Pharmacist led homeless outreach engagement and non-medical independent prescribing (Rx) (PHOENIx) intervention for people experiencing homelessness: a non- randomised feasibility study.

BACKGROUND: Homelessness and associated mortality and multimorbidity rates are increasing. Systematic reviews have demonstrated a lack of complex interventions that decrease unscheduled emergency health services utilisation or increase scheduled care. Better evidence is needed to inform policy responses. We examined the feasibility of a complex intervention (PHOENIx: Pharmacist led Homeless Outreach Engagement Nonmedical Independent prescribing (Rx)) to inform a subsequent pilot randomised controlled trial (RCT). METHODS: Non-randomised trial with Usual Care (UC) comparator group set in Greater Glasgow and Clyde Health Board, Scotland. Participants were adult inpatients experiencing homelessness in a city centre Glasgow hospital, referred to the PHOENIx team at the point of hospital discharge, from 19th March 2018 until 6th April 2019. The follow up period for each patient started on the day the patient was first seen (Intervention group) or first referred (UC), until 24th August 2019, the censor date for all patients. All patients were offered and agreed to receive serial consultations with the PHOENIx team (NHS Pharmacist prescriber working with Simon Community Scotland (third sector homeless charity worker)). Patients who could not be reached by the PHOENIx team were allocated to the UC group. The PHOENIx intervention included assessment of physical/mental health, addictions, housing, benefits and social activities followed by pharmacist prescribing with referral to other health service specialities as necessary. All participants received primary (including specialist homelessness health service based general practitioner care, mental health and addictions services) and secondary care. Main outcome measures were rates of: recruitment; retention; uptake of the intervention; and completeness of collected data, from recruitment to censor date. RESULTS: Twenty four patients were offered and agreed to participate; 12 were reached and received the intervention as planned with a median 7.5 consultations (IQR3.0-14.2) per patient. The pharmacist prescribed a median of 2 new (IQR0.3-3.8) and 2 repeat (1.3-7.0) prescriptions per patient; 10(83%) received support for benefits, housing or advocacy. Twelve patients were not subsequently contactable after leaving hospital, despite agreeing to participate, and were assigned to UC. Two patients in the UC group died of drug/alcohol overdose during follow up; no patients in the Intervention group died. All 24 patients were retained in the intervention or UC group until death or censor date and all patient records were accessible at follow up: 11(92%) visited ED in both groups, with 11(92%) hospitalisations in intervention group, 9(75%) UC. Eight (67%) intervention group patients and 3(25%) UC patients attended scheduled out patient appointments. CONCLUSIONS: Feasibility testing of the PHOENIx intervention suggests merit in a subsequent pilot RCT.

Towards Climate Resilient and Environmentally Sustainable Health Care Facilities.

The aim of building climate resilient and environmentally sustainable health care facilities is: (a) to enhance their capacity to protect and improve the health of their target communities in an unstable and changing climate; and (b) to empower them to optimize the use of resources and minimize the release of pollutants and waste into the environment. Such health care facilities contribute to high quality of care and accessibility of services and, by helping reduce facility costs, also ensure better affordability. They are an important component of universal health coverage. Action is needed in at least four areas which are fundamental requirements for providing safe and quality care: having adequate numbers of skilled human resources, with decent working conditions, empowered and informed to respond to these environmental challenges; sustainable and safe management of water, sanitation and health care waste; sustainable energy services; and appropriate infrastructure and technologies, including all the operations that allow for the efficient functioning of a health care facility. Importantly, this work contributes to promoting actions to ensure that health care facilities are constantly and increasingly strengthened and continue to be efficient and responsive to improve health and contribute to reducing inequities and vulnerability within their local settings. To this end, we propose a framework to respond to these challenges.

Extending the use of the World Health Organisations' water sanitation and hygiene assessment tool for surveys in hospitals - from WASH-FIT to WASH-FAST.

BACKGROUND: Poor water sanitation and hygiene (WASH) in health care facilities increases hospital-associated infections, and the resulting greater use of second-line antibiotics drives antimicrobial resistance. Recognising the existing gaps, the World Health Organisations' Water and Sanitation for Health Facility Improvement Tool (WASH-FIT) was designed for self-assessment. The tool was designed for small primary care facilities mainly providing outpatient and limited inpatient care and was not designed to compare hospital performance. Together with technical experts, we worked to adapt the tool for use in larger facilities with multiple inpatient units (wards), allowing for comparison between facilities and prompt action at different levels of the health system. METHODS: We adapted the existing facility improvement tool (WASH-FIT) to create a simple numeric scoring approach. This is to illustrate the variation across hospitals and to facilitate monitoring of progress over time and to group indicators that can be used to identify this variation. Working with stakeholders, we identified those responsible for action to improve WASH at different levels of the health system and used piloting, analysis of interview data to establish the feasibility and potential value of the WASH Facility Survey Tool (WASH-FAST) to demonstrate such variability. RESULTS: We present an aggregate percentage score based on 65 indicators at the facility level to summarise hospitals' overall WASH status and how this varies. Thirty-four of the 65 indicators spanning four WASH domains can be assessed at ward level enabling within hospital variations to be highlighted. Three levels of responsibility for WASH service monitoring and improvement were identified with stakeholders: the county/regional level, senior hospital management and hospital infection prevention and control committees. CONCLUSION: We propose WASH-FAST can be used as a survey tool to assess, measure and monitor the progress of WASH in hospitals in resource-limited settings, providing useful data for decision making and tracking improvements over time.

Predicting Unbound Phenytoin Concentrations: Effects of Albumin Concentration and Kidney Dysfunction.

STUDY OBJECTIVE: Several methods are available to predict unbound (free) phenytoin concentrations in patients with hypoalbuminemia; however, predictive methods have not been evaluated in patients with concurrent hypoalbuminemia and kidney dysfunction or in patients with mild to moderate (estimated glomerular filtration rate [eGFR] 30-90 ml/min/1.73 m2 ) kidney dysfunction alone. Thus the objective was to evaluate the accuracy and precision of predictive methods to estimate free phenytoin concentrations in patients with varying albumin concentrations and/or kidney dysfunction. DESIGN: Retrospective chart review. SETTING: Large academic medical center. PATIENTS: A total of 344 patients with free and total phenytoin, albumin, and serum creatinine concentrations obtained between November 2012 and May 2017. MEASUREMENTS AND MAIN RESULTS: Free phenytoin concentrations were estimated in patients without kidney dysfunction using the Winter-Tozer, Anderson, Kane, and Cheng equations. For the analysis in patients with eGFR lower than 90 ml/min/1.73 m2 , free phenytoin concentrations were estimated using the Shiner-Tozer derivation with adjusted affinity coefficients (C = 0.15, 0.20, 0.25, and 0.30). For both analyses, accuracy of predictive methods was evaluated by P20, the proportion of estimations within 20% of the measured free phenytoin concentration. In 158 patients with normal kidney function/normal albumin concentrations, 73 with normal kidney function/hypoalbuminemia, or 47 with mild kidney dysfunction/normal albumin concentrations, the Anderson method had the highest accuracy (86%, 82%, and 92%, respectively) and highest precision compared with the other methods. In 47 patients with normal albumin concentrations and mild kidney dysfunction or 13 with moderate kidney dysfunction, the free fraction was unchanged, and total phenytoin concentrations accurately reflected free concentrations. In 17 patients with hypoalbuminemia and mild or 17 with moderate kidney dysfunction, the Winter-Tozer (67% and 50%, respectively) and the Anderson (56% and 67%, respectively) methods had the highest accuracy compared with other methods with significantly lower accuracy compared with patients with normal kidney function. In the 14 patients with severe kidney dysfunction and hypoalbuminemia, none of the coefficients had a P20 accuracy greater than 45%. CONCLUSION: In patients with normal albumin concentrations, with or without mild or moderate kidney dysfunction and not receiving a protein-binding displacer, the free fraction of phenytoin is unchanged, and it is not necessary to measure a free phenytoin concentration. Free phenytoin concentrations should be measured directly in patients with hypoalbuminemia and kidney dysfunction.

Effectiveness of SBIRT for Alcohol Use Disorders in the Emergency Department: A Systematic Review.

INTRODUCTION: Alcohol use disorders (AUD) place a significant burden on individuals and society. The emergency department (ED) offers a unique opportunity to address AUD with brief screening tools and early intervention. We undertook a systematic review of the effectiveness of ED brief interventions for patients identified through screening who are at risk for AUD, and the effectiveness of these interventions at reducing alcohol intake and preventing alcohol-related injuries. METHODS: We conducted systematic electronic database searches to include randomized controlled trials of AUD screening, brief intervention, referral, and treatment (SBIRT), from January 1966 to April 2016. Two authors graded and abstracted data from each included paper. RESULTS: We found 35 articles that had direct relevance to the ED with enrolled patients ranging from 12 to 70 years of age. Multiple alcohol screening tools were used to identify patients at risk for AUD. Brief intervention (BI) and brief motivational intervention (BMI) strategies were compared to a control intervention or usual care. Thirteen studies enrolling a total of 5,261 participants reported significant differences between control and intervention groups in their main alcohol-outcome criteria of number of drink days and number of units per drink day. Sixteen studies showed a reduction of alcohol consumption in both the control and intervention groups; of those, seven studies did not identify a significant intervention effect for the main outcome criteria, but nine observed some significant differences between BI and control conditions for specific subgroups (i.e., adolescents and adolescents with prior history of drinking and driving; women 22 years old or younger; low or moderate drinkers); or secondary outcome criteria (e.g. reduction in driving while intoxicated). CONCLUSION: Moderate-quality evidence of targeted use of BI/BMI in the ED showed a small reduction in alcohol use in low or moderate drinkers, a reduction in the negative consequences of use (such as injury), and a decline in ED repeat visits for adults and children 12 years of age and older. BI delivered in the ED appears to have a short-term effect in reducing at-risk drinking.

Assessing the National Cancer Institute's SmokefreeMOM Text-Messaging Program for Pregnant Smokers: Pilot Randomized Trial.

BACKGROUND: Automated text messages on mobile phones have been found to be effective for smoking cessation in adult smokers. OBJECTIVE: This study aims to test the acceptability and feasibility of SmokefreeMOM, a national smoking cessation text-messaging program for pregnant smokers. METHODS: Participants were recruited from prenatal care and randomized to receive SmokefreeMOM (n=55), an automated smoking cessation text-messaging program, or a control text message quitline referral (n=44). Participants were surveyed by phone at baseline and at 1 month and 3 months after enrollment. RESULTS: Results indicate that the SmokefreeMOM program was highly rated overall and rated more favorably than the control condition in its helpfulness at 3-month follow-up (P<.01) and in its frequency of messaging at both 1-month and 3-month follow-ups (P<.001, P<.01, respectively). Despite the presence of technical problems, the vast majority of intervention participants read all program messages, and few participants unsubscribed from the program. There were no significant differences between groups on the use of extra treatment resources or on smoking-related outcomes. However, at the 3-month follow-up, some outcomes favored the intervention group. CONCLUSIONS: SmokefreeMOM is acceptable for pregnant smokers. It is recommended that SmokefreeMOM be further refined and evaluated. TRIAL REGISTRATION: Clinicaltrials.gov NCT02412956; https://clinicaltrials.gov/ct2/show/NCT02412956 (Archived by WebCite at http://www.webcitation.org/6tcmeRnbC).

A double-blind, placebo-controlled trial of tiagabine for the treatment of cocaine dependence.

BACKGROUND: The potential efficacy of tiagabine for treating cocaine dependence is suggested by both pre-clinical research and two small clinical trials. METHOD: One hundred and forty one participants who met DSM-IV criteria for cocaine dependence were enrolled into this 12-week, double blind, placebo controlled outpatient trial. Participants received either tiagabine (20 mg/day) or matching placebo. All participants received 1h of manualized individual cognitive behavioral therapy on a weekly basis. Outcome measures included cocaine use as determined by self-report confirmed with urine benzoylecgonine (BE) results, and qualitative and quantitative urine toxicology measures. Safety measures included adverse events, EKGs, vital signs, and laboratory tests. RESULTS: Seventy-nine participants (i.e., 56%) completed the 12-week trial. The safety results suggest that tiagabine was safe and generally well tolerated by the participants. Participants in both groups improved significantly on cocaine craving and global functioning, with no significant differences between the groups. There were no significant changes in cocaine use as measured by self-report confirmed by urine BE or by quantitative urine toxicology results. Qualitative urine toxicology results suggest a possible weak effect for tiagabine in reducing cocaine use. CONCLUSION: These results suggest that tiagabine, at a dose of 20 mg/day, did not have a robust effect in decreasing cocaine use.

A double-blind, placebo-controlled trial of reserpine for the treatment of cocaine dependence.

BACKGROUND: Cocaine's increase of dopamine is strongly associated with its reinforcing properties and, thus, agents that reduce dopamine have received much attention as candidate cocaine-dependence treatments. The potential efficacy of reserpine, a dopamine depletor, for treating cocaine dependence is suggested by both pre-clinical research and a small clinical trial. METHOD: One hundred and nineteen participants who met DSM-IV criteria for cocaine dependence were enrolled into this 12-week, double-blind, placebo-controlled outpatient trial. Participants received either reserpine (0.5 mg/day) or matching placebo. All participants received 1h of manualized individual cognitive behavioral therapy on a weekly basis. Outcome measures included cocaine use as determined by self-report confirmed with urine benzoylecgonine results, cocaine craving, addiction severity index scores, and clinical global impression scores. Safety measures included adverse events, EKGs, vital signs, laboratory tests, and the Hamilton Depression Inventory. RESULTS: Seventy-nine participants (i.e., 66%) completed the 12-week trial. The safety results suggest that reserpine was safe and well tolerated by the participants. The efficacy measures indicated no significant differences between reserpine and placebo. CONCLUSION: These results do not support the efficacy of reserpine as a cocaine-dependence treatment.

Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence.

AIMS: The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence. DESIGN: A multi-arm, modified blinded, placebo-controlled design was used. SETTING: The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU). PARTICIPANTS: Participants met criteria for cocaine dependence during a 2-week screening period. INTERVENTION: Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study. MEASUREMENTS: Urine benzoylecgonine (BE) concentrations, self-report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period. FINDINGS: None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end-point compared to the placebo group. Significant within-group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self-reported cocaine use declined over the study period. Overall, the active medications were well tolerated. CONCLUSIONS: This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.

A medication screening trial evaluation of reserpine, gabapentin and lamotrigine pharmacotherapy of cocaine dependence.

AIMS: To conduct a preliminary evaluation of the safety and efficacy of reserpine, gabapentin or lamotrigine versus an unmatched placebo control as a treatment for cocaine dependence. DESIGN: A 10-week out-patient study using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design. SETTING: The study was conducted at the Cincinnati Medication Development Research Unit (MDRU). PARTICIPANTS: Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty participants were enrolled, with 50 participants completing the final study measures. INTERVENTION: The targeted daily doses of medication were reserpine 0.5 mg, gabapentin 1800 mg and lamotrigine 150 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis. MEASUREMENTS: Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression scale--observer and self-report of cocaine use. Safety measures included adverse events, electrocardiograms (ECGs), vital signs and laboratory tests. FINDINGS: Subjective measures of cocaine dependence indicated significant improvement for all study groups. Urine BE results indicated a significant improvement for the reserpine group (P < 0.05) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. The medications appeared to be tolerated well. CONCLUSIONS: The present findings suggest that reserpine may be worthy of further study as a cocaine dependence treatment.

A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments.

AIMS: To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence. DESIGN: A 10-week out-patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design. SETTING: This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio. PARTICIPANTS: Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty-seven participants were enrolled with 55 completing final study measures. INTERVENTION: The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis. MEASUREMENTS: Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale-Observer and self-report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests. FINDINGS: Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5-8 (P = 0.10) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. CONCLUSIONS: The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment.

Randomized controlled pilot trial of cabergoline, hydergine and levodopa/carbidopa: Los Angeles Cocaine Rapid Efficacy Screening Trial (CREST).

AIM: This study tested three dopaminergic medications against a common unmatched placebo condition: hydergine 1 mg three times daily (n = 15); levodopa/carbidopa 25/100 mg three times daily (n = 15); cabergoline 0.5 mg per week (n = 15); and placebo three times daily (n = 15) as potential pharmacotherapies for cocaine dependence. DESIGN: The four-parallel group, Cocaine Rapid Efficacy Screening Trial (CREST) design featured a 2-week baseline period followed by randomization to an 8-week medication condition that included 1 hour per week of cognitive behavioral drug counseling. A safety evaluation was conducted 4 weeks after termination. MEASURES: Outcomes included cocaine metabolites measured in urine, retention and self-reports for drug use, cocaine craving, clinical improvement, mood and HIV risk behaviors. RESULTS: Participants assigned to receive cabergoline provided more urine samples negative for cocaine metabolites (42.4%) than those assigned to receive placebo (25.0%), a statistically significant difference after controlling for baseline differences in self-reported cocaine use (F = 2.95, df = 3; P = 0.05). Cabergoline-treated participants demonstrated a significant improvement over placebo from baseline to week 8 when measured using the Addiction Severity Index (ASI) employment subscale (overall change = - 0.09, SD = 0.10, t = 2.36, P < 0.05). Safety and adverse event measures showed similar rates and types of complaints by treatment condition. CONCLUSIONS: These results, combined with the apparent safety of cabergoline when used with this population, provide empirical support for conducting a larger study of the medication.

Cocaine Rapid Efficacy Screening Trials (CREST): lessons learned.

AIMS: The Cocaine Rapid Efficacy Screening Trials (CREST) were designed by the National Institute on Drug Abuse Division of Treatment Research and Development (NIDA, DT R&D) to rapidly screen a number of medications potentially useful for the treatment of cocaine dependence. DESIGN: Each CREST trial was designed to compare several medications in a single trial against an unmatched placebo. The placebo group was included in each trial to avoid the nearly universal positive response to medications seen in open-label trials. In addition, a common set of procedures and outcome measures were employed throughout to increase comparability of results obtained from different trials and from different times. PARTICIPANTS: In all, 18 medications were screened in seven different trials, conducted in four different sites throughout the United States involving 398 cocaine-dependent patients. FINDINGS: Three medications were found to be promising enough to include in subsequent larger trials. Common statistical procedures for evaluating medications were developed to facilitate comparisons across sites and across time. A portion of the data were pooled and analyzed, which yielded some useful insights into cocaine dependence and its treatment. Finally, a review of individual trials together with the pooled analysis revealed several potential improvements for future screening trials. CONCLUSIONS: Overall, the CREST trials proved to be useful for rapidly screening medications for treatment of cocaine dependence, but several modifications in design should be made before this framework is applied further.

An open-label pilot study of methylphenidate in the treatment of cocaine dependent patients with adult attention deficit/hyperactivity disorder.

A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted.