Efficacy and safety of radiofrequency ablation versus cryoballoon ablation for persistent atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Persistent Atrial Fibrillation (PeAF) is a challenging case for rhythm control modalities. Catheter ablation is the mainstay in PeAF management; however, data regarding the comparative safety and efficacy of cryoballoon ablation (CBA) versus radiofrequency ablation (RFA) for PeAF is still limited. We aim to compare the safety and efficacy of CBA versus RFA for PeAF ablation. METHODS: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through October 2023. RevMan version 5.4 software was used to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42023480314. RESULTS: Three RCTs with 400 patients were included. There was no significant difference between RFA and CBA regarding AF recurrence (RR: 0.77, 95% CI [0.50, 1.20], P = 0.25), atrial tachycardia or atrial flutter recurrence (RR: 0.54, 95% CI [0.11, 2.76], P = 0.46), and any arrhythmia recurrence (RR: 0.96, 95% CI [0.70, 1.31], P = 0.80). CBA was significantly associated with decreased total procedure duration (MD: - 45.34, 95% CI [- 62.68, - 28.00], P < 0.00001), with no significant difference in fluoroscopy duration (MD: 3.59, 95% CI [- 5.13, 12.31], P = 0.42). Safety parameters were similar in both groups, including the incidence of any complications, phrenic nerve palsy (RR: 2.91 with 95% CI [0.31, 27.54], P = 0.35), access site complications (RR: 0.33 with 95% CI [0.05, 2.03], P = 0.23), and pericardial effusion. CONCLUSIONS: In PeAF catheter ablation, CBA is comparable to RFA in terms of safety and efficacy. Also, CBA is associated with a shorter total procedure duration.

Clinical, phenotypic, and genotypic characteristics of ESBL-producing Salmonella enterica bloodstream infections from Qatar.

Background: Resistant Salmonella infections are a major global public health challenge particularly for multidrug-resistant (MDR) isolates manifesting as bloodstream infections (BSIs). Objectives: To evaluate clinical, phenotypic, and genotypic characteristics of extended-spectrum beta-lactamase (ESBL) producing Salmonella enterica BSIs from Qatar. Methods: Phenotypic ESBL Salmonella enterica from adult patients presenting with positive BSIs were collected between January 2019 to May 2020. Microbiological identification and characterization were performed using standard methods while genetic characteristics were examined through whole genome sequencing studies. Results: Of 151 episodes of Salmonella enterica BSI, 15 (10%) phenotypic ESBL isolates were collected. Recent travel was recorded in most cases (80%) with recent exposure to antimicrobials (27%). High-level resistance to quinolines, aminoglycosides, and cephalosporins was recorded (80-100%) while meropenem, tigecycline and colistin demonstrated universal susceptibility. Genomic evaluation demonstrated dominance of serotype Salmonella Typhi sequence type 1 (93%) while antimicrobial resistance genes revealed dominance of aminoglycoside resistance (100%), qnrS1 quinolones resistance (80%), blaCTX-M-15 ESBLs (86.7%), and paucity of AmpC resistance genes (6.7%). Conclusions: Invasive MDR Salmonella enterica is mainly imported, connected to patients from high prevalent regions with recent travel and antimicrobial use caused by specific resistant clones. In suspected cases of multidrug resistance, carbapenem therapy is recommended.

Clinical decision support systems to optimize adherence to anticoagulant guidelines in patients with atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Clinical decision support systems (CDSS) have been utilized as a low-cost intervention to improve healthcare process measures. Thus, we aim to estimate CDSS efficacy to optimize adherence to oral anticoagulant guidelines in eligible patients with atrial fibrillation (AF). METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through August 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). PROSPERO ID: CRD42023471806. RESULTS: We included nine RCTs with a total of 25,573 patients. There was no significant difference, with the use of CDSS compared to routine care, in the number of patients prescribed anticoagulants (RR: 1.06, 95% CI [0.98, 1.14], P = 0.16), the number of patients prescribed antiplatelets (RR: 1.01 with 95% CI [0.97, 1.06], P = 0.59), all-cause mortality (RR: 1.19, 95% CI [0.31, 4.50], P = 0.80), major bleeding (RR: 0.84, 95% CI [0.21, 3.45], P = 0.81), and clinically relevant non-major bleeding (RR: 1.05, 95% CI [0.52, 2.16], P = 0.88). However, CDSS was significantly associated with reduced incidence of myocardial infarction (RR: 0.18, 95% CI [0.06, 0.54], P = 0.002) and cerebral or systemic embolic event (RR: 0.11, 95% CI [0.01, 0.83], P = 0.03). CONCLUSION: We report no significant difference with the use of CDSS compared to routine care in anticoagulant or antiplatelet prescription in eligible patients with AF. CDSS was associated with a reduced incidence of myocardial infarction and cerebral or systemic embolic events.

Efficacy and safety of high-power short-duration ablation for atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: High-power short-duration (HPSD) ablation has emerged as an alternative to conventional standard-power long-duration (SPLD) ablation. We aim to assess the efficacy and safety of HPSD versus SPLD for atrial fibrillation (AF) ablation. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed, WOS, SCOPUS, EMBASE, and CENTRAL were performed through August 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42023471797. RESULTS: We included six RCTs with a total of 694 patients. HPSD was significantly associated with a decreased total procedure time (MD: -22.88 with 95% CI [-36.13, -9.63], P = 0.0007), pulmonary vein isolation (PVI) time (MD: -19.73 with 95% CI [-23.93, -15.53], P < 0.00001), radiofrequency time (MD: -10.53 with 95% CI [-12.87, -8.19], P < 0.00001). However, there was no significant difference between HPSD and SPLD ablation with respect to the fluoroscopy time (MD: -0.69 with 95% CI [-2.00, 0.62], P = 0.30), the incidence of esophageal lesions (RR: 1.15 with 95% CI [0.43, 3.07], P = 0.77), and the incidence of first pass isolation (RR: 0.98 with 95% CI [0.88, 1.08], P = 0.65). CONCLUSION: HPSD ablation was significantly associated with decreased total procedure time, PVI time, and radiofrequency time compared with SPLD ablation. On the contrary, SPLD ablation was significantly associated with low maximum temperature.

Intensive Blood Pressure Control After Endovascular Thrombectomy for Acute Ischemic Stroke: a Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Optimal clinical outcome with successful recanalization from endovascular thrombectomy (EVT) requires optimal blood pressure (BP) management. We aimed to evaluate the efficacy and safety of the intensive BP target (< 140 mm Hg) versus the standard BP target (< 180 mm Hg) after EVT for acute ischemic stroke. METHODS: We conducted a systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until September 7th, 2023. We used the fixed-effect model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). PROSPERO ID: CRD42023463206. RESULTS: We included four RCTs with 1559 patients. There was no difference between intensive BP and standard BP targets regarding the National Institutes of Health Stroke Scale (NIHSS) change after 24 h [MD: 0.44 with 95% CI (0.0, 0.87), P = 0.05]. However, the intensive BP target was significantly associated with a decreased risk of excellent neurological recovery (mRS ≤ 1) [RR: 0.87 with 95% CI (0.76, 0.99), P = 0.03], functional independence (mRS ≤ 2) [RR: 0.81 with 95% CI (0.73, 0.90), P = 0.0001] and independent ambulation (mRS ≤ 3) [RR: 0.85 with 95% CI (0.79, 0.92), P < 0.0001]. CONCLUSIONS: An intensive BP target after EVT is associated with worse neurological recovery and significantly decreased rates of functional independence and independent ambulation compared to the standard BP target. Therefore, the intensive BP target should be avoided after EVT for acute ischemic stroke.

Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar.

In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including blaNMD-5 and blaOXA derivative types, as well as a mutated outer membrane porin protein (OmpK37).

Efficacy and safety of restrictive versus liberal blood transfusion strategies in acute myocardial infarction and anemia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Blood transfusion strategies in patients with acute myocardial infarction (AMI) and anemia are yet to be conclusively identified. Thus, we aim to assess the efficacy and safety of restrictive versus liberal blood transfusion strategies for AMI and anemia. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed, web of science, SCOPUS, EMBASE, and Cochrane Central Register of Controlled Trials were performed through November 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). (PROSPERO): ID: CRD42023490692. RESULTS: We included four RCTs with 4.325 patients. There was no significant difference between both groups regarding MACE whether at 30 days (RR: 0.93 with 95% CI [0.57-1.51], P  = 0.76) or ≥ six months (RR: 1.17 with 95% CI [0.95-1.45], P  = 0.14), all-cause mortality at 30 days (RR: 1.16 with 95% CI [0.95-1.40], P  = 0.14) or ≥ six months (RR: 1.16 with 95% CI [0.88-1.53], P  = 0.28). However, the liberal strategy was significantly associated with increased hemoglobin level change (MD: -1.44 with 95% CI [-1.68 to -1.20], P  < 0.00001). However, the restrictive strategy was significantly associated with a lower incidence of acute lung injury (RR: 0.11 with 95% CI [0.02-0.60], P  = 0.01). CONCLUSION: There was no significant difference between the restrictive blood transfusion strategy and the liberal blood transfusion strategy regarding the clinical outcomes. However, restrictive blood transfusion strategy was significantly associated with a lower incidence of acute lung injury than liberal blood transfusion strategy.

The efficacy and safety of exercise regimens to mitigate chemotherapy cardiotoxicity: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cardiotoxicity is one of the most common adverse events of the chemotherapy. Physical exercise was shown to be cardioprotective. We aim to estimate the efficacy and safety of exercise in cancer patients receiving cardiotoxic chemotherapy. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, Cochrane, Clinical Trials.gov, and MedRxiv through July 17th, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI). PROSPERO ID: CRD42023460902. RESULTS: We included thirteen RCTs with a total of 952 patients. Exercise significantly increased VO2 peak (MD: 1.95 with 95% CI [0.59, 3.32], P = 0.005). However, there was no significant effect regarding left ventricular ejection fraction, global longitudinal strain, cardiac output, stroke volume, left ventricular end-diastolic volume, left ventricular end-systolic volume, E/A ratio, resting heart rate, peak heart rate, resting systolic blood pressure, and resting diastolic blood pressure. Also, there was no significant difference regarding any adverse events (AEs) (RR: 4.44 with 95% CI [0.47, 41.56], P = 0.19), AEs leading to withdrawal (RR: 2.87 with 95% CI [0.79, 10.43], P = 0.11), serious AEs (RR: 3.00 with 95% CI [0.14, 65.90], P = 0.49), or all-cause mortality (RR: 0.25 with 95% CI [0.03, 2.22], P = 0.21). CONCLUSION: Exercise is associated with increased VO2 peak in cancer patients receiving cardiotoxic chemotherapy. However, there was no significant difference between exercise and usual care regarding the echocardiographic and safety outcomes.

Outcome of Respiratory Viral Infections in Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Respiratory viral infections (RVIs) commonly cause morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. This study aimed at the prevalence of RVIs in adult HSCT recipients and their outcomes. METHODS: A retrospective observational cohort study was conducted on all adult patients who underwent HSCT in the period between January 2016 and December 2020. Data were retrospectively abstracted from electronic medical records from a total of 400 patients. All cases with polymerase chain reaction-confirmed RVIs based on real-time reverse transcription polymerase chain reaction were included in the data analysis. RESULT: A total of 79 patients had positive results. Sixty-three patients had allogeneic stem cell transplants. Women were 53% of the patients, and the mean age was 32 years (±13.5). The prevalence of documented respiratory virus infections was around 20% during the 4 years of the study. The most common virus was rhinovirus (60.76%), followed by respiratory syncytial virus (15.19%), then parainfluenza (11.39%). Among the 9 patients (11%) who required intensive care unit admission, 67% had lymphopenia (P = .03), 71% had abnormal chest computed tomography scan with pleural effusion (P = .03), 22% required renal support (P = .057), and 2 patients (22%) died (P = .057). CONCLUSIONS: The study highlights the associated morbidity and mortality with RVIs among HSCT recipients and the need for more preventive measures and treatment studies.

Once-weekly Insulin Icodec Versus Once-daily Long-acting Insulin for Type II Diabetes: A Meta-analysis of Randomized Controlled Trials.

Background: Insulin icodec is a novel basal insulin analog with once-weekly subcutaneous administration. We aim to estimate the efficacy and safety of insulin icodec vs long-acting insulin (insulin glargine and degludec) in type II diabetic patients. Methods: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through May 29, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Our primary outcome was glycated hemoglobin (HbA1C) change. Results: We included 7 RCTs with a total of 3183 patients. Insulin icodec was associated with significantly decreased HbA1C (MD: -0.15 with 95% CI [-0.24, -0.06], P = .002) and increased percentage of time with glucose in range (TIR) (MD: 4.06 with 95% CI [2.06, 6.06], P = .0001). However, insulin icodec was associated with increased body weight (MD: 0.57 with 95% CI [0.45, 0.70], P = .00001). Also, there was no difference regarding any serious adverse events (AEs) (RR: 0.96 with 95% CI [0.76, 1.20], P = .7) or AEs leading to withdrawal (RR: 1.54 with 95% CI [0.84, 2.82], P = .16). However, insulin icodec was associated with increased any AEs incidence (RR: 1.06 with 95% CI [1.01, 1.12], P = .02). Conclusion: Insulin icodec was associated with decreased HbA1C, increased TIR, with similar hypoglycemic and serious AEs. However, it was also associated with increased body weight and the incidence of any AEs.

The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis.

Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed-effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02-1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57-0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24-0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89-1.17), P = 0.76] and serum potassium change [MD: -0.31 with 95% CI (-0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12-2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head-to-head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).

The epidemiology and microbiological characteristics of infections caused by Gram-negative bacteria in Qatar: national surveillance from the Study for Monitoring of Antimicrobial Resistance Trends (SMART): 2017 to 2019.

Background: The global Study of Monitoring Antimicrobial Resistance Trends (SMART) is a surveillance program for evaluation of antimicrobial resistance (AMR) in Gram-negative bacteria (GNB) from different regions including Gulf countries. Objectives: To evaluate AMR in GNB from various clinical specimens including microbiological and genetic characteristics for existing and novel antimicrobials. Methods: A prospective study was conducted on clinical specimens from Hamad Medical Corporation, Qatar, between 2017 and 2019 according to the SMART protocol. Consecutive GNB from different sites were evaluated including lower respiratory, urinary tract, intrabdominal and bloodstream infections. Results: Over the 3 years study period, 748 isolates were evaluated from the specified sites comprising 37 different GNB outlining four key pathogens: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia.For the two major pathogens E. coli and K. pneumoniae, phenotypic ESBL was identified in 55.77% (116/208) compared to 39% (73/187), while meropenem resistance was 3.8% compared to 12.8% and imipenem/relebactam resistance was 2.97% compared to 11.76%, respectively. The overall ceftolozane/tazobactam resistance for E. coli was 9.6% (20/208) compared to 14.97% (28/187) for K. pneumoniae while resistance for ceftazidime/avibactam was 3.65% (5/137) and 5.98% (10/117), respectively. Genomic characteristics of 70 Enterobacterales including 48 carbapenem-resistant, revealed prevalence of ß-lactamases from all classes, predominated by blaCXM-15 while carbapenem resistance revealed paucity of blaKPC and dominance of blaOXA-48 and blaNDM resistance genes. Conclusions: Surveillance of GNB from Qatar showed prevalence of key pathogens similar to other regions but demonstrated significant resistance patterns to existing and novel antimicrobials with different underlying resistance mechanisms.

Prevalence and microbiological and genetic characteristics of multidrug-resistant Pseudomonas aeruginosa over three years in Qatar.

Objectives: Antimicrobial resistance (AMR) is a global priority with significant clinical and economic consequences. Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the major pathogens associated with significant morbidity and mortality. In healthcare settings, the evaluation of prevalence, microbiological characteristics, as well as mechanisms of resistance is of paramount importance to overcome associated challenges. Methods: Consecutive clinical specimens of P. aeruginosa were collected prospectively from 5 acute-care and specialized hospitals between October 2014 and September 2017, including microbiological, clinical characteristics and outcomes. Identification and antimicrobial susceptibility test were performed using the BD Phoenix identification and susceptibility testing system, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), and minimum inhibitory concentration (MIC) test strips. Overall, 78 selected MDR P. aeruginosa isolates were processed for whole-genome sequencing (WGS). Results: The overall prevalence of MDR P. aeruginosa isolates was 5.9% (525 of 8,892) and showed a decreasing trend; 95% of cases were hospital acquired and 44.8% were from respiratory samples. MDR P. aeruginosa demonstrated >86% resistance to cefepime, ciprofloxacin, meropenem, and piperacillin-tazobactam but 97.5% susceptibility to colistin. WGS revealed 29 different sequence types: 20.5% ST235, 10.3% ST357, 7.7% ST389, and 7.7% ST1284. ST233 was associated with bloodstream infections and increased 30-day mortality. All ST389 isolates were obtained from patients with cystic fibrosis. Encoded exotoxin genes were detected in 96.2% of isolates. Conclusions: MDR P. aeruginosa isolated from clinical specimens from Qatar has significant resistance to most agents, with a decreasing trend that should be explored further. Genomic analysis revealed the dominance of 5 main clonal clusters associated with mortality and bloodstream infections. Microbiological and genomic monitoring of MDR P. aeruginosa has enhanced our understanding of AMR in Qatar.

High platelet distribution width can independently predict testicular survival in testicular torsion among patients with steady-state sickle cell anemia.

Objective: This study aimed to evaluate the predictive value of platelet volume indices (PVI), such as mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT), as prognostic indicators of testicular viability in torsion patients with steady-state sickle cell anemia (SCA) who underwent surgical exploration. Methods: Forty-eight patients with SCA with testicular torsion and 46 male control subjects were enrolled in the study. All patients underwent scrotal color Doppler ultrasonography before surgery, and PVI (MPV, PDW, and PCT) values were measured in all participants. Symptom duration and testicular volume were also recorded. Results: The testicular salvage rate in patients with SCA was 73% after surgery. Analyses showed that MPV, PDW, and PCT values were significantly higher in torsed SCA as compared with controls (p<0.05). Orchiectomy in patients with SCA showed significantly higher MPV, PDW, and PCT values than the orchiopexy group (p<0.05). The MPV values of orchiectomy patients showed a higher significant cut-off of ≥11.5 fL, which is higher than in torsed patients without SCA, as an indicator of testis survival. PDW also demonstrated a higher significant cut-off of ≥12.7 fL for detorsion outcomes in patients with SCA. Symptom duration of less than 7 hours was also significantly correlated with orchiopexy (p≤0.001). Univariate analysis showed that higher MPV, increased PDW, and symptom duration were indicative of the outcome of testicular detorsion in SCA. Multivariable analysis showed that increased PDW and symptom duration are prognostic parameters for testicular viability in SCA. Conclusion: Increased PDW and symptom duration can be used as parameters for predicting testicular detorsion outcomes in patients with steady-state SCA.

Early-onset burdensome multimorbidity: an exploratory analysis of sentinel conditions, condition accrual sequence and duration of three long-term conditions using the 1970 British Cohort Study.

OBJECTIVES: The prevalence of multiple long-term condition (LTC) multimorbidity is increasing with younger onset among socioeconomically deprived populations. Research on life course trajectories towards multimorbidity is limited and early-onset multimorbidity poorly characterised. Understanding sentinel conditions (the first LTC occurring in the life course), the sequence of LTC accrual and the permanency of the reporting of LTCs may help identify time points for prevention efforts. We used a longitudinal birth cohort to estimate the prevalence of a common three-condition early-onset multimorbidity (multiple long-term condition multimorbidity (MLTC-M)) group at midlife, describe the frequency of sentinel conditions, the sequence of LTC accrual and explore the permanency of one of these conditions: psychological distress. SETTING: 1970 British Cohort Study (BCS70). PARTICIPANTS: 17 196 cohort members born in 1970. OUTCOME MEASURES: Prevalence of the most common three-condition multimorbidity group at age 46. The nature and timing of sentinel conditions, the sequencing patterns of subsequent LTC accrual and the permanency of the reporting of psychological distress. RESULTS: At age 46 high blood pressure, psychological distress and back pain were the most common three-condition MLTC-M group, (4.3%, n=370). A subgroup of 164 (44.3%) people provided complete information on LTC across all time points. Psychological distress measured by the Malaise Index was the most common sentinel condition, occurring in 25.0% (n=41), followed by back pain (22%, n=36). At age 26, 45.1% (75/164) reported their sentinel condition. The most common sequence of LTC accrual was the co-reporting of psychological distress and back pain followed by high blood pressure. Almost one-third (30.5%, n=50) reported a variation of psychological distress across the adult life course. CONCLUSION: In these exploratory analyses, psychological distress and back pain were the most common sentinel conditions, and along with high blood pressure these three conditions represented the most common three-condition MLTC-M group. These analyses suggest that birth cohorts, like the BCS70, may usefully inform life course-multimorbidity research.

Evaluation of in Vitro Activity of Ceftazidime/Avibactam and Ceftolozane/Tazobactam against ESBL-producing Enterobacterales Isolated from Intensive Care Units from Qatar.

Objectives: Extended-spectrum -lactamases (ESBLs) mechanism of resistance in Enterobacterales leads to poor clinical outcomes. Ceftazidime/avibactam and ceftolozane/tazobactam are two broad-spectrum antimicrobial combinations that are effective against multidrug-resistant organisms with regional variations. This study aims to evaluate the antimicrobial susceptibility test (AST) for both combinations against ESBL-producing Enterobacterales isolated from intensive care units (ICUs) in tertiary hospitals from November 2012 to October 2013 in Qatar. Methods: A total of 629 Enterobacterales isolates from ICUs were screened for ESBL production using BD-PhoenixTM confirmed by double-disk potentiation, while ESBL-genes were detected by polymerase chain reaction. The ASTs for ceftazidime/avibactam and ceftolozane/tazobactam were assessed by minimum inhibitory concentration (MIC) test strips. A single isolate that was resistant to both combinations was subjected to whole-genome sequencing. Results: The prevalence of ESBL-producing Enterobacterales isolated from ICUs was 17.3% (109/629) with predominance of Klebsiella pneumoniae (56/109; 51.4%) and Escherichia coli (38/109; 34.9%). The susceptibility of ceftazidime/avibactam and ceftolozane/tazobactam against ESBL-producers was 99.1% (108/109) and most (81/109; 74.3%) had MICs < 0.5 for both combinations. The predominant ESBL-gene was blaCTX-M (72/109; 66.1%). A single isolate that was resistant to both combinations harbored multiple ESBL resistant-genes including blaVEB-5 and blaVIM-2. Conclusions: ESBL-producing Enterobacterales isolated from ICUs were predominantly K. pneumoniae and E. coli, mainly harboring blaCTX-M gene. They were highly susceptible to ceftazidime/avibactam and ceftolozane/tazobactam suggesting potential alternatives to currently available therapeutic options.

COVID-19 Oximetry @home: evaluation of patient outcomes.

BACKGROUND: COVID-19 has placed unprecedented demands on hospitals. A clinical service, COVID-19 Oximetry @home (CO@h) was launched in November 2020 to support remote monitoring of COVID-19 patients in the community. Remote monitoring through CO@h aims to identify early patient deterioration and provide timely escalation for cases of silent hypoxia, while reducing the burden on secondary care. METHODS: We conducted a retrospective service evaluation of COVID-19 patients onboarded to CO@h from November 2020 to March 2021 in the North Hampshire (UK) community led service (a collaboration of 15 General Practitioner (GP) practices covering 230 000 people). We have compared outcomes for patients admitted to Basingstoke and North Hampshire Hospital who were CO@h patients (COVID-19 patients with home monitoring of oxygen saturation (SpO2; n=115), with non-CO@h patients (those directly admitted without being monitored by CO@h (n=633)). Crude and adjusted OR analysis was performed to evaluate the effects of CO@h on patient outcomes of 30-day mortality, Intensive care unit (ICU) admission and hospital length of stay greater than 3, 7, 14 and 28 days. RESULTS: Adjusted ORs for CO@h show an association with a reduction for several adverse patient outcome: 30-day hospital mortality (p<0.001, OR 0.21, 95% CI 0.08 to 0.47), hospital length of stay larger than 3 days (p<0.05, OR 0.62, 95% CI 0.39 to 1.00), 7 days (p<0.001, OR 0.35, 95% CI 0.22 to 0.54), 14 days (p<0.001, OR 0.22 95% CI, 0.11 to 0.41), and 28 days (p<0.05, OR 0.21, 95% CI 0.05 to 0.59). No significant reduction ICU admission was observed (p>0.05, OR 0.43, 95% CI 0.15 to 1.04). Within 30 days of hospital admission, there were no hospital readmissions for those on the CO@h service as opposed to 8.7% readmissions for those not on the service. CONCLUSIONS: We have demonstrated a significant association between CO@h and better patient outcomes; most notably a reduction in the odds of hospital lengths of stays longer than 7, 14 and 28 days and 30-day hospital mortality.

Association of blaVIM-2, blaPDC-35, blaOXA-10, blaOXA-488 and blaVEB-9 ß-Lactamase Genes with Resistance to Ceftazidime-Avibactam and Ceftolozane-Tazobactam in Multidrug-Resistant Pseudomonas aeruginosa.

Ceftazidime-avibactam and ceftolozane-tazobactam are approved for the treatment of complicated Gram-negative bacterial infections including multidrug-resistant (MDR) Pseudomonas aeruginosa. Resistance to both agents has been reported, but the underlying mechanisms have not been fully explored. This study aimed to correlate ß-lactamases with phenotypic resistance to ceftazidime-avibactam and/or ceftolozane-tazobactam in MDR-P. aeruginosa from Qatar. A total of 525 MDR-P. aeruginosa isolates were collected from clinical specimens between 2014 and 2017. Identification and antimicrobial susceptibility were performed by the BD PhoenixTM system and gradient MIC test strips. Of the 75 sequenced MDR isolates, 35 (47%) were considered as having difficult-to-treat resistance, and 42 were resistant to ceftazidime-avibactam (37, 49.3%), and/or ceftolozane-tazobactam (40, 53.3%). They belonged to 12 sequence types, with ST235 being predominant (38%). Most isolates (97.6%) carried one or more ß-lactamase genes, with blaOXA-488 (19%) and blaVEB-9 (45.2%) being predominant. A strong association was detected between class B ß-lactamase genes and both ceftazidime-avibactam and ceftolozane-tazobactam resistance, while class A genes were associated with ceftolozane-tazobactam resistance. Co-resistance to ceftazidime-avibactam and ceftolozane-tazobactam correlated with the presence of blaVEB-9, blaPDC-35, blaVIM-2, blaOXA-10 and blaOXA-488. MDR-P. aeruginosa isolates resistant to both combination drugs were associated with class B ß-lactamases (blaVIM-2) and class D ß-lactamases (blaOXA-10), while ceftolozane-tazobactam resistance was associated with class A (blaVEB-9), class C (blaVPDC-35), and class D ß-lactamases (blaOXA-488).

Clinical outcomes, molecular epidemiology and resistance mechanisms of multidrug-resistant Pseudomonas aeruginosa isolated from bloodstream infections from Qatar.

BACKGROUND: Bloodstream infections (BSIs) caused by multidrug-resistant (MDR)-Pseudomonas aeruginosa are associated with poor clinical outcomes, at least partly due to delayed appropriate antimicrobial therapy. The characteristics of MDR-P. aeruginosa bloodstream isolates have not been evaluated in Qatar. Our study aimed to examine in vitro susceptibility, clinical and molecular characteristics, and mechanisms of resistance of MDR-P. aeruginosa bloodstream isolates from Qatar. MATERIALS AND METHODS: We included all MDR-P. aeruginosa isolated from blood cultures taken between October 2014 and September 2017. Blood cultures were processed using BD BACTEC™ FX automated system. BD Phoenix™ was used for identification, Liofilchem® MIC Test Strips for MIC determination. Whole-genome sequencing was performed using the Illumina-HiSeq-2000. RESULTS: Out of 362 P. aeruginosa bloodstream isolates, 16 (4.4%) were MDR. The median patient age was 55 years (range 43-81) and all patients presented with septic shock. Most patients received meropenem (12/16) and/or colistin (10/16). Clinical response was achieved in eight patients, and five patients died within 30-days. MDR-P. aeruginosa isolates belonged to 13 different sequence types. All isolates were non-susceptible to cefepime and ciprofloxacin. The most active agents were colistin (16/16) and aztreonam (10/16). Seven isolates produced blaVIM, and four possessed genes encoding extended-spectrum ß-lactamases. Aminoglycoside modifying enzymes were present in 15/16, transferable qnr-mediated quinolone resistance gene was detected in 3/16, and the novel ciprofloxacin modifying enzyme CrpP-encoding gene in one isolate. CONCLUSION: MDR-P. aeruginosa BSIs are relatively uncommon in Qatar but are highly resistant, harbour multiple resistance genes, and are commonly associated with unfavourable clinical outcomes. Colistin was the only agent with consistent activity against the study isolates.Key messagesMDR-P. aeruginosa constituted <5% of P. aeruginosa blood isolates over three years.Typical risk factors for MDR infections were highly prevalent in the study population and overall clinical outcomes are consistent with those previously reported.Colistin was the only agent with consistent antibacterial activity against the study isolates.

ß-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar.

BACKGROUND: The distribution of ß-lactam resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. We used whole-genome sequencing (WGS) to identify the predominant sequence types (ST) and ß-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from Qatar METHODS: Microbiological identification and susceptibility tests were performed by automated BD Phoenix™ system and manual Liofilchem MIC Test Strips. RESULTS: Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n = 36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n = 21, 28%) and aztreonam (n = 16, 21.3%). All isolates possessed Class C and/or Class D ß-lactamases (n = 72, 96% each), while metallo-ß-lactamases were detected in 20 (26.7%) isolates. Eight (40%) metallo-ß-lactamase producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum ß-lactamases. High risk ST235 (n = 16, 21.3%), ST357 (n = 8, 10.7%), ST389 and ST1284 (6, 8% each) were most frequent. Nearly all ST235 isolates (15/16; 93.8%) were resistant to all tested ß-lactams. CONCLUSION: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal ß-lactams. High-risk STs are predominant in Qatar and their associated MDR phenotypes are a cause for considerable concern.