DESIGN: Retrospective cohort study.
SETTING: Operation theater with postoperative inpatient follow-up.
PATIENTS: The medical records of 315 patients who underwent sequential bilateral TKA were reviewed.
INTERVENTIONS: Patients who received intrathecal levobupicavaine 0.5% were compared with patients who received hyperbaric bupivacaine 0.5% with fentanyl 25 μg for spinal anesthesia.
MEASUREMENTS: The primary outcome was the use of rescue analgesia (systemic opioids, conversion to general anesthesia) during surgery for both groups. Secondary outcomes included adverse effects of local anesthetics (hypotension and bradycardia) during surgery and morbidity related to spinal anesthesia (postoperative nausea, vomiting, and bleeding) during hospital stay.
MAIN RESULTS: One hundred fifty patients who received intrathecal levobupivacaine 0.5% (group L) were compared with 90 patients given hyperbaric bupivacaine 0.5% with fentanyl 25 μg (group B). The mean volume of levobupivacaine administered was 5.8 mL (range, 5.0-6.0 mL), and that of bupivacaine was 3.8 mL (range, 3.5-4.0 mL). Both groups achieved similar maximal sensory level of block (T6). The time to maximal height of sensory block was significantly shorter in group B than group L, 18.2 ± 4.5 vs 23.9 ± 3.8 minutes (P< .001). The time to motor block of Bromage 3 was also shorter in group B (8.7 ± 4.1 minutes) than group L (16.0 ± 4.5 minutes) (P< .001). Patients in group B required more anesthetic supplement than group L (P< .001). Hypotension and postoperative bleeding were significantly less common in group L than group B.
CONCLUSION: Levobupivacaine at a higher dosage provided longer duration of spinal anesthesia with better safety profile in sequential bilateral TKA.
OBJECTIVES: In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of β-lactam antibiotics.
METHODS: We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of β-lactam antibiotics in critically ill patients with severe sepsis. We assessed the quality of the studies according to four criteria. We combined individual patient data from studies and assessed data integrity for common baseline demographics and study endpoints, including hospital mortality censored at 30 days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis.
MEASUREMENTS AND MAIN RESULTS: We identified three randomized controlled trials in which researchers recruited a total of 632 patients with severe sepsis. The two groups were well balanced in terms of age, sex, and illness severity. The rates of hospital mortality and clinical cure for the continuous versus intermittent infusion groups were 19.6% versus 26.3% (relative risk, 0.74; 95% confidence interval, 0.56-1.00; P = 0.045) and 55.4% versus 46.3% (relative risk, 1.20; 95% confidence interval, 1.03-1.40; P = 0.021), respectively. In a multivariable model, intermittent β-lactam administration, higher Acute Physiology and Chronic Health Evaluation II score, use of renal replacement therapy, and infection by nonfermenting gram-negative bacilli were significantly associated with hospital mortality. Continuous β-lactam administration was not independently associated with clinical cure.
CONCLUSIONS: Compared with intermittent dosing, administration of β-lactam antibiotics by continuous infusion in critically ill patients with severe sepsis is associated with decreased hospital mortality.
METHODS: A comprehensive search was conducted in CENTRAL, MEDLINE, SCOPUS, Google Scholars, World Health Organization Trials Portal, ClinicalTrials.gov, Clinical Trial Registry of India, and AYUSH Research Portal for all appropriate trials. Randomized controlled trials that examined the effect of Ashwagandha extract versus placebo on sleep in human participants 18 years old and above were considered. Two authors independently read all trials and independently extracted all relevant data. The primary outcomes were sleep quantity and sleep quality. The secondary outcomes were mental alertness on rising, anxiety level, and quality of life.
RESULTS: A total of five randomized controlled trials containing 400 participants were analyzed. Ashwagandha extract exhibited a small but significant effect on overall sleep (Standardized Mean Difference -0.59; 95% Confidence Interval -0.75 to -0.42; I2 = 62%). The effects on sleep were more prominent in the subgroup of adults diagnosed with insomnia, treatment dosage ≥600 mg/day, and treatment duration ≥8 weeks. Ashwagandha extract was also found to improve mental alertness on rising and anxiety level, but no significant effect on quality of life. No serious side effects were reported.
CONCLUSION: Ashwagandha extract appears to has a beneficial effect in improving sleep in adults. However, data on the serious adverse effects of Ashwagandha extract are limited, and more safety data would be needed to assess whether it would be safe for long-term use.
SUMMARY: Background Nonacog beta pegol is a recombinant glycoPEGylated factor IX with an extended half-life, developed to improve care for patients with hemophilia B. Objectives To investigate the safety, efficacy and pharmacokinetics of nonacog beta pegol for the prophylaxis and treatment of bleeds in previously treated children with hemophilia B. Patients/Methods This phase 3 trial, paradigm(™) 5, enrolled and treated 25 children (aged ≤ 12 years) with hemophilia B (FIX ≤ 2%). Patients were stratified by age (0-6 years and 7-12 years), and received once-weekly prophylaxis with 40 IU kg(-1) nonacog beta pegol for 50 exposure days. Results No patient developed inhibitors, and no safety concerns were identified. Forty-two bleeds in 15 patients were reported to have been treated; the overall success rate was 92.9%, and most bleeds (85.7%) resolved after one dose. The median annualized bleeding rates (ABRs; bleeds per patient per year) were 1.0 in the total population, 0.0 in the 0-6-year group, and 2.0 in the 7-12-year group; the estimated mean ABRs were 1.44 in the total population, 0.87 in the 0-6-year group, and 1.88 in the 7-12-year group. For 22 patients who had previously been receiving prophylaxis, the estimated mean ABR was 1.38 versus a historical ABR of 2.51. Estimated mean steady-state FIX trough levels were 0.153 IU mL(-1) (0-6 years) and 0.190 IU mL(-1) (7-12 years). Conclusion Nonacog beta pegol was well tolerated in previously treated children with hemophilia B; a 40 IU kg(-1) dose provided effective once-weekly prophylaxis and hemostasis when bleeds were treated.
DESIGN: Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration.
METHODS: Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the 'intention-to-treat' effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting.
RESULTS: A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens.
CONCLUSIONS: Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine.