Drug-related Death Rates Research Articles

Treatment for drug dependence in England needs investment and reform

In 2019, England's Department of Health and Social Care invited me to oversee an independent review of illicit drug use to inform the UK Government's policy on addressing the harms that drugs cause. The UK has some of the most serious and enduring drug problems in the world 1 UN Office on Drugs and CrimeWorld drug report 2021. UN Office on Drugs and Crime, Vienna2021 Google Scholar and one of the highest rates of drug-related deaths in Europe. 2 European Monitoring Centre for Drugs and Drug AddictionEuropean drug report 2020. European Monitoring Centre for Drugs and Drug Addiction, Lisbon2020 Google Scholar

P547 Safety and efficacy of vedolizumab in the treatment of patients with moderate to severe Ulcerative Colitis: a systematic review and meta-analysis

Abstract Background To perform a systematic review and meta-analysis discussing the efficacy and safety of vedolizumab (VDZ) treatment in patients with active moderate to severe ulcerative colitis (UC). Methods Using relevant keywords, we searched PubMed, Web of Science, Scopus, and Cochrane Central databases, until June 2020. We included interventional and observational cohort studies which assessed the safety and effectiveness of VDZ 300 mg intravenous infusion, in patients with active moderate to severe UC. We used the Cochrane risk of bias assessment tool and the Newcastle-Ottawa scale to assess the quality of included interventional and cohort studies, respectively. Dichotomous outcomes were pooled as proportion, 95% Confidence interval (CI), and p-value under the random-effects model in the open meta-analyst software. Results We found 10 interventional studies and 35 cohort studies, including 4,794 patients eligible for our review. Most of the included citations were single-arm studies. Our meta-analysis showed that VDZ therapy could induce a significant clinical response in UC patients up to 54 weeks (proportion 0.516, 95% CI [0.453, 0.578], p < 0.001). VDZ was associated with clinically significantly clinical remission and steroid-free clinical remission after 54 weeks (p < 0.0001). Durable clinical remission, histological remission, and endoscopic response rates were maintained in UC patients taking VDZ at the 52nd week. There was no significant difference between VDZ and placebo regarding the incidence of drug-related serious adverse events (p = 0.113) and death rates (p = 0.085). Conclusion Our systematic review and meta-analysis showed that the use of VDZ in patients with active moderate to severe UC was associated with high percentages of clinical response and remission rates in induction and maintenance treatment stages. VDZ seems to be well tolerated in UC patients, apart from some infections and inflammations. Future RCTs should compare VDZ to active treatments for longer follow-up periods with larger sample size.

Is disinvestment from alcohol and drug treatment services associated with treatment access, completions and related harm? An analysis of English expenditure and outcomes data.

The positive impact of substance use treatment is well-evidenced but there has been substantial disinvestment from publicly funded treatment services in England since 2013/2014. This paper examines whether this disinvestment from adult alcohol and drug treatment provision was associated with changes in treatment and health outcomes, including: treatment access, successful completions from treatment, alcohol-specific hospital admissions, alcohol-specific mortality and drug-related deaths. Annual administrative data from 2013/2014 to 2018/2019 was matched at local government level and multi-level time series analysis using linear mixed-effect modelling conducted for 151 upper-tier local authorities in England. Between 2013/2014 and 2018/2019, £212.2 million was disinvested from alcohol and drug treatment services, representing a 27% decrease. Concurrently, 11% fewer people accessed, and 21% fewer successfully completed, treatment. On average, controlling for other potential explanatory factors, a £10 000 disinvestment from alcohol and drug treatment services was associated with reductions in all treatment outcomes, including 0.3 fewer adults in treatment (95% confidence interval 0.16-0.45) and 0.21 fewer adults successfully completing treatment (95% % confidence interval 0.12-0.29). A £10 000 disinvestment from alcohol treatment was not significantly associated with changes in alcohol-specific hospital admissions or mortality, nor was disinvestment from drug treatment associated with the rate of drug-related deaths. Local authority spending cuts to alcohol and drug treatment services in England were associated with fewer people accessing and successfully completing alcohol and drug treatment but were not associated with changes in related hospital admissions and deaths.

Why are drug-related deaths among women increasing in Scotland? A mixed-methods analysis of possible explanations

Drug-related deaths have increased significantly in Scotland in recent years, with a much greater percentage increase in deaths among women than among men. We undertook a mixed-methods project to identify explanations for this trend, comprising three parallel methodological strands: (i) an analysis of available routine data, including drug treatment data, death registrations, and surveys of people using needle exchanges; (ii) thematic analysis of interviews and focus groups with professional stakeholders and (iii) secondary analysis of interviews with women who use drugs. Results indicated that the observed trend is likely to reflect multiple, interacting causes. Potential contributors identified were: ageing; changing patterns of substance use; increasing prevalence of physical and mental health co-morbidities; changing relationships and parenting roles; changes to treatment services and wider health and social care provision; unintended consequences or poor implementation of recovery-oriented practice; and changes in the social security system. Policy responses to rising drug-related death rates require a gender-informed approach, recognising the commonalities and differences between men and women who use drugs; the diversity of experiences within each gender; and the intersections between gender and other forms of inequality, such as poverty.

Intersections of Firearm Suicide, Drug-Related Mortality, and Economic Dependency in Rural America

BackgroundRural counties in the United States have higher firearm suicide rates and opioid overdoses than urban counties. We sought to determine whether rural counties can be grouped based on these “diseases of despair.” MethodsAge-adjusted firearm suicide death rates per 100,000; drug-related death rates per 100,000; homicide rate per 100,000, opioid prescribing rate, %black, %Native American, and %veteran population, median home price, violent crime rates per 100,000, primary economic dependency (nonspecialized, farming, mining, manufacturing, government, and recreation), and economic variables (low education, low employment, retirement destination, persistent poverty, and persistent child poverty) were obtained for all rural counties and evaluated with hierarchical clustering using complete linkage. ResultsWe identified five distinct rural county clusters. The firearm suicide rates in the clusters were 5.9, 6.8, 6.4, 8.5, and 3.8 per 100,000, respectively. The counties in cluster 1 were poor, mining dependent, with population loss, cluster 2 were nonspecialized economies, with high opioid prescription rates, cluster 3 were manufacturing and government economies with moderate unemployment, cluster 4 were recreational economies with substantial veterans and Native American populations, high median home price, drug death rates, opioid prescribing, and violent crime, and cluster 5 were farming economies, with high population loss, low median home price, low rates of drug mortality, opioid prescribing, and violent crime. Cluster 4 counties were spatially adjacent to urban counties. ConclusionsMore than 300 counties currently face a disproportionate burden of diseases of despair. Interventions to reduce firearm suicides should be community-based and include programs to reduce other diseases of despair.

Hepatitis C diagnosis and treatment, impact on engagement and behaviour of people who inject drugs, a service evaluation, the hooked C project.

There is emerging evidence that Hepatitis C (HCV) treatment engagement is associated with change in drug behaviours and reduced drug-related death rates among people who inject drugs (PWID). The project aims to investigate whether HCV diagnosis and treatment engagement reduces all-cause mortality and drug-related death, and whether any effect is dependent on treatment regimen and intensity of engagement with staff. Case-control studies comparing: PWID with active HCV infection (PCR positive) to PWID HCV infected but spontaneously resolved (PCR negative); PCR-positive patients who engaged with treatment services to nonengagers; and patients who received interferon vs direct-acting antiviral (DAA) based treatment. No differences in risk of all-cause mortality or drug-related death between PCR-negative controls and PCR-positive cases were detected. The odds of all-cause mortality was 12.2 times higher in nonengaging persons compared to treatment engaging cases (aOR 12.15, 95% CI 7.03-20.99, P<.001). The odds of a drug-related death were 5.5 times higher in nonengaging persons compared with treatment engaging cases (aOR 5.52, 95% CI 2.67- 11.44, P<.001). No differences in risk of all-cause mortality or drug-related death between interferon-treated cases and DAA-treated controls were detected. HCV treatment engagement is significantly protective against all-cause mortality and drug-related death. This engagement effect is independent of treatment regimen, with the introduction of DAA therapies not increasing risk of drug-related death, suggesting intensity of HCV therapy provider interaction is not an important factor.

Availability of Buprenorphine Treatment in the 10 States With the Highest Drug Overdose Death Rates in the United States.

The objective of this study was to assess the accuracy of the Substance Abuse and Mental Health Services Administration (SAMHSA) database for patients who use it to seek buprenorphine treatment. Buprenorphine providers within a 25-mile radius of the county with the highest drug-related death rates within the 10 states with the highest drug-related death rates were identified and called to determine whether the provider worked there, prescribed buprenorphine, accepted insurance, had appointments, or charged for visits. The number of providers listed in each county ranged from 1 to 166, with 5 counties having <10 providers. In 3 counties no appointments were obtained, and another 3 counties had ≤3 providers with availability. Of the 505 providers listed, 355 providers (70.3%) were reached, 310 (61.4%) of the 505 listings were correct numbers, and 195 (38.6%) of the 505 providers in the listings provided buprenorphine. Of the 173 clinics that provided buprenorphine and were asked about insurance, 131 (75.7%) accepted insurance. Of the 167 clinics that provided buprenorphine and were asked about Medicaid, 105 (62.9%) accepted it. Wait times for appointments ranged from 1 to 120 days, with an average of 16.8 days for those that had a waitlist. Among the 39 providers who reported out-of-pocket costs, the average cost was $231 (range: $90 to $600). One hundred forty of the 505 providers listed in the database had appointments available (27.7%). Three hundred sixty-five of the 505 providers did not have appointments available (72.3%) for various reasons, including the fact that 120 providers (32.9% of the 365 providers) could not be reached, and 137 of the numbers (37.5% of the 365 listed numbers) were wrong. Other reasons appointments could not be obtained included the fact that providers did not treat outpatients, were not accepting new patients, were out of office, or required a referral. Although the SAMHSA buprenorphine practitioner locator is used by patients and providers to locate treatment options, only a small portion of clinicians in the database ultimately offered initial appointments, implying that the database is only marginally useful for patients.

Deaths of Despair and Brexit Votes: Cross-Local Authority Statistical Analysis in England and Wales.

Objectives. To test the hypothesis that deaths of despair, a marker of social suffering, were associated with greater support for Brexit in the United Kingdom's 2016 European Union referendum.Methods. We used cross-local authority regression models of Brexit vote shares on changes in suicide and drug-related death rates before (2005-2007) and after the recession (2014-2016), adjusting for sociodemographic factors. The population comprised 345 local authorities in England and Wales.Results. Mortality rates were associated with voting patterns. An increase of 10 drug-related deaths per 100 000 was associated with a 15.25-percentage-point increase in Brexit votes (95% confidence interval [CI] = 10.27, 20.24), while an increase of 10 suicides per 100 000 was associated with a 9.97-percentage-point increase in vote shares for Brexit (95% CI = 6.25, 13.70). These results were substantially attenuated after we adjusted for education, and reduced to nonsignificance for drug mortality (b = 2.18; 95% CI = -0.21, 4.57) and suicide (b = 0.94; 95% CI = -0.32, 2.21) upon inclusion of other sociodemographic factors.Conclusions. Worsening mortality correlated with Brexit votes. These phenomena appear to share similar antecedents. A rise in such deaths may point to deeper social problems that could have political consequences.

Treatment versus Punishment: Understanding Racial Inequalities in Drug Policy.

Many observers believe that the policy response to the opioid crisis is less punitive than the crack scare and that the reason is that victims are (stereotypically) white. To assess this conjecture, we compile new longitudinal data on district-level drug-related deaths and (co)sponsorship of legislation on drug abuse in the House of Representatives over the past four decades. Using legislator fixed effects models, we then test how changes in drug-related death rates in legislators' districts predict changes in (co)sponsorship of treatment-oriented or punitive legislation in the subsequent year and assess whether these relationships vary by race of victim or drug type. Policy makers were more likely to introduce punitive drug-related bills during the crack scare and are more likely to introduce treatment-oriented bills during the current opioid crisis. The relationship between district-level drug deaths and subsequent sponsorship of treatment-oriented legislation is greater for opioid deaths than for cocaine-related deaths and for white victims than for black victims. By contrast, district-level drug deaths are not significantly related to sponsorship of punishment-oriented bills. These results suggest that the racial inequalities and double standards of drug policy still persist but in different forms.

The special grief following drug related deaths

Background: In most European countries and in the US, there has been a negative trend with increasing incident rates of drug related deaths (DRD) during the last decade. In 2017, the mortality rate due to overdoses reached epidemic proportions in the United States; i.e. the age-adjusted rate of drug overdoses reached 21.7 per 100,000, being 9.6% higher than the 2016 rate. Increasing, still lower, rates are seen in European countries. Behind these figures are many bereaved persons left behind in quiet grief.Results: Research has shown that other kinds of unnatural deaths (e.g. resulting from accident, suicide, homicide) in particular, can lead to intense suffering and reduce quality of life for those left behind. Still, drug death bereaved persons seem to be an understudied, stigmatized and invisible social group. In this paper, we review previous research and deal with strain and stigmatization before drug related deaths and The Special Grief after such deaths.Discussion: We will discuss the possibility of different grief reactions as anticipated-, disenfranchized- and Prolonged Grief Disorder among family members and close friends. Furthermore, we focus on how the phenomenology of grief is connected to contextual and personal relations and interpersonal processes. Finally, we discuss the usefulness of a relational dialectics’ perspective and a family perspective for understanding and relating to The Special Grief.

Drug-related mortality after discharge from treatment: A record-linkage study of substance abuse clients in Texas, 2006–2012

BackgroundPatients have higher mortality immediately after substance abuse treatment discharge, but there are few data on post-discharge mortality differences across treatment modalities. MethodsA retrospective cohort study examined individuals discharged from substance abuse treatment during 2006–2012 and probabilistically matched treatment records to death records. Logistic regression examined associations between drug-related death (DRD) and demographics; route, frequency, and classes of drugs abused; and treatment. Primary outcome was DRD during post-discharge days 0–28; secondary outcomes examined DRD during days 29–90 and 91–365. ResultsWe examined 178,749 patients discharged from 254,814 treatment episodes. There were 97 DRD during days 0–28 (4.1/1000 person-years), 115 DRD during days 29–90 (2.6/1000 person-years; IRR 0.6 [95% CI 0.5–0.8]), and 293 DRD during days 91–365 (1.9/1000 person-years; IRR 0.5 [0.4–0.6]). Higher 28-day DRD was associated with abuse of opioids (aOR 2.5 [1.4–4.4]), depressants (aOR 2.0 [1.2–3.4]), or alcohol (aOR 1.7 [1.1–2.6]); and opioid injection (aOR 2.2 [1.3–3.7]). Lower DRD was associated with treatment completion (aOR 0.6 [0.4–0.9]), female sex (aOR 0.6 [0.4–0.8]), and employment (aOR 0.5 [0.3–0.9]). Among all patients, DRD rates were higher following residential (IRR 2.6, [1.6–4.2]) and detoxification (IRR 2.9, [1.7–4.9]) treatment compared to outpatient. Patients with prior opioid abuse had higher 28-day DRD after outpatient (6.7/1000 person-years; IRR 4.1 [1.8–9.1]), residential (13.6/1000 person-years; IRR 4.2 [2.2–8.2]), and detoxification (8.8/1000 person-years; IRR 3.2 [1.2, 8.5]) compared to those without. ConclusionsDrug-related mortality is highest during days 0–28 after discharge, especially following residential and detoxification treatment. Opioid abuse is strongly associated with early post-discharge mortality.

How do family members experience drug death bereavement? A systematic review of the literature

Despite high rates of drug-related deaths (DRDs), drug-related bereavement has been sparsely investigated. A systematic literature search for qualitative and quantitative studies was conducted. Studies on bereaved DRD family members and systems influencing bereavement were eligible for inclusion. Eight studies were included. Three themes emerged from the thematic analysis (Emotional Roller Coaster, Lack of Understanding by the Social World, and Meaning Making) describing an emotional and existential overload, stigmatization and lack of understanding and help from support systems. The results also shed light on life after the loss. Directions for further research were subsequently outlined.

Opioid-related deaths and previous care for drug use and pain relief in Sweden

AimIn 2006–2014, the rate of drug-related deaths, typically opioid poisonings, more than doubled in Sweden. Opioid prescriptions for pain control or opioid agonist therapy also increased. In this retrospective study, we compared death rates between individuals whose first recorded contact with prescribed opioids was for pain control and individuals that had received substance use disorder (SUD) treatment before their first recorded opioid prescription. MethodsWe included 2834 forensically examined individuals (ages 15–64 years) that died of poisoning in Sweden in 2006–2014. For each death we acquired data on previous opioid prescriptions and SUD treatments. We compared three study groups: pain control (n = 788); a SUD treatment group (n = 1629); and a group with no prescription for pain control or SUD treatment (n = 417). ResultsOverall fatal poisonings increased from 2.77 to 7.79 (per 100,000 individuals) from 2006 to 2014 (relative 181% increase). Fatal poisoning increased from 2006 to 2014 by 269% in the pain control group (0.64 to 2.36 per 100,000) and by 238% in the SUD treatment group (1.35 to 4.57 per 100,000). Heroin-related deaths remained constant; consequently, the increase was likely attributable to prescription opioids. ConclusionA rapid increase in deaths attributable mainly to prescription opioids for pain control, was reported previously in the United States. Our study indicated that increased access to prescription opioids might contribute to higher death rates also in Sweden among patients seeking pain control and individuals with an established SUD; however, deaths related to prescription opioids mainly occurred among those with SUDs.

A cross-national analysis of the association between years of implementation of opioid substitution treatments and drug-related deaths in Europe from 1995 to 2013.

Data at the individual-level provide evidence that opioid substitution treatment (OST) programs protect against mortality for opioid dependent populations. Prior research has not examined the merits of national implementation of opioid substitution programs for reducing mortality at the country-level. This study elucidates longitudinal associations between country-level implementation of opioid substitution treatment programs on mortality rates of drug related deaths (DRD) from 1995 to 2013 in 30 European nations. Cases of DRD were measured using National Definitions for each country from official sources of data. Preliminary analysis of dispersion of cases of DRD using means and variances justified use of the negative binomial regression model with a population offset. Year and country-level fixed effects negative binomial regression models investigated the association between years of implementation of methadone maintenance therapy (MMT), OST in prison, and high dose buprenorphine treatment (HDBT) implementation and mortality rates from drug related deaths after adjusting for unemployment rates, heroin seizures and per capita expenditures on health. Beta coefficients were converted to Incidence Rate Ratios (IRR) and standard errors bootstrapped using non-parametric methods to adjust for bias (SDbs). The mean mortality rate of DRD was 1.81 from 1995 to 2013. In adjusted models, each additional year of MMT (IRR=.61, SD=.04, p<.001; SDbs=.08, p<.001), prison OST (IRR=.90, SD=.01, p<.001; SDbs=.02, p<.001), and HDBT (IRR=.09, SD=.02, p<.001; SDbs=.02, p<.01) was significantly associated with lower rates of DRDs after adjusting for country and year fixed effects. Implementation of OST programs in the general population and in prison settings may have protected against mortality from drug use at the country-level in Europe from 1995 to 2013.

Drug-related deaths: Statistics based on death certificates miss one-third of cases.

Aims: Statistics on drug-related deaths (DRD) provide crucial information on the drug situation. The European Monitoring Centre for Drug and Drug Addiction (EMCDDA) has published a specification for extracting DRD from national mortality registers to be used in international comparisons. However, surprisingly little is known of the accuracy of DRD statistics derived from national mortality registers. This study assesses the accuracy of Swedish data derived from national mortality registers by comparing it with other sources of data. Methods: We compared five Swedish datasets. Three were derived from national mortality registers, two according to a Swedish specification and one according to the EMCDDA specification. A fourth dataset was based on toxicological analyses. We used a fifth dataset, an inventory of DRD in Stockholm, to assess the completeness and coverage of the Swedish datasets. Results: All datasets were extracted from high-quality registers, but still did not capture all DRD, and both the numbers and demographic characteristics varied considerably. However, the time trends were consistent between the selections. In international comparisons, data completeness and investigation procedures may impact even more on stated numbers. Conclusions: Basing international comparisons on numbers or rates of DRDs gives misleading results, but comparing trends is still meaningful.

The efficacy and safety in elderly patients with advanced renal cell carcinoma: Real-world use of sorafenib in Japan.

476 Background: Multiple treatment options are available for patients with advanced renal cell carcinoma (RCC). However, the safety and efficacy data of these agents in elderly patients are limited. In this study, the data, which prospectively collected practical use of sorafenib amongst all RCC patients as a nationwide post-marketing surveillance, were analyzed using propensity-matched cohorts. Methods: A total of 3,255 patients with advanced RCC were enrolled and 772 patients selected by propensity score were matched for &lt;75 (n=386) and ≥75 year old patients (n=386). Progression free survival (PFS), tumor response, adverse events (AEs), doses of sorafenib, and estimated glomerular filtration rate (eGFR) were analyzed. Results: The median PFS in &lt;75 and ≥75 year old patients was 233 days (194, 274) vs. 219 days (190, 263), respectively. The mean starting dose (702 mg vs. 688 mg) and median treatment duration (222 days vs. 175 days) were similar in two groups, but mean dose intensity (70.3% vs. 61.4%, p&lt;0.001) was lower in ≥75 year old patients than that in &lt;75 year old patients. Complete response rates were 0.9% and 3.7%, partial response rates were 27.9% and 27.1%, stable disease rates were 58.4% and 55.6%, progressive disease rates were 12.8% and 12.8% in &lt;75 and ≥75 year old patients, respectively. Objective response rate (CR+PR) was comparable in both groups (28.8% and 30.8%). Safety was analyzed for 772 patients, and any grade AEs observed ≥20% were hand-foot skin reaction (HFSR) (55.8%), hypertension (36.7%), rash (27.4%), and increase in lipase / amylase (26.2%), and diarrhea (21.8%). The common serious AEs were rash (7.4%), HFSR (6.0%), hepatic dysfunction (5.6%), cytopenia (4.9%), and hypertension (2.8%). The incidence of these common AEs was similar between the two groups. The discontinuation due to AE and drug related death rates were 65.3% vs. 74.9% (p&lt;0.01) and 3.4% vs. 4.9% in &lt;75 and ≥75 year old patients, respectively. In both groups, the eGFR value did not change from the baseline, and even slightly increased after 12 months of sorafenib treatment. Conclusions: This study indicated that sorafenib provides clinical benefits and is tolerable amongst patients with advanced RCC regardless of age.

Assessing the impact of prescribing directives on opioid prescribing practices among Veterans Health Administration providers.

The study aimed to test whether directives on opioid prescribing released by the Veterans Health Administration (VHA) or the Food and Drug Administration (FDA) had an impact on prescribing among VHA providers. We used the VHA's linked pharmacy and patient medical records database to identify new prescriptions written for propoxyphene, fentanyl, and controlled release (CR) oxycodone between 1/1/2000 and 12/31/2009. We plotted the monthly proportion of these prescriptions that complied with components of four specific safety alerts or directives for these substances issued by the VHA or FDA between 1/1/2001 and 12/31/2008. We modeled compliance using interrupted time series analysis and a generalized additive model with the addition of an indicator variable to flag prescriptions that followed the directive's release date. A total of 32.2 million new prescriptions for fentanyl, oxycodone CR, and propoxyphene were written for VHA patients meeting inclusion criteria. Compliance with guidelines in the directives increased steadily throughout the entire study period, with no clinically meaningful inflection point near the date of each directive's release. Generalized additive modeling and interrupted time series analysis found that the indicator flag slightly improved the fit of the data, but visual inspection of the plots revealed no change at a level of practical significance. While prescribing compliance increased throughout the period, release of FDA and VHA alerts and guidelines did not appear to contribute to this change. Given the fivefold increase in the rate of drug-related overdose deaths since 1990, identifying effective methods to communicate safety messages and change prescriber behavior remains a priority for future work. Copyright © 2016 John Wiley & Sons, Ltd.

Impact of opioid substitution therapy for Scotland's prisoners on drug-related deaths soon after prisoner release.

AimTo assess whether the introduction of a prison‐based opioid substitution therapy (OST) policy was associated with a reduction in drug‐related deaths (DRD) within 14 days after prison release.DesignLinkage of Scotland's prisoner database with death registrations to compare periods before (1996–2002) and after (2003–07) prison‐based OST was introduced.SettingAll Scottish prisons.ParticipantsPeople released from prison between 1 January 1996 and 8 October 2007 following an imprisonment of at least 14 days and at least 14 weeks after the preceding qualifying release.MeasurementsRisk of DRD in the 12 weeks following release; percentage of these DRDs which occurred during the first 14 days.FindingsBefore prison‐based OST (1996–2002), 305 DRDs occurred in the 12 weeks after 80 200 qualifying releases, 3.8 per 1000 releases [95% confidence interval (CI) = 3.4–4.2]; of these, 175 (57%) occurred in the first 14 days. After the introduction of prison‐based OST (2003–07), 154 DRDs occurred in the 12 weeks after 70 317 qualifying releases, a significantly reduced rate of 2.2 per 1000 releases (95% CI = 1.8–2.5). However, there was no change in the proportion which occurred in the first 14 days, either for all DRDs (87: 56%) or for opioid‐related DRDs.ConclusionsFollowing the introduction of a prison‐based opioid substitution therapy (OST) policy in Scotland, the rate of drug‐related deaths in the 12 weeks following release fell by two‐fifths. However, the proportion of deaths that occurred in the first 14 days did not change appreciably, suggesting that in‐prison OST does not reduce early deaths after release.

Evaluation of the efficacy and safety of anti-PD-1 and anti-PD-L1 antibody in the treatment of non-small cell lung cancer (NSCLC): a meta-analysis.

Currently, blockade of the programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling pathway has been proved one of the most promising immunotherapeutic strategies against cancer. Several antibodies have been developed to either block the PD-1 or its ligand PD-L1 are under development. So far, a series of phase I trials on PD-1/PD-L1 antibodies for non-small cell lung cancer (NSCLC) have been completed, without reports of results from phase II studies. Thus, we sought to perform a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of PD-1 or PD-L1 inhibition therapy. Electronic databases were searched for eligible literatures. Data of objective respond rate (ORR) and rate of adverse effects (AEs) with 95% confidence interval (CI) evaluated by immunohistochemistry (IHC) was extracted. The outcomes were synthesized based on random-effect model. Subgroup analyses were proposed. In overall, ORR in the whole population with PD-1 blockage treatment is 22.5% (95% CI: 17.6% to 28.2%). Additionally, the rate of Grade 3-4 AEs is 16.7% (95% CI: 6.5% to 36.8%) and drug-related death rate is 2.5% (95% CI: 1.3% to 4.6%). As for patients with PD-L1 inhibition therapy, an overall ORR is 19.5% (95% CI: 13.2% to 27.7%). A higher rate of Grade 3-4 AEs (31.7%, 95% CI: 14.2% to 56.5%) is observed with a lower drug-related death rate (1.8%, 95% CI: 0.4% to 8.3%). In exploratory analyses of anti-PD-1 agents, we observed that greater ORR was presented in the median-dose cohort (3 mg/kg) than that of both low-dose (1 mg/kg) and high-dose (10 mg/kg) cohort (low-dose vs. median-dose: OR =0.12, P=0.0002; median-dose vs. high-dose: OR =1.47, P=0.18). Anti-PD-1 and anti PD-L1 antibodies showed objective responses in approximately one fourth NSCLC patients with a tolerable adverse-effect profile. In addition, median-dose (3 mg/kg) might be a preferential dosage of anti-PD-1 agents.

Prescription opioid use and non-fatal overdose in a cohort of injection drug users

Background: There is growing concern regarding rising rates of prescription drug-related deaths among the general North American population as well as increasing availability of illicitly obtained prescription opioids. Concurrently among people who inject drugs (IDU), illicit prescription opioid use has increased while non-fatal overdose remains a major source of morbidity. Objectives: To evaluate whether the use of prescription opioids was associated with non-fatal overdose among IDU in Vancouver, Canada. Methods: Data was obtained from two open prospective cohorts of IDU between December 2005 and May 2013. We used generalized estimating equation (GEE) logistic regression to evaluate the association between prescription opioid use and non-fatal overdose, adjusting for various social, demographic, and behavioral factors. Results: There were 1614 IDU, including 541 (33.5%) women, who were recruited and included in this analysis. At baseline, 526 (32.6%) reported using prescription opioids and 118 (7.3%) reported experiencing an overdose in the previous six months. In a multivariable analysis, prescription opioid use remained independently associated with non-fatal overdose (adjusted odds ratio: 1.61, 95% confidence interval: 1.32–1.95), after adjusting for confounders. Conclusion: We observed relatively high rates of prescription opioid use among IDU in this setting, and found an independent association between prescription opioid use and non-fatal overdose. Our data is likely representative of riskier substance use associated with those who use prescription opioids within our sample. Interventions to prevent and respond to overdoses should consider the higher risk profiles of IDU who use prescription opioids.