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Background The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes. Methods and Results Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all‐cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo‐observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62±12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75±10.8 years; women, 38.1%), and individuals without diabetes (73±13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change −0.48% [95% CI, −0.52% to −0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, −0.33% [95% CI, −0.43% to −0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, −0.18% [95% CI, −0.53% to 0.17%]). Similar trends were observed with regard to 1‐year death, cardiovascular death, and major adverse cardiovascular events. Conclusions During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.

OBJECTIVES: This study aimed to evaluate effects of night and shift work patterns on type 2 diabetes (T2D) and hypertension in a longitudinal study, with detailed information on working hours. METHODS: The cohort comprised about 28 000 nurses and nursing assistants employed for more than one year 2008–2016 in Stockholm, Sweden. The employee register held detailed individual information on daily working hours. Information on diagnoses came from national and regional registers. Hazard ratios (HR) and confidence intervals (CI) were estimated by discrete-time proportional hazard models, adjusting for sex, age, country of birth, and profession. RESULTS: During follow-up in 2013–2017, we identified 232 cases of T2D and 875 of hypertension. We observed an increased risk of T2D, but not hypertension, among employees who worked only night shifts the previous year (HR 1.59, 95% CI 1.02–2.43) and those with intensive shift work (>120 afternoon and/or night shifts the previous year: HR 1.67, 95% CI 1.11–2.48) compared to only day work. There was a non-significantly increased risk of T2D related to mixed day and afternoon shifts (HR 1.34, 95% CI 0.97–1.88). We observed tendencies in increased risk of T2D related to frequent spells of ≥3 consecutive night shifts and with number of years with exclusive (but not mixed) night work. CONCLUSIONS: Permanent night work and frequent afternoon and/or night shifts were associated with an increased risk of T2D the following year, but not hypertension. The T2D risk was, to some extent, affected by frequent spells of several night shifts in a row and by cumulative years with permanent night work.

Abstract Although the development of therapies and tools for the improved management of heart failure (HF) continues apace, day‐to‐day management in clinical practice is often far from ideal. A Cardiovascular Round Table workshop was convened by the European Society of Cardiology (ESC) to identify barriers to the optimal implementation of therapies and guidelines and to consider mitigation strategies to improve patient outcomes in the future. Key challenges identified included the complexity of HF itself and its treatment, financial constraints and the perception of HF treatments as costly, failure to meet the needs of patients, suboptimal outpatient management, and the fragmented nature of healthcare systems. It was discussed that ongoing initiatives may help to address some of these barriers, such as changes incorporated into the 2021 ESC HF guideline, ESC Heart Failure Association quality indicators, quality improvement registries (e.g. EuroHeart), new ESC guidelines for patients, and the universal definition of HF. Additional priority action points discussed to promote further improvements included revised definitions of HF ‘phenotypes’ based on trial data, the development of implementation strategies, improved affordability, greater regulator/payer involvement, increased patient education, further development of patient‐reported outcomes, better incorporation of guidelines into primary care systems, and targeted education for primary care practitioners. Finally, it was concluded that overarching changes are needed to improve current HF care models, such as the development of a standardized pathway, with a common adaptable digital backbone, decision‐making support, and data integration, to ensure that the model ‘learns’ as the management of HF continues to evolve.

Abstract Background Diabetes and prediabetes are known risk factors for cardiovascular disease and associated with increased mortality risk. Whether patients with a random elevated blood glucose level but no history of diabetes are at a higher mortality and cardiovascular risk is not entirely known. Methods A retrospective cohort study where patients (18–80 years) with no history of diabetes between 2006 and 2016 attending the emergency department (ED) in Sweden were included. Based on the first (index) blood glucose level patients were categorized into four groups: hypoglycemia ( 11.1 mmol/L). Data was collected from four nationwide registers (National Patient Register, National Cause of Death Register, Prescribed Drug Register and Statistics Sweden). Cox regression was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for all-cause mortality and cardiovascular outcomes using NGT as reference. Results 618,694 patients were included during a mean follow-up time of 3.9 years. According to the index blood glucose level: 1871 (0.3%) had hypoglycemia, 525,636 (85%) had NGT, 77,442 (13%) had dysglycemia, and 13,745 (2%) patients had hyperglycemia, respectively. During follow-up 44,532 (7.2%) deaths occurred. After multiple adjustments, mortality risk was highest in patients with hypoglycemia HR 2.58 (2.26–2.96) followed by patients with hyperglycemia HR 1.69 (1.63–1.76) and dysglycemia HR 1.16 (1.13–1.19). Risk for cardiovascular events: i.e., myocardial infarction, stroke and heart failure, were highest among patients with hyperglycemia HR 2.28 (2.13–2.44), HR 1.62 (1.51–1.74) and HR 1.60 (1.46–1.75), respectively. Conclusion Patients with disturbed blood glucose level at ED admission have a higher mortality risk than patients with NGT. Patients with hyperglycemia have almost a two folded increased long-term mortality risk and more than a doubled risk for cardiovascular events compared to patients with NGT.

OBJECTIVE: This study aimed to examine the effects of various aspects of night and shift work on the risk of incident ischemic heart disease (IHD) and atrial fibrillation (AF) using detailed and registry-based exposure data. METHODS: This prospective cohort study included >30 300 healthcare employees (eg, nurses, nursing assistants) employed for at least one year in Region Stockholm 2008–2016. Information on daily working hours was obtained from a computerized administrative employee register and outcomes from national and regional registers. Using discrete-time proportional hazard models, we analyzed the outcomes as functions of working hour characteristics the preceding year, adjusted for sex, age, country of birth, education, and profession. RESULTS: We observed 223 cases of IHD and 281 cases of AF during follow-up 2009–2016. The risk of IHD was increased among employees who the preceding year had permanent night shifts compared to those with permanent day work [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.06–2.43] and among employees working night shifts >120 times per year compared to those who never worked night (HR 1.53, 95% CI 1.05–2.21). When restricted to non-night workers, the risk of IHD was increased for employees having frequent quick returns from afternoon shifts. No increased risks were observed for AF. CONCLUSIONS: Night work, especially working permanent night shifts and frequent night shifts, is associated with an increased risk of incident IHD but not AF. Moreover, frequent quick returns from afternoon shifts (among non-night workers) increased IHD risk. Organizing work schedules to minimize these exposures may reduce IHD risk.

Abstract Background Maternal smoking during pregnancy was reported to be associated with a reduced risk of type 1 diabetes in the offspring. We investigated whether this association is consistent with a causal interpretation by accounting for familial (shared genetic and environmental) factors using family-based, quasi-experimental designs. Methods We included 2,995,321 children born in Sweden between 1983 and 2014 and followed them for a diagnosis of type 1 diabetes until 2020 through the National Patient, Diabetes and Prescribed Drug Registers. Apart from conducting a traditional cohort study, we performed a nested case–control study (quasi-experiment) comparing children with type 1 diabetes to their age-matched siblings (or cousins). Information on maternal smoking during pregnancy was retrieved from the Swedish Medical Birth Register. Multivariable adjusted Cox proportional hazards regression and conditional logistic regression were used. Results A total of 18,617 children developed type 1 diabetes, with a median age at diagnosis of 9.4 years. The sibling and cousin comparison design included 14,284 and 7988 of these children, respectively. Maternal smoking during pregnancy was associated with a 22% lower risk of offspring type 1 diabetes in the full cohort (hazard ratio 0.78, 95% confidence interval [CI] 0.75–0.82). The corresponding odds ratio was 0.78 (95% CI 0.69–0.88) in the sibling and 0.72 (95% CI 0.66–0.79) in the cousin comparison analysis. Conclusions This nationwide, family-based study provides support for a protective effect of maternal smoking on offspring type 1 diabetes. Mechanistic studies are needed to elucidate the underlying pathways behind this link.

Background Geographical mapping of variations in the treatment and outcomes of a disease is a valuable tool for identifying inequity. We examined international and intranational variations in initiating oral anticoagulation (OAC) therapy and clinical outcomes among patients with atrial fibrillation (AF) in Nordic countries. We also tracked real-world trends in initiating OAC and the clinical outcomes. Methods We conducted a registry-based multinational cohort study of OAC-naive patients with an incident hospital diagnosis of AF in Denmark (N = 61,345), Sweden (N = 124,120), and Finland (N = 59,855) and a CHA2DS2-VASc score of ≥1 in men and ≥2 in women between 2012 and 2017. Initiation of OAC therapy was defined as dispensing at least one prescription between 90 days before and 90 days after the AF diagnosis. Clinical outcomes included ischemic stroke, intracerebral hemorrhage, intracranial bleeding, other major bleeding, and all-cause mortality. Results The proportion of patients initiating OAC therapy ranged from 67.7% (95% CI: 67.5–68.0) in Sweden to 69.6% (95% CI: 69.2–70.0) in Finland, with intranational variation. The 1-year risk of stroke varied from 1.9% (95% CI: 1.8–2.0) in Sweden and Finland to 2.3% (95% CI: 2.2–2.4) in Denmark, with intranational variation. The initiation of OAC therapy increased with a preference for direct oral anticoagulants over warfarin. The risk of ischemic stroke decreased with no increase in intracranial and intracerebral bleeding. Conclusion We documented inter- and intranational variation in initiating OAC therapy and clinical outcomes across Nordic countries. Adherence to structured care of patients with AF could reduce future variation.

Background Patients who experience acute myocardial infarction (AMI) are at risk of recurrent AMI. Contemporary data on recurrent AMI and its association with return emergency department (ED) visits for chest pain are needed.Methods This Swedish retrospective cohort study linked patient-level data from six participating hospitals to four national registers to construct the Stockholm Area Chest Pain Cohort (SACPC). The AMI cohort included SACPC participants visiting the ED for chest pain diagnosed with AMI and discharged alive (first primary diagnosis of AMI during the study period not necessarily the patient’s first AMI). The rate and timing of recurrent AMI events, return ED visits for chest pain and all-cause mortality were determined during the year following index AMI discharge.Results Among 1 37 706 patients presenting to the ED with chest pain as principal complaint from 2011 to 2016, 5.5% (7579/137 706) were hospitalised with AMI. In total, 98.5% (7467/7579) of patients were discharged alive. In the year following index AMI discharge, 5.8% (432/7467) of AMI patients experienced ≥1 recurrent AMI event. Return ED visits for chest pain occurred in 27.0% (2017/7467) of index AMI survivors. During a return ED visit, recurrent AMI was diagnosed in 13.6% (274/2017) of patients. One-year all-cause mortality was 3.1% in the AMI cohort and 11.6% in the recurrent AMI cohort.Conclusions In this AMI population, 3 in 10 AMI survivors returned to the ED for chest pain in the year following AMI discharge. Furthermore, over 10% of patients with return ED visits were diagnosed with recurrent AMI during that visit. This study confirms the high residual ischaemic risk and associated mortality among AMI survivors.

OBJECTIVE: This study aimed to investigate the effects of various aspects of night and shift work regarding incident cerebrovascular disease (CeVD). METHODS: The cohort included 26 667 women and 3793 men (nurses and nursing assistants) who were employed for at least one year 2008–2016 in Region Stockholm, Sweden. Information about the cohort and working hours were obtained from a computerized employee-register and diagnoses were retrieved from national and regional registers. We used discrete time proportional hazard models to assess the risk of CeVD (2009–2017), in relation to work hour characteristics, adjusting for sex, age, country of birth, education and profession. RESULTS: We observed an excess risk of CeVD (N=223) among employees who, during the preceding year, worked night shifts >30 times [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.04–1.99] or ≥3 consecutive night shifts >15 times (HR 1.69, 95% CI 1.18–2.42) or with >30 quick returns (5 years) of exposure to night shift work (HR 1.87, 95% CI 1.27–2.77), all supported by a dose–response pattern. CONCLUSIONS: Our results show that the risk of CeVD among nurses and nursing assistants is associated with night shift work. The number of years with night shift work, the frequency of night shifts per year, the frequency of consecutive night shifts, and short recovery after night shifts influenced the risk. Work schedules aiming at minimizing these aspects of night shift work may reduce the risk.

Abstract Background Interest in the application of machine learning (ML) to the design, conduct, and analysis of clinical trials has grown, but the evidence base for such applications has not been surveyed. This manuscript reviews the proceedings of a multi-stakeholder conference to discuss the current and future state of ML for clinical research. Key areas of clinical trial methodology in which ML holds particular promise and priority areas for further investigation are presented alongside a narrative review of evidence supporting the use of ML across the clinical trial spectrum. Results Conference attendees included stakeholders, such as biomedical and ML researchers, representatives from the US Food and Drug Administration (FDA), artificial intelligence technology and data analytics companies, non-profit organizations, patient advocacy groups, and pharmaceutical companies. ML contributions to clinical research were highlighted in the pre-trial phase, cohort selection and participant management, and data collection and analysis. A particular focus was paid to the operational and philosophical barriers to ML in clinical research. Peer-reviewed evidence was noted to be lacking in several areas. Conclusions ML holds great promise for improving the efficiency and quality of clinical research, but substantial barriers remain, the surmounting of which will require addressing significant gaps in evidence.

Abstract Objective To identify occupations where employees with type 2 diabetes have a high risk of cardiovascular disease (CVD) and mortality, and their prevalence of CVD risk factors. This study can contribute in the creation of targeted interventions at the workplace. Research design and methods This nationwide registry-based study included all employees with type 2 diabetes born in Sweden in 1937–1979 (n = 180,620) and followed up in 2002–2015. We calculated age-standardized incidence (per 100,000 person-years) of all-cause and CVD mortality, ischemic heart disease (IHD) and stroke across the 30 most common occupations. Information on prognostic factors was retrieved from the National Diabetes Register. Results In males with type 2 diabetes, mortality rates were highest in manufacturing workers (1782) and machine operators (1329), and lowest in specialist managers (633). The risk of death at age 61–70 years was 21.8% in manufacturing workers and 8.5% in managers. In females with type 2 diabetes, mortality rates were highest in manufacturing workers (1150) and cleaners (876), and lowest in writers and artists (458); the risk of death at age 61–70 years was 12.4% in manufacturing workers and 4.3% in writers and artists. The same occupations also had relatively high incidences of CVD mortality, IHD and stroke. Occupational groups with poor prognosis had high prevalence of CVD risk factors including poor glycemic control, smoking and obesity. Conclusions Manufacturing workers, machine operators and cleaners with type 2 diabetes have two to three times higher mortality rates than managers, writers and artists with type 2 diabetes. Major health gains would be made if targeted workplace interventions could reduce CVD risk factors in these occupations.

Data on the future diabetes burden in Scandinavia is limited. Our aim was to project the future burden of diabetes in Sweden by modelling data on incidence, prevalence, mortality, and demographic factors.To project the future burden of diabetes we used information on the prevalence of diabetes from the national drug prescription registry (adults ≥ 20 years), previously published data on relative mortality in people with diabetes, and population demographics and projections from Statistics Sweden. Alternative scenarios were created based on different assumptions regarding the future incidence of diabetes.Between 2007 and 2013 the prevalence of diabetes rose from 5.8 to 6.8% in Sweden but incidence remained constant at 4.4 per 1000 (2013). With constant incidence and continued improvement in relative survival, prevalence will increase to 10.4% by year 2050 and the number of afflicted individuals will increase to 940 000. Of this rise, 30% is accounted for by changes in the age structure of the population and 14% by improved relative survival in people with diabetes. A hypothesized 1% annual rise in incidence will result in a prevalence of 12.6% and 1 136 000 cases. Even with decreasing incidence at 1% per year, prevalence of diabetes will continue to increase.We can expect diabetes prevalence to rise substantially in Sweden over the next 35 years as a result of demographic changes and improved survival among people with diabetes. A dramatic reduction in incidence is required to prevent this development.

The validity of exposure data collected from proxy respondents of myocardial infarction patients has scarcely been studied. We assessed the level of disagreement between myocardial infarction patients and their spouses with respect to the reporting of the patient´s cardiovascular risk exposures.Within the frame of the Stockholm Heart Epidemiology Program (SHEEP), a case-control study of risk factors of myocardial infarction performed in Stockholm county 1992-1994, a subset of 327 first time myocardial infarction cases aged 45-70 who survived >28 days after the event and who co-habited with a spouse or common-law spouse (proxy) were identified between 1993-04-05 and 1993-12-31. Among these, 243 cases participated along with their respective proxy in the present study. Control individuals, matched to cases by age, sex and residential area were also included (n = 243). Data were collected using questionnaires. Using conditional logistic regression we calculated for each of 82 exposures the odds ratio based on information collected from 1) myocardial infarction cases and controls [odds ratio A] and 2) proxies and the same set of controls [odds ratio B]. Disagreement was measured by calculating the ratio between odds ratio B and odds ratio A with 95% confidence intervals (CI) calculated using resampling bootstrap.For the vast majority of the exposures considered including diet, smoking, education, work-related stress, and family history of CVD, there was no statistically significant disagreement between myocardial infarction patients and proxies (n = 243 pairs). However, leisure time physical inactivity (proxy bias = 1.59, 95% CI 1.05-3.57) was overestimated by spouses compared to myocardial infarction patients. A few other exposures including some sleep-related problems and work-related issues also showed disagreement.Myocardial infarction patients and their spouses similarly reported data on a wide range of exposures including the majority of the traditional cardiovascular risk factors, leisure time physical inactivity being an exception.

BACKGROUND: Diabetes is on the rise in the western world, but data from Scandinavia are inconsistent with indications of stable or even reverse trends. To shed new light on this issue, we investigated diabetes trends in Stockholm County 1990-2010, taking into account trends in risk factors and mortality. METHODS: We used data from a large population-based quadrennial public health survey conducted between 1990 and 2010 in Stockholm County (∼ 2.1 million inhabitants), supplemented with data from national registers. The age-standardized prevalence and incidence rates of diabetes and related risk factors 1990-2010 were estimated in adult inhabitants. We also modelled the influence of potential risk factors on the diabetes trends and estimated the life time risk of diabetes. RESULTS: The prevalence of diabetes was 4.6% (95% confidence interval (CI); 4.5-4.8%) in 2010 compared to 2.8% (95% CI; 2.3-3.5%) in 1990. Between 1990 and 2002 the prevalence rose annually by 3.8% (95% CI; 2.1-5.5). Incidence rates showed a similar pattern and rose by 3.0% (95% CI; 0.3-5.7%) annually 1990-2002. The rising incidence was mainly attributable to increasing prevalence of overweight/obesity, which rose by 46% during the observation period. In 2010, the lifetime risk of adult onset diabetes was 28% (95% CI; 26-31%) in men and 19% (95% CI; 17-21%) in women. CONCLUSIONS: Diabetes rates have been increasing in Stockholm over the last decades, both in terms of incidence and prevalence, and this development is most likely the result of increasing overweight and obesity in the population.

BACKGROUND: Life expectancy and time to first hospitalization have been prolonged, indicating that people live longer without needing hospital care. Life expectancy increased partially due to improved survival from severe diseases, which, however, could lead to a more fragile population. If so, time to a subsequent hospitalization could decrease. Alternatively, the overall trend of improved health could continue after the first hospitalization, prolonging also the time to subsequent hospitalizations. This study analyzes trends in subsequent hospitalizations among Swedish men and women above the age of 60, relating them to first hospitalization. It also looks at trends in the proportion of never hospitalized. METHODS: Individuals were followed in national registers for hospital admissions and deaths between 1972 and 2010. The proportion of never hospitalized individuals at given ages and time points, and the annual change in the risks of first and subsequent hospitalizations, were calculated. FINDINGS: An increase in the proportion of never hospitalized was seen over time. The risks of first as well as subsequent hospitalizations were reduced by almost 10% per decade for both men and women. Improvements were observed mainly for individuals below the ages of 90 and up to the year 2000. CONCLUSIONS: The reduction in annual risk of both first and subsequent hospitalizations up to 90 years of age speaks in favor of a postponement of the overall morbidity among the elderly and provides no support for the hypothesis that the population becomes more fragile due to increased survival from severe diseases.

BACKGROUND: It is not clear if the downward trend in cardiovascular disease (CVD) observed for ages up to 85 years can be extended to the oldest old, those 85 years and above. METHODS AND FINDINGS: This nationwide cohort study presents age specific trends of CVD as well as for myocardial infarction (MI) and stroke separately for the period 1994 to 2010 for individuals 85 to 99 years old in Sweden. Data were extracted from national registries. All analyses were based on one-year age- and sex- specific figures. The risk for CVD increased with every age above 85 years although the rate of increase leveled off with age. Over time, the risk for CVD and MI decreased for all ages, and for stroke for ages up to 89 years. However, the risk of MI increased until around 2001 in all age groups and both sexes but decreased after that. The overall mortality improved for all outcomes over the period 1994 to 2010, so did the survival within 28 days from an event. The average annual decline in mortality over all ages, 85 and above was 3% for MI, 2% for stroke and for 2% CVD. Corresponding figures for ages 60-84 was 4% for each of MI, stroke and CVD. The results were similar for men and women. CONCLUSIONS: Improvements in CVD risks observed among ages up to 85 years appear to have extended also to ages above 85 years, even if the rate of improvement plateaued with age. The improvements in survival for all ages up to 99 years give no support to the hypothesis that more fragile individuals reach higher ages. Additional research is needed to find out if improvement in survival can be seen also for the second and third event of CVD, stroke and MI.

The article presents information on the 2006 election monitoring project which was part of a larger election observation led by the Carter Center in Venezuela. The project main purpose was to assess election coverage in the major television channels. It is stated that the media monitoring project took place in a strongly polarized society with an unstable democratic situation. The media monitoring project was performed using quantitative content analysis of the television stations news coverage of a referendum, respectively the presidential election in Venezuela.

Abstract An editorial in this issue explains that the degree of biological interaction between risk factors is measured as the deviation from additivity by the corresponding disease rates and not for example as deviation from multiplicativity. It is the purpose of this article to describe how a logistic regression model, or a Cox regression model, can be defined in order to produce the output that is needed for assessment of biological interaction. We will also demonstrate how common software can be programmed to deliver this output. Finally, we show how this output can be used as input in an Excel sheet that is set up to calculate the measures of biological interaction to be used for the assessment. [ABSTRACT FROM AUTHOR]

Public health recommendations promote physical activity to improve health and longevity. Recent data suggest that the association between physical activity and mortality may be due to genetic selection. Using data on twins, the authors investigated whether genetic selection explains the association between physical activity and mortality. Data were based on a postal questionnaire answered by 13,109 Swedish twin pairs in 1972. The national Cause of Death Register was used for information about all-cause mortality (n = 1,800) and cardiovascular disease mortality (n = 638) during 1975–2004. The risk of death was reduced by 34% for men (relative risk = 0.64, 95% confidence interval: 0.50, 0.83) and by 25% for women (relative risk = 0.75, 95% confidence interval: 0.50, 1.14) reporting high physical activity levels. Within-pair comparisons of monozygotic twins showed that, compared with their less active co-twin, the more active twin had a 20% (odds ratio = 0.80, 95% confidence interval: 0.65, 0.99) reduced risk of all-cause mortality and a 32% (odds ratio = 0.68, 95% confidence interval: 0.49, 0.95) reduced risk of cardiovascular disease mortality. Results indicate that physical activity is associated with a reduced risk of mortality not due to genetic selection. This finding supports a causal link between physical activity and mortality. [ABSTRACT FROM AUTHOR]

Mitoxantrone has a broad anti-tumour activity including lymphoma with potentially less cardiotoxicity than doxorubicin, which may be of particular importance in elderly patients. However, an important issue is whether mitoxantrone is as efficacious as doxorubicin in the treatment of aggressive lymphomas. Through search of several relevant databases and contacts with lymphoma investigators worldwide, we identified nine randomised studies of previously untreated patients comparing CHOP and CNOP chemotherapy in aggressive non-Hodgkin lymphoma. Five trials were included where doxorubicin (50 mg/m2) was compared with mitoxantrone (10-12 mg/m2) and the interval between chemotherapy courses was 3-4 wk. In none of these trials rituximab was used. Odds ratios of complete remission (CR) were pooled using a fixed effects model, and odds ratios of overall survival (OS) were pooled using a random effects model. CNOP was significantly inferior to CHOP with regard to CR rate. CNOP was also inferior, but not significantly to CHOP with regard to OS. No formal testing of side effects could be made. However, the two regimens were equally myelosuppressive. Clinical evidence of symptomatic congestive heart disease was not more frequent among patients treated with CHOP. However, gastrointestinal toxicities and alopecia were more common in this group. CHOP chemotherapy is more efficacious than CNOP at equitoxic (myelosuppression) doses. CHOP is, however, associated with more alopecia and gastrointestinal toxicity.