Contemporary Management and Outcomes of Veterans Hospitalized With Alcohol Withdrawal: A Multicenter Retrospective Cohort Study.

OBJECTIVES: Few studies describe contemporary alcohol withdrawal management in hospitalized settings or review current practices considering the guidelines by the American Society of Addiction Medicine (ASAM). METHODS: We conducted a retrospective cohort study of patients hospitalized with alcohol withdrawal on medical or surgical wards in 19 Veteran Health Administration (VHA) hospitals between October 1, 2018, and September 30, 2019. Demographic and comorbidity data were obtained from the Veteran Health Administration Corporate Data Warehouse. Inpatient management and hospital outcomes were obtained by chart review. Factors associated with treatment duration and complicated withdrawal were examined. RESULTS: Of the 594 patients included in this study, 51% were managed with symptom-triggered therapy alone, 26% with fixed dose plus symptom-triggered therapy, 10% with front loading regimens plus symptom-triggered therapy, and 3% with fixed dose alone. The most common medication given was lorazepam (87%) followed by chlordiazepoxide (33%), diazepam (14%), and phenobarbital (6%). Symptom-triggered therapy alone (relative risk [RR], 0.68; 95% confidence interval [CI], 0.57-0.80) and front loading with symptom-triggered therapy (RR, 0.75; 95% CI, 0.62-0.92) were associated with reduced treatment duration. Lorazepam (RR, 1.20; 95% CI, 1.02-1.41) and phenobarbital (RR, 1.28; 95% CI, 1.06-1.54) were associated with increased treatment duration. Lorazepam (adjusted odds ratio, 4.30; 95% CI, 1.05-17.63) and phenobarbital (adjusted odds ratio, 6.51; 95% CI, 2.08-20.40) were also associated with complicated withdrawal. CONCLUSIONS: Overall, our results support guidelines by the ASAM to manage patients with long-acting benzodiazepines using symptom-triggered therapy. Health care systems that are using shorter acting benzodiazepines and fixed-dose regimens should consider updating alcohol withdrawal management pathways to follow ASAM recommendations.

Establishing the safety of phenobarbital treatment of alcohol withdrawal syndrome on general medical wards: A retrospective cohort study.

INTRODUCTION: Concern about adverse effects from phenobarbital limits its use in treating alcohol withdrawal syndrome (AWS) on general medical wards. Benzodiazepines are the recommended treatment for inpatient management of AWS, yet a subset of patients have an inadequate response or experience complications of AWS despite treatment with benzodiazepines. Data supporting an alternative treatment are needed. We set out to estimate the rate of serious adverse events (SAEs) of phenobarbital treatment for AWS on general medical wards. METHODS: Retrospective cohort study of all general medical ward patients hospitalized at a single tertiary urban VA Medical Center from October 2018-May 2021 who received phenobarbital for treatment of AWS. Primary outcomes were SAEs attributed to phenobarbital and treatment failure. SAEs were defined as ICU transfer or intubation for over-sedation, pneumonia, and death. Treatment failure was defined as progression of withdrawal resulting in seizure, ICU transfer, behavioral emergencies, or death. RESULTS: During the study period, phenobarbital was administered in 29% (244) of all AWS hospitalizations. Among them, 93% had a history of AWS hospitalization and 68% had a history of complicated AWS. Fifty-three percent of patients met criteria for moderate, severe, or complicated withdrawal prior to phenobarbital initiation. The mean cumulative dose of phenobarbital per patient was 966.5 mg (13.6 mg/kg). SAEs occurred in 1 of 244 hospitalizations (0.4%): there were no intubations, ICU transfers for oversedation, or deaths due to phenobarbital or AWS. One case of pneumonia was possibly attributable to phenobarbital. Treatment failures (6 ICU transfers, 9 behavioral emergencies) were identified during 12 of 244 hospitalizations (4.9%). CONCLUSIONS: SAEs and treatment failures were infrequent among 148 patients treated with phenobarbital across 244 hospitalizations with a mean cumulative dose of 966.5 mg per patient. Our findings suggest that phenobarbital is a safe alternative treatment of AWS in general medical ward patients.

Alcohol-Related Hospitalizations During the Initial COVID-19 Lockdown in Massachusetts: An Interrupted Time-Series Analysis.

Background: The effect of initial COVID-19 pandemic-associated lockdowns on alcohol-related hospitalizations remains uncertain. This study compares alcohol-related hospitalizations at a US Department of Veterans Affairs (VA) system in Massachusetts before, during, and after the initial COVID-19 lockdown. Methods: This study is an interrupted time-series analysis at the VA Boston Healthcare System. Participants included all patients hospitalized on the medical, psychiatry, and neurology services at VA Boston Healthcare System from January 1, 2017, to December 31, 2020, excluding those under observation status. The period January 1, 2017, to March 9, 2020, was defined as prelockdown (the reference group); March 10, 2020, to May 18, 2020, was lockdown; and May 19, 2020, to December 31, 2020, was postlockdown. Alcohol-related hospitalizations were determined using International Statistical Classification of Diseases, Tenth Revision primary diagnosis codes. Results: We identified 27,508 hospitalizations during the study periods. There were 72 alcohol-related hospitalizations per 100,000 patient-months during the prelockdown period, 10 per 100,000 patient-months during the lockdown, and 46 per 100,000 patient-months in the postlockdown period. Compared with the prelockdown period, the adjusted rate ratio for daily alcohol-related hospitalizations during lockdown was 0.20 (95% CI, 0.10-0.39) vs 0.72 (95% CI, 0.57-0.92) after the lockdown. A similar pattern was observed for all-cause hospitalizations. Conclusions: Our results suggest that COVID-19 pandemic lockdown measures were associated with fewer alcohol-related hospitalizations. Proactive outreach for vulnerable populations during lockdowns is needed.

Report of a Novel Molecular Profile in Malignant Insulinoma.

Pancreatic neuroendocrine tumors, or pNETs, represent a rare and clinically heterogenous subset of pancreatic neoplasms. One such pNET, the insulinoma, is found to be malignant in just 4% of all insulinomas. Due to the exceedingly uncommon occurrence of these tumors, there is controversy regarding the optimal evidence-based management for these patients. We therefore report on a 70-year-old male patient admitted with 3 months of episodic confusion with concurrent hypoglycemia. The patient was found to have inappropriately elevated endogenous insulin levels during these episodes, and somatostatin-receptor subtype 2 selective imaging revealed a pancreatic mass metastatic to local lymph nodes, spleen, and the liver. Fine needle aspiration of pancreatic and liver lesions confirmed the diagnosis of a low grade pancreatic neuroendocrine tumor. Molecular analysis of tumor tissue revealed a novel mutational profile consistent with pNET. The patient was initiated on octreotide therapy. However, treatment with octreotide alone demonstrated limited efficacy in controlling the patient's symptoms, prompting consideration of other therapies.

Factors Associated With Severe COVID-19 Among Vaccinated Adults Treated in US Veterans Affairs Hospitals.

Importance: With a large proportion of the US adult population vaccinated against SARS-CoV-2, it is important to identify who remains at risk of severe infection despite vaccination. Objective: To characterize risk factors for severe COVID-19 disease in a vaccinated population. Design, Setting, and Participants: This nationwide, retrospective cohort study included US veterans who received a SARS-CoV-2 vaccination series and later developed laboratory-confirmed SARS-CoV-2 infection and were treated at US Department of Veterans Affairs (VA) hospitals. Data were collected from December 15, 2020, through February 28, 2022. Exposures: Demographic characteristics, comorbidities, immunocompromised status, and vaccination-related variables. Main Outcomes and Measures: Development of severe vs nonsevere SARS-CoV-2 infection. Severe disease was defined as hospitalization within 14 days of a positive SARS-CoV-2 diagnostic test and either blood oxygen level of less than 94%, receipt of supplemental oxygen or dexamethasone, mechanical ventilation, or death within 28 days. Association between severe disease and exposures was estimated using logistic regression models. Results: Among 110 760 patients with infections following vaccination (97 614 [88.1%] men, mean [SD] age at vaccination, 60.8 [15.3] years; 26 953 [24.3%] Black, 11 259 [10.2%] Hispanic, and 71 665 [64.7%] White), 10 612 (9.6%) had severe COVID-19. The strongest association with risk of severe disease after vaccination was age, which increased among patients aged 50 years or older with an adjusted odds ratio (aOR) of 1.42 (CI, 1.40-1.44) per 5-year increase in age, such that patients aged 80 years or older had an aOR of 16.58 (CI, 13.49-20.37) relative to patients aged 45 to 50 years. Immunocompromising conditions, including receipt of different classes of immunosuppressive medications (eg, leukocyte inhibitor: aOR, 2.80; 95% CI, 2.39-3.28) or cytotoxic chemotherapy (aOR, 2.71; CI, 2.27-3.24) prior to breakthrough infection, or leukemias or lymphomas (aOR, 1.87; CI, 1.61-2.17) and chronic conditions associated with end-organ disease, such as heart failure (aOR, 1.74; CI, 1.61-1.88), dementia (aOR, 2.01; CI, 1.83-2.20), and chronic kidney disease (aOR, 1.59; CI, 1.49-1.69), were also associated with increased risk. Receipt of an additional (ie, booster) dose of vaccine was associated with reduced odds of severe disease (aOR, 0.50; CI, 0.44-0.57). Conclusions and Relevance: In this nationwide, retrospective cohort of predominantly male US Veterans, we identified risk factors associated with severe disease despite vaccination. Findings could be used to inform outreach efforts for booster vaccinations and to inform clinical decision-making about patients most likely to benefit from preexposure prophylaxis and antiviral therapy.

Management of opioid use disorder, opioid withdrawal, and opioid overdose prevention in hospitalized adults: A systematic review of existing guidelines.

BACKGROUND: Hospitalizations related to the consequences of opioid use are rising. National guidelines directing in-hospital opioid use disorder (OUD) management do not exist. OUD treatment guidelines intended for other treatment settings could inform in-hospital OUD management. OBJECTIVE: Evaluate the quality and content of existing guidelines for OUD treatment and management. DATA SOURCES: OVID MEDLINE, PubMed, Ovid PsychINFO, EBSCOhost CINHAL, ERCI Guidelines Trust, websites of relevant societies and advocacy organizations, and selected international search engines. STUDY SELECTION: Guidelines published between January 2010 to June 2020 addressing OUD treatment, opioid withdrawal management, opioid overdose prevention, and care transitions among adults. DATA EXTRACTION: We assessed quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. DATA SYNTHESIS: Nineteen guidelines met the selection criteria. Most recommendations were based on observational studies or expert consensus. Guidelines recommended the use of nonstigmatizing language among patients with OUD; to assess patients with unhealthy opioid use for OUD using the Diagnostic Statistical Manual of Diseases-5th Edition criteria; use of methadone or buprenorphine to treat OUD and opioid withdrawal; use of multimodal, nonopioid therapy, and when needed, short-acting opioid analgesics in addition to buprenorphine or methadone, for acute pain management; ensuring linkage to ongoing methadone or buprenorphine treatment; referring patients to psychosocial treatment; and ensuring access to naloxone for opioid overdose reversal. CONCLUSIONS: Included guidelines were informed by studies with various levels of rigor and quality. Future research should systematically study buprenorphine and methadone initiation and titration among people using fentanyl and people with pain, especially during hospitalization.

Clinical guideline highlights for the hospitalist: 2020 American Society of Addiction Medicine clinical practice guideline on alcohol withdrawal management.

GUIDELINE TITLE: The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management RELEASE DATE: May 2020 PRIOR VERSION: 2004 American Society of Addiction Medicine guideline on management of alcohol withdrawal delirium DEVELOPER: American Society of Addiction Medicine FUNDING SOURCE: American Society of Addiction Medicine TARGET POPULATION: Adults hospitalized with alcohol withdrawal syndrome of any severity.

Disparities in United States hospitalizations for serious infections in patients with and without opioid use disorder: A nationwide observational study.

BACKGROUND: Patients with opioid use disorder (OUD) who are hospitalized for serious infections requiring prolonged intravenous antibiotics may face barriers to discharge, which could prolong hospital length of stay (LOS) and increase financial burden. We investigated differences in LOS, discharge disposition, and charges between hospitalizations for serious infections in patients with and without OUD. METHODS AND FINDINGS: We utilized the 2016 National Inpatient Sample-a nationally representative database of all discharges from US acute care hospitals. The population of interest was all hospitalizations for infective endocarditis, epidural abscess, septic arthritis, or osteomyelitis. The exposure was OUD, and the primary outcome was LOS until discharge, assessed by using a competing risks analysis to estimate adjusted hazard ratios (aHRs). Adjusted odds ratio (aOR) of discharge disposition and adjusted differences in hospital charges were also reported. Of 95,470 estimated hospitalizations for serious infections (infective endocarditis, epidural abscess, septic arthritis, and osteomyelitis), the mean age was 49 years and 35% were female. 46% had Medicare (government-based insurance coverage for people age 65+ years), and 70% were non-Hispanic white. After adjustment for potential confounders, OUD was associated with a lower probability of discharge at any given LOS (aHR 0.61; 95% CI 0.59-0.63; p < 0.001). OUD was also associated with lower odds of discharge to home (aOR 0.38; 95% CI 0.33-0.43; p < 0.001) and higher odds of discharge to a post-acute care facility (aOR 1.85; 95% CI 1.57-2.17; p < 0.001) or patient-directed discharge (also referred to as "discharge against medical advice") (aOR 3.47; 95% CI 2.80-4.29; p < 0.001). There was no significant difference in average total hospital charges, though daily hospital charges were significantly lower for patients with OUD. Limitations include the potential for unmeasured confounders and the use of billing codes to identify cohorts. CONCLUSIONS: Our findings suggest that among hospitalizations for some serious infections, those involving patients with OUD were associated with longer LOS, higher odds of discharge to post-acute care facilities or patient-directed discharge, and similar total hospital charges, despite lower daily charges. These findings highlight opportunities to improve care for patients with OUD hospitalized with serious infections, and to reduce the growing associated costs.

Experiential Learning Through Local Implementation of a National Chief Resident in Quality and Patient Safety Curriculum.

The Clinical Learning Environment Review was created to evaluate quality improvement and patient safety (QIPS) beginning in 2013. Little guidance has been offered on implementing QIPS curricula for residency education. The aim was to provide a model QIPS residency curriculum from VA Boston Healthcare System (VABHS), wherein a chief resident in quality and patient safety (CRQS) participates in a national curriculum implementing skills and concepts locally. The CRQS mentors a patient safety resident with faculty oversight. The program involves case investigations, educational conferences, and experiential learning. Participants are residents from Beth Israel Deaconess Medical Center, Boston Medical Center, and Brigham and Women's Hospital and medical students from Boston University Medical School and Harvard Medical School. Local and national CRQS programs are evaluated. The patient safety rotation is evaluated locally. The local curriculum at VABHS augments the national curriculum and deploys a patient safety education that develops experiential learning skills.

Safe Opioid Prescribing for Acute Noncancer Pain in Hospitalized Adults: A Systematic Review of Existing Guidelines.

BACKGROUND: Pain is common among hospitalized patients. Inpatient prescribing of opioids is not without risk. Acute pain management guidelines could inform safe prescribing of opioids in the hospital and limit associated unintended consequences. PURPOSE: To evaluate the quality and content of existing guidelines for acute, noncancer pain management. DATA SOURCES: The National Guideline Clearinghouse, MEDLINE via PubMed, websites of relevant specialty societies and other organizations, and selected international search engines. STUDY SELECTION: Guidelines published between January 2010 and August 2017 addressing acute, noncancer pain management among adults were considered. Guidelines that focused on chronic pain, specific diseases, and the nonhospital setting were excluded. DATA EXTRACTION: Quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. DATA SYNTHESIS: Four guidelines met the selection criteria. Most recommendations were based on expert consensus. The guidelines recommended restricting opioids to severe pain or pain that has not responded to nonopioid therapy, using the lowest effective dose of short-acting opioids for the shortest duration possible, and co-prescribing opioids with nonopioid analgesics. The guidelines generally recommended checking the prescription drug monitoring program when prescribing opioids, developing goals for patient recovery, and educating patients regarding the risks and side effects of opioid therapy. Additional recommendations included using an opioid dose conversion guide, avoidance of co-administration of parenteral and oral opioids, and using caution when co-prescribing opioids with other central nervous system depressants. CONCLUSIONS: Guidelines, based largely on expert opinion, recommend judicious prescribing of opioids for severe, acute pain. Future work should assess the implications of these recommendations on hospital-based pain management.

The 60-Minute Root Cause Analysis: A Workshop to Engage Interdisciplinary Clinicians in Quality Improvement.

Introduction: We created a standardized workshop to engage residents in quality improvement (QI) using the root cause analysis model. The workshop allows for a robust learning experience while providing solutions derived from clinicians to address important local problems. No prerequisite knowledge or experience is required. Methods: The workshop is facilitated by one or more moderators, ideally with experience in QI. An interdisciplinary group of residents, medical students, nurses, and other attendees comprise an audience which actively engages in workshop activities. Facilitators follow a scripted model to teach important patient safety concepts with frequent break-outs for hands-on application of QI tools. During the workshop, participants create a process map and fishbone diagram, as well as develop and critically evaluate novel interventions. Results: Over the course of one academic year, the workshop has been implemented 17 times with roughly 25 internal medicine residents in attendance at each workshop. In addition, the workshop was run online for 126 participants with varied exposure to QI techniques. Forty percent of these participants completed a survey indicating that over 89% learned something new, 87% felt they could apply the material to their work, and 95% would recommend the workshop to a colleague. Discussion: This 60-minute workshop can provide hands-on QI experience in a standardized format to achieve the dual objectives of teaching QI to clinicians and allowing them to generate innovations. The module can be used for internal case development and trainee participation, but prepared cases are provided for facilitators without the resources for local case development.

Inpatient Management of Opioid Use Disorder: A Review for Hospitalists.

The United States is experiencing an epidemic of nonmedical opioid use and opioid overdose-related deaths. As a result, there have been a number of public health interventions aimed at addressing this epidemic. However, these interventions fail to address care of individuals with opioid use disorder during hospitalizations and, therefore, miss a key opportunity for intervention. The role of hospitalists in managing hospitalized patients with opioid use disorder is not established. In this review, we discuss the inpatient management of individuals with opioid use disorder, including the treatment of withdrawal, benefits of medication-assisted treatment, and application of harm-reduction strategies. Journal of Hospital Medicine 2017;12:369-374.

Hospitalizations Related To Opioid Abuse/Dependence And Associated Serious Infections Increased Sharply, 2002-12.

Serious infection is a recognized complication of intravenous drug abuse and a major cause of morbidity and mortality among intravenous drug users. Trends in rates of serious infection and the associated costs related to opioid abuse/dependence have not been previously investigated in the context of the US opioid use epidemic. Our study, using a nationally representative sample of US inpatient hospitalizations, showed that hospitalizations related to opioid abuse/dependence both with and without associated serious infection significantly increased from 2002 to 2012, respectively, from 301,707 to 520,275 and from 3,421 to 6,535. Additionally, inpatient charges for both types of hospitalizations almost quadrupled over the same time period, reaching almost $15 billion for hospitalizations related to opioid abuse/dependence and more than $700 million for those related to associated infection in 2012. Medicaid was the most common primary payer for both types of hospitalizations. Our results characterize the financial burden on the health care system related to opioid abuse/dependence and one of the more serious downstream complications of this epidemic: serious infection. These findings have important implications for the hospitals and government agencies that disproportionately shoulder these costs and for clinicians, researchers, and policy makers interested in estimating the potential impact of targeted public health interventions on a national level.

Enhancement of the recombinagenic and mutagenic activities of bleomycin in yeast by intercalation of acridine compounds into DNA.

Strain D7 of Saccharomyces cerevisiae was used to measure the induction by bleomycin (BLM) of mitotic recombination at the trp5 locus and point mutations at ilv1 in the presence and absence of acridine compounds. BLM is a potent mutagen and recombinagen in the D7 assay. The acridines vary, some being mutagenic or recombinagenic and others not. Combined treatments were used to distinguish whether a genetically inactive acridine has no effect on the genetic activity of BLM or modulates its action. When an acridine is itself genetically active, combined treatments were used to determine whether its effects are additive with those of BLM or whether there is interaction between the two compounds. Acridine compounds that share the ability to intercalate between the base pairs of DNA but differ in their mutagenic specificity owing to the presence of different substituent groups were analysed. Clear potentiation and synergistic interactions were detected in combined treatments with BLM and aminoacridines, nitroacridines or an acridine mustard. Potentiation and synergy were also observed in sequential exposures in which the yeast were grown in the presence of acridine compounds and then treated with BLM in the absence of free acridine. The results are consistent with an increase in BLM susceptibility conferred by acridine intercalation. It is likely that the intercalating agents increase the access of BLM to the minor groove of DNA, where it abstracts a hydrogen from the 4' position of deoxyribose, creating a free radical that is processed into strand breaks.

Modulation of the genotoxicity of bleomycin by amines through noncovalent DNA interactions and alteration of physiological conditions in yeast.

The effects of amines on the induction of mitotic gene conversion by bleomycin (BLM) were studied at the trp5 locus in Saccharomyces cerevisiae strain D7. BLM induces double-strand breaks in DNA and is a potent recombinagen in this assay. The polyamine spermidine causes concentration-dependent protection against the genotoxicity of BLM, reducing the convertant frequency by over 90% under the most protective conditions. Spermine, diethylenetriamine, ethylenediamine, putrescine, and ethylamine were also antigenotoxic in combined treatments with BLM. There was a general correspondence between the protective effect and the number of amino groups, suggesting that more strongly cationic amines tend to be stronger antirecombinagens. Electrostatic association of the amines with DNA probably hinders BLM access to the 4' position of deoxyribose where it generates a free radical. Other amines interact with BLM differently from these unbranched aliphatic amines. The aminothiol cysteamine inhibits the genotoxicity of BLM under hypoxic conditions but increases it under euoxic conditions. In contrast, pargyline potentiates the genotoxicity of BLM under hypoxic conditions but not under euoxic conditions. The antirecombinagenic effect of cysteamine apparently involves DNA binding and depletion of oxygen needed for BLM activity, whereas its potentiation of BLM entails its serving as an electron source for the activation of BLM. Pargyline may enhance BLM indirectly by preventing the depletion of oxygen by monoamine and polyamine oxidase. The planar 9-aminoacridine weakly induces gene conversion in strain D7, but it is strongly synergistic with BLM. Enhancement of BLM activity by this compound and by the related nitroacridine Entozon is apparently mediated by intercalation of the acridine ring system into DNA. Thus, the influence of amines on the genotoxicity of BLM in yeast encompasses antigenotoxic, potentiating, and synergistic interactions. The underlying mechanisms involve noncovalent association with DNA, altered BLM access to DNA, and modulation of physiological conditions.