Death by Detox: Substance Withdrawal, a Possible Death Row for Individuals in Custody.

Suffering through substance withdrawal is a major problem for the majority of individuals in custody, yet there are no guidelines or standards to ensure their safety. Instead, individuals in custody are having their Constitutional rights violated and many die at the hands of the justice system. When their families seek accountability for the lack of adequate care provided by correctional facilities and employees, families are faced with a lack of consistency from one circuit to the next for knowing as to the correct standard to have a successful claim. Strain v. Regalado was a chance for the Supreme Court to address this issue, but by denying cert in that case, the Court has signed off on the injustice these individuals face. This note proposed having the subjective prong for the deliberate indifference claim for inadequate medical care for withdrawal for individuals in custody presumed. Allowing the subjective prong to be presumed better aligns with the reality of this issue because correctional officers see many inmates suffering withdrawal and the symptoms which indicate the need for medical intervention are similar to those that would indicate a medical need in any other situation. Additionally, correctional officers are purportedly held to a higher standard. This note then proposed a federal standard for claims and medical care. These are both basic rights in the United States, unless and until a person is in custody.

Alcohol withdrawal syndrome in ICU patients: Clinical features, management, and outcome predictors.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is a common condition in hospitalized patients, yet its epidemiology in the ICU remains poorly characterized. METHODS: Retrospective cohort of patients admitted to the Nantes University Hospital ICU between January 1, 2017, and December 31, 2019, and coded for AWS using ICD-10 criteria. The objective of the study was to identify factors associated with complicated hospital stay defined as ICU length of stay ≥7 days or hospital mortality. RESULTS: Among 5,641 patients admitted to the ICU during the study period, 246 (4.4%) were coded as having AWS. Among them, 42 had exclusion criteria and 204 were included in the study. The three main reasons for ICU admission were sepsis (29.9%), altered consciousness (29.4%), and seizures (24%). At ICU admission, median Cushman's score was 6 [4-9] and median SOFA score was 3 [2-6]. Delirium tremens occurred in half the patients, seizures in one fifth and pneumonia in one third. Overall, 48% of patients developed complicated hospital stay, of whom 92.8% stayed in the ICU for ≥7 days, 36.7% received MV for ≥7 days, and 16.3% died during hospital stay. By multivariable analysis, two factors were associated with complicated hospital stay: a higher number of organ dysfunctions at ICU admission was associated with a higher risk of complicated hospital stay (OR, 1.18; 95CI, 1.05-1.32, P = 0.005), whereas ICU admission for seizures was associated with a lower risk of complicated hospital stay (OR, 0.14; 95%CI, 0.026-0.80; P = 0.026). CONCLUSIONS: AWS in ICU patients chiefly affects young adults and is often associated with additional factors such as sepsis, trauma, or surgery. Half the patients experienced an extended ICU stay or death during the hospital stay. The likelihood of developing complicated hospital stay relied on the reason for ICU admission and the number of organ dysfunctions at ICU admission.

Suspension of ulipristal acetate for uterine fibroids during ongoing EMA's review of liver injury risk: Unfortunate timing during the Covid-19 pandemic!

OBJECTIVE: EMA decided that with ulipristal acetate (UPA) treatment for uterine fibroids, should be discontinued due to the associated risk of hepatic failure, We analyzed whether the risk of recurrent symptoms due to fibroids may lead to an increased risk of Covid -19 infection and death, that would exceed the former risk of hepatic failure and transplantation. STUDY DESIGN, SIZE, DURATION: We used a Markov model to generate probabilities. PARTICIPANTS/MATERIALS, SETTING, METHODS: There are currently about 36,250 treated patients in Europe. We estimated bleeding probabilities, while using or discontinuing UPA, which may induce a need of medical or surgical management in symptomatic patients, and increase the risk of acquiring a Covid-19 infection, and die from it. We also estimated the risk of suffering a hepatic failure and hepatic transplantation. MAIN RESULTS AND THE ROLE OF CHANCE: Based on our assumptions, ceasing UPA during a Covid 19 pandemic may be associated with a fatality ratio between 4 and 18, due to the Pandemic, whereas pursuing UPA would be associated with a fatality rate due to the pandemic between 1-2, and an added fatality rate due to hepatic impairment of 1. The added risk of stopping UPA may range between 2 and 15 additional deaths. Our calculations suggest that the decision to stop UPA in the middle of the Covid- 19 pandemic may be untimely, since it may result in an increased risk of Covid-19 infection, due to the recurrence of symptoms and the need for medical and surgical treatment. WIDER IMPLICATIONS OF THE FINDINGS: A decision, like the one EMA took need to be taken in a wider health context of a population, than simply analyzing its role as regulating agent for medications.

A prospective evaluation of thiamine and magnesium status in relation to clinicopathological characteristics and 1-year mortality in patients with alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is routinely treated with B-vitamins. However, the relationship between thiamine status and outcome is rarely examined. The aim of the present study was to examine the relationship between thiamine and magnesium status in patients with AWS. METHODS: Patients (n = 127) presenting to the Emergency Department with AWS were recruited to a prospective observational study. Blood samples were drawn to measure whole blood thiamine diphosphate (TDP) and serum magnesium concentrations. Routine biochemistry and haematology assays were also conducted. The Glasgow Modified Alcohol Withdrawal Score (GMAWS) measured severity of AWS. Seizure history and current medications were also recorded. RESULTS: The majority of patients (99%) had whole blood TDP concentration within/above the reference interval (275-675 ng/gHb) and had been prescribed thiamine (70%). In contrast, the majority of patients (60%) had low serum magnesium concentrations (< 0.75 mmol/L) and had not been prescribed magnesium (93%). The majority of patients (66%) had plasma lactate concentrations above 2.0 mmol/L. At 1 year, 13 patients with AWS had died giving a mortality rate of 11%. Male gender (p < 0.05), BMI < 20 kg/m2 (p < 0.01), GMAWS max ≥ 4 (p < 0.05), elevated plasma lactate (p < 0.01), low albumin (p < 0.05) and elevated serum CRP (p < 0.05) were associated with greater 1-year mortality. Also, low serum magnesium at time of recruitment to study and low serum magnesium at next admission were associated with higher 1-year mortality rates, (84% and 100% respectively; both p < 0.05). CONCLUSION: The prevalence of low circulating thiamine concentrations were rare and it was regularly prescribed in patients with AWS. In contrast, low serum magnesium concentrations were common and not prescribed. Low serum magnesium was associated more severe AWS and increased 1-year mortality.

The maximum alcohol withdrawal syndrome score associates with worse clinical outcomes-A retrospective cohort study.

BACKGROUND: The Wetterling alcohol withdrawal syndrome (AWS) scale determines withdrawal severity and guides treatment. We investigated associations between maximum AWS scores and clinical outcomes. METHODS: This retrospective cohort study considered AWS assessments measured from 8/2015-8/2017. We used multivariable linear and logistic regression to analyze associations between the maximum score and increased length of stay (LOS) and in-hospital mortality, respectively. Firstly, we investigated the maximum score of all AWS assessments any time during the stay, secondly, the maximum measured only within the first 3 days of withdrawal. RESULTS: A total of 2,464 hospital stays showed that, patients with "mild" (<6), "moderate" (6-9), and "severe" (>9) maximum scores had median LOS of 5.93, 9.35, 14.71 days, mortality was 1.7%, 4.8%, 8.0%, respectively. Regression showed that a higher maximum score was independently associated with increased LOS and mortality (both p < 0.001). Based on the maximum AWS score within the first 3 days, the median LOS was 6.18, 9.00, 12.89 days, mortality was 2.2%, 3.6%, 7.6%, respectively. A higher maximum score in the first 3 days was independently associated with increased LOS (p = 0.036) and mortality (p = 0.001). Severe maximum AWS scores within 3 days of withdrawal had an odds ratio of 2.53 (95% CI: 1.27, 4.82; p = 0.0060) for in-hospital death. CONCLUSIONS: Maximum AWS scores associate independently with increased LOS and in-hospital mortality. This association is reproducible within the first 3 days of withdrawal. Development of such a 3-day tool could help clinicians assess the risk of worse clinical outcomes early on and adjust care accordingly.

Comparison of In-Hospital Outcomes of Patients With-Versus-Without Atrial Fibrillation and Alcohol Withdrawal Syndrome.

Alcohol withdrawal syndrome (AWS) has been associated with significant medical complications and length of stay. Cardiovascular effects from AWS include a physiologic tachycardia and hypertensive response. Although atrial fibrillation (AF) is one of the most common arrhythmias, the impact of a known history of AF on AWS is unclear. The purpose of our study is to assess the impact of history of AF on clinical outcomes, cost, and length of stay on AWS. The Nationwide Inpatient Sample was used to identify patients aged 18 years or older who underwent AWS with or without AF using the International Classification of Disease 9 Clinical Modification codes from January 2010 to December 2014. Outcomes were compared between those with or without AF using propensity score method-stratified morbidity ratio weighing- to adjust for baseline patient and hospital characteristics. A total of 280,451 patients with AWS of which 14,459 (5.2%) had history of AF. Patients with AF was older, less likely female, and more had higher burden of co-morbidities. In an adjusted model, in-hospital mortality (odds ratio [OR] 1.98 95% confidence interval [CI] 1.61 to 2.45), ischemic stroke (OR 1.67 95% CI 1.42 to 1.95), acute kidney injury (OR 1.36 95% CI 1.24 to 1.49), acute kidney injury requiring dialysis (OR 1.89 95% CI 1.39 to 2.50), and cost (mean ratio 1.27 95% CI 1.21 to 1.33) were higher in the AF cohort. Length of stay was shorter in patients with AF (mean ratio 0.85 95% CI 0.81 to 0.90). In conclusion, a known history of AF increased the risk of in-hospital mortality, morbidity, and hospital expense in AWS.

Clinical Significance of Mycophenolate Mofetil Withdrawal in Kidney Transplant Recipients.

INTRODUCTION: The most effective immunosuppressant protocol in kidney transplantation (KT) is the combination of a calcineurin inhibitor, steroid, and mycophenolate mofetil (MMF) until now. However, MMF withdrawal (MW) is performed for many reasons, and the clinical course of the KT recipients after MW is not clearly known. The purpose of this study was to investigate the clinical outcomes of KT after MW. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 626 KT recipients between 2000 and 2016. We evaluated the incidence of biopsy-proven acute rejection (BPAR), graft and patient survival rates, and risk factors related with graft failure. RESULTS: The proportion of MW was 33.2% (208 of 626 patients). The median time between KT and MW was 6.4 months (range, 3.2-32.1 months). The common causes of MW were infection (70.7%), hematologic abnormalities (9.1%), and gastrointestinal trouble (7.7%). The incidence of BPAR was significantly higher in the MW group compared with the MMF continuation group (27.4% vs 8.9%, respectively, P < .001). Death-censored graft survival and patient survival rates were significantly lower in the MW group compared with the MMF continuation group (P < .001; P < .001, respectively). In the multivariate analysis, BPAR after MW was an independent risk factor for graft failure (hazard ratio 6.058, 95% confidence interval, 3.172-11.569, P < .001). CONCLUSIONS: The incidence of rejection, graft failure, and patient mortality in KT were high after MW. Therefore, MW should be considered carefully.

Deaths in Unlicensed Alcohol Rehabilitation Facilities.

Non-English-speaking people do not always seek medical care through established institutions. This paper reports a series of deaths in unlicensed alcohol rehabilitation facilities serving Spanish-speaking men. These facilities are informal groups of alcohol abusing men who live together. New members receive various treatments, including administration of ethanol or isopropanol, restraint, and seclusion. We reviewed 42 deaths in unlicensed alcohol rehabilitation facilities in Los Angeles County during the years 2003-2014. Data gathered included age, length of time spent in the facility, blood alcohol and drugs at autopsy, and cause and manner of death. Causes of death included acute alcohol poisoning, alcohol withdrawal, and a variety of other causes. Three cases were considered homicides from restraint asphyxia. The Department of Medical Examiner-Coroner has worked with the police, district attorney, and State Department of Health Services to try to prevent additional deaths in unlicensed alcohol rehabilitation facilities. Nevertheless, prevention has been difficult.

Increased Cardiovascular Mortality Risk in Women Discontinuing Postmenopausal Hormone Therapy.

CONTEXT: Current guidelines recommend annual discontinuation of postmenopausal hormone therapy (HT) to evaluate whether a woman could manage without the treatment. The impact of HT on cardiovascular health has been widely studied, but it is not known how the withdrawal of HT affects cardiovascular risk. OBJECTIVE: We evaluated the risk of cardiac or stroke death after the discontinuation of HT. Design, Patients, Interventions, and Main Outcome Measures: Altogether 332 202 Finnish women discontinuing HT between 1994 and 2009 (data from National Reimbursement register) were followed up from the discontinuation date to death due to cardiac cause (n = 3177) or stroke (n = 1952), or to the end of 2009. The deaths, retrieved from the national Cause of Death Register, were compared with the expected number of deaths in the age-standardized background population. In a subanalysis we also compared HT stoppers with HT users. RESULTS: Within the first posttreatment year, the risk of cardiac death was significantly elevated (standardized mortality ratio; 95% confidence interval 1.26; 1.16-1.37), whereas follow-up for longer than 1 year was accompanied with a reduction (0.75; 0.72-0.78). The risk of stroke death in the first posttreatment year was increased (1.63; 1.47-1.79), but follow-up for longer than 1 year was accompanied with a reduced risk (0.89; 0.85-0.94). The cardiac (2.30; 2.12-2.50) and stroke (2.52; 2.28-2.77) death risk elevations were even higher when compared with HT users. In women who discontinued HT at age younger than 60 years, but not in women aged 60 years or older, the cardiac mortality risk was elevated (1.94; 1.51-2.48). CONCLUSIONS: Increased cardiovascular death risks question the safety of annual HT discontinuation practice to evaluate whether a woman could manage without HT.

Ethosuximide Reduces Mortality and Seizure Severity in Response to Pentylenetetrazole Treatment During Ethanol Withdrawal.

AIMS: We recently demonstrated that T-type calcium channels are affected by alcohol abuse and withdrawal. Treatment with ethosuximide, an antiepileptic drug that blocks T-type calcium channels, reduces seizure activity induced by intermittent ethanol exposures and withdrawals. Here, we expand on these findings to test whether ethosuximide can reduce the sensitivity to pentylenetetrazole-induced seizures during ethanol withdrawal. METHODS: We used an intermittent ethanol exposure model to produce withdrawal-induced hyperexcitability in DBA/2J mice. RESULTS: Ethosuximide (250 mg/kg) reduced seizure severity in mice undergoing ethanol withdrawal with concurrent PTZ treatment (20 mg/kg). Importantly, ethosuximide did not produce rebound excitability and protected against ethanol withdrawal-induced mortality produced by concurrent PTZ treatment (40 mg/kg). CONCLUSION: These results, in addition to previous preclinical findings, suggest that ethosuximide should be further evaluated as a safe, effective alternative to benzodiazepines for the treatment of alcohol withdrawal.

Withdrawal syndrome caused by naltrexone in opioid abusers.

STUDY OBJECTIVE: Naltrexone is a competitive opioid receptor antagonist acting at the µ- and k-opioid receptors that blocks the euphoric effects of exogenous administered opioids. When used in opioid-dependent patients, naltrexone can cause acute and severe withdrawal symptoms. METHODS: This was a cross-sectional study conducted from December 2007 to March 2008 and consisted of patients who had used naltrexone accidentally or deliberately and were referred to Loghman-Hakim Poison Hospital, Tehran, Iran. All symptoms and signs were assessed and the relationship between the dose of naltrexone, opioid dependence, and outcome was evaluated. RESULTS: In 132 patients referred to our hospital, the most frequently reported symptoms and signs occurring in more than 10% of patients were agitation (96.2%), altered level of consciousness (38.6%), nausea (28%), vomiting (27.3%), abdominal pain (24.2%), diarrhea (16.7%), bone and muscle pain (15.9%), tachycardia (12.9%), and dilated pupils (11.4%). Being the most prominent symptom, the agitation was the most difficult aspect of withdrawal to manage. Except for agitation, no relationship was found between the presence of these symptoms and the dose of naltrexone used. Outcome of the patients (classified as complete recovery, partial recovery, death, and no follow-up) was related to the substance of addiction (p < 0.05) but not to the naltrexone dose. CONCLUSION: Emergency physicians should be aware of the potential for severe agitation from naltrexone-precipitated hyperacute withdrawal and its appropriate management. Opioid-dependent patients who wish to continue withdrawal and abstinence must be encouraged to visit trained physicians and be warned about misuse of naltrexone.

The effectiveness of pharmacological approaches in the treatment of alcohol withdrawal syndrome (AWS): a literature review.

Mortality statistics for excessive alcohol consumption show no signs of abatement, with a report published in 2011 from the World Health Organization (WHO) estimating that 2.5 million people worldwide died because of their alcohol consumption. Serious physiological, psychological, social and legal problems are thought to affect many more. Alcohol withdrawal syndrome (AWS) is a potentially life-threatening condition that often occurs in those individuals who significantly reduce or stop their intake after a prolonged and excessive period of drinking. Pharmacological treatment of the AWS has traditionally been undertaken by the use of the benzodiazepines, but recent years have witnessed the emergence of several alternatives. The aim of this paper was (1) to review the evidence base supporting the use of various pharmacological agents currently employed to treat AWS, and (2) to consider the efficacy and safety of the emerging alternatives to the benzodiazepines. The Cochrane Database of Systematic Reviews, CINAHL, Embase, PsycINFO, MEDLINE and BNI databases were extensively searched in order to retrieve the maximum number of relevant articles. Reference lists from relevant literature were also used to identify other potential studies for inclusion. All studies concerned with measuring the efficacy and safety of the various pharmacological treatment options for AWS were considered and a total of 63 trials were included in this review. Findings support the use of benzodiazepines as the recommended drug of choice for the treatment of AWS in the absence of adequate evidence to support the use of alternative agents. There is a lack of evidence of a superior pharmacological agent to the benzodiazepines for the treatment of AWS. There are several studies that have shown that there are pharmacological alternatives that could compete or act as an adjunct with the benzodiazepines in terms of high efficacy and safety in the treatment of AWS, but there is a need for further quality research to be carried out before definitive conclusions can be drawn.

[Homicide and acute cortico-induced psychosis: A case report]. / Homicide et épisode psychotique aigu cortico-induit : à propos d'un cas.

BACKGROUND: Since their commercialization in 1950, the first psychiatric side effects of steroids have been reported. Today, steroids have become an important therapeutic tool in many diseases, but pharmacological mechanisms responsible for their side effects are still little known. The neuropsychiatric side effects concern 15% of patients while severe reactions occur in 5% of cases, mostly as acute psychotic episodes such as delusion. Serious forensic risks in this context are poorly documented and underestimated. CASE REPORT: We report the case of a 77 year-old man, treated by methylprednisolone for chronic lymphoid leukemia. After two months of treatment, although stabilized for the neoplastic disease, he stabbed his wife to death with a knife. In the emergency unit, an acute delirious state, a disorganization syndrome, and confusion items such as amnesia, disorientation and symptomatology fluctuation were observed. Mr. M also presented with hyponatremia and infectious pneumonia. Steroids were stopped and his condition rapidly declined, he died one month later during the hospitalization. DISCUSSION: This clinical case underlines the importance of the early detection of steroid psychosis and its management. Treatment should not be stopped brutally and a dose reducing strategy should be applied in combination with a mood stabilizer or antipsychotic treatment. Disease management strategies are insufficiently documented to be recommended. The extremely acute onset of the symptoms, a partial insight into delusions, a history of iatrogenic neuropsychiatry, the existence of somatic precipitating disorders and confusion factors should always alert the practitioner. The patient, and eventually his family circle, must be aware of the risks of adverse psychiatric effects of steroids for both ethical and forensic reasons, and must report them as early as possible to the clinician if they occur.

Hot-topic debate on tolerance: immunosuppression withdrawal.

KEY POINTS: 1. Liver allografts exhibit intrinsic tolerogenic properties that result in their spontaneous acceptance in many experimental animal models. 2. In clinical transplantation, liver allografts require milder immunosuppression regimens than other organs, are relatively resistant to antibody-mediated rejection, and only very rarely are lost because of immunological insults. 3. A fraction of stable liver transplant recipients can withdraw from all immunosuppression therapy and then maintain normal graft function and not experience rejection. This phenomenon is known as spontaneous operational tolerance (SOT). 4. The intentional discontinuation of immunosuppression in stable liver transplant recipients has led to successful weaning in almost 20% of recipients, but the true prevalence of SOT in unselected recipients is still unknown. 5. The prevalence could be higher in pediatric recipients undergoing transplantation before 1 year of age and in adult recipients with more than 10 years of posttransplant follow-up. 6. Rejection occurring during medically supervised immunosuppression weaning trials tends to be mild and, in the overwhelming majority of cases, can be easily resolved without the administration of high-dose immunosuppression. 7. Tolerant liver recipients exhibit specific transcriptional patterns in peripheral blood and liver tissue that may constitute future diagnostic markers of tolerance. 8. There is still no formal proof that the discontinuation of low-dose immunosuppression in long-term survivors of liver transplantation improves the morbidity and mortality rates associated with immunosuppression therapy.

The failure of immunosuppression withdrawal: patient benefit is not detectable, inducible, or reproducible.

KEY POINTS: (1) Immunosuppression is responsible for excellent patient outcomes. (2) Immunosuppression withdrawal fails in most patients. (3) Patients who may benefit from immunosuppression withdrawal cannot currently be identified. (4) No data suggest that immunosuppression withdrawal decreases patient morbidity (ie, nephrotoxicity). (5) The minimization of immunosuppression instead of withdrawal may be adequate for improving patient outcomes.

Long-term mortality of patients admitted to the hospital with alcohol withdrawal syndrome.

BACKGROUND: Although it is well known that alcoholism increases long-term mortality, there is a paucity of data regarding long-term prognosis in alcoholic patients who have an episode of alcohol withdrawal syndrome (AWS). METHODS: We studied a cohort of 1,265 individuals with severe AWS who were admitted to a single university hospital between 1996 and 2006. Median age was 49 years (range 18 to 89 years). A total of 1,085 (85.8%) were men. Median follow-up was 34 months (range 0 to 121 months). Survival of patients with AWS was compared with that of a reference cohort of 1,362 individuals from the same area. In addition, age- and sex-standardized mortality ratios were calculated using the general population from the region (Galicia, Spain) as the reference. RESULTS: The risk of mortality was higher in the cohort of patients with AWS than in the reference cohort after adjusting for age, sex, and smoking (hazard ratio 12.7; 95% CI 9.1 to 17.6; p < 0.001). The standardized mortality ratio in patients with AWS was 8.6 (95% CI 7.7 to 9.7). Age, smoking, serum creatinine, serum bilirubin, and prothrombin time at baseline were independently associated with mortality among patients with AWS. CONCLUSIONS: Long-term mortality is highly increased in patients who have a history of AWS. Liver and kidney dysfunction are independent predictors of long-term mortality in patients with AWS.