1H-NMR urinary metabolomic profiling for diagnosis of gastric cancer

Background: Metabolomics has shown promise in gastric cancer (GC) detection. This research sought to identify whether GC has a unique urinary metabolomic profile compared with benign gastric disease (BN) and healthy (HE) patients. Methods: Urine from 43 GC, 40 BN, and 40 matched HE patients was analysed using 1H nuclear magnetic resonance (1H-NMR) spectroscopy, generating 77 reproducible metabolites (QC-RSD Results: GC displayed a clear discriminatory biomarker profile; the BN profile overlapped with GC and HE. LASSO-LR identified three discriminatory metabolites: 2-hydroxyisobutyrate, 3-indoxylsulfate, and alanine, which produced a discriminatory model with an area under the ROC of 0.95. Conclusions: GC patients have a distinct urinary metabolite profile. This study shows clinical potential for metabolic profiling for early GC diagnosis

Metformin treatment in diabetes and heart failure: when academic equipoise meets clinical reality

<p>Abstract</p> <p>Objective</p> <p>Metformin has had a 'black box' contraindication in diabetic patients with heart failure (HF), but many believe it to be the treatment of choice in this setting. Therefore, we attempted to conduct a pilot study to evaluate the feasibility of undertaking a large randomized controlled trial with clinical endpoints.</p> <p>Study Design</p> <p>The pilot study was a randomized double blinded placebo controlled trial. Patients with HF and type 2 diabetes were screened in hospitals and HF clinics in Edmonton, Alberta, Canada (population ~1 million). Major exclusion criteria included the current use of insulin or high dose metformin, decreased renal function, or a glycosylated hemoglobin <7%. Patients were to be randomized to 1500 mg of metformin daily or matching placebo and followed for 6 months for a variety of functional outcomes, as well as clinical events.</p> <p>Results</p> <p>Fifty-eight patients were screened over a six month period and all were excluded. Because of futility with respect to enrollment, the pilot study was abandoned. The mean age of screened patients was 77 (SD 9) years and 57% were male. The main reasons for exclusion were: use of insulin therapy (n = 23; 40%), glycosylated hemoglobin <7% (n = 17; 29%) and current use of high dose metformin (n = 12; 21%). Overall, contraindicated metformin therapy was the most commonly prescribed oral antihyperglycemic agent (n = 27; 51%). On average, patients were receiving 1,706 mg (SD 488 mg) of metformin daily and 12 (44%) used only metformin.</p> <p>Conclusion</p> <p>Despite uncertainty in the scientific literature, there does not appear to be clinical uncertainty with regards to the safety or effectiveness of metformin in HF making a definitive randomized trial virtually impossible.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00325910</p

A pragmatic cluster randomized trial evaluating the impact of a community pharmacy intervention on statin adherence: rationale and design of the Community Pharmacy Assisting in Total Cardiovascular Health (CPATCH) study

<p>Abstract</p> <p>Background</p> <p>Traditional randomized controlled trials are considered the gold standard for evaluating the efficacy of a treatment. However, in adherence research, limitations to this study design exist, especially when evaluating real-world applicability of an intervention. Although adherence interventions by community pharmacists have been tested, problems with internal and external validity have limited the usefulness of these studies, and further well-designed and well-conducted research is needed. We aimed to determine the real-world effectiveness of a community pharmacy adherence intervention using a robust study design. This novel design integrates cluster randomization and an outcome evaluation of medication adherence using a population-based administrative data source in the province of Saskatchewan, Canada.</p> <p>Methods/Design</p> <p>Community pharmacies from across the province of Saskatchewan, Canada were randomized to deliver an adherence intervention to their patients or usual care. Intervention pharmacies were trained to employ a practical adherence strategy targeted at new users of statin medications. While randomization and implementation of the intervention occurred at the community pharmacy level, the outcome analysis will occur at the level of the individual subjects. The primary outcome is the mean statin adherence among all eligible new users of statin medications. Secondary outcomes include the proportion of new statin users who exhibit adherence ≥80%, and persistence with statin use.</p> <p>Discussion</p> <p>This novel study design was developed to combine the rigor of a randomized trial with a pragmatic approach to implementing and capturing the results in a real-world fashion. We believe this approach can serve as an example for future study designs evaluating practice-based adherence interventions.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov no. NCT00971412.</p

The frequency and availability of population-specific patient reported outcome measures and minimal clinically important differences among approved drugs in Canada

Abstract Background Patient reported outcome measures (PROMs) and minimal clinically important differences (MCIDs) are included in Canada’s Common Drug Review (CDR) process to approve new drugs. Often, the measures report on the health-related quality of life (HRQoL), but can also describe the symptoms, efficacy and harms important to patients. They can be generic or population/condition specific, validated or not. We examined the frequency, availability and accessibility of validated, specific PROMs and MCIDs reported in the CDR reports. Methods We searched the Canadian Agency for Drugs and Technologies in Health (CADTH) on-line database for completed Common Drug Review, Clinical Review Reports (CDR-CRR) between November 2013 and February 2017. Two independent reviewers examined the reports and references for PROMs and MCIDs. Both reviewers separately categorized the PROMs and MICDs according to purpose, validation, availability and funding received. Discrepancies were rectified by consensus with a third investigator. Results One-hundred and five unique PROMs were extracted from 39 CDR-CRR, 57% with a HRQoL component. 91/105 (87%) referenced a validation study and 62/105 (59%) referenced a validation study in the study population of interest. Fifty-seven MCID references were extracted from 39 CDR-CRR. 34/57 (60%) were specific to the study population of interest, and 36% had a HRQoL component. 50% of PROM and 53% of MCID references were publicly available. Conclusions PROMs and MCIDs referenced in CDR-CRR show similar trends. The majority are validated, but not necessarily in the study population of interest. Continued critical examination is required to evaluate new drugs specific to the population of interest

Completion of multiple-dose travel vaccine series and the availability of pharmacist immunizers: A retrospective analysis of administrative data in Alberta, Canada.

Pharmacists in a number of countries are being trained in the administration of injections with the aim of improving access and adherence to vaccinations. However, little is known about population-level adherence to multiple-dose travel vaccines, and whether the availability of pharmacist immunizers is associated with adherence. Health administrative data from Alberta, Canada, from April 2008 to May 2017 identified adults dispensed at least one vaccine for hepatitis A, hepatitis B, Japanese encephalitis, or rabies. Individuals were coded as completers or non-completers of the vaccine series based on the number of doses dispensed over a time period comprising the duration of the standard series plus 6 months to account for late doses. The association between the proportion of Alberta pharmacists with injection authorization (according to pharmacist registration data) and completion of vaccine series was assessed using linear regression. Over the study period, 24,164 patients initiated a vaccine series for hepatitis A monovalent, 195,480 for hepatitis B monovalent, 169,802 for combined hepatitis A&B, 1,726 for Japanese encephalitis, and 1,908 for rabies. There were fewer than 5 individuals receiving Japanese encephalitis vaccine per year from 2008-2010 or rabies vaccine from 2008-2009. While statistically significant positive associations were seen across all vaccines except for Japanese encephalitis, the magnitude of these associations was small. Each 1% increase in the proportion of injections-authorized pharmacists saw a corresponding increase in the proportion of individuals with completed vaccine series by 0.31% for hepatitis A monovalent, 0.19% for hepatitis B monovalent, 0.22% for combined hepatitis A&B, and 0.21% for rabies. This may suggest that challenges remain with implementing reminder systems to ensure adherence among travellers. Strategies to develop or improve patient and clinician reminder systems in pharmacies for travel vaccines should therefore be explored

Population-based cohort study of outpatients with pneumonia: rationale, design and baseline characteristics

Abstract Background The vast majority of research in the area of community-acquired pneumonia (CAP) has been based on patients admitted to hospital. And yet, the majority of patients with CAP are treated on an ambulatory basis as outpatients, either by primary care physicians or in Emergency Departments. Few studies have been conducted in outpatients with pneumonia, and there is a paucity of data on short and long term morbidity or mortality and associated clinical correlates in this group of patients. Methods From 2000–2002, all CAP patients presenting to 7 Emergency Departments in Edmonton, Alberta, Canada were prospectively enrolled in a population-based registry. Clinical data, including pneumonia severity index (PSI) were collected at time of presentation. Patients discharged to the community were then followed for up to 5 years through linkage to the provincial administrative databases. The current report provides the rationale and design for the cohort, as well as describes baseline characteristics and 30-day morbidity and mortality. Results The total sample included 3874 patients. After excluding patients who were hospitalized, died or returned to the Emergency Department the same day they were initially discharged (n = 451; 12 %), and patients who could not be linked to provincial administrative databases (n = 237; 6 %), the final cohort included 3186 patients treated according to a validated clinical management pathway and discharged back to the community. Mean age was 51 (SD = 20) years, 53 % male; 4 % resided in a nursing home, 95 % were independently mobile, and 88 % had mild (PSI class I-III) pneumonia. Within 30-days, return to Emergency Department was common (25 %) as was hospitalization (8 %) and 1 % of patients had died. Conclusions To our knowledge, this represents the largest clinically-detailed outpatient CAP cohort assembled to date and will add to our understanding of the determinants and outcomes in this under-researched patient population. The rich clinical data along with the long term health care utilization and mortality will allow for the identification of novel prognostic indicators. Given how under studied this population is, the findings should aid clinicians in the routine care of their outpatients with pneumonia and help define the next generation of research questions.</p

Optimal threshold of adherence to lipid lowering drugs in predicting acute coronary syndrome, stroke, or mortality: A cohort study.

OBJECTIVE:Thresholds defining medication adherence are rarely evidence-based. A threshold of 0.8 is typically presumed to achieve improved outcomes. We aimed to assess the optimal threshold of adherence to lipid-lowering drugs (LLD) in predicting cardiovascular-related (CV) outcomes in patients with hypertension. DESIGN:Cohort study of new users of LLDs. SETTING:Comprehensive healthcare administrative databases of the province of Alberta (Canada) from 2008 to 2016. PARTICIPANTS:Patients with hypertension, who were new users of LLDs. Patients who had the outcomes prior to the initiation of LLD were excluded. MAIN OUTCOMES MEASURES:Hospitalization for acute coronary syndrome (ACS)/stroke, CV-related mortality and all-cause mortality. STATISTICAL ANALYSIS:Adherence to LLDs was assessed as the proportion of days covered (PDC) by any LLD, from drug initiation to censoring, outcome, or study end. Three methods were used to assess the threshold: Contal and O'Quigley method, minimum distance method, and Youden's J index. Cox regressions were used to assess the risk associated with each method-specific threshold and Akaike information criteria were used to retain the optimal threshold after adjustment. RESULTS:52229 patients were included; 4.0% were hospitalized for ACS/stroke, 3.4% died, and 1.3% died from CV-related cause. In predicting ACS/stroke, CV-related and all-cause mortality, the optimal adherence threshold was 0.52 (range: 0.51-0.54), 0.79 (0.45-0.87), and 0.84 (0.79-0.89), respectively. These results were consistent among patients aged ≥ 65 years (n = 19804). However, the results varied among those aged < 65 years, where the incidence rates of outcomes were low. CONCLUSION:In new-users of LLDs with hypertension, approximately 50% days covered by LLDs may be enough to prevent long-term occurrence of ACS, or stroke. However, a threshold near 0.80 may be needed to prevent or reduce the risk of all-cause or CV-related mortality

Invasive Pneumococcal Disease: Still Lots to Learn and a Need for Standardized Data Collection Instruments

Background. Large studies of invasive pneumococcal disease (IPD) are frequently lacking detailed clinical information. Methods. A population-based 15-year study of IPD in Northern Alberta. Results. 2435 patients with a mean age of 54.2 years formed the study group. Males outnumbered females and Aboriginal and homeless persons were overrepresented. High rates of smoking, excessive alcohol use, and illicit drug use were seen. Almost all (87%) had a major comorbidity and 15% had functional limitations prior to admission. Bacteremia, pneumonia, and meningitis were the most common major manifestations of IPD. Almost half of the patients had alteration of mental status at the time of admission and 22% required mechanical ventilation. Myocardial infarction, pulmonary embolism, and new onset stroke occurred in 1.7, 1.3, and 1.1% of the patients, respectively; of those who had echocardiograms, 35% had impaired ventricular function. The overall in-hospital mortality was 15.6%. Conclusions. IPD remains a serious infection in adults. In addition to immunization, preventative measures need to consider the sociodemographic features more carefully. A standard set of data need to be collected so that comparisons can be made from study to study. Future investigations should target cardiac function and pulmonary embolism prevention in this population