but its use has decreased since 2010. In the US, 48.8% of operators never use ultrasound and 92.6% of OUS operators never use it; only 4.4% overall use ultrasound in >50% of cases. Use of bivalirudin has decreased in the US and OUS. Nearly, 30% of operators do not assess for radial artery patency following hemostasis. US respondents used TRA less commonly for primary PCI for STEMI than their global counterparts. CONCLUSIONS: There is wide variation in how TRA procedures are performed including relatively low rates of adherence to practices that are known to improve outcomes. Further education aimed at increasing use of best practices will impact patient outcomes.

Mortality among patients due to adverse drug reactions that occur following hospitalisation: a meta-analysis.

PURPOSE: To estimate the prevalence of mortality among patients that develop adverse drug reactions during hospitalisation (ADRIn), to examine heterogeneity through subgroup analysis and to identify system-organ class (SOC) and their causative drugs. METHODS: Two investigators searched PubMed, Google Scholar and related bibliography for studies reporting ADRIn-related mortality data. The primary outcome was to compute overall prevalence of fatal ADRIn (95% CI) using double arcsine method. We explored the heterogeneity (I2) in its estimation based on study design, study population and data collection methods. The secondary outcomes were the pattern of fatal reactions and their causative drugs. PROSPERO register number-CRD42018090331. RESULTS: Out of 349 full text assessed, 48 studies satisfying the selection criteria were included. The fatal ADRIn prevalence was 0.11% (95% CI 0.06-0.18%; I2 = 93%). The fatal ADRIn prevalence ranged from 0.03% (I2 = 0%) in all ages to 0.27% (I2 = 90%) in elderly population studies. Elderly studies varied for all study characteristics. Among study wards, a higher trend of prevalence was observed in 'internal medicine and ICU' (0.46%, I2 = 51%) and 'neonatal/paediatric ward and ICU' (0.34%, I2 = 58%) studies. The commonly involved SOC were 'gastrointestinal disorders' (28.79%), 'blood and lymphatic system disorders' (19.69%) and 'renal and urinary disorders' (13.64%). Most commonly observed causative drug-fatal ADRIn pairs were antithrombotics and nonsteroidal anti-inflammatory drugs induced gastrointestinal bleeding, and antineoplastic agents induced cytopenia. CONCLUSION: ADRIn is an important cause of mortality. Age groups and study wards have important influence on prevalence of fatal ADRIn and its heterogeneity across studies. Few class drugs contribute to sizable proportion of ADRIn-related mortality.

Effect of substitution of plasticizer dibutyl phthalate with dibutyl sebacate on Eudragit® RS30D drug release rate control.

In the current study, the influence of type of plasticizer used with Eudragit® RS 30D on the drug release was investigated in solid dosage form extrusion/spheronization, and film coating. The drug pellets were coated for controlling drug release with Eudragit® RS 30D containing dibutyl phthalate and compared with dibutyl sebacate as an alternative plasticizer. To study the influence of pH of the dissolution medium on the drug release profile, capsules are tested for drug release profile at pH 1.2, 4.4, and 6.3. Additionally, the aging effect on the curing of Eudragit® RS 30D is evaluated by exposing the capsules dosage form to room temperature (25 °C ± 2 °C/60% ± 5% RH) for time 0, 3, 6, and 9 months, accelerated temperature (40 °C ± 2 °C/75% ± 5% RH) for time 0, 3, and 6 months, and intermediate temperature (30 °C ± 2 °C/65% ± 5% RH) for time 0, 6, and 9 months. The replacement of dibutyl phthalate, with dibutyl sebacate for polymer coating system in similar concentration is comparable with respect to plasticization effect. The coalescence of the polymer particles is not changed and requires no additional processing parameter control or additional curing time.

Paclitaxel-Eluting versus Everolimus-Eluting Coronary Stents in Diabetes.

BACKGROUND: The choice of drug-eluting stent in the treatment of patients with diabetes mellitus and coronary artery disease who are undergoing percutaneous coronary intervention (PCI) has been debated. Previous studies comparing paclitaxel-eluting stents with stents eluting rapamycin (now called sirolimus) or its analogues (everolimus or zotarolimus) have produced contradictory results, ranging from equivalence between stent types to superiority of everolimus-eluting stents. METHODS: We randomly assigned 1830 patients with diabetes mellitus and coronary artery disease who were undergoing PCI to receive either a paclitaxel-eluting stent or an everolimus-eluting stent. We used a noninferiority trial design with a noninferiority margin of 4 percentage points for the upper boundary of the 95% confidence interval of the risk difference. The primary end point was target-vessel failure, which was defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization at the 1-year follow-up. RESULTS: At 1 year, paclitaxel-eluting stents did not meet the criterion for noninferiority to everolimus-eluting stents with respect to the primary end point (rate of target-vessel failure, 5.6% vs. 2.9%; risk difference, 2.7 percentage points [95% confidence interval, 0.8 to 4.5]; relative risk, 1.89 [95% confidence interval, 1.20 to 2.99]; P=0.38 for noninferiority). There was a significantly higher 1-year rate in the paclitaxel-eluting stent group than in the everolimus-eluting stent group of target-vessel failure (P=0.005), spontaneous myocardial infarction (3.2% vs. 1.2%, P=0.004), stent thrombosis (2.1% vs. 0.4%, P=0.002), target-vessel revascularization (3.4% vs. 1.2%, P=0.002), and target-lesion revascularization (3.4% vs. 1.2%, P=0.002). CONCLUSIONS: In patients with diabetes mellitus and coronary artery disease undergoing PCI, paclitaxel-eluting stents were not shown to be noninferior to everolimus-eluting stents, and they resulted in higher rates of target-vessel failure, myocardial infarction, stent thrombosis, and target-vessel revascularization at 1 year. (Funded by Boston Scientific; TUXEDO-India Clinical Trials Registry-India number, CTRI/2011/06/001830).