Use Of Adjunctive Medications Research Articles

Assessment of a Hospital-Wide CIWA-Ar Protocol for Management of Alcohol Withdrawal Syndrome.

ObjectiveTo determine if a hospital-wide symptom-based alcohol withdrawal protocol may result in significant clinical improvements to patient outcomes, safety, and hospital efficiency.MethodsRetrospective/prospective cohort study between January 1, 2016 and December 31, 2016 (pre-protocol), and between March 1, 2017 and August 7, July 2017 (post-protocol). Pre-protocol patients were identified retrospectively using International Classification of Diseases, 10th revision codes (F10.1, F10.2, and Z71.4). Post-protocol patients were identified by the use of a unique alcohol withdrawal order set in their electronic medical record. The primary endpoint was average length of stay. Secondary outcomes included death, escalation of care as defined as requiring intensive care unit (ICU) consultation or the rapid response team, average ICU length of stay, respiratory failure, average benzodiazepine usage, and incidence of seizures.ResultsThe study included 276 patients in the pre-protocol group and 145 patients in the post-protocol group. There was a significant reduction found in the primary endpoint of average length of stay (7.15 ± 6.5 days vs 5.7 ± 5.6 days; P=.02). There was a significant reduction in the average benzodiazepine use, use of adjunctive medications, need for ICU consultation or rapid response team, respiratory failure, average ICU length of stay, use of neurologic imaging, and the need for lumbar puncture.ConclusionImplementation of a Clinical Institute Withdrawal Assessment for Alcohol, Revised–based alcohol withdrawal protocol may significantly improve quality of care, patient safety, and treatment effectiveness in a large, mixed medical/surgical, urban community-based academic medical center.

Optimizing Preanesthesia Care for the Gynecologic Patient.

In the past, best practices for perioperative management have been based as much on dogma as science. The creation of optimized perioperative pathways, known as enhanced recovery after surgery, has been shown to simultaneously improve patient outcomes and reduce cost. In this article, we critically review interventions (and omission of interventions) that should be considered by every surgical team to optimize preanesthesia care. This includes patient education, properly managing existing medical comorbidities, optimizing nutrition, and the use of medications before incision that have been shown to reduce surgical stress, opioid requirements, and postoperative complications. Anesthetic techniques, the use of adjunct medications administered after incision, and postoperative management are beyond the scope of this review. When possible, we have relied on randomized trials, meta-analyses, and systematic reviews to support our recommendations. In some instances, we have drawn from the general and colorectal surgery literature if evidence in gynecologic surgery is limited or of poor quality. In particular, hospital systems should aim to adhere to antibiotic and thromboembolic prophylaxis for 100% of patients, the mantra, "nil by mouth after midnight" should be abandoned in favor of adopting a preoperative diet that maintains euvolemia and energy stores to optimize healing, and bowel preparation should be abandoned for patients undergoing gynecologic surgery for benign indications and minimally invasive gynecologic surgery.

Impact of a pharmacist-directed pain management service on inpatient opioid use, pain control, and patient safety.

To evaluate the impact of a pharmacy-directed pain management service (PPMS) designed to optimize analgesic pharmacotherapy, minimize adverse events, and improve patients' experience of pain management. A retrospective analysis was conducted to evaluate the PPMS consisting of 3 dedicated pain management clinical pharmacists who perform both consult-based and stewardship functions. Multiple measures of opioid use and associated patient satisfaction outcomes during 3-year periods before and after implementation of the PPMS were compared. Significant decreases in use of institutionally defined high-risk opioid medications (e.g., parenteral hydromorphone, fentanyl, transdermal fentanyl patches), a decrease in total institutional opioid use, increased coanalgesic and adjunctive medication use, and a decrease in rapid response team (RRT) and code blue events associated with opioid-induced oversedation were seen after service implementation. Despite decreased opioid use, available patient satisfaction data suggested ongoing improvement in associated Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey domains. Our data highlights the impact of a pharmacy directed pain management service on institutional opioid use with available data suggesting improved patient satisfaction scores and indirect cost savings. Despite decreased opioid use, available patient satisfaction data suggested ongoing improvement in associated HCAHPS survey pain management domains.

A Review of Opioid-Sparing Modalities in Perioperative Pain Management: Methods to Decrease Opioid Use Postoperatively.

There is an epidemic of opioid use, abuse, and misuse in the United States, which results in significant morbidity and mortality. It may be difficult to reduce perioperative opioid use given known acute surgical trauma and resultant pain; however, the discrete and often limited nature of postoperative pain also may make management easier in part by utilizing nonopioid modalities, such as regional anesthesia/analgesia, and multimodal analgesia, which may decrease the need for powerful opioids. This article reviews the relevant literature describing the use of adjunct medications, regional anesthesia and analgesic techniques, and regional block additives in the context of providing adequate pain control while lessening opioid use.

Evaluating Clinical Effectiveness and Pharmacokinetic Profile of Atomized Intranasal Midazolam in Children Undergoing Laceration Repair

BackgroundAtomized intranasal midazolam is a common adjunct in pediatrics for procedural anxiolysis. There are no previous studies of validated anxiety scores with pharmacokinetic data to support optimal procedure timing. ObjectivesWe describe the clinical and pharmacokinetic profile of atomized intranasal midazolam in children presenting for laceration repair. MethodsChildren 11 months to 7 years of age and weighing <26 kg received 0.4 mg/kg of atomized intranasal midazolam for simple laceration repair. Blood samples were obtained at 3 time points in each patient, and the data were fit with a 1-compartment model. Patient anxiety was rated with the Observational Scale of Behavioral Distress. Secondary outcomes included use of adjunctive medications, successful completion of procedure, and adverse events. ResultsSixty-two subjects were enrolled, with a mean age of 3.3 years. The median time to peak midazolam concentration was 10.1 min (interquartile range 9.7–10.8 min), and the median time to the procedure was 26 min (interquartile range 21–34 min). There was a trend in higher Observational Scale of Behavioral Distress scores during the procedure. We observed a total of 2 adverse events, 1 episode of vomiting (1.6%) and 1 paradoxical reaction (1.6%). Procedural completion was successful in 97% of patients. ConclusionsAtomized intranasal midazolam is a safe and effective anxiolytic to facilitate laceration repair. The plasma concentration was >90% of the maximum from 5 to 17 min, suggesting this as an ideal procedural timeframe after intranasal midazolam administration.

A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease.

Up to 40% of patients report persistent gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy. This review outlines the evidence for medical therapy for PPI nonresponsive GERD. A literature search for GERD therapies from 2005 to 2015 in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews identified 2928 unique citations. Of those, 40 unique articles specific to the impact of PPI metabolizer genotype on PPI response and the use adjunctive medical therapies were identified. Thirteen articles reported impacts on CYP genotypes on PPI metabolism demonstrating lower endoscopic healing rates in extensive metabolizers; however, outcomes across genotypes were more uniform with more CYP independent PPIs rabeprazole and esomeprazole. Twenty-seven publications on 11 adjunctive medications showed mixed results for adjunctive therapies including nocturnal histamine-2 receptor antagonists, promotility agents, transient lower esophageal sphincter relaxation inhibitors, and mucosal protective agents. Utilizing PPI metabolizer genotype or switching to a CYP2C19 independent PPI is a simple and conservative measure that may be useful in the setting of incomplete acid suppression. The use of adjunctive medications can be considered particularly when the physiologic mechanism for PPI nonresponse is suspected. Future studies using adjunctive medications with improved study design and patient enrollment are needed to better delineate medical management options before proceeding to antireflux interventions.

Discontinuing benzodiazepines: best practices.

In July 2015, the Canadian Agency for Drugs and Technologies in Health (CADTH) released a Rapid Response report summary, with a critical appraisal, on discontinuation strategies for patients with long-term benzodiazepines (BDZ) use. The CADTH document is a review of the literature. It includes studies whose intervention is BDZ discontinuation. Also, clinical guidelines, systematic reviews and meta-analyses are included. What emerges from the CADTH guidelines is that the best strategy remains gradual tapering of BDZ with little evidence for the use of adjunctive medications. The results show that simple interventions such as discontinuation letters from clinicians, self-help information and support in general, added to gradual tapering may be associated with a two- to three-fold higher chance of successful withdrawal, compared with treatment as usual. We suggest possible implications for day-to-day clinical practice.

83: Management of Infants with Neonatal Abstinence Syndrome

The rate of neonatal abstinence syndrome (NAS) has risen dramatically in North America, resulting in increased health care resource utilization. Marked variation in management of NAS has been reported in the United States and Europe, but data from Canada are limited. Describe current NAS management practices in NICUs in Canada, including location for infant monitoring (admission to NICU vs. room-in with mother); location for pharmacological treatment; use of cardiorespiratory monitors when pharmacological treatment is initiated; breastfeeding recommendations; and discharge of infants on medication. Qualified personnel in all Level II and Level III NICUs in Canada were emailed to request their participation, with follow-up if no response was received. A medical resident administered a structured, pre-tested telephone survey and data were analyzed using SPSS. Surveys were completed by 65 of 103 units (63.1%). Common practices included having a written NAS practice guideline (92.3%); using the original or modified Finnegan's scoring system to monitor NAS signs (89.5%); using non-pharmacological treatment methods (e.g. dim lights, swaddling) (100%); using morphine as the first-line medication (96.9%); using monitors routinely during pharmacological treatment (93.8%); and admitting infants to the NICU for pharmacological treatment (89.2%). Practices that showed greater variability included where high-risk infants are observed (44.6% in the NICU, 52.3% rooming-in with the mother, 3.1% in either location or on a pediatric ward); use of adjunct medications (65.1% use overall with phenobarbital used most commonly [82.9%] followed by clonidine [41.5%]); breastfeeding practices (53.8% always encourage breastfeeding, 44.6% discourage breastfeeding if the mother is using illicit drugs, and 1.5% make recommendations on a case-by-case basis); and discharge of infants on first-line (36.9%) and adjunct medications (38.9%), where used. While most NICUs surveyed follow similar practices in scoring NAS signs and use of non-pharmacological and first-line pharmacological treatment, there is notable variation in practices related to parent involvement in care, such as maintaining the mother-infant dyad during monitoring and treatment, encouraging breastfeeding, and discharging the infant on medication. This underscores the need for further research that can be translated into best practices.

Implementation of a CIWA-Ar alcohol withdrawal protocol in a veterans hospital.

The South Texas Veterans Health Care System (STVHCS) implemented a Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)-based alcohol-withdrawal protocol in June 2013. The aim of this study was to determine the efficacy and safety of the new protocol. The primary objective was the evaluation of whether implementation of the CIWA-Ar alcohol-withdrawal protocol decreased the average length of hospital stay for patients admitted with alcohol withdrawal syndrome (AWS) as compared with treatment before the introduction of the protocol. Secondary endpoints evaluated benzodiazepine (BZD)-prescribing practices, use of adjunctive medications for AWS, and safety outcomes. We reviewed 748 admissions with documented AWS or alcohol-related diagnoses during the study periods of July 2012 to December 2012 (preprotocol) and July 2013 to December 2013 (postprotocol). Patients in the preprotocol group needed to have a scheduled dose of a BZD in the electronic medical record, and those assigned to the postprotocol group needed to have at least one documented CIWA-Ar note in their electronic medical record. Exclusion criteria included prior conditions that interfered with accurate treatment of alcohol withdrawal. There were no statistical differences in baseline characteristics between groups. No difference was found in the primary endpoint of length of stay when comparing hospitalizations pre- and postprotocol implementation (3.84 ± 2.31 days vs 3.82 ± 2.7 days; P = 0.667). There was no statistical significance in total cumulative dose of BZD, daily dose of BZD, or duration of BZD use when compared pre- and postprotocol. No safety events requiring further intervention occurred. Implementation of a CIWA-Ar protocol at our institution did not result in a decreased duration of hospital stay; however, a decline in prescribing fixed-schedule BZDs was documented.

Neonatal abstinence syndrome: evaluating the effectiveness of an evidence-based multidisciplinary care approach.

An evidence-based, multidisciplinary neonatal abstinence syndrome protocol was developed using a stepwise continuous quality improvement (CQI) approach with the goal of standardizing care procedures for these infants. A retrospective secondary data analysis was performed to evaluate the differential effects of each step of the CQI project on 4 key clinical outcome measures: length of stay (total and post-opioid wean), weaning time from opioids, and use of adjunct medications. Data were analyzed from 386 newborn infants with a diagnosis of neonatal abstinence syndrome undergoing treatment in a level III neonatal intensive care unit. After implementation of a pharmacologic weaning protocol as a foundational first step of the CQI project, the weaning time from opioids remained stable throughout each of the subsequent CQI steps (P = .905). The overall total neonatal intensive care unit length of stay was reduced by 10.35 days (P = .002), and the length of neonatal intensive care unit stay after completing wean from opioids was reduced by 2.79 days (P < .001). Use of adjunct medications also decreased from 30.1% of infants at the initiation of the CQI project to 24.5% at the completion of the project (P = .020). These findings indicate that this multidisciplinary treatment approach led to an overall improved efficiency of both opioid weaning and symptom management for these infants.

Evaluation of a symptom-triggered protocol approach to the management of alcohol withdrawal syndrome in older adults.

To evaluate whether implementation of symptom-triggered administration of a benzodiazepine protocol reduces the severity (total cumulative dose), duration, and complications of alcohol withdrawal syndrome (AWS). Retrospective health record review. Tertiary care center in Vancouver, Canada. Individuals aged 70 and older admitted to the Acute Care for Elders and Acute Medicine Unit wards with diagnostic codes for AWS from 2008 to 2012. Median duration and cumulative dose of benzodiazepine treatment, number of severe AWS complications, severe benzodiazepine-associated adverse effects, and need for adjunct therapy. Thirty-three participants in the preprotocol group and 30 in the protocol-implemented group met the inclusion criteria. Median duration of benzodiazepine treatment decreased from 96 hours (interquartile range (IQR) 72-120 hours) in the preprotocol period to 48 hours (IQR 0-108 hours; P=.04), and median cumulative benzodiazepine dose administered decreased from 9 mg (IQR 5-19.8 mg) to 3 mg (IQR 0-10 mg; P=.001). Statistically significantly lower incidence of severe AWS complications (P=.007) and adjunct therapy use (P=.02) was seen in the protocol-implemented group. A symptom-triggered protocol for dosing of benzodiazepine therapy in the management of AWS in individuals aged 70 and older significantly reduced the total duration of benzodiazepine use, cumulative benzodiazepine dose, and use of adjunctive medications in the treatment of AWS.

Central changes associated with chronic pelvic pain and endometriosis.

Chronic pelvic pain (CPP) is a significant public health problem with 1 million affected women in the UK. Although many pathologies are associated with CPP, the pain experienced is often disproportionate to the extent of disease identified and frequently no pathology is found (chronic pelvic pain syndrome). The central nervous system (CNS) is central to the experience of pain and chronic pain conditions in general are associated with alterations in both the structure and function of the CNS. This review describes the available evidence for central changes in association with conditions presenting with CPP. A detailed literature search was performed to identify relevant papers, however, this is not a systematic review. CPP is associated with central changes similar to those identified in other pain conditions. Specifically these include, alterations in the behavioural and central response to noxious stimulation, changes in brain structure (both increases and decreases in the volume of specific brain regions), altered activity of both the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS) and psychological distress. The evidence reviewed in this paper demonstrates that CPP is associated with significant central changes when compared with healthy pain-free women. Moreover, the presence of these changes has the potential to both exacerbate symptoms and to predispose these women to the development of additional chronic conditions. These findings support the use of adjunctive medication targeting the CNS in these women.

Poster #S145 HEALTH-RELATED QUALITY OF LIFE OUTCOMES AMONG PATIENTS WITH SCHIZOPHRENIA: RESULTS FROM A LONG-TERM NATURALISTIC TRIAL OF PATIENTS SWITCHING TO LURASIDONE FROM OTHER ANTIPSYCHOTICS

The most commonly used pharmacologic therapies for bipolar depression are mood stabilizers, atypical antipsychotics, and antidepressants. This paper reviews common side effects associated with these medications and provides recommendations for managing adverse medication effects in clinical practice.Narrative review based on literature searches of Medline and evidence-based treatment guidelines for agents that have been approved by the US Food and Drug Administration and/or are commonly used to treat bipolar depression.Side effects of bipolar depression pharmacotherapies are common and vary by medication, with weight gain, metabolic dysregulation, sedation/somnolence, and akathisia among those observed most frequently. These adverse events (weight gain and sedation/somnolence, in particular) negatively affect treatment adherence in patients with bipolar disorder. Furthermore, endocrine and metabolic comorbidities, weight gain, and obesity may reduce the likelihood of positive clinical responses to pharmacologic therapies. Clinicians may consider switching patients to bipolar depression medication(s) with a lower propensity for sedation or adverse metabolic effects. Lifestyle modification (e.g., dietary changes, exercise) is an important component in the treatment of weight gain/obesity, dyslipidemia, hypertension, and hyperglycemia; in addition, a wide range of medications are available as therapeutic options for patients in whom non-pharmacologic management strategies are insufficient. The use of adjunctive medication may also reduce treatment-related sedation and somnolence.The selection of relevant studies from the literature search relied primarily on the author's expertise in the area of bipolar depression and knowledge of the issues addressed.Successful treatment of bipolar depression extends beyond managing mood symptoms to also monitoring adverse medication events and managing associated medical disorders.

S.25.03 Pharmacogenetics of efficacy and treatment side effects in bipolar disorder

The most commonly used pharmacologic therapies for bipolar depression are mood stabilizers, atypical antipsychotics, and antidepressants. This paper reviews common side effects associated with these medications and provides recommendations for managing adverse medication effects in clinical practice.Narrative review based on literature searches of Medline and evidence-based treatment guidelines for agents that have been approved by the US Food and Drug Administration and/or are commonly used to treat bipolar depression.Side effects of bipolar depression pharmacotherapies are common and vary by medication, with weight gain, metabolic dysregulation, sedation/somnolence, and akathisia among those observed most frequently. These adverse events (weight gain and sedation/somnolence, in particular) negatively affect treatment adherence in patients with bipolar disorder. Furthermore, endocrine and metabolic comorbidities, weight gain, and obesity may reduce the likelihood of positive clinical responses to pharmacologic therapies. Clinicians may consider switching patients to bipolar depression medication(s) with a lower propensity for sedation or adverse metabolic effects. Lifestyle modification (e.g., dietary changes, exercise) is an important component in the treatment of weight gain/obesity, dyslipidemia, hypertension, and hyperglycemia; in addition, a wide range of medications are available as therapeutic options for patients in whom non-pharmacologic management strategies are insufficient. The use of adjunctive medication may also reduce treatment-related sedation and somnolence.The selection of relevant studies from the literature search relied primarily on the author's expertise in the area of bipolar depression and knowledge of the issues addressed.Successful treatment of bipolar depression extends beyond managing mood symptoms to also monitoring adverse medication events and managing associated medical disorders.

Seizures From Valproate–Carbapenem Interaction

Antiepileptic medication interactions can complicate the management of epilepsy, by either increasing or reducing the effective serum concentrations thereby causing adverse effects or loss of seizure control. A 14-year-old girl with well-controlled juvenile absence epilepsy lost control of her seizures acutely following the administration of carbapenem for pneumonia. Serum valproate concentrations fell by 90% within 48hours following carbapenem and returned to baseline following its discontinuation. Awareness of this clinically significant interaction alters clinical practice by avoiding carbapenem or temporary use of adjunctive medication to prevent the clinical consequences of this significant drug interaction.

The long-term outcomes of heroin dependent-treatment-resistant patients with bipolar 1 comorbidity after admission to enhanced methadone maintenance

ObjectiveThe aim of this study was to compare the long-term outcomes of treatment-resistant bipolar 1 heroin addicts with peers who were without DSM-IV axis I psychiatric comorbidity (dual diagnosis). Method104 Heroin-dependent patients (TRHD), who also met criteria for treatment resistance – 41 of them with DSM-IV-R criteria for Bipolar 1 Disorder (BIP1-TRHD) and 63 without DSM-IV-R axis I psychiatric comorbidity (NDD-TRHD) – were monitored prospectively (3 years on average, min. 0.5, max. 8) along a Methadone Maintenance Treatment Programme (MMTP). ResultsThe rates for survival-in-treatment were 44% for NDD-TRHD patients and 58% for BIP1-TRHD patients (p=0.062). After 3 years of treatment such rates tended to become progressively more stable. BIP1-TRHD patients showed better outcome results than NDD-TRHD patients regarding CGI severity (p<0.001) and DSM-IV GAF (p<0.001). No differences were found regarding urinalyses for morphine between groups during the observational period. Bipolar 1 patients needed a higher methadone dosage in the stabilization phase, but this difference was not statistically significant. LimitationsThe observational nature of the protocol, the impossibility of evaluating a follow-up in the case of the patients who dropped out, and the multiple interference caused by interindividual variability, the clinical setting and the temporary use of adjunctive medications. ConclusionsContrary to expectations, treatment-resistant patients with bipolar 1 disorder psychiatric comorbidity showed a better long-term outcome than treatment-resistant patients without psychiatric comorbidity.

Pain Management After Surgery for Single-Ventricle Palliation Using the Hybrid Approach

The hybrid pathway for the management of patients with hypoplastic left heart syndrome was pioneered at our institution and is the preferred approach compared with the traditional Norwood pathway. Patients undergoing this surgery are generally <6 months of age, and pain management in this age group after surgery for complex congenital heart disease (CHD) may be particularly challenging. We retrospectively reviewed our pain-management strategy after stage 1 hybrid procedure (HS1) and evaluated its efficacy, especially in the setting of early tracheal extubation. We retrospectively reviewed the records of patients receiving fentanyl analgesia after HS1 palliation for single-ventricle anatomy between June 2008 and August 2011. In addition to demographic data, we also recorded the mode of analgesia, total fentanyl administered during the first 48 postoperative hours, and total hours of fentanyl use. Other data collected included pain scores, adverse effects, time of tracheal extubation, and use of adjunctive medications, such as dexmedetomidine. Nurse-controlled analgesia (NCA) with fentanyl was used in 21 of the 33 patients in the study cohort, with the remainder receiving a continuous fentanyl infusion. NCA-fentanyl was the method of choice in 12 of the 13 patients whose tracheas were extubated in the operating room versus 9 of 20 patients who received postoperative mechanical ventilation and tracheal intubation (p = 0.0093). During the first and second 24 h after surgery, fentanyl requirements were lower in patients whose tracheas were extubated (11.8 ± 7.6 vs. 20.6 ± 18.1 and 6.6 ± 10.3 vs. 24.3 ± 20.4 μg/kg, respectively). Adverse effects were noted in 3 of the 33 patients (9%) and included one episode each of respiratory depression requiring reintubation of the trachea, pruritus, and excessive sedation. Dexmedetomidine was used as an adjunct medication in 5 patients and resulted in decreased fentanyl use (6.3 ± 1.3 vs. 19 ± 15.9 μg/kg in the first 24 postoperative hours and 7.9 ± 3.5 vs. 19 ± 20.3 μg/kg in the second 24 postoperative hours). Fentanyl administered by way of continuous infusion or NCA provided effective postoperative analgesia with a limited adverse effect profile after HS1 surgery in neonates with complex CHD. Fentanyl requirements were lower in patients who achieved early tracheal extubation as well as those who received dexmedetomidine.

Evaluation of an Alcohol Withdrawal Protocol and a Preprinted Order Set at a Tertiary Care Hospital

Alcohol withdrawal protocols involving symptom-triggered administration of benzodiazepine have been established to reduce the duration of treatment and the cumulative benzodiazepine dose (relative to usual care). However, the effects of a protocol combining fixed-schedule and symptom-triggered benzodiazepine dosing are less clear. To assess the efficacy and safety of a combination fixed-scheduled and symptom-triggered benzodiazepine dosing protocol for alcohol withdrawal, relative to usual care, for medical inpatients at a tertiary care hospital. A chart review of admissions to the internal medicine service for alcohol withdrawal was conducted to compare treatment outcomes before (October 2005 to April 2007) and after (October 2007 to April 2009) implementation of the combination protocol. The primary outcome was duration of benzodiazepine treatment for alcohol withdrawal. The secondary outcomes were cumulative benzodiazepine dose administered, safety implications, and use of adjunctive medications. A total of 159 patients met the inclusion criteria. Assessable data were available for 71 charts from the pre-implementation period and 72 charts from the post-implementation period. The median duration of benzodiazepine treatment was 91 h before implementation and 57 h after implementation (p < 0.001). Use of the protocol was also associated with a significant reduction in severe complications of alcohol withdrawal (50% versus 33%, p = 0.019), median cumulative benzodiazepine dose (in lorazepam equivalents) (20.0 mg versus 15.5 mg, p = 0.026), and use of adjunctive medications (65% versus 38%, p = 0.001). The incidence of serious adverse outcomes of treatment with benzodiazepines was not significantly different between the 2 groups. Implementation of an alcohol withdrawal protocol with a combination of fixed-schedule and symptom-triggered benzodiazepine dosing in a medical ward was associated with a shorter duration of benzodiazepine use and a lower incidence of severe complications of alcohol withdrawal.

Adherence in Glaucoma: Objective Measurements of Once-Daily and Adjunctive Medication Use

To determine with electronic monitoring an objective measurement of adherence in two populations of subjects: those using once-daily prostaglandin analogs as sole ocular hypotensive therapy (one-drug group) and those requiring an adjunctive medicine to the prostaglandin analog (two-drug group). Single-site, open-label, nonrandomized, parallel design of 60 days. Sixty-two consecutive adult subjects with a diagnosis of open-angle glaucoma (OAG) or ocular hypertension: 31 were taking one drug and 31 were taking two drugs. An electronic event medication monitoring device was used to record each bottle opening. The main outcome measures were dosing errors (number of under-adherence or over-adherence events) and coverage (proportion of pharmacologic duration covered by dosing) relative to the ophthalmologist-prescribed regimen. Adherence to the prostaglandins once daily was good in both groups by all measures (<or=10% of subjects with more than five dosing errors and mean coverage of 97.2% +/- 6.1%). Adherence to the second medication in the two-drug group was poorer (37% of subjects with more than five dosing errors and mean coverage of 85.6% +/- 12.6%). For the subjects using beta-adrenoceptor antagonists, 24.8% +/- 18.4% of doses were taken at less than 10-hour intervals (over-adherence). The incorporation of a time component in electronic monitoring provides more information than prescription refill rate or other methods. We found that more complex dosing regimens result in poorer adherence, although once-daily drugs in a complex dosing regimen were found to have good adherence.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.