Large variations in all-cause and overdose mortality among >13,000 patients in and out of opioid maintenance treatment in different settings: a comparative registry linkage study.

Background: Opioid maintenance treatment (OMT) has the potential to reduce mortality rates substantially. We aimed to compare all-cause and overdose mortality among OMT patients while in or out of OMT in two different countries with different approaches to OMT. Methods: Two nation-wide, registry-based cohorts were linked by using similar analytical strategies. These included 3,637 male and 1,580 female patients enrolled in OMT in Czechia (years 2000-2019), and 6,387 male and 2,078 female patients enrolled in OMT in Denmark (years 2007-2018). The direct standardization method using the European (EU-27 plus EFTA 2011-2030) Standard was employed to calculate age-standardized rate to weight for age. All-cause and overdose crude mortality rates (CMR) as number of deaths per 1,000 person years (PY) in and out of OMT were calculated for all patients. CMRs were stratified by sex and OMT medication modality (methadone, buprenorphine, and buprenorphine with naloxone). Results: Age-standardized rate for OMT patients in Czechia and Denmark was 9.7/1,000 PY and 29.8/1,000 PY, respectively. In Czechia, the all-cause CMR was 4.3/1,000 PY in treatment and 10.8/1,000 PY out of treatment. The overdose CMR was 0.5/1,000 PY in treatment and 1.2/1,000 PY out of treatment. In Denmark, the all-cause CMR was 26.6/1,000 PY in treatment and 28.2/1,000 PY out of treatment and the overdose CMR was 7.3/1,000 PY in treatment and 7.0/1,000 PY out of treatment. Conclusion: Country-specific differences in mortality while in and out of OMT in Czechia and Denmark may be partly explained by different patient characteristics and treatment systems in the two countries. The findings contribute to the public health debate about OMT management and may be of interest to practitioners, policy and decision makers when balancing the safety and accessibility of OMT.

Cause-Specific Mortality among Patients in Treatment for Opioid Use Disorder in Multiple Settings: A Prospective Comparative Cohort Study.

INTRODUCTION: Among people receiving current or previous opioid maintenance treatment (OMT), the leading cause of premature death is an opioid overdose. However, other causes of mortality remain high in this group. An understanding of causes of deaths across multiple settings can be useful in informing more comprehensive prevention responses. The aim of this study was to describe all non-overdose causes of death in three national cohorts (Czechia, Denmark, and Norway) among OMT patients and to explore associations of non-overdose mortality with age and gender. METHODS: This prospective comparative cohort study used national mortality registry databases for OMT patients from Czechia (2000-2019), Denmark (2000-2018), and Norway (2010-2019). Crude mortality rates and age-standardized mortality rates (ASMRs) were calculated as deaths per 1,000 person years for cause-specific mortality. RESULTS: In total, 29,486 patients were included, with 5,322 deaths recorded (18%). We found variations in causes of death among the cohorts and within gender and age groups. The leading non-overdose causes of death were accidents in Czechia and Denmark, and neoplasms in Norway. Cardiovascular deaths were highest in Czechia, particularly for women in OMT (ASMR 3.59 vs. 1.24 in Norway and 1.87 in Denmark). CONCLUSION: This study found high rates of preventable death among both genders and all age groups. Different demographic structures, variations in risk exposure, as well as variations in coding practices can explain the differences. The findings support increased efforts towards screening and preventative health initiatives among OMT patients specific to the demographic characteristics in different settings.

Morbidity through 3 Years of Age in Children of Women Using Methamphetamine during Pregnancy: A National Registry Study.

BACKGROUND: There is a lack of studies on methamphetamine (MA) exposure and morbidity in children beyond the perinatal period. OBJECTIVES: We compared morbidity in children (0-3 years) with prenatal MA exposure to opioid-exposed and to non-exposed children. METHODS: We used data from a Czech nationwide, registry-based cohort study (2000-2014). Children, who reached 3 years of age, of mothers hospitalized with (i) MA use disorder during pregnancy (MA; n = 194), (ii) opioid use disorder during pregnancy (opioids; n = 166), and (iii) general population (GP; n = 1,294,349) with no recorded history of substance use disorder (SUD). Information on inpatient contacts, length of stay, and diagnoses (International Statistical Classification of Diseases and Related Health Problems 10th Revision [ICD-10]) were assessed. Crude and adjusted odds ratios (aOR), 95% confidence interval (CI) for the risk of hospitalization, and for getting diagnosis from the ICD-10 diagnosis chapters were calculated using binary logistic regression. A stratified analysis on hospitalizations with SUD of mothers was performed. RESULTS: No significant differences were found in the measures of hospitalization between the MA and opioid groups. Children prenatally exposed to MA and opioids had higher numbers of hospitalizations and diagnoses and longer stays in hospital than children in the GP. Increased risks of certain infectious and parasitic diseases were found in both MA (aOR = 1.6; CI: 1.1-2.3) and opioid (aOR = 1.9; 1.3-2.8) groups as compared to the GP group. The most pronounced difference in stratified analysis on maternal hospitalizations related to SUD after birth was observed for injury, poisoning, and certain other consequences of external causes in the strata of the MA group who had hospitalized mothers (aOR 6.3, 1.6-24.6) compared to the strata without maternal hospitalizations (aOR 1.4, 0.9-2.3). CONCLUSION: This study suggests that children born to mothers using MA during pregnancy have similar morbidity during the first 3 years of life but higher than the GP. The excess of risk was primarily due to infections and injuries in the MA group.

Opioid maintenance treatment in the Czech Republic, Norway and Denmark: a study protocol of a comparative registry linkage study.

INTRODUCTION: Opioid maintenance treatment (OMT) varies across settings and between countries. We plan to use data from several nationwide health and population registers to further improve the knowledge base established from earlier studies. Our aim is to study OMT adherence trajectories and to identify factors associated with improved outcomes for OMT patients across the Czech Republic, Norway and Denmark, in order to further improve OMT and our understanding of the key elements of treatment success. METHODS AND ANALYSIS: The registry-based cohort approach across the three countries allows us to link data from a range of registers on the individual level, by using personal identifiers in nationwide cohorts of OMT and non-OMT patients and the general non-using populations. A total of ~21 500 OMT patients over the last two decades in all three countries will be included in the study. The following outcome variables (based on the International Classification of Diseases, 10th Revision codes) will be obtained from relevant registers: treatment adherence to OMT, comorbidity (somatic and mental health), and all-cause and cause-specific mortality. Outcomes of the country-specific analyses will be pooled. ETHICS AND DISSEMINATION: The national OMT cohorts have been approved by the ethics committees in the respective countries. Data will be stored according to national and local guidelines and treated confidentially, and all data will be analysed separately for each country and compared across countries. Findings will be disseminated in peer-reviewed scientific journals, national and international conferences, and in briefings to inform clinical decision-making.

Prenatal Methamphetamine Exposure and Adverse Neonatal Outcomes: A Nationwide Cohort Study.

BACKGROUND: There is limited knowledge on the adverse outcomes in newborns after maternal methamphetamine (MA) use during pregnancy. OBJECTIVES: To compare neonatal outcomes in newborns exposed to MA with the newborns of opioid-exposed mothers and of mothers from the general population (GP). METHOD: A cohort study using nationwide registries in Czechia (2000-2014). Women hospitalized with a main diagnosis of MA use disorder during pregnancy (n = 258) and their newborns were defined as MA-exposed. The comparison groups consisted of women (n = 199) diagnosed with opioid use disorder during pregnancy, defined as opioid-exposed, and women (n = 1,511,310) with no substance use disorder diagnosis (GP). The neonatal outcomes studied were growth parameters, gestational age, preterm birth, and Apgar score. To explore the associations between MA exposure and neonatal outcomes, regression coefficients (b) and odds ratios from multivariable linear and binary logistic regression were estimated. RESULTS: MA-exposed women had similar socio-economic characteristics to opioid-exposed, both of which were worse than in the GP. After adjustment, MA exposure was associated with a more favourable birthweight when compared to the opioid-exposed (adjusted mean differences [aMD] b = 122.3 g, 95% CI: 26.0-218.5) and length (aMD b = 0.6 cm, 0.0-1.1). Unadjusted results from the comparison with the GP showed that the MA group had poorer neonatal outcomes, especially in the growth parameters. Adjustment for background characteristics had a profound effect on the comparison with the GP. After adjustment, MA exposure was associated only with a slightly reduced birthweight (aMD b = -63.0 g, -123.0 to -3.1) and birth length (aMD b = -0.3 cm, -0.6 to 0.0). CONCLUSIONS: Although the observed negative outcomes were large in the MA-exposed newborns, the adjustment had a profound effect on the comparison with the GP, indicating the large influence of lifestyle and socio-economic factors in these high-risk pregnancies. MA-exposed newborns had better neonatal outcomes compared to opioids-exposed.

Socioeconomic characteristics of women with substance use disorder during pregnancy and neonatal outcomes in their newborns: A national registry study from the Czech Republic.

BACKGROUND: Maternal substance use can pose a risk to the fetal health. We studied the background characteristics of women with substance use disorders (SUDs) and selected neonatal outcomes in their children. MATERIAL AND METHODS: A database-linkage study was performed. The sample consisted of pregnant women with a SUD during pregnancy (ICD-10 diagnosis F10-F19 except F17, n = 1710), women not diagnosed with a SUD (n = 1,511,310) in Czechia in 2000-2014, and their children. The monitored neonatal outcomes were gestational age, birth weight, preterm birth, and small-for-gestational age (SGA). Binary logistic regression adjusted for age, marital status, education, concurrent substance use, and prenatal care was performed. RESULTS: Women with illicit SUDs were younger, more often unmarried, with a lower level of education, a higher abortion rate, a higher smoking rate, and lower compliance to prenatal care than women with a SUD related to alcohol, or sedatives and hypnotics (SH). Women with a SUD had worse socioeconomic situations, poorer pregnancy care, and worse neonatal outcomes than women without a SUD. After adjustment, we found no difference in SGA between the illicit SUD groups and the alcohol and the SH groups. The newborns from all SUD groups had a higher risk of SGA when compared to women without a SUD. However after adjustment, the difference remained significant just in the alcohol group (OR = 1.9, 95 % CI = 1.4-2.6). CONCLUSION: Mother's SUD during pregnancy increased risk of fetal growth restriction as measured by SGA. The role of maternal socioeconomic and lifestyle factors for the risk of SGA was substantial.

Prenatal exposure to opioid maintenance treatment and neonatal outcomes: Nationwide registry studies from the Czech Republic and Norway.

There is lack of knowledge about the safety of treatment with methadone and buprenorphine as part of opioid maintenance treatment (OMT) during pregnancy. The purpose of this study was to examine neonatal outcomes concerning the use of OMT during pregnancy. We used nationwide registry linkages from the Czech Republic (2000-2014) and Norway (2004-2013). We compared prenatally OMT-exposed newborns with (a) newborns of women hospitalized with opioid use disorder during pregnancy in the Czech sample and (b) newborns with neonatal abstinence syndrome (NAS) in Norway. We performed multivariate linear and binary logistic regression exploring the associations between OMT and neonatal outcomes (growth parameters, gestational age, fetal death, small for gestational age, Apgar score, and NAS). Regression coefficients (b) and odds ratios (ORs) were estimated. The cohorts consisted of 333 Czech, and 235 Norwegian OMT-exposed newborns, and 106 and 294 newborns in the comparison groups, respectively. In both countries, the neonatal growth parameters were similar in the OMT and the comparison groups. In Norway, OMT exposure prolonged gestational age (adjusted b = 0.96 weeks, 95% confidence interval [CI] =0.39-1.53) while the odds of preterm birth and Apgar score at 5 minutes were lower than in the comparison group (adjusted OR = 0.35, 0.16-0.75 and aOR = 0.21, 0.06-0.78, respectively). Newborns of women in OMT had similar growth parameters as newborns of women with opioid use disorders who were not in OMT during pregnancy. Overall, our findings do not suggest that OMT results in worse neonatal outcomes.

Hospitalization of children after prenatal exposure to opioid maintenance therapy during pregnancy: a national registry study from the Czech Republic.

BACKGROUND AND AIMS: Our understanding of the long-term safety of prenatal exposure to opioid maintenance treatment (OMT) is insufficient. We compared childhood morbidity (0-3 years) between OMT-exposed and relevant comparison groups. DESIGN: Nation-wide, registry-based cohort study. Registries on reproductive health, addiction treatment, hospitalization and death were linked using identification numbers. SETTING: The Czech Republic (2000-14). PARTICIPANTS: Children with different prenatal exposure: (i) mother in OMT during pregnancy (OMT; n = 218), (ii) mother discontinued OMT before pregnancy (OMT-D; n = 55), (iii) mother with opioid use disorder, but not in OMT during pregnancy (OUD; n = 85) and (iv) mother in the general population (GP) (n = 1 238 452) MEASUREMENTS: Episodes of hospitalization were observed as outcomes. Information on in-patient contacts, length of stay and diagnoses (International Classification of Diseases version 10) were assessed. Binary logistic regressions were conducted to estimate the associations between OMT exposure and the outcomes, crude and adjusted for the socio-economic status and smoking. FINDINGS: No significant differences were found in the overall proportion of hospitalization among OMT-exposed children, children of OMT-D and children of women with OUD [54.1%, 95% confidence interval (CI) = 47.3-60.1%; 47.3%, 95% CI = 33.9-61.1%; 51.8%, 95% CI = 40.7%-62.6%], while the proportion was significantly lower (35.8%, 95% CI = 35.7-35.8%) in the GP. There were no significant differences in risk of specific diagnoses between OMT-exposed children, children of OMT-D and children of women with OUD. In the adjusted analyses, differences between OMT-exposed and children in the GP were still present for infections and parasitic diseases (OR = 2.0, 95% CI = 1.4-2.7), diseases of the digestive system (OR = 1.7, 95% CI = 1.2-2.6) and diseases of the skin and subcutaneous tissue (OR = 1.9, 95% CI = 1.2-3.2). CONCLUSION: This study did not find clear evidence for an increase in risk of morbidity during the first 3 years of life in children with prenatal opioid maintenance treatment exposure compared with children of women who discontinued such treatment before pregnancy or suffered from opioid use disorder without this treatment. Compared the general population, there appears to be an increased risk of hospitalizations for infectious, gastrointestinal and skin diseases.

Alcohol use and its consequences in the Czech Republic.

OBJECTIVE: Alcohol consumption is associated with substantial public health burden. This article summarises available information on the patterns and prevalence of alcohol use in the Czech Republic with a focus on the heavy alcohol use and its health and social consequences. METHODS: A non-systematic literature review was conducted. The data sources included primarily 3 series of surveys in the adult population, 2 series of surveys in the school population, routine monitoring system of per capita alcohol consumption, routine statistics on alcohol-related morbidity and mortality, and alcohol-related crime. RESULTS: In recent years the registered alcohol consumption in the Czech Republic has been very high; 9.8 litres of pure alcohol were consumed per capita in 2017. Recently, the prevalence of hazardous alcohol consumption in the adult population has reached 16.8-17.6% and harmful alcohol consumption 9.0-9.3%. From 12% to 17% of adult population and 12% of adolescent population were heavy episodic drinkers. Alcohol-related disorders are disproportionately higher (2-3 times) among men. Mortality for alcohol-related causes fully attributable to alcohol (AAF = 100%) and their proportion in overall mortality is on increase. CONCLUSIONS: Alcohol consumption as well as the prevalence of heavy episodic drinking in the Czech Republic belongs among the highest globally. On the other hand, declines in alcohol use have been recently observed among children and adolescents. Available data on alcohol-related morbidity indicate stable situation, though alcohol-related mortality is increasing. Alcohol-related burden is rather underestimated and evidence-based alcohol policy should be increasingly implemented.

Long-Term Opioid Agonist Treatment Participation after First Treatment Entry is Similar across 4 European Regions but Lower in Non-Nationals.

Heroin users in opioid agonist treatment (OAT) show markedly reduced heroin consumption, less crime and a lower mortality rate. However, the extent of long-term OAT participation over subsequent treatment episodes remains unclear. We analysed the annual proportion of patients in treatment (at least 1 day) since the start of first OAT in 4 European regions: Barcelona (BA) 1996-2012: 8,602 patients; Czech -Republic (CZ) 2000-2014: 4,377 patients; Netherlands (NL) 1994-2014: 33,235 patients, Zurich (ZU) 1992-2015: 11,795. We estimated the long-term decline of treatment need due to mortality or abstinence and also a "nuisance" short-term decline until the equilibrium level of cycling in and out of OAT is reached to obtain the adjusted treatment participation value. The adjusted treatment participation was around 50% (BA: 47.4-51.4%; CZ: 49.8-53.9%; NL: 52.3-54.0%; ZU: 46.4-49.3%), and the annual decline of treatment need was close to 4%. Non-nationals (NL patients with a migrant background) showed substantial lower adjusted treatment participation (rate ratio BA: 0.059-0.343; NL: 0.710-0.751; ZU: 0.681-0.797; CZ: n.a.). Our method may provide a policy-relevant indicator of long-term provision, quality and access to OAT following first treatment.

Neonatal outcomes after fetal exposure to methadone and buprenorphine: national registry studies from the Czech Republic and Norway.

BACKGROUND AND AIMS: Opioid maintenance treatment (OMT) is recommended to opioid-dependent females during pregnancy. However, it is not clear which medication should be preferred. We aimed to compare neonatal outcomes after prenatal exposure to methadone (M) and buprenorphine (B) in two European countries. DESIGN: Nation-wide register-based cohort study using personalized IDs assigned to all citizens for data linkage. SETTING: The Czech Republic (2000-14) and Norway (2004-13). [Correction added after online publication on 26 April 2018: The Czech Republic (2000-04) corrected to (2000-14).] PARTICIPANTS: Opioid-dependent pregnant Czech (n = 333) and Norwegian (n = 235) women in OMT who received either B or M during pregnancy and their newborns. MEASUREMENTS: We linked data from health registries to identify the neonatal outcomes: gestational age, preterm birth, birth weight, length and head circumference, small for gestational age, miscarriages and stillbirth, neonatal abstinence syndrome (NAS) and Apgar score. We performed multivariate linear regression and binary logistic regression to explore the associations between M and B exposure and outcomes. Regression coefficient (ß) and odds ratio (OR) were computed. FINDINGS: Most neonatal outcomes were more favourable after exposure to B compared with M, but none of the differences was statistically significant. For instance, in the multivariate analysis, birth weight was ß = 111.6 g [95% confidence interval (CI) = -10.5 to 233.6 and ß = 83.1 g, 95% CI = -100.8 to 267.0] higher after B exposure in the Czech Republic and Norway, respectively. Adjusted OR of NAS for B compared with M was 0.94 (95% CI = 0.46-1.92) in the Norwegian cohort. CONCLUSIONS: Two national cohorts of women receiving opioid maintenance treatment during pregnancy showed small but not statistically significant differences in neonatal outcomes in favour of buprenorphine compared with methadone.

A Unique Opportunity to Study Short and Long Term Consequences in Children Prenatally Exposed to Illicit Drugs and Opioid Maintenance Treatment Using Czech and Scandinavian Registers.

Licit and illicit drug use in pregnant women constitutes a long lasting and serious problem worldwide. Information on long-term effects of maternal drug use on the child is limited. Nationwide registers provide a great potential to study short and long-term consequences for children exposed to licit and illicit drugs during pregnancy. We discuss this potential, with a special emphasis on exposure to methamphetamine, heroin and prescription drugs used for opioid maintenance treatment (OMT). We also discuss the advantages of register data and of merging such data from different regions. The Czech and Scandinavian registers are largely comparable and provide great opportunities to conduct innovative research. For instance, using Czech and Scandinavian cohorts we can compare groups with similar characteristics, such as mothers in OMT and mothers addicted to other drugs while also controlling for important confounding factors such as health and socio-economic status.

Suicides following inpatient psychiatric hospitalization: A nationwide case control study.

BACKGROUND: Research shows the elevated risk of suicide associated with current or recent inpatient psychiatric hospitalization. However, it is unclear whether this applies in the area of post-communist Central and Eastern Europe where mental health care has not been deinstitutionalized yet. The present study aims to examine the rates of suicides among psychiatric patients during and shortly after discharge from inpatient hospitalization in the Czech Republic. METHODS: All inpatient psychiatric hospitalizations and all suicides committed between 2008 and 2012 have been merged on an individual data basis. The time horizon between the admission and two months after the discharge from inpatient psychiatric facility was utilized and multiple logistic regression was performed to calculate the odds of committing suicide. RESULTS: A total of 137,290 inpatients were hospitalized in Czech psychiatric facilities between 2008 and 2012, and 402 of the inpatients committed suicide during the hospitalization or within the 2 months after the discharge. Highly elevated risks of suicides were found to be associated with being a male, having a history of multiple hospitalizations, and having a diagnosis of affective, anxiety, or personality disorder. LIMITATIONS: Limitations are related to the design of the study, and its reliance on routinely collected data. Also, it was not possible to assess the odds of suicide associated with inpatient psychiatric hospitalization against the odds of suicide in general population. CONCLUSIONS: During psychiatric treatment and recovery, suicial behavior and idealiation is increased. In psychiatry, hospitalization may be a risky period for suicide behavior. Suicide rates during and soon after the psychiatric hospitalization identified in this study from Central and Eastern Europe are similar to the findings from Western Europe. Preventive strategies should be tailored accordingly.

[The use of diagnoses related to tobacco use in the Czech Republic]. / Vyuzívání diagnóz souvisejících s uzíváním tabáku v Ceské republice.

BACKGROUND: According to the International Statistical Classification of Diseases and Related Health Problems 10th Revision, tobacco dependence is coded by group F17 - Mental and behavioral disorders due to use of tobacco. There are other codes for diagnoses and conditions associated with tobacco use. The aim of our analysis was to determine how often these codes are reported in clinical practice. METHODS AND RESULTS: We observed the incidence of diagnoses F17, P04.2, Z72.0 or T65.2 in years 2002-2011 in hospitalized patients and the F17 diagnosis in patients of psychiatric health facilities. According to data from the Institute of Health Information and Statistics of the Czech Republic diagnoses indicating smoking patients were reported in 1.5% of hospitalized patients in 2011, although the prevalence of smoking in the population is around 30% in last 15 years. Smoking-related diagnoses were reported in 2.1% of cases in Internal medicine departments. Codes F17, T65.2 and Z72.0 occurred as an accessory diagnose in vascular brain disease in 1.8% of hospitalizations and for respiratory tract neoplasms (dg. C32-C34) it was 7.1% of hospitalizations. CONCLUSIONS: These results demonstrate the underestimation of the importance of smoking and its relationship to clinical disciplines. Although it is one of the most common diseases in the population with a direct relation to fatal diseases of civilization, the information on its incidence is not used in clinical practice.