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While opioid use confers a known risk for respiratory depression, the incremental risk of in-hospital cardiopulmonary arrest, respiratory arrest, or cardiopulmonary resuscitation (CPRA) has not been studied. Our aim was to investigate the prevalence, outcomes, and risk profile of in-hospital CPRA for patients receiving opioids and medications with central nervous system sedating side effects (sedatives). A retrospective analysis of adult inpatient discharges from 2008-2012 reported in the Premier Database. Patients were grouped into four mutually exclusive categories: (1) opioids and sedatives, (2) opioids only, (3) sedatives only, and (4) neither opioids nor sedatives. Among 21,276,691 inpatient discharges, 53% received opioids with or without sedatives. A total of 96,554 patients suffered CPRA (0.92 per 1000 hospital bed-days). Patients who received opioids and sedatives had an adjusted odds ratio for CPRA of 3.47 (95% CI: 3.40-3.54; p<0.0001) compared with patients not receiving opioids or sedatives. Opioids alone and sedatives alone were associated with a 1.81-fold and a 1.82-fold (p<0.0001 for both) increase in the odds of CPRA, respectively. In opioid patients, locations of CPRA were intensive care (54%), general care floor (25%), and stepdown units (15%). Only 42% of patients survived CPRA and only 22% were discharged home. Opioid patients with CPRA had mean increased hospital lengths of stay of 7.57 days and mean increased total hospital costs of $27,569. Opioids and sedatives are independent and additive risk factors for in-hospital CPRA. The impact of opioid sparing analgesia, reduced sedative use, and better monitoring on CPRA incidence deserves further study.

Sepsis is one of the leading causes of acute kidney injury (AKI). Septic patients who develop acute kidney injury (AKI) are at increased risk of death. To date there is no effective treatment for AKI or septic AKI. Based on their anti-inflammatory properties, we examined the effects of nicotinic acetylcholine receptor agonists on renal damage using a mouse model of lipopolysaccharide (LPS)-induced AKI where localized LPS promotes inflammation-mediated kidney damage. Administration of nicotine (1 mg/kg) or GTS-21 (4 mg/kg) significantly abrogated renal leukocyte infiltration (by 40%) and attenuated kidney injury. These renoprotective effects were accompanied by reduced systemic and localized kidney inflammation during LPS-induced AKI. Consistent with these observations, nicotinic agonist treatment significantly decreased renal IκBα degradation and NFκB activation during LPS-induced AKI. Treatment of human kidney cells with nicotinic agonists, an NFκB inhibitor (Bay11), or a proteasome inhibitor (MG132) effectively inhibited their inflammatory responses following stimulation with LPS or TNFα. Renal proteasome activity, a major regulator of NFκB-mediated inflammation, was enhanced by approximately 50% during LPS-induced AKI and elevated proteasome activity was significantly blunted by nicotinic agonist administration in vivo. Taken together, our results identify enhanced renal proteasome activity during LPS-induced AKI and the suppression of both proteasome activity and inflammation by nicotinic agonists to attenuate LPS-induced kidney injury.

•Cystic Fibrosis is a multisystem disease that affects 30,000 people in the United States.•The average life expectancy for CF patients in the United States is 45.2years.•Anesthesiologists are increasing faced with the challenge of anesthetic management of these patients.•Massive hemoptysis can be a lethal complication of CF under general endotracheal anesthesia.•Two cases of intraoperative massive hemoptysis in adult CF patients are described.

There are many sources of contamination in the perioperative environment. Patient experience can be negatively affected by the presence of environmental contamination, especially if it is the cause of a surgical site infection. Perioperative and environmental services staff members and leaders are tasked with ensuring a clean and safe environment for their patients while maintaining an awareness of time and budgetary constraints. In addition, leaders are responsible for the competency of their staff members and must address performance issues when needed. New technological advances designed to streamline monitoring and reporting processes related to OR cleanliness are available for use. This article describes the quality improvement project that one multifacility organization completed related to the use of remote video auditing and the positive effect it had on the organization's environmental contamination.

To identify whether adding intrathecal ketamine to intrathecal bupivacaine prolongs the time to first analgesic request in adult humans. A meta-analysis of randomized controlled trials in humans. The majority of data was obtained in an operating room and postoperative recovery area. A total of 750 ASA physical status I and II patients were included in the study. Procedures performed include: cesarean section, lower abdominal surgery, lower limb surgery, and urologic surgery. Databases including PubMed, Embase, Web of Science, and Cochrane were searched. Google Scholar was also queried. Multiple reviewers screened the papers for inclusion. The primary outcome assessed was time to first analgesic request. Secondary outcomes included onset of sensory blockade, onset of motor blockade, duration of sensory blockade, and duration of motor blockade. Data were extracted to include means, 95% confidence intervals, tests for heterogeneity, and use of the Cochrane Collaboration guidelines to assess for publication bias. Eleven randomized controlled trials met inclusion criteria. When comparing intrathecal bupivacaine plus ketamine to intrathecal bupivacaine alone, the time to first analgesic request was prolonged (effect size = 58.23 min (95% CI 37.36 to 79.10) p < 0.0001). Secondary outcomes showed the onset time of sensory blockade was shortened (effect size = −0.87 min (95% CI -1.361 to 0.378) p = 0.0005), the onset time of motor blockade was reduced (effect size = −0.88 min (95% CI -1.77 to 0.013) p = 0.05), the duration of sensory blockade was prolonged (effect size = 39.73 min (95% CI 15.97 to 63.50) p = 0.001), and the duration of motor blockade was prolonged (effect size = 4.02 min (95% CI 3.27 to 4.78) p < 0.0001). Studies were shown to have high heterogeneity. Egger tests for all outcomes were non-significant and funnel plots assessing publication bias were all asymmetrical. The studies analyzed suggest there may be a benefit to using intrathecal ketamine as an adjunct to bupivacaine. Additional studies are warranted to optimize dosing, clarify the safety and efficacy of this intrathecal drug combination, and examine the various ketamine formulations as intrathecal bupivacaine adjuvants. •Single dose intrathecal injection of both bupivacaine and ketamine can be combined for multimodal analgesia•Perioperative intrathecal ketamine and bupivacaine may improve analgesia compared to intrathecal bupivacaine alone•Intrathecal ketamine and bupivacaine statistically and clinically prolonged the time to first analgesic request•Additional studies are warranted to investigate intrathecal ketamine as an adjuvant to intrathecal bupivacaine in humans

The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families 1 , 2 . We localized the disease gene to 16q12–21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3 ). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion.

Most colonoscopies are completed in the left lateral (LL) position but in cases of suboptimal caecal preparation, changing the patient's position to supine (S) and, if needed, to right lateral (RL) improves caecal intubation rate, mucosal visibility, and adenoma detection. To determine if position change during colonoscopy facilitates optimal visualisation of the caecum. A total of 359 patients were grouped into three categories based on the initial caecal intubation position. After caecal intubation, caecal visibility was scored on a four-point scale depending on the number of imaginary quadrants of the caecum completely visualized - Arya Caecal Prep Score. A score of 1 or 2 was unsatisfactory, while 3 or 4 was considered satisfactory. In patients with unsatisfactory score, position was changed from LL to S and then RL and visibility was scored again. The initial caecal intubation in the LL position was achieved in 66.8% of patients, S in 28.5%, and RL in 4.8% of patients. 84.5% (300/355) of patients had an acceptable visualisation score at the initial caecal intubation position. Of the 55 patients with unsatisfactory caecum visualisation scores in the initial intubation position, 30 (8.5%) had satisfactory scores after the first position change (95% CI: 5.77-11.84). Twenty-five (7.04%) subjects required two position changes (95% CI: 4.61-10.22%). An additional 9.3% (11/118) of adenomas were detected in caecum and ascending colon following position change. Changing patient position improves caecal intubation rate, mucosal visibility, and adenoma detection.

Advances in the digitization of health systems and expedited regulatory approvals of innovative treatments have led to increased potential for the use of real-world data (RWD) to generate real-world evidence (RWE) to complement evidence from clinical trials. However, health technology assessment (HTA) bodies and payers have concerns about the ability to generate RWE of sufficient quality to be pivotal evidence of relative treatment effectiveness. Consequently, there is a growing need for HTA bodies and payers to develop guidance for the industry and other stakeholders about the use of RWD/RWE to support access, reimbursement, and pricing. We therefore sought to (i) understand barriers to the use of RWD/RWE by HTA bodies and payers; (ii) review potential solutions in the form of published guidance; and (iii) review findings with selected HTA/payer bodies. Four themes considered key to shaping the generation of robust RWE for HTA bodies and payers were identified as: (i) data (availability, governance, and quality); (ii) methodology (design and analytics); (iii) trust (transparency and reproducibility); and (iv) policy and partnerships. A range of guidance documents were found from trusted sources that could address these themes. These were discussed with HTA experts. This commentary summarizes the potential guidance solutions available to help resolve issues faced by HTA decision-makers in the adoption of RWD/RWE. It shows that there is alignment among stakeholders about the areas that need improvement in the development of RWE and that the key priority to move forward is better collaboration to make data usable for multiple purposes.

ImportanceCompliance with the surgical safety checklist during operative procedures has been shown to reduce inhospital mortality and complications but proper execution by the surgical team remains elusive.ObjectiveWe evaluated the impact of remote video auditing with real-time provider feedback on checklist compliance during sign-in, time-out and sign-out and case turnover times.Design, settingProspective, cluster randomised study in a 23-operating room (OR) suite.ParticipantsSurgeons, anaesthesia providers, nurses and support staff.ExposureORs were randomised to receive, or not receive, real-time feedback on safety checklist compliance and efficiency metrics via display boards and text messages, followed by a period during which all ORs received feedback.Main outcome(s) and measure(s)Checklist compliance (Pass/Fail) during sign-in, time-out and sign-out demonstrated by (1) use of checklist, (2) team attentiveness, (3) required duration, (4) proper sequence and duration of case turnover times.ResultsSign-in, time-out and sign-out PASS rates increased from 25%, 16% and 32% during baseline phase (n=1886) to 64%, 84% and 68% for feedback ORs versus 40%, 77% and 51% for no-feedback ORs (p<0.004) during the intervention phase (n=2693). Pass rates were 91%, 95% and 84% during the all-feedback phase (n=2001). For scheduled cases (n=1406, 71%), feedback reduced mean turnover times by 14% (41.4 min vs 48.1 min, p<0.004), and the improvement was sustained during the all-feedback period. Feedback had no effect on turnover time for unscheduled cases (n=587, 29%).Conclusions and relevanceOur data indicate that remote video auditing with feedback improves surgical safety checklist compliance for all cases, and turnover time for scheduled cases, but not for unscheduled cases.