Drug-related Mortality Research Articles

Social determinants of drug-related mortality in a general population

BackgroundWe investigated the association between social determinants and a broad selection of drug-related deaths in a general population. MethodsWe conducted a follow-up of an 11% random sample of working-age Finnish residents for 1996–2007 linked with an oversampling of deaths and population registration data on social characteristics. We defined total drug-related deaths as those from psychoactive substance use disorders and drug-induced poisonings (drug-induced deaths) as well as drug-related accidents, homicides, illnesses, and suicides. ResultsThe number of drug-related deaths was three times that of drug-induced deaths. We found the highest hazard ratios (HRs) for total drug-related mortality for long-term unemployment (4.9; 95% confidence interval [CI], 4.3–5.6), short-term unemployment (3.9; 95% CI, 3.5–4.4), and retirement (5.8; 95% CI, 5.1–6.8). The HRs were highest for mortality related to psychoactive substance use disorders and lowest for mortality related to drug-related suicides. The differences were large for both sexes. ConclusionsDrug-related mortality was associated with social disadvantage; however, the strength of the association varied by drug-related cause of death. Primary and secondary prevention of drug use should particularly target disadvantaged groups.

Integrating Clinical Advisory Pharmacists in the Health Care Home

Introduction: Internationally governments have promoted general practices and community pharmacy working together more closely. Despite examples of co-location, this has not been particularly successful for a number of reasons, including issues of territoriality. There is growing interest in clinical pharmacists working in, and for, general practices.Practice change: This is a change in the model of service delivery with the clinical pharmacist working within the multidisciplinary team of a health care home, and independent of a community pharmacy. This paper explores the changes occurring in the UK and Australia, and presents information of the roles and activities of the fledging clinical advisory pharmacist workforce in New Zealand. It includes the roles of prescribing pharmacists in primary care, using a collaborative prescribing model.A survey of these pharmacists provides information on their roles and contributions to patient care, and creates opportunities for other health care homes to incorporate this resource into their practice.Aim and theory of change: The aim of this change is to allow clinical advisory pharmacists, who by definition have postgraduate qualifications, to work to top-of-scope though working in the health care home, helping to reduce drug-related morbidity and mortality and therefore helping optimise medicines-related health outcomes.The theory of change incorporates the concepts of the power / process and medical dominance models. This requires exposure to the new service, but additionally it has required recognition that the independent clinical advisory pharmacists have a different set of knowledge and skills.Targeted populations and stakeholders: Most of the clinical advisory pharmacists in New Zealand are working in practices with vulnerable populations to improve access to optimal pharmacotherapy. This has been expanding, particularly over the last three years.Highlights: The highlight of this service is the expansion and growing workforce with acceptance of the role of clinical advisory pharmacists within a health care home team and utilising their skills to improve person and whanau care. Evaluations of the different services has shown beneficial outcomes.Sustainability, transferability: With the changing workforce and increasing multidisciplinary teams in health care homes, this model of clinical pharmacist service delivery is very transferable, although requires a transfer of funding and investment for five years to establish it fully and achieve a critical mass.Conclusions: Independent clinical advisory and prescribing pharmacists are a viable way of integrating services into the health care home. We can learn from international evidence, but also the growing evidence in New Zealand.Lessons learnt:The clinical advisory and prescribing pharmacists bring a different skill set and focus into the health care home, but exposure is required to help understand the benefits achieved.

Response of advanced soft tissue sarcoma to apatinib: A retrospective analysis.

e22502 Background: Soft tissue sarcomas (STSs) are rare but malignant tumors with high risks of local recurrence and distant metastasis. Promising efficacy of apatinib was reported in several subtypes of STSs (Dong et al. 2016, Medicine 95: e4368; Ji et al. 2016, OncoTargets and therapy 9:643-647). We aimed to preliminarily assess the short efficacy and safety of apatinib, an oral tyrosine kinase inhibitor targeting VEFGR-2, in patients with advanced STS. Methods: The medical records of 31 patients who received apatinib between September 2015 and August 2016 were retrospectively reviewed to evaluate the short efficacy, time to progression (TTP) and safety. Results: Nineteen (61.3%) patients taken apatinib after failing second or even more lines of cytotoxic chemotherapy, 8 (25.8%) patients received apatinib as second-line therapy, and 4 (12.9%) cases who refused chemotherapy was given apatinib as first-line therapy. In the study cohort, one patient was treated with apatinib as adjunctive therapy after ablation, while the remaining 30 as salvage therapy. Administration was stopped in 6 cases due to adverse events (n = 3) or personal reasons (n = 3). As a result, 24 patients were eligible for tumor response to apatinib evaluation, and 25 patients were available for survival analysis. The objective response rate was 33.3% and clinical benefit rate was as high as 75.0%. The median TTP was 4.3 months (range, 1.8–11.6 months). Most of the AEs were at grade 1 or 2. The grade 3 AEs were hypertension (n = 2, 6.5%), hand-foot syndrome (n = 2, 6.5%), and diarrhea (n = 1, 3.2%). No grade 4 AE or drug-related mortality occurred. Conclusions: Apatinib showed promising efficacy and acceptable safety profile in metastatic or recurrent STS, giving rationale clinical evidence to conduct clinical trials.

The Effects of Wealth on Health. Micro-Evidence from Homeowners' Housing Wealth Misestimation

The debate on the impact of economic conditions on health has been recently amplified by the drug crisis in the US attributed by some to “deaths of despair.” There is little understanding of the magnitude of the impact of economic conditions on health and the reasons why it varies across socioeconomic groups and geographical areas. We show that housing is an important unexplored driver that explains these differences. We exploit the fact that households that overvalue (undervalue) their houses experience an unexpected negative (positive) shock in their housing wealth when they sell their houses. We find that a one standard deviation positive shock in housing wealth increases the probability of an improvement in self-reported health by 1.13 percentage points and decreases the drug-related mortality rate by 0.27. We exploit the geographical variation in unexpected housing wealth shocks and find that households who live in MSAs with more inelastic housing supply experience larger changes in health outcomes.

Drug-related Mortality in Camden: Demographics and Substance Misuse Trends during the 2010 to 2013 Period

Background and Objectives: Mortality from substance misuse has a constantly changing pattern, with notable rising trends in certain regions of the country. In particular, Camden County, New Jersey has historically struggled with this problem. Because of its inclusion of Camden City, with its high poverty rate and high availability of illicit drugs, and the broader regional impact of the economic recession, analysis of substance misuse-related death in this population might facilitate understanding of these contributory factors in the development and maintenance of addiction and resulting mortality. Methods: Mortality and population data were obtained from public sources (N=516). Subjects’ demographic information and substance profile found at death were investigated for regression and trend analysis. Results: Across the study period, an overwhelming majority of subjects were white adult males. Opiate derivatives were the highest offending agent, occurring in 83.7% of deaths, followed by stimulants (50.3%) and benzodiazepines (38.4%). Furthermore, 24.4% of subjects were found to have 3 or more substances at death. No significant trends were found in mortality rates, but Camden County had significantly higher rates of drug mortality than the rest of New Jersey for the study period. Conclusions and Scientific Significance: This study highlights the opiate epidemic as a major player in Camden County, but also notes significant mortality contributions from stimulant drugs and benzodiazepines in the setting of polysubstance use elicited at the time of death. It is imperative to focus on basic needs (particularly housing) and outpatient long-term programs, rather than inpatient rehabilitation, especially in a population with high poverty rate.

Urine drug testing results and paired oral fluid comparison from patients enrolled in long-term medication-assisted treatment in Tennessee

Urine drug testing is recommended for individuals receiving medication-assisted treatment. It provides objective information for practitioners to consider and may serve as a protective factor against drug-related mortality. The primary objective of our study was to describe urine drug testing results for patients undergoing long-term medication-assisted treatment (≥6months). The secondary objective was to provide further evidence to establish oral fluid as a reliable alternative to urine. All subjects (n=639) included in the study were enrolled in one of five treatment centers in the state of Tennessee, and all urine specimens were positive for either methadone or buprenorphine. Nicotine (87%), caffeine (70%), marijuana (15%), alcohol (14%) and gabapentin (10%) were the most prevalent substances identified through urine drug testing. The presence of non-maintenance opioids (prescription and/or heroin) may represent relapse; these drugs were present in 10% of specimens tested. Evidence of illicit drug use (cocaine, heroin, marijuana and/or methamphetamine) was detected in 19% specimens. For 126 of the 639 subjects included in the study, paired oral fluid and urine test results were compared for agreement. Of the total paired urine and oral fluid tests, approximately 7% were positive for a drug in both specimen types and 91% were negative in both, resulting in an overall agreement of 98%. The study demonstrates continued use of illicit and commercially available medications in a medication-assisted treatment population undergoing long-term treatment. The results affirm the reliability of oral fluid as an alternative specimen type for compliance testing in this population.

Infant Deaths and Mortality from Gun Violence: Causal or Casual?

ObjectiveDescribe trends in non-Hispanic black infant mortality (IM) in the New York City (NYC) counties of Bronx, Kings, Queens, and Manhattan and correlations with gun-related assault mortality. MethodsLinked Birth/Infant Death data (1999-2013) and Compressed Mortality data at ages 1 to ≥85 years (1999-2013). NYC and United States (US) Census data for income inequality and poverty. Pearson coefficients were used to describe correlations of IM with gun-related assault mortality and other causes of death. ResultsIn NYC, the risk of non-Hispanic black IM in 2013 was 49% lower than in 1995 (rate ratio: 0.51; 95% CI: 0.43, 0.61). Yearly declines between 1999 and 2013 were significantly correlated with declines in gun-related assault mortality (correlation coefficient (r) = 0.70, p = 0.004), drug-related mortality (r = 0.59, p = 0.020), major heart disease and stroke (r = 0.85, p < 0.001), malignant neoplasms (r = 0.57, p = 0.026), diabetes mellitus (r = 0.63, p = 0.011), and pneumonia and influenza (r = 0.78, p < 0.001). There were no significant correlations of IM with chronic lower respiratory or liver disease, non-drug-related accidental deaths, and non-gun-related assault. Yearly IM (1995-2012) was inversely correlated with income share of the top 1% of the population (r = −0.66, p = 0.007). ConclusionsIn NYC, non-Hispanic black IM declined significantly despite increasing income inequality and was strongly correlated with gun-related assault mortality and other major causes of death. These data are compatible with the hypothesis that activities related to overall population health, including those pertaining to gun-related homicide, may provide clues to reducing IM. Analytic epidemiological studies are needed to test these and other hypotheses formulated from these descriptive data.

Mortality related to methadone maintenance treatment in Stockholm, Sweden, during 2006–2013

Background: Methadone maintenance treatment (MMT) of opiate addiction was introduced in Sweden 50years ago. The first Swedish programs were modeled after the original Dole and Nyswander program, with strict criteria for admittance into treatment, and have been shown to have positive effects on social and health variables, including mortality. During the last 11years, there have been a number of changes in the regulations controlling MMT-programs in Sweden, and the criteria for admittance are now much less strict compared to previous ones. This study aims to characterize the current MMT-programs with respect to mortality and to compare the results to those obtained in earlier periods.Methods: Persons entering into treatment in Stockholm county, between 2006 and 2011, were followed until September 2013 or until death occurred. Death rates for periods in treatment and out of treatment were determined and compared to rates for the general population. Proportional hazards models with treatment status as time-varying covariate were fitted to the data. A competing risk analysis was made to investigate the effects of MMT on drug-related mortality as compared to mortality from other causes. Mortality data for earlier periods were retrieved from the literature.Results: A total of 441 persons entered MMT during the time period. Of these 67 died during follow-up, the death rate being almost twenty times higher than in the general population. Not being in treatment was associated with a significantly increased hazard of dying (hazard ratio: 2.1, 95% confidence interval: 1.3–3.4). The hazard ratio was mainly increased for drug-related deaths (hazard ratio: 4.4 (2.1–9.2)).Conclusions: Mortality rates among persons who entered MMT-programs in Stockholm during 2006–2011 were not increased compared to persons in treatment twenty years ago. The mortality was significantly increased during periods off treatment. Changes in regulations that minimizes the time off treatment are therefore likely to reduce the mortality rates among clients of MMT-programs.

Location of fatal prescription opioid-related deaths in 12 states, 2008–2010: Implications for prevention programs

IntroductionPrescription opioid pain reliever overdose is a major public health issue in the United States. To characterize the location of drug-related deaths, we examined fatal prescription opioid and illicit drug-related deaths reported in 12 states. MethodsData are from the Substance Abuse and Mental Health Services Administration's Drug Abuse Warning Network (DAWN). Medical examiners or coroners in 12 states (MA, MD, ME, NH, NM, OK, OR, RI, UT, VA, VT, WV) reported details of state-wide drug-related mortality during 2008–2010. DAWN data included location and manner of death, age, race, and drugs involved. Deaths were coded into three categories: prescription opioid-related, illicit drug-related, and cases that involved both a prescription opioid and an illicit drug. ResultsDuring a 3-year period, there were 14,091 opioid or illicit drug-related deaths in 12 states. More than half of the prescription opioid-related deaths in all states, except Maryland, occurred at home, rather than in public or in a health care facility. Although it was still the predominant category, lower percentages of illicit drug-related deaths occurred at home. ConclusionPrescription opioid overdoses have increased substantially, and the location of the person at the time of death can have important public health implications for interventions. Practical applicationsThis paper highlights that bystander support can be a critical lifesaving factor in drug related deaths but may be more likely for illicit drug-related deaths than for prescription opioid-related deaths.

Drug-related mortality among inpatients: a retrospective observational study.

Hospital mortality related to adverse drug reactions (ADRs) is a relevant clinical problem with major health and economic consequences. We conducted a study to assess hospital mortality related to ADRs, the drugs most frequently involved, and the possible risk factors associated with fatal ADRs. A retrospective observational study was conducted, reviewing the clinical records of 1388 consecutive adult patients (18-101years) who died during a 22-month period in a tertiary hospital in Southern Europe (Granada, Spain). The main outcome was the prevalence of hospital death suspected to be related to administered drugs. Out of the 1388 adult deaths studied, 256 (18.4%) were suspected of being related to drugs. Drugs were suspected of causing death in 146 inpatients (10.5%) and contributing to death in 110 (7.9%). Drugs related to death were administered during the hospital stay in 161 cases (11.5%) and before hospital admission in 95 (6.84%). The most frequent fatal ADRs were cardiac arrhythmia, gastrointestinal bleeding, and respiratory failure. The drugs most frequently involved in fatal ADRs were antithrombotics (anticoagulants or antiplatelets) (23%), psychotropic drugs (21.2%), and digoxin (11.3%). Independent risk factors for ADR-related death were the presence of ≥4 diseases (OR=1.43) and the receipt of ≥10 drugs (OR=3.24), but no significant association with gender or age was found. A high percentage of hospital deaths were suspected of being associated with ADRs, especially in patients with comorbidity and/or polypharmacy. Antithrombotics, psychotropics, and digoxin were the drugs most frequently associated with in-hospital drug-related deaths.

Pharmacovigilance awareness among the teaching staffs of a medical college in Karnataka: a cross sectional study

Background: Pharmacovigilance deals with adverse drug reactions and required for early detection and prevention of drug-related morbidity and mortality. The objective of the present is to evaluate the Pharmacovigilance awareness among the teaching staffs of a private medical college in Karnataka. Methodology: A cross sectional, questionnaire based study was conducted in a private medical college of Karnataka. A total of 219 (n=219) medical staffs were participated in this study. Participation in this study was purely on voluntary basis. The questionnaire form was validated by two subject experts prior to the study. A preformed questionnaire form was distributed to all the teaching staffs of medical college and requested them to fill accordingly. All the participants filled the forms completely. Results: The results were analyzed by using SPS software. Statistical analysis was done by chi square test. Most of the teaching staffs (55.3%) heard about Pharmacovigilance, 69% of teaching staff wants to report adverse reactions, 55% teaching staffs undergone training on reporting of ADR, 40% staff wants to report ADR to pharmaceutical company, 31% of staff knows about Pharmacovigilance work structure in India and 48% of teaching staff knows about classification of ADR. But, only 22% of teaching staff attended Pharmacovigilance training programme and the rest 78% of teaching staff willing to undergo training for Pharmacovigilance. Conclusion: This study revealed that majority of the teaching staff knows about Pharmacovigilance and wants to know more about the functioning and structure of Pharmacovigilance in India, in order to prevent adverse drug reactions in patients. Key words: Pharmacovigilance, Adverse drug reactions, Questionnaire form, Cross sectional study, Teaching staff

Exploring the life-saving potential of naloxone: A systematic review and descriptive meta-analysis of take home naloxone (THN) programmes for opioid users

BackgroundThe epidemic of drug-related mortality continues to endure. The most common cause of death associated with drugs is overdose and opioids are consistently the substances most prominently involved. As well as efforts to control the availability of illicit drugs and increase engagement in treatment services, the use of naloxone for peer administration has increasingly been championed as a mechanism for addressing the DRD epidemic. Despite increasing adoption and use of take-home naloxone (THN) as a primary response to DRD internationally the evidence base remains limited. MethodsA systematic review and descriptive meta-analysis of the international THN literature was undertaken to determine an effect size for THN programmes. For each study, a proportion of use (PoU) was calculated using the number of ‘peer administered uses’ and the ‘total number of participant/clients’ trained and supplied with naloxone with a specific focus on people who use drugs (PWUD). This was constrained to a three month period as the lowest common denominator. As a percentage this gives the three month rate of use (per 100 participants). ResultsFrom twenty-five identified THN evaluations, nine studies allowed a PoU to be determined. Overall, the model shows a range of 5.2–13.1 (point estimate 9.2) naloxone uses every three months for every 100 PWUD trained. ConclusionOur model estimates that around 9% of naloxone kits distributed are likely to be used for peer administration within the first three months of supply for every 100 PWUD trained. Future evaluations should directly compare different training structures to test relative effectiveness and use a series of fixed time periods (3, 6 and 12 months) to determine whether time since training affects rate of naloxone use.

Risk of mortality on and off methadone substitution treatment in primary care: a national cohort study.

To assess whether risk of death increases during periods of treatment transition, and investigate the impact of supervised methadone consumption on drug-related and all-cause mortality. National Irish cohort study. Primary care. A total of 6983 patients on a national methadone treatment register aged 16-65 years between 2004 and 2010. Drug-related (primary outcome) and all-cause (secondary outcome) mortality rates and rate ratios for periods on and off treatment; and the impact of regular supervised methadone consumption. Crude drug-related mortality rates were 0.24 per 100 person-years on treatment and 0.39 off treatment, adjusted mortality rate ratio 1.63 [95% confidence interval (CI) = 0.66-4.00]. Crude all-cause mortality rate per 100 person-years was 0.51 on treatment versus 1.57 off treatment, adjusted mortality rate ratio 3.64 (95% CI = 2.11-6.30). All-cause mortality off treatment was 6.36 (95% CI = 2.84-14.22) times higher in the first 2 weeks, 9.12 (95% CI = 3.17-26.28) times higher in weeks 3-4, compared with being 5 weeks or more in treatment. All-cause mortality was lower in those with regular supervision (crude mortality rate 0.60 versus 0.81 per 100 person-years) although, after adjustment, insufficient evidence exists to suggest that regular supervision is protective (mortality rate ratio = 1.23, 95% CI = 0.67-2.27). Among primary care patients undergoing methadone treatment, continuing in methadone treatment is associated with a reduced risk of death. Patients' risk of all-cause mortality increases following treatment cessation, and is highest in the initial 4-week period.

Community pharmacist intervention in patients with renal impairment.

In France, community pharmacists do not have free access to patients' lab results, and it is therefore impossible for them to identify patients with renal impairment. (1) to evaluate the ability of community pharmacists (CPs) to identify drug related problems (DRP) in patients at risk for or suffering from renal impairment; (2) to evaluate the proportions of recommendations by CPs that lead to a modification by GP. A prospective and observational study involving 24 community pharmacists in France. Following special training, community pharmacists were asked to select 52 patients with the following characteristics: ≥65 years of age; prescribed at least two diabetic and/or antihypertensive drugs. Serum creatinine value was obtained for each patient and glomerular filtration rate estimated (eGFR) with the aMDRD formula. Those with a eGFR 60 ml/min/1.73 m² were considered having chronic kidney disease (CKD). Data was collected concerning whether the community pharmacists identified drug related problems and tried to inform the GP who prescribed the medications. Identified DRP were reviewed by a team of nephrologists and hospital clinical pharmacists. The proportion of CKD patients and those without serum creatinine monitoring, the number of drug related problems identified by community pharmacists, and the proportion of drug related problems resolved by the community pharmacists intervention to the GP. Of the total 791 patients identified, 180 (22.8 %) exhibited CKD, and 57 (7.2 %) had not undergone serum creatinine monitoring. Among the 1297 drugs prescribed, 260 had to be adapted to eGFR. The proportion of DRP was 21.5 % (56/260), of which 40 % (20) were identified by community pharmacists. Once the GP was informed, 33.3 % (6/18) of DRP were resolved. Community pharmacists identified 40 % of DRP related to CKD prescriptions, leading to prescription modification by GPs in a third of the cases. These interventions are likely to decrease drug-related morbidity and mortality.

Mortality risk of opioid substitution therapy with methadone versus buprenorphine: a retrospective cohort study

Opioid dependence increases risk of premature mortality. Opioid substitution therapy with methadone or buprenorphine reduces mortality risk, especially for drug-related overdose. Clinical guidelines recommend methadone as the first line of opioid substitution therapy. We aimed to test whether buprenorphine treatment has a lower mortality risk than does methadone treatment by comparing all-cause mortality and drug-related overdose mortality at treatment induction, after in-treatment medication switches, and following treatment cessation. We did a retrospective cohort study of all patients with opioid dependency (n=32,033) in New South Wales, Australia, who started a methadone or buprenorphine treatment episode from Aug 1, 2001, to Dec 31, 2010, including 190,232·6 person-years of follow-up. We compared crude mortality rates (CMRs) for all-cause and drug-related overdose mortality, and mortality rate ratios (MRRs) according to age, sex, period in or out of treatment, medication type, and in-treatment switching. Patients who initiated with buprenorphine had reduced all-cause and drug-related mortality during the first 4 weeks of treatment compared with those who initiated with methadone (adjusted all-cause MRR 2·17, 95% CI 1·29-3·67; adjusted drug-related MRR 4·88, 1·73-13·69). For the remaining time on treatment, drug-related mortality risk did not differ (adjusted MRR 1·18, 95% CI 0·89-1·56), but weak evidence suggested that all-cause mortality was lower for buprenorphine than methadone (1·66, 1·40-1·96). In the 4 weeks after treatment cessation, all-cause mortality did not differ, but drug-related mortality was lower for methadone (adjusted all-cause MRR 1·12, 0·79-1·59; adjusted drug-related MRR 0·50, 0·29-0·86). Patients who switched from buprenorphine to methadone during treatment had lower mortality in the first 4 weeks of methadone treatment than matched controls who received methadone only (CMR difference 7·1 per 1000 person-years, 95% CI 0·1-14·0); no mortality difference was noted for switches from buprenorphine to methadone or for switches to either medication beyond the first 4 weeks of treatment. In a setting with high risk of death in the first 4 weeks of opioid substitution therapy, buprenorphine seemed to reduce mortality in this period, but little difference between buprenorphine and methadone was noted thereafter or for in-treatment switching of medications. Cross-cohort corroboration of our findings and further assessment of the stepped treatment model is warranted. Australian National Health & Medical Research Council.

Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial

Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤ 4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov, number NCT01030809. This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66·0% [SD 14·0] and 61·9% [16·9]; adjusted difference 2·5%, 95% CI -5·2% to 10·2%, p=0·5169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (27·7% and 35·1%, absolute difference [AD] 7·3%, hazard ratio [HR]: 0·73, 95% CI 0·62 to 0·86, p=0·0003). There were no differences in serious drug-related adverse events. Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. AbbVie Pharmaceuticals.

Drug-Induced Nephrotoxicity and Dose Adjustment Recommendations: Agreement Among Four Drug Information Sources.

Hospitalized patients require the use of a variety of drugs, many of which individually or in combination have the potential to cause kidney damage. The use of potentially nephrotoxic drugs is often unavoidable, and the need for dose adjustment should be evaluated. This study is aimed at assessing concordance in information on drug-induced nephrotoxicity and dose adjustment recommendations by comparing four drug information sources (DRUGDEX®, UpToDate®, Medscape® and the Brazilian Therapeutic Formulary) using the formulary of a Brazilian public hospital. A total of 218 drugs were investigated. The global Fleiss’ kappa coefficient was 0.265 for nephrotoxicity (p < 0.001; CI 95%, 0.211–0.319) and 0.346 for recommendations (p < 0.001; CI 95%, 0.292–0.401), indicating fair concordance among the sources. Anti-infectives and anti-hypertensives were the main drugs cited as nephrotoxic by the different sources. There were no clear definitions for qualitative data or quantitative values for dose adjustments among the four information sources. There was no advice for dosing for a large number of the drugs in the international databases. The National Therapeutic Formulary offered imprecise dose adjustment recommendations for many nephrotoxic drugs. Discrepancies among information sources may have a clinical impact on patient care and contribute to drug-related morbidity and mortality.

Drug-related mortality in psychiatric patients

Drug-related mortality in psychiatric patients

Exploring issues arising from survey non-response.

In their paper, Christensen et al. 1 used data from a large Danish survey to examine the impact of non-response on estimated rates of morbidity and mortality. The key findings of this study were that non-respondents were at increased risks of all forms of morbidity/mortality when compared with respondents. Furthermore, there was evidence of heterogeneity in morbidity/mortality rates depending on the type of non-response, with those respondents who were non-contactable (n = 1539) having hazards of morbidity/mortality which were 2.51–7.70 times higher than respondents. At first sight, these figures seem alarming, and suggest substantial bias in the sample and a serious mis-estimation of morbidity/mortality rates. These conclusions are, however, somewhat misleading, and the findings are shaped by two factors that affect the interpretation of analyses using hazard rates and tests of significance. The first feature of the study design is that the overall sample (n = 39 540) is large. The use of a large sample implies that even small between-group differences will be found to be significant. The second feature of the design is that the base rates for morbidity/mortality are low, ranging from 0.10% (drug-related mortality) to 12.75% (all-cause mortality). The low base rate of morbidity/mortality implies that relatively small differences in the number of deaths between the respondent and non-respondent populations may generate large hazard rates. These features are illustrated in Table 1, which presents rates of morbidity/mortality in the respondent and each of the non-respondent groups and the total population. These comparisons show that in terms of rates of morbidity/mortality there were only small differences between the respondents and non-respondents. Although it is clear from Table 1 that there were generally small differences between groups in terms of morbidity/mortality, it is also the case that, for some applications, biases caused by using the respondent sample to calculate rates of morbidity/mortality may be of substantive importance. For example, the overall rate of mortality for the total sample was 12 746.58 deaths per 100 000, whereas the estimated rate from the respondent data was 11 249.64 per 100 000, a mortality rate that is 11.7% lower. This suggests that for some applications, such as investigations of mortality in large samples, the use of respondent-only data may lead to conceptually important differences in estimates. One interesting aspect of the analysis of the sources of bias in the present paper is the suggestion that much of the non-respondent group can be accounted for by those who were non-contactable. These findings suggest that in terms of reducing sample selection biases a major priority should be placed on minimizing rates of non-contact. In assigning this priority, however, there are a number of issues that need to be considered. Perhaps the most important issue to consider is the trade-off between overall sample size and risks of non-contact. As a general rule in most survey settings, as sample size increases the resources available to trace difficult-to-contact respondents decrease. For example, in the present study it could be proposed that rates of non-contact could have been reduced by reducing the sample size by (for example) 50% and spending the funding saved on improved methods of respondent tracing. The literature in this area suggests that there are a number of strategies that can be used to reduce non-contact rates in surveys. These include the use of personally addressed hand-signed letters 2, using repeat contact via telephone and mailing 3, using monetary incentives 4 or using face-to-face contact 5. A final issue that needs consideration is that the paper by Christensen et al. examines the impacts of non-response on estimates of population rates. While estimation of population rates is of general interest, the focus of many longitudinal studies is upon the associations between risk factors and outcomes. There is considerable reason to believe that estimates of such associations are less likely to be influenced by sample attrition than estimates of population rates. As shown by Gustavson et al., for sample attrition to adversely affect estimates of associations high levels of attrition must exist in both the risk factor and outcome measures 6. In summary, the paper by Christensen et al. 1 adds to the growing literature on sample attrition in longitudinal research. Consistent with most previous research, the study found that the impacts of sample attrition on estimates of population statistics are detectable but relatively modest. These findings clearly suggest that findings from longitudinal studies subject to attrition should be treated as providing ‘ballpark’ estimates of population parameters, and that care should be taken in drawing inferences based on these estimates. None.

What is wrong with non-respondents? Alcohol-, drug- and smoking-related mortality and morbidity in a 12-year follow-up study of respondents and non-respondents in the Danish Health and Morbidity Survey.

AimResponse rates in health surveys have diminished over the last two decades, making it difficult to obtain reliable information on health and health‐related risk factors in different population groups. This study compared cause‐specific mortality and morbidity among survey respondents and different types of non‐respondents to estimate alcohol‐, drug‐ and smoking‐related mortality and morbidity among non‐respondents.DesignProspective follow‐up study of respondents and non‐respondents in two cross‐sectional health surveys.SettingDenmark.ParticipantsA total sample of 39 540 Danish citizens aged 16 years or older.MeasurementsRegister‐based information on cause‐specific mortality and morbidity at the individual level was obtained for respondents (n = 28 072) and different types of non‐respondents (refusals n = 8954; illness/disabled n = 731, uncontactable n = 1593). Cox proportional hazards models were used to examine differences in alcohol‐, drug‐ and smoking‐related mortality and morbidity, respectively, in a 12‐year follow‐up period.FindingsOverall, non‐response was associated with a significantly increased hazard ratio (HR) of 1.56 [95% confidence interval (CI) = 1.36–1.78] for alcohol‐related morbidity, 1.88 (95% CI = 1.38–2.57) for alcohol‐related mortality, 1.55 (95% CI = 1.27–1.88) for drug‐related morbidity, 3.04 (95% CI = 1.57–5.89) for drug‐related mortality and 1.15 (95% CI = 1.03–1.29) for smoking‐related morbidity. The hazard ratio for smoking‐related mortality also tended to be higher among non‐respondents compared with respondents, although no significant association was evident (HR = 1.14; 95% CI = 0.95–1.36). Uncontactable and ill/disabled non‐respondents generally had a higher hazard ratio of alcohol‐, drug‐ and smoking‐related mortality and morbidity compared with refusal non‐respondents.ConclusionHealth survey non‐respondents in Denmark have an increased hazard ratio of alcohol‐, drug‐ and smoking‐related mortality and morbidity compared with respondents, which may indicate more unfavourable health behaviours among non‐respondents.