Efficacy and safety of Ciprofol compared with Propofol during general anesthesia induction: A systematic review and meta-analysis of randomized controlled trials (RCT).

BACKGROUND: Ciprofol, a newer entrant with similarities to propofol, has shown promise with a potentially improved safety profile, making it an attractive alternative for induction of general anesthesia. This meta-analysis aimed to assess the safety and efficacy of ciprofol compared with propofol during general anesthesia induction. METHODS: A comprehensive literature search was conducted using PubMed, Clinical Trial.gov, and Cochrane Library databases from inception to July 2023 to identify relevant studies. All statistical analyses were conducted using R statistical software version 4.1.2. RESULTS: Thirteen Randomized Controlled Trials (RCTs) encompassing a total of 1998 participants, were included in our analysis. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for postoperative hypertension, bradycardia, or tachycardia. CONCLUSION: In conclusion, Ciprofol is not inferior to Propofol in terms of its effectiveness in general anesthesia. Ciprofol emerges as a valuable alternative sedative with fewer side effects, especially reduced injection pain, when compared to Propofol. SUMMARY: Propofol, frequently utilized as an anesthetic, provides swift onset and quick recovery. However, it has drawbacks such as a narrow effective dosage range and a high occurrence of adverse effects, particularly pain upon injection. Ciprofol, a more recent drug with propofol-like properties, has demonstrated promise and may have an improved safety profile, making it a compelling alternative for inducing general anesthesia. This meta-analysis compared the safety and effectiveness of Ciprofol with Propofol for general anesthesia induction in a range of medical procedures, encompassing thirteen Randomized Controlled Trials (RCTs) and 1998 individuals. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for hypertension, bradycardia, or tachycardia. In conclusion, ciprofol is equally effective at inducing and maintaining general anesthesia as propofol. When compared to propofol, ciprofol is a better alternative sedative for operations including fiberoptic bronchoscopy, gynecological procedures, gastrointestinal endoscopic procedures, and elective surgeries because it has less adverse effects, most notably less painful injections.

Risk Prediction Models for Hospital Mortality in General Medical Patients: A Systematic Review.

Objective: To systematically review contemporary prediction models for hospital mortality developed or validated in general medical patients. Methods: We screened articles in five databases, from January 1, 2010, through April 7, 2022, and the bibliography of articles selected for final inclusion. We assessed the quality for risk of bias and applicability using the Prediction Model Risk of Bias Assessment Tool (PROBAST) and extracted data using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist. Two investigators independently screened each article, assessed quality, and extracted data. Results: From 20,424 unique articles, we identified 15 models in 8 studies across 10 countries. The studies included 280,793 general medical patients and 19,923 hospital deaths. Models included 7 early warning scores, 2 comorbidities indices, and 6 combination models. Ten models were studied in all general medical patients (general models) and 7 in general medical patients with infection (infection models). Of the 15 models, 13 were developed using logistic or Poisson regression and 2 using machine learning methods. Also, 4 of 15 models reported on handling of missing values. None of the infection models had high discrimination, whereas 4 of 10 general models had high discrimination (area under curve >0.8). Only 1 model appropriately assessed calibration. All models had high risk of bias; 4 of 10 general models and 5 of 7 infection models had low concern for applicability for general medical patients. Conclusion: Mortality prediction models for general medical patients were sparse and differed in quality, applicability, and discrimination. These models require hospital-level validation and/or recalibration in general medical patients to guide mortality reduction interventions.

Remdesivir-induced conduction abnormalities: A molecular model-based explanation.

Purpose: Remdesivir use in COVID-19 is associated with cardiac conduction abnormalities from unclear mechanisms. A proposed mechanism is the bioaccumulation of the intermediate metabolite GS-441524 resulting in exogenous activation of cardiac adenosine A1 due to the structural similarity between adenosine and GS-441524. The prolonged half-life of GS-441524 can result in sustained activation of adenosine A1 receptors. In this study, we used molecular modeling of adenosine, GS-441524 and the adenosine A1 receptor to assess the potential mechanistic association of the proposed mechanism. Methods: Adenosine and GS-441524 structures were acquired from the PubChem database. Ligand docking was carried out using UCSF Chimera. Models were chosen based on greatest binding affinity and minimum root mean square deviation. Figures of resulting structural models were prepared using UCSF Chimera or PyMOL 2.3.5. Results: By modeling the interaction between the A1 G protein complex and both adenosine and GS-441524, we found that the proposed mechanism of exogenous A1 receptor activation is feasible based on docking compatibility. Conclusion: The proposed mechanism of exogenous cardiac A1 receptor activation from bioaccumulation of GS-441524 as a cause of observed cardiac conduction abnormalities with the use of remdesivir in COVID-19 is viable. Further studies are needed to assess causality.

Assessing Naltrexone Prescribing and Barriers to Initiation for Alcohol Use Disorder: A Multidisciplinary, Multisite Survey.

Objective: To survey barriers in prescribing naltrexone for alcohol use disorder. Methods: A 12-question survey related to naltrexone prescribing patterns, perceptions, and knowledge was sent to 770 prescribers in the departments of internal medicine, family medicine, and psychiatry across a health system with sites in Arizona, Florida, and Minnesota. Results: Responses were obtained and included for 146/770 prescribers (19.0% response rate). Most respondents were in the department of internal medicine (n = 94, 64.4%), but the departments of psychiatry (n = 22, 15.1%) and family medicine (n = 30, 20.5%) were also represented. Only 34 (23.3%) respondents indicated they had prescribed naltrexone in the previous 3 months. The most common reasons for not prescribing naltrexone were "unfamiliarity with naltrexone for treatment of alcohol use disorder" and "patients do not have appropriate follow-up or are not in a formal treatment program." Compared with those representing internal/family medicine, psychiatry respondents were more likely to prescribe naltrexone and answer knowledge questions correctly. Conclusion: In this survey among primarily non-addiction-trained prescribers, a disparity was shown for prescribing naltrexone and in knowledge barriers between staff in internal/family medicine and psychiatry. There exist opportunities for education and quality improvement that promote the prescribing of naltrexone for alcohol use disorder by non-addiction specialists.

Medications and Patient Factors Associated With Increased Readmission for Alcohol-Related Diagnoses.

OBJECTIVE: To investigate medication factors and patient characteristics associated with readmissions following alcohol-related hospitalizations. PATIENTS AND METHODS: Adult patients admitted from September 1, 2016, through August 31, 2019, who had an alcohol-related hospitalization were identified through electronic health records. Patient characteristics and medications of interest administered during hospitalization or prescribed at discharge were identified. Medications of interest included US Food and Drug Administration-approved medications for alcohol use disorder, benzodiazepines, barbiturates, gabapentin, opioids, and muscle relaxants. The primary outcome was to identify medications and patient factors associated with 30-day alcohol-related readmission. Secondary outcomes included medications and patient characteristics associated with multiple alcohol-related readmissions within a year from the index admission (ie, two or more readmissions) and factors associated with 30-day all-cause readmission. RESULTS: Characteristics of the 932 patients included in this study associated with a 30-day alcohol-related readmission included younger age, severity of alcohol withdrawal, history of psychiatric disorder, marital status, and the number of prior alcohol-related admission in the previous year. Benzodiazepine or barbiturate use during hospitalization or upon discharge was associated with 30-day alcohol-related readmission (P=.006). Gabapentin administration during hospitalization or upon discharge was not associated with 30-day alcohol-related readmission (P=.079). CONCLUSION: The findings reinforce current literature identifying patient-specific factors associated with 30-day readmissions. Gabapentin use was not associated with readmissions; however, there was an association with benzodiazepine/barbiturate use.

Relative Age Effect on Problematic Alcohol Use in Adolescents.

Objective: Relative age refers to a difference in age between peers in the same academic year. Although younger age of alcohol use is associated with a higher risk of lifetime problematic alcohol use, the potential effects of relative age are poorly understood. We hypothesized that a younger relative age would be associated with a younger chronological age of testing positive for alcohol in a medical setting. Methods: Problematic alcohol use was operationalized and identified as a positive alcohol test (PAT) in a medical setting. This was a retrospective population study of all 12 to 18-year-old residents (n = 4610) of Olmsted County, Minnesota (USA), who were tested for alcohol in a medical care setting from 1998 through 2016. Cox regression models examined the relationship between relative age and the age at testing positive for alcohol. Results: Relative age was not associated with age at first PAT. Results remained nonsignificant after stratifying by gender, and after adjusting for race, number of nonalcohol-related psychiatric comorbidities, and type of alcohol testing. Conclusions: The results did not support a relative age effect as a risk factor for alcohol use in adolescents in Olmsted County, Minnesota. These results contrast with findings from previous studies on this topic, which suggested older relative age increases risk of alcohol use in adolescence.

Naltrexone Initiation in the Inpatient Setting for Alcohol Use Disorder: A Systematic Review of Clinical Outcomes.

Alcohol use disorder (AUD) is a highly prevalent health issue in the United States. The number of those receiving medication-assisted treatment (MAT) is limited, despite strong evidence for their effectiveness. The inpatient setting may represent an important opportunity to initiate MAT. The goal of this study was to summarize the data on naltrexone initiation in the emergency department or inpatient setting for the management of AUDs. We searched ClinicalTrials.gov, Ovid EBM Reviews, Ovid Embase, Ovid Medline, Ovid PsycINFO, Scopus, and Web of Science from inception through October 31, 2019. Search strategies were created using a combination of keywords (Supplemental Appendix 1, available online at http://www.mcpiqojournal.org) and standardized index terms related to naltrexone therapy for medically hospitalized patients with AUD. Two uncontrolled pre-post study designs evaluated naltrexone prescription rates, 30-day readmission rates, and rehospitalization rates. Two authors independently abstracted data on study characteristics, results, and study-level risk of bias. The research team collaborated to assess the strength of evidence across studies. Two studies reported that implementing a protocol for naltrexone initiation increased MAT rates, with one study noting a substantial decrease in 30-day hospital readmissions. Overall, we found that there is a paucity of data on naltrexone initiation in the inpatient setting for AUDs. This likely reflects the nature of current clinical practice and prescriber comfortability. There is a need for further studies evaluating MAT initiation in the inpatient setting. Furthermore, efforts to increase provider knowledge of these therapeutic options are in need of further exploration.

Spiritual Care of Inpatients Focusing on Outcomes and the Role of Chaplaincy Services: A Systematic Review.

OBJECTIVE: To identify demographic trends associated with patient utilization and healthcare provider request for spiritual care services and to describe the impact of spiritual care on the quality of life (QoL), spiritual well-being (SWB) and level of satisfaction (SAT) of hospitalized patients. PATIENTS AND METHODS: A systematic search of Ovid MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, was combined with review of relevant bibliographies. A total of 464 titles and abstracts were reviewed. Data were independently extracted by reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data on the effects of spiritual interventions on QoL, SWB and SAT were extracted, along with demographic data reflecting chaplain services. The results of the studies are presented narratively and in a qualitative manner. RESULTS: Observational or experimental studies investigating chaplain utilization demographics (n = 12), patient satisfaction (n = 9) and QoL/SWB (n = 3) were included. Perceived severity of illness, average length of stay and older age were consistently found to be predictors of higher need for spiritual care. Receipt of spiritual care was correlated with increased patient and family satisfaction, independent of clinical outcome. Chaplain interventions were associated with improvement in perceived QoL and SWB. In spite of this, healthcare workers rarely attempt to explore the patient's or family's need for spiritual care, with the majority of chaplaincy consults occurring in the final day of the patient's life, potentially leading to a failure to meet the spiritual needs of non-terminal patients who have spiritual trauma related to their resolving illnesses. CONCLUSION: Attention to the spiritual needs of hospitalized patients is an essential yet often overlooked aspect of patient care. Chaplains serve as spiritual care specialists whose services can enhance the hospital experience, improve patient satisfaction and help to bridge potential gaps between the patient and medical providers.

Role of gut microbiota in cardiovascular diseases.

The human gut is colonized by a community of microbiota, primarily bacteria, that exist in a symbiotic relationship with the host. Intestinal microbiota-host interactions play a critical role in the regulation of human physiology. Deleterious changes to the composition of gut microbiota, referred to as gut dysbiosis, has been linked to the development and progression of numerous diseases, including cardiovascular disease (CVD). Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites, including trimethylamine-N-oxide and short-chain fatty acids, that may facilitate the development of CVD. This article reviews the normal function and composition of the gut microbiome, mechanisms leading to the leaky gut syndrome, its mechanistic link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. As CVD is the leading cause of deaths globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research.

Demystifying airline syncope.

Syncope forms a major part of medical in-flight emergencies contributing one-in-four in-flight medical events accounting to 70% of flight diversions. In such patients, it is important to elucidate the pathophysiology of syncope prior to diversion. Postural hypotension is the most common etiology of in-flight syncopal events. However, individuals without any underlying autonomic dysfunction can still experience syncope from hypoxia also known as airline syncope. Initial steps in managing such patients include positioning followed by the airway, breathing and circulation of resuscitation. These interventions need to be in close coordination with ground control to determine decision for flight diversion. Interventions which have been tried for prevention include mental challenge and increased salt and fluid intake. The current paper enhances the understanding of airline syncope by summarizing the associated pathophysiologic mechanisms and the management medical personnel can initiate with limited resources.

Venous Thromboembolism Prophylaxis: Need for Continuous Assessment Due to Changes in Risk During the Same Hospitalization.

OBJECTIVE: To explore the role of venous thromboembolism (VTE) risk reassessment in hospitalized medically ill patients without a change in level of care. PATIENTS AND METHODS: In this exploratory retrospective study, the medical records of 171 consecutive adult patients (≥18 years) hospitalized under the medicine service for more than 3 days without a change in the level of care from January 1, 2015, to March 1, 2015, were reviewed. The primary outcome was a change in the risk score between day 1 and day 3 of hospital stay (using the Padua Prediction Score). The secondary outcomes were changes in risk stratification class (low vs high) and cost-benefit analysis. RESULTS: The risk score was significantly different between day 1 and day 3 (4.7±1.7 vs 4.2±1.8; P=.008). All the patients with low risk on day 1 remained at low risk on day 3. However, 25 of 136 patients (18.4%) with high risk on day 1 were reclassified as low risk on day 3 (P<.001). No patients changed from low risk to high risk at day 3. The reclassification could have saved $35 per patient-day of inappropriate pharmacological prophylaxis in addition to patient discomfort, bleeding risk, and heparin-induced thrombocytopenia. CONCLUSION: This is the first study to suggest the need for regular assessment for VTE risk on medicine wards because of changing patient risk. Regular reassessment could reduce health care waste and patient discomfort.

Lumbar and thoracic perforators: vascular anatomy and clinical implications.

BACKGROUND: Pedicled perforator flaps in the thoracic and lumbar regions allow reconstruction of the posterior trunk. They enable reconstruction of various local defects without microvascular anastomoses and with minimal donor-site morbidity and excellent cosmesis. The authors examined the locations of perforators in the lumbar and thoracic regions. METHODS: Ten cadaver hemithoraces and lumbar regions were freshly harvested and dissected. Intraarterial injections were performed with colored latex, followed by dissection in the suprafascial plane. Perforators with a diameter larger than 0.5 cm were located and measured from the midline and from C7 (thoracic) and coccygeal (lumbar) reference points. The most dominant perforators were injected with radiopaque dye and scanned with high-resolution computed tomography. The patterns were analyzed by the quadrat counting test (based on chi-square statistics) for the null hypothesis of complete spatial randomness. RESULTS: A total of 164 thoracic and 216 lumbar perforators were identified. These were clustered in highest density in two major areas within 10 to 20 cm of the C7 and coccygeal reference points and 10 cm from the midline; this pattern was not a random distribution (p < 0.001). Perforasomes of lumbar perforators in some instances crossed the midline, joining adjacent contralateral lumbar perforators by means of direct and indirect linking vessels. CONCLUSIONS: Lumbar and thoracic pedicled perforator flaps provide useful options for reconstructing complex defects. Use of these flaps is aided by anatomical knowledge of the location of major clusters of perforators.