Outcomes After Implementation of a Benzodiazepine-Sparing Alcohol Withdrawal Order Set in an Integrated Health Care System.

Importance: Alcohol withdrawal syndrome (AWS) is a common inpatient diagnosis managed primarily with benzodiazepines. Concerns about the adverse effects associated with benzodiazepines have spurred interest in using benzodiazepine-sparing treatments. Objective: To evaluate changes in outcomes after implementation of a benzodiazepine-sparing AWS inpatient order set that included adjunctive therapies (eg, gabapentin, valproic acid, clonidine, and dexmedetomidine). Design, Setting, and Participants: This difference-in-differences quality improvement study was conducted among 22 899 AWS adult hospitalizations from October 1, 2014, to September 30, 2019, in the Kaiser Permanente Northern California integrated health care delivery system. Data were analyzed from September 2020 through November 2021. Exposures: Implementation of the benzodiazepine-sparing AWS order set on October 1, 2018. Main Outcomes and Measures: Adjusted rate ratios for medication use, inpatient mortality, length of stay, intensive care unit admission, and nonelective readmission within 30 days were calculated comparing postimplementation and preimplementation periods among hospitals with and without order set use. Results: Among 904 540 hospitalizations in the integrated health care delivery system during the study period, AWS was present in 22 899 hospitalizations (2.5%), occurring among 16 323 unique patients (mean [SD] age, 57.1 [14.8] years; 15 764 [68.8%] men). Of these hospitalizations, 12 889 (56.3%) used an order set for alcohol withdrawal. Among hospitalizations with order set use, any benzodiazepine use decreased after implementation from 6431 hospitalizations (78.1%) to 2823 hospitalizations (60.7%) (P < .001), with concomitant decreases in the mean (SD) total dosage of lorazepam before vs after implementation (19.7 [38.3] mg vs 6.0 [9.1] mg; P < .001). There were also significant changes from before to after implementation in the use of adjunctive medications, including gabapentin (2413 hospitalizations [29.3%] vs 2814 hospitalizations [60.5%]; P < .001), clonidine (1476 hospitalizations [17.9%] vs 2208 hospitalizations [47.5%]; P < .001), thiamine (6298 hospitalizations [76.5%] vs 4047 hospitalizations [87.0%]; P < .001), valproic acid (109 hospitalizations [1.3%] vs 256 hospitalizations [5.5%]; P < .001), and phenobarbital (412 hospitalizations [5.0%] vs 292 hospitalizations [6.3%]; P = .003). Compared with AWS hospitalizations without order set use, use of the benzodiazepine-sparing order set was associated with decreases in intensive care unit use (adjusted rate ratio [ARR], 0.71; 95% CI, 0.56-0.89; P = .003) and hospital length of stay (ARR, 0.71; 95% CI, 0.58-0.86; P < .001). Conclusions and Relevance: This study found that implementation of a benzodiazepine-sparing AWS order set was associated with decreased use of benzodiazepines and favorable trends in outcomes. These findings suggest that further prospective research is needed to identify the most effective treatments regimens for patients hospitalized with alcohol withdrawal.

The hyperthermic effect of central cholecystokinin is mediated by the cyclooxygenase-2 pathway.

Cholecystokinin (CCK) increases core body temperature via CCK2 receptors when administered intracerebroventricularly (icv). The mechanisms of CCK-induced hyperthermia are unknown, and it is also unknown whether CCK contributes to the fever response to systemic inflammation. We studied the interaction between central CCK signaling and the cyclooxygenase (COX) pathway. Body temperature was measured in adult male Wistar rats pretreated with intraperitoneal infusion of the nonselective COX enzyme inhibitor metamizol (120 mg/kg) or a selective COX-2 inhibitor, meloxicam, or etoricoxib (10 mg/kg for both) and, 30 min later, treated with intracerebroventricular CCK (1.7 µg/kg). In separate experiments, CCK-induced neuronal activation (with and without COX inhibition) was studied in thermoregulation- and feeding-related nuclei with c-Fos immunohistochemistry. CCK increased body temperature by ∼0.4°C from 10 min postinfusion, which was attenuated by metamizol. CCK reduced the number of c-Fos-positive cells in the median preoptic area (by ∼70%) but increased it in the dorsal hypothalamic area and in the rostral raphe pallidus (by ∼50% in both); all these changes were completely blocked with metamizol. In contrast, CCK-induced satiety and neuronal activation in the ventromedial hypothalamus were not influenced by metamizol. CCK-induced hyperthermia was also completely blocked with both selective COX-2 inhibitors studied. Finally, the CCK2 receptor antagonist YM022 (10 µg/kg icv) attenuated the late phases of fever induced by bacterial lipopolysaccharide (10 µg/kg; intravenously). We conclude that centrally administered CCK causes hyperthermia through changes in the activity of "classical" thermoeffector pathways and that the activation of COX-2 is required for the development of this response.NEW & NOTEWORTHY An association between central cholecystokinin signaling and the cyclooxygenase-prostaglandin E pathway has been proposed but remained poorly understood. We show that the hyperthermic response to the central administration of cholecystokinin alters the neuronal activity within efferent thermoeffector pathways and that these effects are fully blocked by the inhibition of cyclooxygenase. We also show that the activation of cyclooxygenase-2 is required for the hyperthermic effect of cholecystokinin and that cholecystokinin is a modulator of endotoxin-induced fever.

Factors Associated with Benzodiazepines Prolonged-Term Use in Post-Stroke Subjective Sleep Disturbance: A Single-Centre Retrospective Study from China.

PURPOSE: To investigate the prevalence of short- and long-term benzodiazepine and z-drugs (BZD) for the treatment of post-stroke subjective sleep disturbance (SSD) and to evaluate the risk factors associated with prolonged BZD treatment in this patient body. PATIENTS AND METHODS: Between 1st January 2018 and 1st December 2018, we identified 542 inpatients suffering from acute stroke in Heyuan People's Hospital. Of these, 290 inpatients were included in our final analysis. These patients were divided into three groups according to the treatment they received: non/occasional BZD (non-BZD), short-term BZD (short-term) and prolonged-term BZD (prolonged-term) treatment. We investigated the prevalence of each BZD treatment term and identified differences between the groups. Univariate logistic regression analysis was used to identify potential predictors for the prolonged use of BZD. Multinomial logistic regression analysis was used to assess the correlation between the prolonged use of BZD and potential predictors. RESULTS: The prevalence of cases receiving short and prolonged BZD treatments were 40.35% and 31.72%, respectively; none of the patients received polysomnography (PSG) screening from obstructive sleep apnoea (OSP). Treatment strategies were limited to BZD and traditional Chinese medicine; none of the patients received cognitive-behavioral treatment (CBT) or other forms of treatment. Logistic regression analysis showed that the short-term use was associated with z-drugs (odds ratio [OR]: 2.189, 95% confidence interval [CI]: 1.419-3.378), non-communication barriers (OR =0.535, 95% CI: 0.325-0.880) and posterior circulation infarct (POCI) (OR =2.199, 95% CI: 1.112-4.349). The prolonged-term use was associated with z-drugs (OR =3.012, 95% CI: 1.637-5.542), non-communication barriers (OR =0.530, 95% CI: 0.307-0.916), partial anterior circulation infarct (PACI) (OR =0.455, 95% CI: 0.250-0.827), and non pain after stroke (OR =0.315, 95% CI: 0.207-0.480). CONCLUSION: The status of BZD abuse for post-stroke SSD is worrying. Additional research attention and treatment options are needed for the treatment of post-stroke SSD. In particular, the potential combination of stroke and OSP appears to be underestimated and neglected. Post-stroke SSD patients should receive more comprehensive assessment and rigid follow-up to avoid the prolonged use of BZD. Additional and effective therapeutic strategies (such as positive pressure ventilation treatment or CBT) are urgently needed for cause-specific intervention.

Profiles of polypharmacy in older adults and medication associations with signs of aspiration.

BACKGROUND: Polypharmacy and specific medication classes are prevalent in older adults. Their relationships with swallowing disorders are not well explored, which would best be managed holistically, with consideration of medication profiles. This study aimed to establish profiles of polypharmacy in older adults and investigate the associations of polypharmacy and medication class with signs of aspiration during swallowing. METHODS: This was a secondary retrospective analysis of data from 291 adults aged 60 years and older. Polypharmacy was profiled numerically and described. Multivariate logistic regression was used to identify associations between medication classes with signs of aspiration, while controlling for independent variables of demographics, functional status, and medical history. RESULTS: Three distinct profiles of polypharmacy were described. Higher numbers of medications were associated with higher age, lower functional status, nursing home residency, multimorbidity, and showing signs of aspiration. Thirty-four classes of medications were found in this study, benzodiazepines were the only class independently associated with signs of aspiration. CONCLUSIONS: Different profiles of polypharmacy can be observed in older adults, but none were independently associated with signs of aspiration. In addition to known demographic and functional status variables, benzodiazepine-use was found to be independently associated with signs of aspiration (p = .005, B = 7.94).

Perioperative Cannabis as a Potential Solution for Reducing Opioid and Benzodiazepine Dependence.

Importance: Cannabis is increasingly being used for medicinal purposes but remains outside Western medical practice. Data on perioperative use and outcomes are scarce. Few surgeons receive training regarding legal endorsement, reported medicinal benefits, and potential risks, making it difficult to advise patients. Guidelines and additional research are needed. Observations: It is legal to recommend cannabis, which can be obtained in states with medical cannabis programs. There are many methods of consumption, oral being the safest. Activity is primarily through Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) via cannabinoid receptors, which may be potentiated when taken together in the plant or plant extract. The known effects of cannabis on inflammation and malignancy are largely limited to laboratory experiments. However, there are higher-quality data to support adjunctive use of cannabis for relief of pain, nausea, and insomnia, which may be useful postoperatively and could potentially decrease reliance on opiates and benzodiazepines. There are prospective trials in surgical patients, but no reported data regarding surgical complications or other surgical outcomes. Currently, cannabis is regulated differently than other controlled substances, and there are issues with purity/homogeneity, making it difficult for surgeons to accept or significantly explore its medical benefits. Conclusions and Relevance: Recommendations are made for surgeons advising patients who use cannabis based on the limited existing data. While cannabis likely has some therapeutic benefits, it must be treated as other medical controlled substances to truly elucidate its role in surgical patient care.

[Need for Prescription Suggestions for Long-term Inpatients in the Psychiatric Ward].

Additional fees for ward pharmacists' services have been valued for hospitals in Japan. However, the calculation period for services provided to inpatients in the psychiatric ward is limited to 8 weeks. This study aimed to reveal the need for the services of pharmacists in the hospital ward for inpatients hospitalized for >8 weeks in the psychiatric ward. Patients who were hospitalized in the psychiatric ward from September 2016 to February 2017 were analyzed retrospectively. The pharmacists suggested prescriptions for inpatients admitted for >8 weeks, similar to those admitted for <9 weeks, and this supported pharmacotherapy without exacerbating patient outcomes. Moreover, significant decreases in benzodiazepine doses were found between the prior and post prescription suggestions of the pharmacist for inpatients >8 weeks of admission. Healthcare expenditures were also reduced. These results suggest that the prescriptions suggested by pharmacists for inpatients admitted for >8 weeks in the psychiatric ward were useful. In conclusion, our findings show that ward pharmacists' services were necessary not only for the inpatients hospitalized for <9 weeks, but also for those hospitalized for >8 weeks.

Benzodiazepine Use and Risk of Acute Angle-Closure Glaucoma: A Population-Based Case-Crossover Study.

INTRODUCTION: Theoretically, benzodiazepines (BZDs) can narrow the iridocorneal angle and induce acute angle-closure glaucoma (AACG). However, little evidence exists regarding this association. OBJECTIVE: The objective of this study was to assess whether the use of BZDs is associated with the risk of AACG. METHODS: We conducted a population-based case-crossover study using the nationwide claims database of the National Health Insurance Service in Korea. Patients with newly diagnosed AACG-between 1 January 2013 and 31 December 2016-who had received at least one BZD prescription prior to AACG diagnosis were enrolled. The date of AACG diagnosis was set as the index date. We assessed BZD use by each patient during a 30-day case period prior to the index date and three consecutive control periods that preceded this date. We used conditional logistic regression that adjusted for concomitant medications to determine the odds ratio for the use of BZDs in the case period compared with that in the control period in patients with incident AACG. RESULTS: Of the 11,093 patients with incident AACG, 6709 received a prescription for BZD prior to diagnosis. BZD use was associated with an increased risk of AACG [adjusted odds ratio (aOR) = 1.40; 95% confidence interval (CI) 1.27-1.54]. AACG risk was similar for short-acting (aOR = 1.40, 95% CI 1.24-1.57) and long-acting BZDs (aOR = 1.33, 95% CI 1.18-1.50). CONCLUSION: We found that BZD use was associated with AACG risk in the Korean population. Clinicians should carefully monitor the occurrence of visual disturbance in BZD-treated patients.

Conscious Sedation in Dentistry.

Invasive dental procedures can be performed only with local anesthesia; in some cases, it may be useful to combine the administration of drugs to obtain anxiolysis with local anesthesia. Sedation required level should be individually adjusted to achieve a proper balance between the needs of the patient, the operator, and the safety of the procedure. Surgical time is an important factor for post-operative phases, and this could be greatly increased by whether the patient interrupts the surgeon or if it is not collaborative. In this manuscript some dentistry-used methods to practice conscious sedation have been evaluated. This manuscript could be a useful reading on the current state of conscious sedation in dentistry and an important starting point for future perspectives. Surely the search for safer drugs for our patients could have beneficial effects for them and for the clinicians.

Early polytherapy for benzodiazepine-refractory status epilepticus.

The transition from single seizures to status epilepticus (SE) is associated with malaptive trafficking of synaptic gamma-aminobutyric acid (GABAA) and glutamate receptors. The receptor trafficking hypothesis proposes that these changes are key events in the development of pharmacoresistance to antiepileptic drugs (AEDs) during SE, and that blocking their expression will help control drug-refractory SE (RSE). We tested this hypothesis in a model of SE induced by very high-dose lithium and pilocarpine (RSE), and in a model of SE induced by sc soman. Both models are refractory to benzodiazepines when treated 40 min after seizure onset. Our treatments aimed to correct the loss of inhibition because of SE-associated internalization of synaptic GABAA receptors (GABAAR), using an allosteric GABAAR modulator, sometimes supplemented by an AED acting at a nonbenzodiazepine site. At the same time, we reduced excitation because of increased synaptic localization of NMDA and AMPA (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate) receptors (NMDAR, AMPAR (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, N-methyl-D-aspartate receptors)) with an NMDAR channel blocker, since AMPAR changes are NMDAR-dependent. Treatment of RSE with combinations of the GABAAR allosteric modulators midazolam or diazepam and the NMDAR antagonists dizocilpine or ketamine terminated RSE unresponsive to high-dose monotherapy. It also reduced RSE-associated neuronal injury, spatial memory deficits, and the occurrence of spontaneous recurrent seizures (SRS), tested several weeks after SE. Treatment of soman-induced SE also reduced seizures, behavioral deficits, and epileptogenesis. Addition of an AED further improved seizure outcome in both models. Three-dimensional isobolograms demonstrated positive cooperativity between midazolam, ketamine, and valproate, without any interaction between the toxicity of these drugs, so that the therapeutic index was increased by combination therapy. The midazolam-ketamine-valproate combination based on the receptor trafficking hypothesis was far more effective in stopping RSE than the midazolam-fosphenytoin-valproate combination inspired from clinical guidelines for the treatment of SE. Furthermore, sequential administration of midazolam, ketamine, and valproate was far less effective than simultaneous treatment with the same drugs at the same dose. These data suggest that treatment of RSE should be based at least in part on its pathophysiology. The search for a better treatment should focus on the cause of pharmacoresistance, which is loss of synaptic GABAAR and gain of synaptic glutamate receptors. Both need to be treated. Monotherapy addresses only half the problem. Improved pharmacokinetics will not help pharmacoresistance because of loss of receptors. Waiting for one drug to fail before giving the second drugs gives pharmacoresistance time to develop. Future clinical trials should consider treating both the failure of inhibition and the runaway excitation which characterize RSE, and should include an early polytherapy arm. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Medicalization and Indigenous Health: An analysis of the consumption of psychotropics by the Xukuru de Cimbres indigenous people. / Medicalização e Saúde Indígena: uma análise do consumo de psicotrópicos pelos índios Xukuru de Cimbres.

OBJECTIVE: To investigate the process of medicalization among the Xukuru indigenous people of Pesqueira (PE), Brazil following the 2003 conflict. METHOD: This is a descriptive, cross-sectional, quantitative study developed with the indigenous attended at the Xukuru de Cimbres basic center. The final sample consisted of 75 individuals who used psychotropic drugs. Data were analyzed by SPSS version 18.0, using the chi-square test. RESULTS AND DISCUSSION: We observed that 8% of the studied population use psychotropic drugs, and the most used is BZD (78.67%). Regarding age, 68% are young adults and 26.67% are elderly. The income of 81.33% of households is more than one minimum wage. As for marital status, 50.85% and 66.67%, respectively of the indigenous group using BZD and other psychotropic drugs are married. CONCLUSION: The study outlined the profile of the Xukuru de Cimbres indigenous people who used psychotropics and showed a fragmented mental health care focused on the disease and the use of medication. Results reveal a socioeconomically vulnerable adult population, a pattern of chronic use of psychotropic drugs and distancing from traditional indigenous healing, typical of the health medicalization process.

O objetivo deste artigo é investigar o processo de medicalização dos indígenas do povo Xukuru de Pesqueira, PE, após o conflito ocorrido em 2003. Estudo descritivo, quantitativo, desenvolvido com indígenas atendidos no polo base Xukuru de Cimbres. A amostra final foi composta por 75 usuários em uso de medicamentos psicotrópicos. Os dados foram analisados no SPSS versão 18.0, utilizando a prova do qui quadrado. Observou-se que 8% da população estudada faz uso de psicotrópicos, sendo os mais usados os BZD (78,67%). Com relação à idade, 68% são adultos jovens e 26,67% são idosos. A renda de 81,33% das famílias perfaz mais de um salário mínimo. Com relação ao estado civil, do grupo de indígenas que faz uso dos BZD e outros psicotrópicos, 50,85% e 66,67%, respectivamente, são casados. O estudo delineou o perfil dos índios Xukuru de Cimbres usuários de psicotrópicos e evidenciou uma assistência à saúde mental fragmentada, focada na doença e no uso da medicação. Os achados revelam uma população adulta vulnerável do ponto de vista socioeconômico, um padrão de cronificação do consumo dos psicotrópicos e o distanciamento das práticas de curas tradicionais indígenas, característicos do processo de medicalização da saúde.

Medicalização e Saúde Indígena: uma análise do consumo de psicotrópicos pelos índios Xukuru de Cimbres / Medicalization and Indigenous Health: An analysis of the consumption of psychotropics by the Xukuru de Cimbres indigenous people

Resumo O objetivo deste artigo é investigar o processo de medicalização dos indígenas do povo Xukuru de Pesqueira, PE, após o conflito ocorrido em 2003. Estudo descritivo, quantitativo, desenvolvido com indígenas atendidos no polo base Xukuru de Cimbres. A amostra final foi composta por 75 usuários em uso de medicamentos psicotrópicos. Os dados foram analisados no SPSS versão 18.0, utilizando a prova do qui quadrado. Observou-se que 8% da população estudada faz uso de psicotrópicos, sendo os mais usados os BZD (78,67%). Com relação à idade, 68% são adultos jovens e 26,67% são idosos. A renda de 81,33% das famílias perfaz mais de um salário mínimo. Com relação ao estado civil, do grupo de indígenas que faz uso dos BZD e outros psicotrópicos, 50,85% e 66,67%, respectivamente, são casados. O estudo delineou o perfil dos índios Xukuru de Cimbres usuários de psicotrópicos e evidenciou uma assistência à saúde mental fragmentada, focada na doença e no uso da medicação. Os achados revelam uma população adulta vulnerável do ponto de vista socioeconômico, um padrão de cronificação do consumo dos psicotrópicos e o distanciamento das práticas de curas tradicionais indígenas, característicos do processo de medicalização da saúde.

Abstract Objective: To investigate the process of medicalization among the Xukuru indigenous people of Pesqueira (PE), Brazil following the 2003 conflict. Method: This is a descriptive, cross-sectional, quantitative study developed with the indigenous attended at the Xukuru de Cimbres basic center. The final sample consisted of 75 individuals who used psychotropic drugs. Data were analyzed by SPSS version 18.0, using the chi-square test. Results and Discussion: We observed that 8% of the studied population use psychotropic drugs, and the most used is BZD (78.67%). Regarding age, 68% are young adults and 26.67% are elderly. The income of 81.33% of households is more than one minimum wage. As for marital status, 50.85% and 66.67%, respectively of the indigenous group using BZD and other psychotropic drugs are married. Conclusion: The study outlined the profile of the Xukuru de Cimbres indigenous people who used psychotropics and showed a fragmented mental health care focused on the disease and the use of medication. Results reveal a socioeconomically vulnerable adult population, a pattern of chronic use of psychotropic drugs and distancing from traditional indigenous healing, typical of the health medicalization process.

Acute Carbon Monoxide Poisoning Secondary to Cigarette Smoking in a 40-Year-Old Man: A Case Report.

BACKGROUND AND OBJECTIVES: Carbon monoxide is one of the most common causes of fatal intoxications in the United States, and multiple previous studies have demonstrated that cigarette smokers have higher levels of carbon monoxide in their blood. However, the potential negative effects due to acute carbon monoxide poisoning from excessive cigarette smoking have not been well established. METHODS: This is a single patient case report. RESULTS: In this case report, a 40-year-old male with a past medical history of depression, anxiety, panic attacks, and substance use disorder developed symptomatic, acute carbon monoxide poisoning secondary to heavy cigarette smoking in a confined space. In this patient, the cessation of clonazepam therapy coincided with increasing anxiety and panic disorder with agoraphobia triggering an escalation in his cigarette smoking. The patient smoked three packs of cigarettes in 3 hours and developed worsening of his symptoms. He required inpatient treatment with benzodiazepines and hyperbaric oxygen. DISCUSSION AND CONCLUSIONS: Therefore, it is important to recognize cigarette smoke as a significant source of carbon monoxide exposure. SCIENTIFIC SIGNIFICANCE: While the negative effects of cigarette smoking are often perceived as being chronic and only coming to fruition after numerous years of exposure, it is important for both physicians and patients to recognize the possibility for potentially life-threatening acute toxicity secondary to carbon monoxide exposure. (Am J Addict 2019;28:413-415).

Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy.

Importance: Attempts to discontinue opioid therapy to reduce the risk of overdose and adhere to prescribing guidelines may lead patients to be exposed to variability in opioid dosing. Such dose variability may increase the risk of opioid overdose even if therapy discontinuation is associated with a reduction in risk. Objective: To examine the association between opioid dose variability and opioid overdose. Design, Setting, and Participants: A nested case-control study was conducted in a large Colorado integrated health plan and delivery system from January 1, 2006, through June 30, 2018. Cohort members were individuals prescribed long-term opioid therapy. Exposures: Dose variability was defined as the SD of the milligrams of morphine equivalents across each patient's follow-up and categorized based on the quintile distribution of the SD in the cohort (0-5.3, 5.4-9.1, 9.2-14.6, 14.7-27.2, and >27.2 mg of morphine equivalents). Main Outcomes and Measures: Opioid overdose cases were identified using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Each case patient with overdose was matched to up to 20 control patients using risk set sampling. Conditional logistic regression models were used to generate matched odds ratios and 95% CIs, adjusted for age, sex, race/ethnicity, drug or alcohol use disorder, tobacco use, benzodiazepine dispensings, medical comorbidities, mental health disorder, opioid dose, and opioid formulation. Results: In a cohort of 14 898 patients (mean [SD] age, 56.3 [16.0] years; 8988 [60.3%] female) prescribed long-term opioid therapy, 228 case patients with incident opioid overdose were matched to 3547 control patients. The mean (SD) duration of opioid therapy was 36.7 (33.7) months in case patients and 33.0 (30.9) months in control patients. High-dose variability (SD >27.2 mg of morphine equivalents) was associated with a significantly increased risk of overdose compared with low-dose variability (matched odds ratio, 3.32; 95% CI, 1.63-6.77) independent of opioid dose. Conclusions and Relevance: Variability in opioid dose may be a risk factor for opioid overdose, suggesting that practitioners should seek to minimize dose variability when managing long-term opioid therapy.

Complicated Withdrawal Phenomena During Benzodiazepine Cessation in Older Adults.

The cause of prolonged or recurrent symptoms following the cessation of long-term benzodiazepine use is proposed to be related to downregulation and allosteric decoupling of the γ-aminobutyric acid/benzodiazepine receptor complex. This case series describes 2 patients with prolonged (>2 weeks) recurrent complications during attempted tapering of benzodiazepine doses after long-term treatment. Excited catatonia developed in a 90-year-old woman, and prolonged delirium developed in a 69-year-old woman. Both patients showed improvement of symptoms after resumption of higher doses of benzodiazepine treatment and recurrence of symptoms when the dose was again lowered. Caution should be exercised regarding the long-term use of benzodiazepines in older adults (aged ≥65 years). Tapering of benzodiazepines in older patients after long-term treatment may require slow decreases in dose over long periods. Psychotherapeutic interventions, such as brief cognitive therapy with psychoeducation and motivational enhancement, and osteopathic manipulative treatment to decrease paravertebral muscle tension may be beneficial during the tapering process.

Opioid Adjuncts: Optimizing Opioid Therapy With Nonopioid Medications.

In this article, we describe a variety of medications that physicians managing outpatient chronic pain should familiarize themselves with to better aid their approach to multimodal pain therapy. Physicians should always consider the use of an adjuvant or coanalgesic drug as first-line treatments. Although many of these medications are not primarily analgesics, in clinical practice they have independent analgesic effects or synergistic analgesic properties when used with opioids. The use of adjunct analgesics reduces opioid-related adverse effects and optimizes pain management. Although there may be some medication overlap with this section and the ERAS section, the purpose of this article is to understand prolonged use in the outpatient setting to reduce opioid use or limit opioid dose with adjuvant therapy.

Electroacupuncture for tapering off long-term benzodiazepine use: A randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of using electroacupuncture as an adjunct treatment in enhancing the benzodiazepine cessation rate in long-term benzodiazepine users. METHODS: This was a randomized, assessor- and subject-blinded, controlled trial. One hundred and forty-four long-term benzodiazepine users were randomly assigned to receive either electroacupuncture or placebo acupuncture (a sham itervention using non-invasive placebo needles) combined with a gradual benzodiazepine tapering schedule for 4 weeks. The primary outcome was the cessation rate of benzodiazepine use. Subjects were assessed on their benzodiazepine usage, benzodiazepine withdrawal symptoms, insomnia severity, and anxiety and depressive symptoms at baseline, week 6 and week 16. RESULTS: The cessation rates of the electroacupuncture and placebo acupuncture groups at 12 weeks post-treatment were 9.17% and 10.83%, respectively. Both groups showed a reduction in benzodiazepine usage by a self-completed drug record at week 16 (compared to baseline: electroacupuncture group -40.23% versus placebo acupuncture group -48.76%). However, no significant between-group differences were found in the benzodiazepine cessation rate, reduction in benzodiazepine usage, and other secondary measures across all the study time points. CONCLUSIONS: Electroacupuncture showed a similar cessation rate in benzodiazepine use to that of non-invasive placebo acupuncture in long-term users during a 4-week gradual tapering schedule. The evidence did not support advantages of electroacupuncture over non-invasive placebo acupuncture on reducing insomnia, anxiety, depression, or other withdrawal symptoms during the gradual tapering schedule. Despite a 40% decrease in the benzodiazepine usage in both groups, the effects may be attributed to the non-specific effects of acupuncture. TRIAL REGISTRATION: ClinicalTrials.gov # NCT02475538.

Work-Related Stressors and Increased Risk of Benzodiazepine Long-Term Use: Findings From the CONSTANCES Population-Based Cohort.

Objectives. To examine whether stressful job exposure to the public could be associated with having long-term benzodiazepine use.Methods. From the participants included between 2012 and 2016 in the French population-based CONSTANCES cohort, 13 934 men and 19 261 women declared a daily job exposure to the public and rated the frequency of stressful exposure. We examined benzodiazepine long-term use by using drug reimbursement administrative registries. Logistic regressions provided odds ratios (ORs) of benzodiazepine long-term use, with stratification for gender and adjustment for age, education, and area deprivation index. Occupational grade, job strain, depression, self-rated health, and alcohol use disorder were additional stratification variables.Results. Benzodiazepine long-term use was positively associated with stressful exposure to the public ("often or always" vs "rarely or never") in men (OR = 2.2; 95% confidence interval [CI] = 1.8, 2.8) and women (OR = 1.6; 95% CI = 1.4, 1.9), with dose-dependent relationships (P trends < .001). Adjustments and analyses in subgroups without other individual or environmental vulnerability factors led to similar results.Conclusions. Stressful job exposure to the public increases the risk of benzodiazepine long-term use. Prevention programs aiming at reducing the burden of benzodiazepine long-term use would benefit in targeting this specific population.

Correlates of Benzodiazepine Use and Adverse Outcomes Among Patients with Chronic Pain Prescribed Long-term Opioid Therapy.

OBJECTIVE: To examine the correlates and odds of receiving overlapping benzodiazepine and opioid prescriptions and whether co-prescription was associated with greater odds of falling or visiting the emergency department. DESIGN: Cross-sectional study. SETTING: A large private integrated health system and a Veterans Health Administration integrated health system. SUBJECTS: Five hundred seventeen adults with musculoskeletal pain and current prescriptions for long-term opioid therapy. METHODS: A multivariate logistic regression model examined correlates of having overlapping benzodiazepine and opioid prescriptions in the year before enrollment in the cross-sectional study. Negative binomial models analyzed the number of falls in the past three months and past-year emergency department visits. In addition to propensity score adjustment, models controlled for demographic characteristics, psychiatric diagnoses, medications, overall comorbidity score, and opioid morphine equivalent dose. RESULTS: Twenty-five percent (N = 127) of participants had co-occurring benzodiazepine and opioid prescriptions in the prior year. Odds of receiving a benzodiazepine prescription were significantly higher among patients with the following psychiatric diagnoses: anxiety disorder (adjusted odds ratio [AOR] = 4.71, 95% confidence interval [CI] = 2.67-8.32, P < 0.001), post-traumatic stress disorder (AOR = 2.24, 95% CI = 1.14-4.38, P = 0.019), and bipolar disorder (AOR = 3.82, 95% CI = 1.49-9.81, P = 0.005). Past-year overlapping benzodiazepine and opioid prescriptions were associated with adverse outcomes, including a greater number of falls (risk ratio [RR] = 3.27, 95% CI = 1.77-6.02, P = 0.001) and emergency department visits (RR = 1.66, 95% CI = 1.08-2.53, P = 0.0194). CONCLUSIONS: Among patients with chronic pain prescribed long-term opioid therapy, one-quarter of patients had co-occurring prescriptions for benzodiazepines, and dual use was associated with increased odds of falls and emergency department visits.

Phantom menace: novel psychoactive substances and the UK Armed Forces.

Novel psychoactive substances (NPS) encompass a large group of synthesised compounds specifically designed to mimic traditional recreational drugs. Current UK Armed Forces compulsory drug testing does not screen for these substances, making them tempting to the small proportion of UK Armed Forces personnel who indulge in recreational drug use. The acute and chronic sequelae of NPS misuse are widely variable and associated with high morbidity. In this paper, we discuss NPS pharmacology and clinical presentation. We describe toxidromes and management of patients who have misused NPS.Finally, we reflect on the legal, ethical and military consequences of NPS misuse for both the service person misusing NPS and the Military Physician providing their care.