Risk Factors for Falls Among Hospitalized Medical Patients - A Systematic Review and Meta-analysis.

OBJECTIVE: To identify and quantify risk factors for in-hospital falls in medical patients. DATA SOURCES: Six databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, and Google Scholar) were systematically screened until April 11, 2023, to identify relevant articles. STUDY SELECTION: All titles and abstracts of the retrieved articles were independently screened by 2 researchers who also read the full texts of the remaining articles. Quantitative studies that assessed risk factors for falls among adult patients acutely hospitalized were included in the review. Publications that did not capture internal medicine patients or focused on other specific populations were excluded. DATA EXTRACTION: Information on study characteristics and potential risk factors were systematically extracted. Risk of bias was assessed using the Quality in Prognosis Studies tool. Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analyses of Observational Studies in Epidemiology guidelines were followed for reporting. DATA SYNTHESIS: The main outcome was any in-hospital falls. Using a random-effects meta-analysis model, association measures for each risk factor reported in 5 or more studies were pooled. Separate analyses according to effect measure and studies adjusted for sex and age at least were performed. Of 5067 records retrieved, 119 original publications from 25 countries were included. In conclusion, 23 potential risk factors were meta-analyzed. Strong evidence with large effect sizes was found for a history of falls (odds ratio [OR], 2.54; 95% confidence interval [CI], 1.63-3.96; I2, 91%), antidepressants (pooled OR, 2.25; 95% CI, 1.92-2.65; I2, 0%), benzodiazepines (OR, 1.97; 95% CI, 1.68-2.31; I2, 0%), hypnotics-sedatives (OR, 1.90; 95% CI, 1.53-2.36; I2, 46%), and antipsychotics (OR, 1.61; 95% CI, 1.33-1.95; I2, 0%). Furthermore, evidence of associations with male sex (OR, 1.22, 95% CI, 0.99-1.50; I2, 65%) and age (OR, 1.17, 95% CI, 1.02-1.35; I2, 72%) were found, but effect sizes were small. CONCLUSIONS: The comprehensive list of risk factors, which specifies the strength of evidence and effect sizes, could assist in the prioritization of preventive measures and interventions.

Opioid and CNS-Depressant Medication Prescribing among Older Adults Enrolled in Medicare Advantage Versus Fee-for-Service Medicare.

OBJECTIVE: To examine whether prescription fills of opioids and central nervous system (CNS) depressants are lower in Medicare Advantage (MA) plans, which aim to provide more coordinated and integrated care, than fee-for-service (FFS) Medicare. METHODS: Data from the 2015 National Health and Aging Trends Study linked with Medicare claims. Community-dwelling adults ≥65 enrolled in Medicare Part D were included (n = 5,652). Prescription fills of opioids, antipsychotics, benzodiazepines, gabapentinoids, and co-prescriptions of opioids with the other medications in MA versus FFS Medicare were examined using multivariate logistic models. Propensity score weighting was applied to account for differences in characteristics between MA and FFS beneficiaries. RESULTS: MA enrollees were less likely to fill prescriptions for benzodiazepines (15.6% versus 19.0%; marginal difference: -3.4%, t = -2.54, df = 56, p = 0.01), and co-prescriptions of opioids and gabapentinoids (5.1% versus 6.7%; marginal difference: -1.6%, t = -2.07, df = 56, p = 0.04) than FFS beneficiaries. There were no significant differences among the other prescription outcomes. CONCLUSIONS: MA was associated with slightly lower likelihood of receiving opioids and some CNS depressants.

Prevalence and characteristics of patients prescribed opioids and central nervous system depression agents on discharge to hospice care.

BACKGROUND: Hospice patients with end-stage liver disease (ESLD) have an increased risk of adverse drug events due to physiological changes and changes in pharmacokinetic and pharmacodynamic properties of medications; however, the use of opioid and central nervous system (CNS) depressant prescribing among patients with ESLD is prevalent. This study quantified the frequency and distribution of opioid and concomitant respiratory and CNS depressant prescribing among hospice patients with ESLD compared to other common hospice diagnoses of cancer, chronic obstructive pulmonary disorder (COPD), heart failure, and end-stage renal disease. METHODS: This was a cross-sectional study of adult (age 18 years or older) decedents of a large hospice chain. Patients included had a primary diagnosis of liver, cancer, cardiovascular, or respiratory disease. RESULTS: Among 119,424 hospice decedents, mean age of 77.9 years (standard deviation =13.5 years), 54.6% were female, and 58.9% were of a non-Hispanic white race. There was a similar frequency of prescribing a "scheduled" and "as needed [pro re nata (PRN)]" opioid or benzodiazepine in patients with ESLD compared to other common hospice diagnoses. In addition, there was a high prevalence of concurrent opioid and benzodiazepine prescriptions among patients with ESLD compared to cardiovascular and respiratory disease at admission (65.4% vs. 63.9% and 64.9%). Opioid requirements, oral morphine equivalent (OME) median [interquartile range (IQR)] at discharge were similar between cancer, liver, and respiratory disease, 120 OME [60-300], 120 OME [50-240], and 120 OME [50-240], respectively. CONCLUSIONS: We observed a high frequency of opioid and CNS depressant prescribing in a hospice patient population with ESLD which was similar to other common admitting hospice diagnoses.

Cognitive impairment following sedative overdose.

INTRODUCTION: Patients with sedative overdose may have residual cognitive impairment at the time they are deemed medically cleared for discharge. Impairment could affect the performance of high-risk activities, including driving. The Trail Making Test is an alpha-numeric assessment that can be performed at the bedside to assess cognitive function. We examined whether there were differences in cognitive function when medically cleared between patients that overdosed on sedative and non-sedative drugs. METHODS: A prospective, observational study assessed cognitive function using the Trail Making Test between 2018 and 2021. Patients (16 years and greater) completed testing upon medical clearance if they spoke English and had no previous neurological injury. Continuous covariates were compared using t-tests or Mann-Whitney U tests and multiple linear regression; binary variables were modelled using logistic regression. RESULTS: Of 171 patients enrolled, 111 (65 per cent) had sedative overdose; they were older (median 32.1 versus 22.2 years) and more likely to be male (58.6 per cent versus 36.7 per cent). Benzodiazepines and paracetamol were the commonest drug overdoses. Patients with sedative overdose performed worse on Trail Making Test part A (37.0 versus 33.1 seconds, P = 0.017) and Trail Making Test part B (112.4 versus 81.5 seconds, P = 0.004). Multiple linear regression analysis indicated that patient age (P < 0.001, 1.7 seconds slower per year, 95 per cent confidence interval: 0.9-2.6 seconds) and perception of recovery (P = 0.006, 36.4 seconds slower if perceived not recovered, 95 per cent confidence interval: 10.8-62.0 seconds) were also associated with Trail Making Test part B times. Patients with sedative overdose were more likely to be admitted to the intensive care unit (Odds Ratio: 4.9, 95 percent confidence interval: 1.1-22.0; P = 0.04). DISCUSSION: Our results are broadly in keeping with previously published work, but include a wider range of drug overdose scenarios (polypharmacy and recreational drugs). While patients demonstrated some perception of their cognitive impairment, our model could not reliably be used to provide individual discharge advice. The study design did not allow us to prove causation of cognitive impairment, or to make comparison between the strength of an overdose to the trail making test time. CONCLUSIONS: Trail Making Test results suggested that patients who had sedative drug overdoses may have significant cognitive deficits even when medically cleared. Risk of harm may be minimised with advice to avoid high-risk activities such as driving. More profound impacts seen on the Trail Making Test part B than A may mean higher-order thinking is more affected than simple cognitive function.

Aging out of the federal dependent coverage mandate and purchases of prescription drugs with high rates of misuse.

Prescription central nervous system depressants, opioid pain relievers, and stimulants provide therapeutic value, but misuse for their recreational value is a growing problem in the United States. Because health insurance lowers the cost of purchasing prescription drugs, losing coverage may cause individuals to forgo treatment and decrease prescription drug consumption which could reduce health and increase the likelihood of overdose and death if individuals substitute to using illicit drugs. I estimate the reduced form effect of aging out of the federal dependent coverage mandate at age 26 on legal purchases of prescription central nervous system depressants, opioids, and stimulants. Individuals are 0.5-0.9% points less likely to purchase a prescription central nervous system depressant and 0.8-1.5% points less likely to purchase a prescription opioid after turning 26. These effects are strongest for women, while estimated effects for men are generally negative but imprecise.

Outpatient Off-Label Gabapentin Use for Psychiatric Indications Among U.S. Adults, 2011-2016.

OBJECTIVE: Gabapentin is widely prescribed off label in medical practice, including psychiatry. The U.S. Food and Drug Administration (FDA) warned of risks associated with gabapentin combined with central nervous system depressant (CNS-D) drugs, which are commonly prescribed in psychiatric treatment. This study examined off-label outpatient gabapentin use for psychiatric indications and concomitant CNS-D medication use. METHODS: National Ambulatory Care Medical Survey data (2011-2016) were used to identify encounters involving gabapentin (gabapentin visits) for adults (ages ≥18) (N=5,732). FDA-approved uses and off-label psychiatric use indications were identified with ICD-9-CM and ICD-10-CM diagnosis codes. CNS-D drugs examined were opioids, benzodiazepines, sedatives-hypnotics, antidepressants, antipsychotics, first-generation antihistamines, and skeletal muscle relaxants. Concomitance was prescription of one or more CNS-D medications at the same visit. Visits were stratified by provider type and specialty. RESULTS: Between 2011 and 2016, 2.8% of visits listed gabapentin prescriptions (weighted estimate of 129.6 million visits). A small proportion (<1%) listed an FDA-approved indication. Among off-label gabapentin visits, 5.3% listed a depressive disorder, 3.5% an anxiety disorder, and 1.8% bipolar disorder. Over 6 years, 58.4% of off-label gabapentin visits listed one or more concomitant CNS-D medications, most frequently antidepressants (24.3%), opioids (22.9%), and benzodiazepines (17.3%). Most gabapentin visits were with primary care providers (34.9%) and other provider specialties (i.e., not primary care, neurology, or psychiatry) (48.1%). CONCLUSION: In this nationally representative sample, <1% of outpatient gabapentin use was for approved indications. High concomitant use of CNS-D drugs and off-label gabapentin for psychiatric diagnoses underlines the need for improved communication about safety.

The Physiology and Maintenance of Respiration: A Narrative Review.

Chronic pain is one of the most common reasons adults seek medical care and is often managed with opioid analgesics; however, opioids may cause respiratory depression by suppressing various components of respiration. Respiration is the physiological process that facilitates gas exchange and is mediated through the proper function of and communication among central neural control (respiratory drive), sensory input systems, the lungs, and the muscles involved in respiration. Normal respiratory function can be dampened with the use of central nervous system (CNS) depressants and/or underlying health conditions. Patients with chronic pain are often exposed to CNS depressants other than opioids, including benzodiazepines, barbiturates, nonbenzodiazepine sedative-hypnotics, and ethanol, which can function synergistically with opioids to increase the risk of respiratory depression. Some patients may also have underlying health issues, such as obstructive sleep apnea, that can be exacerbated with the use of opioids and other CNS depressants and further contribute to respiratory depression. Clinicians should have a thorough understanding of respiration, recognize how various CNS depressants suppress it, and take necessary steps to mitigate the risk of opioid-induced respiratory depression by collaborating with a multidisciplinary team (i.e., sleep and pain specialists), choosing appropriate medications, and educating patients on the proper use and storage of opioids.

Association between Use of Methadone, Other Central Nervous System Depressants, and QTc Interval-Prolonging Medications and Risk of Mortality in a Large Cohort of Women Living with or at Risk for Human Immunodeficiency Virus Infection.

STUDY OBJECTIVE: To evaluate the association between use of methadone, other central nervous system (CNS) depressants, and QTc interval-prolonging medications and risk of mortality among human immunodeficiency virus (HIV)-infected and at-risk HIV-uninfected women. DESIGN: Multicenter, prospective, observational cohort study (Women's Interagency HIV Study [WIHS]). PARTICIPANTS: A total of 4150 women enrolled in the WIHS study between 1994 and 2014 who were infected (3119 women) or not infected (1031 women) with HIV. MEASUREMENTS AND MAIN RESULTS: Data on medication utilization were collected from all study participants via interviewer-administered surveys at 6-month intervals (1994-2014). Mortality was confirmed by National Death Index data. With age defining the time scale for the analysis, Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality in HIV-infected and -uninfected women and non-acquired immunodeficiency syndrome (AIDS) deaths in HIV-infected women. A total of 1046 deaths were identified, of which 429 were considered non-AIDS deaths. Use of benzodiazepines, CNS depressants (excluding methadone), and number of medications with conditional QTc interval-prolonging effects were each associated with all-cause mortality in multivariate models of HIV-infected women: hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.60, p=0.037; HR 1.61, 95% CI 1.35-1.92, p<0.0001; and HR 1.15 per drug, 95% CI 1.00-1.33, p=0.047, respectively. Other explanatory variables for all-cause mortality in this model included HIV viral load, CD4+  cell count, renal function, hemoglobin and albumin levels, HIV treatment era, employment status, existence of depressive symptoms, ever use of injection drugs, and tobacco smoking. Of interest, use of CNS depressants (excluding methadone) was also associated with non-AIDS deaths (HR 1.49, 95% CI 1.49-2.2, p<0.0001). Although use of benzodiazepines and conditional QT interval-prolonging medications were associated with increased risk of non-AIDS mortality (HR 1.32 and 1.25, respectively), the effect was not statistically significant (p>0.05). CONCLUSION: In this cohort of HIV-infected and at-risk HIV-uninfected women, use of benzodiazepines, CNS depressants, and conditional QTc interval-prolonging medications were associated with a higher risk of mortality independent of methadone and other well-recognized mortality risk factors. Care must be taken to assess risk when prescribing these medications in this underserved and at-risk patient population.

Chloral Hydrate Overdose Survived after Cardiac Arrest with Excellent Response to Intravenous ß-blocker.

Chloral hydrate (CH) poisoning is not commonly seen in the emergency department. CH is a commonly prescribed sedative agent for various day care procedures despite its toxic profile even when other safe sedative medications are available. We report a case of CH poisoning that manifested with neurotoxicity followed by cardiotoxicity leading to cardiac arrest. With a high index of suspicion and proper management, our patient was discharged with normal neurological outcome. In this case report, we discuss CH poisoning and toxicity with highlights on specific intervention including ß-blockers. CH induced arrhythmias have been reported to be refractory to the standard antiarrhythmic medications and respond well to ß-blockers.

Understanding the pathophysiology behind febrile convulsions.

The most common background to hyperpyrexia and convulsions is immaturity of the child's physiological reactions to infection, so an understanding of the pathophysiology of pyrexia and febrile convulsions in young children enables nurses to take appropriate action. Correct management involves prompt recognition of rising temperature, administration of antipyretic medication, use of other cooling strategies and careful monitoring. Diagnosis of the underlying cause occasionally requires laboratory investigation, if no focus for infection is found, most cases being viral.