Cytarabine dose intensification improves survival in older patients with secondary/high-risk acute myeloid leukemia in matched real-world versus clinical trial data.

Since 1980's, the established/standard treatment of acute myeloid leukemia (AML) is cytarabine infusion with anthracycline (7 + 3 regimen). We compared the 7 + 3 regimen in older secondary/high-risk AML patientsfrom a clinical trial with a matched population from the Swedish AML Registrytreated withan increased cytarabine dose in induction and consolidation as recommended in the Swedish National Guidelines since 2005. After successfulpropensity score matching, 104 patients per group were included. The primary outcome was overall survival (OS), and standard dosed patients had a median OS of 6.4 versus 10.7 months with increased dose intensity (hazard ratio:0.69, p = 0.012), with 5-year OS of 8.7% and 18.1%, andremission rates of 36% and 60%, respectively (p < 0.001). Median OS after allogeneic hematopoietic cell transplantation (in 27.9% per group) was 10.4 and 20.7 months, respectively. We conclude that the more intensive cytarabine schedule seems to provide improved outcomes inthe investigated AML patient group.

Lower respiratory tract infections among newly diagnosed sleep apnea patients.

BACKGROUND: Sleep apnea is associated with chronic comorbidities and acute complications. Existing data suggest that sleep apnea may predispose to an increased risk and severity of respiratory tract infections. METHODS: We investigated the incidence of lower respiratory tract infections in the first and second year before and after diagnosis of sleep apnea in a Finnish nationwide, population-based, retrospective case-control study based on linking data from the national health care registers for primary and secondary care from 2015-2019. Controls were matched for age, sex, hospital district, and multimorbidity status. We furthermore analysed the independent effect of comorbidities and other patient characteristics on the risk of lower respiratory tract infections, and their recurrence. RESULTS: Sleep apnea patients had a higher incidence of lower respiratory tract infections than their matched controls within one year before (hazard ratio 1.35, 95% confidence interval 1.16-1.57) and one year after (hazard ratio1.39, 95% confidence interval1.22-1.58) diagnosis of sleep apnea. However, we found no difference in the incidence of lower respiratory tract infections within the second year before or after diagnosis of sleep apnea in comparison with matched controls. In sleep apnea, history of lower respiratory tract infection prior to sleep apnea, multimorbidity, COPD, asthma, and age greater than 65 years increased the risk of incident and recurrent lower respiratory tract infections. CONCLUSIONS: Sleep apnea patients are at increased risk of being diagnosed with a lower respiratory tract infection within but not beyond one year before and after diagnosis of sleep apnea. Among sleep apnea patients, chronic comorbidities had a significant impact on the risk of lower respiratory tract infections and their recurrence.

Multimorbidity and overall comorbidity of sleep apnoea: a Finnish nationwide study.

The prevalence of sleep apnoea is increasing globally; however, population-based studies have reported a wide variation of prevalence estimates, and data on incidence of clinically diagnosed sleep apnoea are scant. Data on the overall burden of comorbidities or multimorbidity in individuals with incident sleep apnoea are scarce, and the pathways to multimorbidity have only marginally been studied. To study the current epidemiology of sleep apnoea in Finland, overall burden of comorbidities, and multimorbidity profiles in individuals with incident sleep apnoea, we conducted a register-based, nationwide, retrospective study of data from January 2016 to December 2019. The prevalence of clinically diagnosed sleep apnoea was 3.7% in the Finnish adult population; 1-year incidence was 0.6%. Multimorbidity was present in 63% of individuals at the time of sleep apnoea diagnosis. Of those with incident sleep apnoea, 34% were heavily multimorbid (presenting with four or more comorbidities). The three most common chronic morbidities before sleep apnoea diagnosis were musculoskeletal disease, hypertension and cardiovascular disease. In multimorbid sleep apnoea patients, hypertension and metabolic diseases including obesity and diabetes, cardiovascular diseases, musculoskeletal diseases and dorsopathies, in different combinations, encompassed the most frequent disease pairs preceding a sleep apnoea diagnosis. Our study adds to the few population-based studies by introducing overall and detailed figures on the burden of comorbidities in sleep apnoea in a nationwide sample and provides up-to-date information on the occurrence of sleep apnoea as well as novel insights into multimorbidity in individuals with incident sleep apnoea.

Opioid trends in Finland: a register-based nationwide follow-up study.

The opioid epidemic in the U.S has gotten payers, prescribers, and policymakers alike interested in trends in opioid use. Despite no recognized opioid crisis in Europe, several countries have reported an increase in opioid-related deaths, which has further prompted discussion on the need of monitoring of opioid prescriptions. This study was conducted to offer information on opioid use during the escalation of the U.S. opioid epidemic in Finland, a Nordic country with universal tax-based health care. This is a nationwide retrospective register-based cohort study on all individuals in Finland who were dispensed opioids in 2009-2017 (n of unique patients = 1,761,584). By using the unique personal identification code assigned to every Finnish resident, we linked data from nationwide registers on dispensed drugs, medical history, and socio-demographic parameters. We report a wide set of patient demographics, dispensing trends for all opioid Anatomical Therapeutic Chemical (ATC) classes, and reasons for opioid initiation based on diagnostic coding for the most recent health care visit. For a cohort of incident opioid users with a four-year wash-out period (n = 1 370 057), we also present opioid use patterns in a three-year follow-up: the likelihood of becoming a persistent user or escalating from weak to strong opioids. A steady 7% of the Finnish population were dispensed opioids annually in 2009-2017. The mean annual quantity of dispensed opioids per opioid patient increased between 2009 and 2017 by 33%, reaching 2 583 oral morphine equivalent mg (OMEQ)/patient/year in 2017. The median quantity of dispensed opioids was lower: 315 OMEQ/year/patient. Depending on the opioid ATC class, there were either increasing or decreasing numbers of patients who had been dispensed said opioid class, and also in the mean quantity. The most common reason for opioid initiation was post-surgical pain (20%), followed by musculoskeletal pain (15%), injury (8.3%), and non-postsurgical dental pain (6.2%). 94% of new opioid initiators started with a weak opioid, i.e. codeine or tramadol. 85% of the patients who had been dispensed a weak opioid were not dispensed an opioid subsequently 3-6 months after the first one, and 95% of them had not escalated to a strong opioid in a 3-year follow-up. The number of patients dispensed opioids in Finland did not change during the escalation of the opioid epidemic in the U.S., but there were changes in the quantity of opioids dispensed per patient. Opioid therapy was typically initiated with weak opioid, the initial dispensed prescription was relatively small, and escalation to strong opioids was rare. A considerable share of patients had been prescribed opioids for chronic non-cancer pain - a type of pain where the risk-benefit ratio of opioids is controversial.

Mycosis fungoides and Sézary syndrome: a population-wide study on prevalence and health care use in Finland in 1998-2016.

BACKGROUND: Information about health care use and costs of cutaneous T-cell lymphoma (CTCL) patients is limited, particularly in a European setting. METHODS: In this population-wide study we set out to investigate prevalence, and trends in health care use in two CTCL subtypes, mycosis fungoides (MF) and Sézary syndrome (SS) over a time period of 19 years in 1998-2016 by using a nation-wide patient register containing data on all diagnosed MF and SS cases in Finland. RESULTS: The prevalence of diagnosed MF and SS rose from 2.04 to 5.38/100000, and from 0.16 to 0.36/100000 for MF and SS respectively during 1998-2016. We found a substantial decrease in inpatient treatment of MF/SS in the past two decades with a mean of 2 inpatient days/patient/year due to MF/SS in 2016, while the mean numbers of MF/SS related outpatient visits remained stable at 8 visits/year/patient. Most MF/SS-related outpatient visits occurred in the medical specialty of dermatology. In a ten-year follow-up after MF/SS diagnosis, the main causes for outpatient visits and inpatient stays were MF/SS itself, other cancers, and other skin conditions. Also cardiovascular disease and infections contributed to the number of inpatient days. Mean total hospital costs decreased from 11,600 eur/patient/year to 3600 eur/patient/year by year 4 of the follow-up, and remained at that level for the remainder of the 10-year follow-up. MF/SS accounted for approximately half of the hospital costs of these patients throughout the follow-up. CONCLUSIONS: The nearly 3-fold increase in prevalence of diagnosed MF/SS during 1998-2016 puts pressure on the health care system, as this is a high-cost patient group with a heavy burden of comorbidities. The challenge can be in part answered by shifting the treatment of MF/SS to a more outpatient-based practice, and by adapting new pharmacotherapy, as has been done in Finland.

Primary health care utilisation and its costs among middle-aged smokers.

OBJECTIVE: To study and compare the utilisation of primary health care services among 46-year-old current smokers, ex-smokers and never-smokers, and to estimate the corresponding costs. METHODS: This population-based cohort study is based on the Northern Finland Birth Cohort 1966, which is a longitudinal research program in Finland's two northernmost provinces. The study is based on data collected at the 46-year follow-up, during which a total of 4997 individuals completed questionnaires on their primary health care service utilisation. Primary health care covered visits to both occupational and public health care (typically community health centres). RESULTS: Current smokers visited primary health care professionals more often per year than never-smokers, regardless of gender (RR 1.24, 95 % confidence interval 1.10-1.43 for men; RR 1.10, 1.01-1.22 for women). When primary health care services were categorised based on the type of service provided, current smokers of both genders were more likely to visit a dentist (RR 1.56, 1.32-1.84 for men; RR 1.34, 1.15-1.55 for women) or a physician (RR 1.20, 1. 03-1.40 for men; RR 1.15, 1.02-1.30 for women) than their never-smoking counterparts (BMI adjusted for). For men, the total annual costs of primary health care visits were 28 % higher for current smokers versus never-smokers (P < 0.001). For women, the difference was 21 % (P < 0.01). CONCLUSIONS: Smokers visit primary health care professionals more often already at the age of 46, before the expected diagnosis of fatal smoking-related illnesses. This phenomenon not only predicts an elevated incidence of serious illnesses in later life (such as cardiovascular disease), but also causes an economic burden on the health care system.

Cardiovascular disease risk factors in relation to smoking behaviour and history: a population-based cohort study.

OBJECTIVE: To investigate how individual risk factors for cardiovascular disease (CVD) (blood pressure, lipid levels, body mass index, waist and hip circumference, use of antihypertensive or hypolipidemic medication, and diagnosed diabetes) differ in people aged 46 years with different smoking behaviour and history. METHODS: This population-based cohort study is based on longitudinal data from the Northern Finland Birth Cohort 1966 project. Data were collected at the 31-year and 46-year follow-ups, when a total of 5038 and 5974 individuals participated in clinical examinations and questionnaires. Data from both follow-ups were available for 3548 participants. In addition to individual CVD risk factors, Framingham and Systematic Coronary Risk Evaluation (SCORE) algorithms were used to assess the absolute risk of a CVD event within the next decade. RESULTS: The differences in individual risk factors for CVD reached statistical significance for some groups, but the differences were not consistent or clinically significant. There were no clinically significant differences in CVD risk as measured by Framingham or SCORE algorithms between never smokers, recent quitters and former smokers (7.5%, 7.4%, 8.1% for men; 3.3%, 3.0%, 3.2% for women; p<0.001). CONCLUSIONS: The effect of past or present smoking on individual CVD risk parameters such as blood pressure and cholesterol seems to be of clinically minor significance in people aged 46 years. In other words, smoking seems to be above all an independent risk factor for CVD in the working-age population. Quitting smoking in working age may thus reduce calculated CVD risk nearly to the same level with people who have never smoked.

Physicians discuss the risks of smoking with their patients, but seldom offer practical cessation support.

BACKGROUND: Our aim was to study the smoking cessation-related 1) attitudes & experiences and 2) consultation practices of Finnish physicians and to determine if there is a relationship between the two. METHODS: An online survey on smoking cessation was sent to 39 % of all Finnish physicians, with emphasis on physicians working in fields relevant to smoking cessation. A total of 1141 physicians (response rate 15 %) responded to the online survey, 53 % of whom were employed in primary health care. A total of 1066 respondents were eligible for the analysis. The questionnaire included questions on the physician's own smoking status, their attitudes and experiences on smoking cessation, and the implementation of smoking cessation in clinical practice. Two sub-scales concerning smoking-related consultation activities were constructed: one for conversation, and another for practical actions. RESULTS: The most common consultation activities (respondents who reported doing the following actions "nearly always") were asking how much the patient smokes (65 %), marking smoking status in patient records (58 %) and recommending quitting to the patient (55 %). The least common activity was prescribing withdrawal medication (4 %). Primary care physicians were more active than those working in secondary health care in nearly all activities mapped. A positive attitude and experiences on smoking cessation were associated with actively offering withdrawal support. Those who were familiar with the local treatment guidelines for tobacco addiction were 30 % more active in offering practical cessation help to their patient. The respondents were more active in discussing smoking with their patients than in offering practical cessation help. CONCLUSION: Physicians offer their patients practical cessation support relatively infrequently. Practical cessation calls for continuous education of physicians about the nature of tobacco and nicotine addiction, the role of smoking as a risk factor for various diseases, and the practical measures needed for smoking cessation. Secondary care physicians should acknowledge the authority they pose toward smoking patients.

[Tobacco withdrawal in individuals suffering from mental disorders]. / Mielenterveyden häiriöistä kärsivien tupakasta vieroitus.

Smoking is very common in individuals with mental illnesses, but smoking cessation help is inadequately offered to them. Some 54% of Finnish psychiatrists often advise their patients to quit smoking, yet 34% often recommend nicotine replacement therapy, and only 12% of them often prescribe tobacco withdrawal medication. Factors that affect advisement in smoking cessation include the psychiatrists' own attitudes and personal smoking history, barriers within the work settings, and the patient's diagnosis. Because smoking poses detrimental effects on the treatment of psychiatric illnesses, as well as on the health of the patient, tailored and more intensive smoking cessation counseling should be offered to individuals with mental illnesses.

The capricious character of nature.

The on-going whole genome sequencing and whole cell assays of metabolites and proteins imply that complex systems could ultimately be mastered by perfecting knowledge into great detail. However, courses of nature are inherently intractable because flows of energy and their driving forces depend on each other. Thus no data will suffice to predict precisely the outcomes of e.g., engineering experiments. All path-dependent processes, most notably evolution in its entirety, display this capricious character of nature.