Effectiveness of the STOPP/START (Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria: systematic review and meta-analysis of randomized controlled studies.

WHAT IS KNOWN AND OBJECTIVE: STOPP/START are explicit screening tools that identify potentially inappropriate prescribing in older adults. Our objective was to update our 2013 systematic review that showed limited evidence of impact, using new evidence from randomized controlled trials (RCTs) assessing clinical, humanistic and economic outcomes in older adults. METHODS: We performed a search of PubMed, EMBASE, CINAHL, Web of Science and grey literature for RCTs published in English since the previous review through June 2014. The Cochrane Risk of Bias Tool was used. We performed a meta-analysis on the effect of STOPP on potentially inappropriate medication (PIM) rates and a narrative synthesis on other outcomes. RESULTS AND DISCUSSION: Four RCTs (n = 1925 adults) from four countries were included, reporting both acute (n = 2) and long-term care (n = 2) patients. Studies differed in implementation. Two studies were judged to have low risk, and two to have moderate-to-high risk of bias in key domains. Meta-analysis found that the STOPP criteria reduced PIM rates in all four studies, but study heterogeneity (I(2) = 86·7%) prevented the calculation of a meaningful statistical summary. We found evidence that use of the criteria reduces falls, delirium episodes, hospital length-of-stay, care visits (primary and emergency) and medication costs, but no evidence of improvements in quality of life or mortality. WHAT IS NEW AND CONCLUSION: STOPP/START may be effective in improving prescribing quality, clinical, humanistic and economic outcomes. Additional research investigating these tools is needed, especially in frail elderly and community-living patients receiving primary care.

Fluoroquinolone use for uncomplicated urinary tract infections in women: a retrospective cohort study.

OBJECTIVES: The United States Food & Drug Administration released an advisory in 2016 that fluoroquinolones be relegated to second-line agents for uncomplicated urinary tract infections (UTIs) given reports of rare but serious side effects; similar warnings have followed from Health Canada and the European Medicines Agency. The objective was to determine whether alternative non-fluoroquinolone agents are as effective as fluoroquinolones in the treatment of UTIs. METHODS: We conducted a retrospective population-based cohort study using administrative health data from six Canadian provinces. We identified women (n = 1 585 997) receiving antibiotic treatment for episodes of uncomplicated UTIs (n = 2 857 243) between January 1 2005 and December 31 2015. Clinical outcomes within 30 days from the initial antibiotic dispensation were compared among patients treated with a fluoroquinolone versus non-fluoroquinolone agents. High-dimensional propensity score adjustments were used to ensure comparable treatment groups and to minimize residual confounding. RESULTS: Fluoroquinolone use for UTI declined over the study period in five of six Canadian provinces and accounted for 22.3-48.5% of treatments overall. The pooled effect across the provinces indicated that fluoroquinolones were associated with fewer return outpatient visits (OR 0.89, 95%CI 0.87-0.92), emergency department visits (OR 0.74, 95%CI 0.61-0.89), hospitalizations (OR 0.83, 95%CI 0.77-0.88), and repeat antibiotic dispensations (OR 0.77, 95%CI 0.75-0.80) within 30 days. CONCLUSIONS: Fluoroquinolones are associated with improved clinical outcomes among women with uncomplicated UTIs. This benefit must be weighed against the risk of fluoroquinolone resistance and rare but serious fluoroquinolone side effects when selecting first-line treatment for these patients.

Disease progression among multiple sclerosis patients before and during a disease-modifying drug program: a longitudinal population-based evaluation.

Randomized controlled trials have demonstrated the efficacy of disease-modifying drugs (DMDs) in persons with relapsing-remitting multiple sclerosis (MS) and secondary progressive MS with superimposed relapses. However, these brief studies of selected patients have focused mainly on reducing attacks and must be complemented by evaluations in 'realworld' clinical settings to establish the effectiveness of DMD programs in slowing disease progression and to inform health policy and program decision-making. We assessed the effectiveness of DMDs as administered in a comprehensive publicly funded drug insurance program that provides DMDs to a geographically defined population of MS patients who meet specific eligibility criteria. Data from 1752 MS patients (10,312 assessments) seen between 1980 and 2004 at a regional MS Clinic serving the entire population of Nova Scotia, Canada were analysed. Using survival methods we observed a statistically significant reduction in disease progression to specific Expanded Disability Status Scale endpoints following the introduction of this program. Subgroup analyses of patients eligible for treatment using hierarchical linear regression methods also suggested that disease progression was slowed in patients treated with the first DMD prescribed. These findings provide evidence supporting DMD program effectiveness that can be used to inform the broader implementation of such programs.

Concordance with a STOPP (Screening Tool of Older Persons' Potentially Inappropriate Prescriptions) Criterion in Nova Scotia, Canada: Benzodiazepine and Zoplicone Prescription Claims by Older Adults with Fall-related Hospitalizaions.

BACKGROUND: Optimization of prescribing in older adults is needed. The STOPP criteria provide a systematic way of identifying potentially inappropriate prescribing in this population. Previous research indicates poor concordance between benzodiazepine prescribing and STOPP. OBJECTIVES: To determine the extent and predictors of benzodiazepine and zopiclone (BZD-Z) pharmacy dispensations in older adults with a history of a recent fall, in concordance with STOPP. METHODS: Prescription claims data from the Nova Scotia Seniors' Phamacare Program were linked with fall-related injury data from the CIHI Discharge Abstract Database. Adults aged ≥ 66 years making a claim for a BZD-Z in the 100 days prior to fall-related hospitalization were identified. Their BZD-Z claims in the 100 days following discharge were also identified. Descriptive statistics, trend tests and logistical regression modelling were performed to examine predictors for continued use of BZD-Z post-fall. RESULTS: Over 5 years, from a pool of 8,271 older adults discharged following a fall-related hospitalization, 1,789 (21.6%) had made a claim for a BZD-Z in the 100 days prior to admission. Of these, 82% were women. Younger age and female sex were predictors of continuing BZD-Z dispensations post-fall. In the 100 days following discharge, 74.2% (n=1327) made a claim for at least one BZD-Z. CONCLUSION: BZD-Z use continued in 74% of patients following discharge from a fall-related hospitalization, representing limited concordance with the STOPP criterion. Such hospitalizations and follow-up care present an opportunity to address an ongoing modifiable risk factor.

Saline catharsis: effect on aspirin bioavailability in combination with activated charcoal.

The effect of a saline cathartic combined with activated charcoal or activated charcoal alone on aspirin bioavailability was characterized in six healthy volunteers. Using a random, Latin-square design, subjects were given 975 mg aspirin followed by either water alone, 15 Gm activated charcoal (AC), or 15 Gm activated charcoal plus 20 Gm sodium sulfate (AC + SS) separated by one week. Both AC (44.16 +/- 16.85 microgram/ml) and AC + SS (58.61 +/- 10.63 microgram/ml) decreased (P less than 0.001) the maximal plasma salicylate concentration (Cpmax) compared to control (86.61 +/- 12.69 microgram/ml). Urinary salicylate recovery was decreased (P less than 0.01) for AC (57.88 +/- 16.26 per cent) and AC + SS (61.00 +/- 11.49 per cent) as compared to control (93.73 +/- 6.83 per cent), while for area under the plasma concentration-time curve (AUC) only AC showed a decrease (P less than 0.01) compared to control. Neither AC nor AC + SS differed from each other for Cpmax, AUC, or cumulative urinary recovery. Our findings indicate that the addition of sodium sulfate to activated charcoal has no added effect on limiting aspirin adsorption relative to activated charcoal alone.

Drug therapy in multiple sclerosis: a study of Nova Scotia senior citizens.

We conducted a study to determine the types and costs of drugs used by Nova Scotia senior citizens with multiple sclerosis (MS) compared with the types and costs of drugs used by all senior citizens in Nova Scotia. Administrative claims databases from the Nova Scotia Seniors Pharmacare program for persons aged 65 years or older were linked to the Dalhousie Multiple Sclerosis Research Unit (DMSRU) clinical database (1980-1994). Analyses compared persons with MS aged 65 years or older who attended the DMSRU at least once with the general population of senior citizens. Not all persons with MS attended the DMSRU. In aggregate, Pharmacare costs in 1993-1994 for patients with MS aged 65 years or older (N = 52) were $975.00 Canadian per capita compared with $590.00 Canadian for all senior citizens in Nova Scotia (N = 108,646). Thus average drug costs for the senior citizens with MS were 65% greater than those for all senior citizens covered by Nova Scotia's comprehensive, publicly funded Pharmacare program. Compared with other senior citizens, those with MS more frequently received alpha-blockers, anticholinergics, cholinergics, tricyclic antidepressants, anticonvulsants, antifatigue agents, antispasticity agents, and antibiotics for bladder infections.

Possible role of the intestinal P-450 enzyme system in a cyclosporine-clarithromycin interaction.

Clarithromycin is a macrolide antibiotic similar in structure to erythromycin, but suggested to have fewer drug interactions. Although a pharmacokinetic interaction between clarithromycin and cyclosporine was recently reported, its magnitude and mechanism have not been explored. A 43-year-old renal transplant recipient receiving cyclosporine was treated with clarithromycin because of pneumonia. A cyclosporine pharmacokinetic study was performed 8 days after the initiation of the clarithromycin and 14 days after stopping the drug. Clarithromycin coadministration caused an approximately 2-fold increase in the area under the whole blood concentration versus time curve of cyclosporine. The oral clearance of cyclosporine was halved by clarithromycin, but the terminal elimination rate constant decreased only 15% and mean residence time 20%. These observations suggest that clarithromycin inhibits not only the hepatic metabolism but also the intestinal metabolism of cyclosporine. Caution is advised when administering the two drugs concurrently, and additional studies are necessary to elucidate the mechanism of this interaction.

Eight days of cyclosporine overdose: a case report.

A 25-year-old woman was admitted to the hospital because of rising trough cyclosporine concentrations thought to be due to self-administration of 4 times the normal dosage of the drug for 8 days. Her symptoms included colicky central abdominal pains and urinary retention; her serum creatinine concentrations were elevated. Whole blood cyclosporine and metabolite concentrations were measured by high-performance liquid chromatography and monoclonal radioimmunoassays. The highest reported trough cyclosporine concentration was 5877 ng/ml, and AM1 (M17) concentration was 3425 ng/ml. A cyclosporine half-life of 91 hours was calculated. Nine days after the agent was discontinued the patient's serum creatinine concentration had returned to normal and her symptoms resolved. Due to the availability of three sizes of cyclosporine capsules, and the need for frequent dosage changes, continued vigilance is necessary to ensure that patients understand their drug regimen.

Underuse of acetylsalicylic acid in individuals with myocardial infarction, ischemic heart disease or stroke: data from the 1995 population-based Nova Scotia Health Survey.

OBJECTIVE: To determine current patterns of acetylsalicylic acid (ASA) use in Nova Scotia for individuals with self-reported myocardial infarction, stroke or ischemic heart disease. DESIGN: Descriptive, cross-sectional, population-based study using data from the 1995 Nova Scotia Health Survey (NSHS). The NSHS was based on a probability sample and was representative of the Nova Scotia adult population by age, sex and region. Survey data were obtained by standardized home interviews conducted by trained public health nurses. SETTING: The province of Nova Scotia in 1995. PARTICIPANTS: Survey respondents who reported having a myocardial infarction, stroke or ischemic heart disease were assessed. RESULTS: Among those who reported a history of myocardial infarction, stroke or ischemic heart disease, 55% (95% CI 47% to 63%), 49% (95% CI 38% to 61%) and 54% (95% CI 39% to 68%), respectively, reported using ASA at the time of the survey. Overall, only 53% of those with cardiovascular disease were using ASA. Exclusion of persons with potential contraindications to ASA did not significantly increase these proportions. CONCLUSIONS: ASA appears to be underused in those at high risk for future vascular events. Further research is required to investigate determinants of ASA use and to increase appropriate use of ASA.

Compliance with guidelines for monitoring aminoglycoside therapy.

One hundred and twenty-one patients receiving 140 courses of aminoglycoside-therapy (76% gentamicin and 24% tobramycin) were retrospectively studied to assess the monitoring practices for these drugs. Compliance with specific items of the monitoring guidelines ranged from 16 to 93%. An education program regarding aminoglycoside monitoring, particularly the use of serum aminoglycoside concentrations, is necessary in the study institutions.

Methods of controlling cephalosporin use in Canadian hospitals.

Cephalosporin antibiotics contribute significantly to hospital antibiotic costs. A survey was conducted to determine cephalosporin use and prescribing control in Canadian hospitals over 300 beds. Of the 125 hospitals surveyed, 84 responses were received; 76 were included in data analysis. Thirty-two percent of hospitals had no restriction policies for intravenous cephalosporins and 88 percent had none for oral cephalosporins. Restrictions were more common for the second and third generation agents. The most common method of restricting cephalosporins was by requiring consultation with an infectious disease service. The yearly cost of cephalosporins varied considerably and was unrelated to the number of beds in the hospital. The data provided allows hospitals to compare their use of cephalosporin antibiotics with other institutions in Canada.

Prescribing indicators: what can Canada learn from European countries?

BACKGROUND: Drug therapy can improve patients' quality of life and health outcomes; however, underuse, overuse and inappropriate use of drugs can occur. Systematic examination of potential opportunities for improving prescribing and medication use is needed. OBJECTIVE: To convene a diverse group of stakeholders to learn about and discuss advantages and limitations of data sources, tools and methods related to drug prescribing indicators; foster methods to assess safe, appropriate and cost-effective prescribing; increase awareness of international organizations who develop and apply performance indicators relevant to Canadian researchers, practitioners and decision-makers; and provide opportunities to apply information to the Canadian context. METHODS: Approximately 50 stakeholders (health system decision-makers, senior and junior researchers, healthcare professionals, graduate students) met June 1-2, 2009 in Halifax, Canada. Four foundational presentations on evaluating quality of prescribing were followed by discussion in pre-assigned breakout groups of a prepared case (either antibiotic use or prescribing for seniors), followed by feedback presentations. RESULTS: Many European countries have procedures to develop indicators for prescribing and quality use of medicines. Indicators applied in diverse settings across the European Union use various mechanisms to improve quality, including financial incentives for prescribers. CONCLUSION: Further Canadian approaches to develop a system of Canadian prescribing indicators would enable federal/provincial/territorial and international comparisons, identify practice variations and highlight potential areas for improvement in prescribing, drug use and health outcomes across Canada. A more standardized system would facilitate cross-national research opportunities and enable Canada to examine how European countries use prescribing indicators, both within their country and across the European Union.

How effective are disease-modifying drugs in delaying progression in relapsing-onset MS?

OBJECTIVE: Our objective was to estimate the effectiveness of disease-modifying drugs (DMDs) in delaying multiple sclerosis (MS) disability progression in relapsing-onset (R-onset) definite MS patients under "real-world" conditions. METHODS: Treatment effect size, for DMDs as a class, was estimated in absolute terms and relative to MS natural history. A basic model estimated annual Expanded Disability Status Scale (EDSS) change before and after treatment. An expanded model estimated annual EDSS change in pretreatment years, treatment years on first drug, treatment years after drugs were switched, and in years after treatment stopped. Models were populated with 1980 through 2004 clinical data, including 1988 through 2004 data for all Nova Scotians treated with DMDs. Estimates were made for relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and R-onset groups. RESULTS: Estimated pretreatment annual EDSS increases were approximately 0.10 of one EDSS point for the RRMS group, 0.31 for the SPMS group, and 0.16 for the R-onset group. Estimates of EDSS increase avoided per treatment year on the first drug were significant for the RRMS group (-0.103, 0.000), the SPMS group (-0.065, 0.011), and the R-onset group (-0.162, 0.000); relative effect size estimates were 112%, 21%, and 105%. Estimated EDSS progression was faster in years after drug switches and treatment stops. CONCLUSIONS: Our estimates of disease-modifying drug (DMD) relative treatment effect size, in the context of "real-world" clinical practice, are similar to DMD treatment efficacy estimates in pivotal trials, though our findings attained statistical significance. DMDs, as a class, are effective in delaying Expanded Disability Status Scale progression in patients with relapsing-onset definite multiple sclerosis (MS) (90%), although effectiveness is much better for relapsing-remitting MS than for secondary progressive MS groups.

The impact of socioeconomic and demographic factors on the utilization of smoking cessation medications in patients hospitalized with cardiovascular disease in Nova Scotia, Canada.

OBJECTIVE: To determine whether any demographic or socioeconomic factors affect the use of smoking cessation medications in patients hospitalized with heart disease. METHOD: Data were obtained from the Improving Cardiovascular Outcomes in Nova Scotia (ICONS) Canada database, which includes a registry of all hospitalized patients with a diagnosis of ischaemic heart disease, congestive heart failure, or atrial fibrillation since October 1997. Patients agreeing to provide follow-up were sent an enrollment survey to determine demographic and socioeconomic factors including household income, educational background and private drug insurance plans. RESULTS: Between 15 October 1997 and 31 December 2000, 5442 patients who were current smokers and 270 patients using a smoking cessation medication were admitted to hospital registered in the ICONS database. An enrollment survey was completed by 1071 current smokers and 77 patients using a smoking cessation agent. CONCLUSION: Higher education level, presence of private drug insurance plans, and less difficulty paying for basic needs were associated with higher use of smoking cessation medications.

A comparison of health utility measures for the evaluation of multiple sclerosis treatments.

OBJECTIVES: To evaluate the practical application and psychometric properties of three health utility measures in a sample of MS patients with a broad range of neurological disability as measured by the Extended Disability Status Scale (EDSS). METHODS: Patients randomly selected from two MS clinic registries were assessed using standard clinical methods and completed three generic measures of health utility (EQ-5D, HUI Mark III, SF-6D). The proportion of missing data, test/retest reliability, and construct validity of each health utility measure were examined. RESULTS: The assessments were completed by 187 patients. Less than 10% of data were missing for the subscales of the SF-6D (< 3.2%), HUI Mark III (<1.6%), and EQ-5D (< or =7.5%). Severely disabled patients were more likely to omit physical function questions for the SF-6D (20%), and EQ-5D (43%). Retest reliability for the SF-6D (ICC = 0.83), EQ-5D (ICC = 0.81), and HUI Mark III (ICC = 0.87) were adequate for population surveys. Correlations between assessment of clinical function and each health utility measure were strongest for the HUI Mark III (HUI Mark III EDSS rho = -0.77, HUI Mark III ambulation index rho = -0.76, HUI Mark III timed 25 foot walk rho = -0.73, HUI Mark III nine hole peg test rho = -0.65). CONCLUSIONS: The health utility measures were generally feasible and reliable but the HUI Mark III demonstrated highest concordance with the EDSS across the full range of neurological disability. Of the three measures studied, the HUI Mark III may be the most appropriate for cost effectiveness evaluations of MS therapies.

Ipecac syrup for poisonings at home: availability, compliance, and response monitored by telephone.

Ipecac syrup administration at home, following advice by a poison center, was evaluated with respect to the availability of ipecac syrup, length of storage time, compliance with recommended procedures for administration, and time for emetic response. In a three-month period, staff pharmacists of the center completed a survey from when they advised 60 callers to administer ipecac syrup at home. Two follow-up phone calls were made to collect additional data. Fifty-five callers provided adequate data for analysis. Ipecac syrup was available at home for 36%, from a pharmacy for 53%, and from a neighbor for 11% of the callers. Compliances with the recommended doses of ipecac syrup and fluids (+/- S.D.) were 92 +/- 20% and 71 +/- 29%, respectively. Following one dose of ipecac syrup, 86% vomited in 19 +/- 8 minutes; after a second dose, 13% responded in 34 +/- 21 minutes after the first dose. By comparison with those who had ipecac syrup at home, there was an insignificant delay in administration when it was obtained from a neighbor; a significant delay (p less than 0.005) occurred when it was obtained by a pharmacy. The onset of emesis did not correlate with the length of time the ipecac syrup had been stored at home. The findings support the use of ipecac syrup at home based on ready availability, adequate compliance, and rapid emetic response.