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  • Ylihärsilä, Hilkka (Helsingin yliopisto, 2008)
    Theory of developmental origins of adult health and disease proposes that experiences during critical periods of early development may have consequences on health throughout a lifespan. Thesis studies aimed to characterize associations between early growth and some components of the metabolic syndrome cluster. Participants belong to two epidemiological cohorts with data on birth measurements and, for the younger cohort, on serial recordings of weight and height during childhood. They were born as singletons between 1924-33 and 1934-44 in the Helsinki University Central Hospital, and 500 and 2003 of them, respectively, attended clinical studies at the age of 65-75 and 56-70 years, respectively. In the 65-75 year old men and women, the well-known inverse relationship between birth weight and systolic blood pressure (SBP) was confined to people who had established hypertension. Among them a 1-kg increase in birth weight was associated with a 6.4-mmHg (95% CI: 1.0 to 11.9) decrease in SBP. This relationship was further confined to people with the prevailing Pro12Pro polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) gene. People with low birth weight were more likely to receive angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARB, p=0.03), and, again, this relationship was confined to the carriers of the Pro12Pro (p=0.01 for interaction). These results suggest that the inverse association between birth weight and systolic BP becomes focused in hypertensive people because pathological features of BP regulation, associated with slow fetal growth, become self-perpetuating in adult life. Insulin resistance of the Pro12Pro carriers with low birth weight may interact with the renin-angiotensin system leading to raised BP levels. Habitual physical activity protected men and women who were small at birth, and thus at increased risk for the development of type 2 diabetes, against glucose intolerance more strongly. Among subjects with birth weight ≤3000 g, the odds ratio (OR) for glucose intolerance was 5.2 (95% CI: 2.1 to 13) in those who exercised less than 3 times per week compared to regular exercisers; in those who scored their exercise light compared with moderate exercisers (defined as comparable to brisk walking) the OR was 3.5 (1.5 to 8.2). In the 56-70 year old men a 1 kg increase in birth weight corresponded to a 4.1 kg (95% CI: 3.1 to 5.1) and in women to a 2.9 kg (2.1 to 3.6) increase in adult lean mass. Rapid gain in body mass index (BMI), i.e. crossing from an original BMI percentile to a higher one, before the age of 2 years increased adult lean mass index (LMI, lean mass/height squared) without excess fat accumulation whereas rapid gain in BMI during later childhood, despite the concurrent rise in LMI, resulted in a relatively higher increase in adult body fat mass. These findings illustrate how genes, the environment and their interactions, early growth patterns, and adult lifestyle modify adult health risks which originate from early life.
  • Sandboge, Samuel (Helsingin yliopisto, 2015)
    Background. A small birth size, an indicator of a suboptimal intrauterine environment, is a risk factor for several non-communicable diseases (NCDs), a risk that in many cases is modified by childhood growth patterns. Regional variation in NCD prevalence could partly have its origin in early development. Lifestyle factors further influence NCD prevalence. Aims. We aimed to explore the associations between early growth and adult resting metabolic rate (RMR), body composition, non-alcoholic fatty liver disease (NAFLD), and hypertension. We also studied the associations between fructose intake and NAFLD, and differences in birth size between Helsinki and the Åland Islands. Subjects and methods. The Helsinki Birth Cohort Study consists of 13345 individuals born in Helsinki in 1934‒44. Detailed records are available for all participants including information on maternal and birth characteristics and measurements of childhood body size. 2003 individuals participated in a clinical study in 2001‒04 and 1083 of these additionally participated in a follow-up study in 2006‒08. The Åland records include 1697 births for the years 1937‒44. Results. The association between birth weight and RMR was inverse among women and quadratic among men. A higher attained adult weight than expected, based on weight and height measurements before age 11 years and adult height, was associated with higher adult body fat content. The odds ratio (OR) for NAFLD was 18.5 (95% CI 10.1; 33.6) among those who belonged to the lowest BMI tertile at age 2 years and subsequently were obese as adults, compared to those who were still lean or normal weight as adults. NAFLD was most common among individuals with the lowest dietary fructose intake. Systolic blood pressure (SBP) and the presence of hypertension were inversely associated with linear (height) growth between ages 2 and 11 years. Relative weight gain after age 11 years was positively associated with SBP. Ålandic babies born 1937‒44 were 87 grams (95% CI 61; 111) heavier and 0.4 cm (95% CI 0.3; 0.5) longer than their Helsinki peers. Conclusions. A more pronounced increase in relative weight after age 11 years than would be expected from previous body size, was positively associated with body fat content, NAFLD, and hypertension. Conversely, several growth measurements before age 11 years were negatively associated with the outcomes studied. None of the studied individuals were obese in childhood. Instead, a larger relative childhood body size in this group most likely represents a more beneficial childhood environment. Contrary to previous findings, we found that individuals with the highest fructose intake were least likely to suffer from NAFLD. We found a small but significant difference in birth size between the Åland Islands and Helsinki for the years 1937‒44.
  • Salonen, Minna (Helsingin yliopisto, 2011)
    The Developmental Origins of Health and Disease Hypothesis proposes that adverse health outcomes in adult life are in part programmed during fetal life and infancy. This means that e.g. restricted nutrition during pregnancy programmes the offspring to store fat more effectively, to develop faster and to reach puberty earlier. These adaptations are beneficial in terms of short term survival. However, in developed countries these adaptations often lead to an increased risk of obesity and metabolic disturbances in later life, due to a mismatch between the prenatal and postnatal environment. This thesis aimed to study the role of early growth in people who are obese as adults, but metabolically healthy as well as in those who are normal in weight but metabolically obese. Other study aims were to assess whether physical activity and cardiorespiratory fitness are programmed early in life. The role of socioeconomic status in the development of obesity from a life course setting was also studied. These studies included 2003 men and women born in Helsinki between 1934 and 1944 with detailed information of their prenatal and childhood growth as well as living conditions. They participated in the detailed clinical examination during the years 2001-2004. A sub-group of the subjects participated in the UKK Institute 2-kilometre walk test. Metabolic syndrome was defined according to the 2005 criteria of the International Diabetes Federation. Among the obese men and women 20 % were metabolically healthy. Those with metabolic syndrome did not differ in birth size compared to the healthy ones, but by two years of age, they were lighter and thinner, and remained so up to 11 years. The period when changes in BMIs were predictive of the metabolic syndrome was from birth to 7 years. Of the normal weight individuals 17 % were metabolically obese. Again, there were no differences in birth size. However, by the age 7 years, those men who later developed metabolic syndrome were thinner. Gains in BMI during the first two years of life were protective of the syndrome. Children who were heavier, and especially taller, were more physically active, exercised with higher intensity and had higher cardiorespiratory fitness in their adult life than those who were shorter and thinner as children. Lower educational attainment and lower adult social class were associated with obesity in both men and women. Childhood social class was inversely associated with body mass index only in men while lower household income was associated with higher BMI in women. These results support the role of early life factors in the development of metabolic syndrome and adult life style. Early detection of risk factors predisposing to these conditions is highly relevant from a public health point of view.
  • Pesonen, Maria (Helsingin yliopisto, 2008)
    Atopy-related allergic diseases, i.e. allergic rhinoconjunctivitis, atopic dermatitis and asthma, have increased in frequency in the industrialized countries. In order to reverse this trend, effective preventive strategies need to be developed. This requires a better understanding of the early-life events leading to the expression of the atopic phenotype. The present study has aimed at defining early-life factors and markers associated with the subsequent development of allergic diseases in a cohort of 200 healthy, unselected Finnish newborns prospectively followed up from birth to age 20 years. Their mothers were encouraged to start and maintain exclusive breastfeeding as long as it was nutritionally sufficient for the infant. Consequently, all the infants received some duration of exclusive breastfeeding, 58% of the infants were on exclusive breastfeeding for the first 6 months of life, and 18% received this feeding at least for the first 9 months. Of the infants, 42% had a family history of allergy. After the first year of follow-up, the children were re-assessed at ages 5, 11 and 20 years with clinical examination, skin prick testing, and parental and personal interviews. Exclusive breastfeeding for over 9 months was associated with atopic dermatitis and symptoms of food hypersensitivity at age 5 years, and with symptoms of food hypersensitivity at age 11 years in the children with a familial allergy. Subjects with allergic symptoms or a positive skin prick test in childhood or adolescence had lower retinol concentrations during their infancy and childhood than others. An elevated cord serum immunoglobulin E concentration predicted subsequent atopic manifestations though with modest sensitivity. Children and adolescents with allergic symptoms, skin prick test positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the nonatopic subjects. In conclusion, prolonging strictly exclusive breastfeeding for over 9 months of age was not of help in prevention of allergic symptoms; instead, it was associated with increased atopic dermatitis and food hypersensitivity symptoms in childhood. Due to the modest sensitivity, cord serum IgE is not an effective screening method for atopic predisposition in the general population. Retinol and cholesterol concentrations in infancy were inversely associated with the subsequent development of allergic symptoms. Based on these findings, it is proposed that there may be differences in the inborn regulation of retinol and cholesterol levels in children with and without a genetic susceptibility to atopy, and these may play a role in the development of atopic sensitization and allergic diseases.
  • Alastalo, Hanna (Helsingin yliopisto, 2013)
    Experienced stress in childhood might have been so severe that it has effects throughout the life course. It has been suggested that early life stress may extend consequences on psychological and physical well-being. Previous findings focusing upon consequences of early life stress are however limited and mostly based upon retrospective studies. Still little is known about the consequences of early life stress, such as war separation on physical health from a longitudinal aspect. This thesis aimed to study cardiovascular mortality and morbidity in late adulthood among people who experienced separation without their parents to temporary foster care during World War II (WWII). Other study aims were to examine cardiovascular health, blood pressure levels and physical and psychosocial functioning in the separated participants. People who were not separated served as controls. Participants in this study belong to the Helsinki Birth Cohort Study (HBCS) which includes 13,345 people born in Helsinki between 1934 and 1944 and visited child welfare clinics in the city. Of these 13.5% had experienced evacuation abroad. Data on parental separation was obtained from National Archives, and information on use of medication or events on coronary heart disease (CHD), hypertension, stroke and cardiovascular deaths are obtained from national registers during a follow-up period from 1971-2002. Clinical study cohort included 2003 men and women who participated in the detailed clinical examination during the years 2001-2004. All these participants are included the cardiovascular health sub-study and of them 16.0% were separated participants. The blood pressure sub-study consist of 1361 non-obese subjects whose body mass index (BMI) were <30 kg/m2, of whom 14.1% had experienced evacuation abroad. The sub-study of physical and psychosocial functioning included 1803 people and of these separated participants were 14.8%. In all sub-studies the participants who did not experience war separation in childhood served as controls. Among the separated participants over one-third were separated in toddlerhood and approximately duration of separation was two years. The separated group were older and they have lower socioeconomic status in childhood and adulthood than among the non-separated controls. War separation was associated with higher CHD morbidity, the prevalence of cardiovascular disease (CVD) and diabetes. The separation in early childhood and the duration of separation were associated with higher CHD morbidity. Duration of separation over three years showed higher prevalence of CVD in later life. Despite this the evidence of higher hospitalizations and mortality was not found. In addition war separation predicted higher blood pressure levels in late adulthood and moreover increases in the risk of impaired physical functioning. The separation in early childhood was associated with higher blood pressure levels likewise duration in less than a year and over three years. The separation in school age and duration for over two years were associated with the later life lower physical functioning. The effects of separation in overall health were more pronounced among the separated men than women. These studies suggest that early life stress experience such as temporary parental separation may have consequences on cardiovascular health and general well-being through the lifespan. The war separation and its timing and duration are stressors, which could have long-term influence on critical development phases and thereby increases the risk of chronic non-communicable diseases in later life.
  • Sihvola, Elina (Helsingin yliopisto, 2010)
    Early-onset psychiatric illnesses effects scatter to academic achievements as well as functioning in familial and social environments. From a public health point of view, depressive disorders are the most significant mental health disorders that begin in adolescence. Using prospective and longitudinal design, this study aimed to increase the understanding of early-onset depressive disorders, related mental health disorders and developing substance use in a large population-derived sample of adolescent Finnish twins. The participants of this study, FinnTwin12, an ongoing longitudinal population-based study, came from Finnish families with twins born in 1983-87 (exhaustive of five birth cohorts, identified from Finland s Central Population Register). With follow-up ongoing at age 20-24, this thesis assessed adolescent mental health in the first three waves, starting from baseline age 11-12 to follow-ups at age 14 and 17½. Some 5600 twins participated in questionnaire assessments of a wide range of health related behaviors. Mental health was further assessed among an intensively studied subsample of 1852 adolescents, who completed also professionally administered interviews at age 14, which provided data for full DSM-IV/III-R (Diagnostic and Statistical Manual for Mental Health disorders, 4th and 3rd editions) diagnoses. The participation rates of the study were 87-92%. The results of the study suggest, that the diagnostic criteria for major depressive disorder (MDD) may not capture youth with clinically significant early-onset depressive conditions outside clinical settings. Milder cases of depression, namely adolescents fulfilling the diagnostic criteria for minor depressive disorder, a qualitatively similar condition to MDD with fewer symptoms are also associated with marked suicidal thoughts, plans and attempts, recurrences and a high degree of comorbidity. Prospectively and longitudinally, early-onset depressive disorders were of substantial importance in the context of other mental health disorders and substance use behaviors: These data from a large population-derived sample established a substantial overlap between early-onset depressive disorders and attention deficit hyperactivity disorder in adolescent females, both of them significantly predictive for development of substance use among girls. Only in females baseline DSM-IV ADHD symptoms were strong predictors of alcohol abuse and dependence and illicit drug use at age 14 and frequent alcohol use and illicit drug use at age 17.½ when conduct disorder and previous substance use were controlled for. Early-onset depressive disorders were also prospectively and longitudinally associated to daily smoking behavior, smokeless tobacco use, frequent alcohol use and illicit drug use and eating disorders. Analysis of discordant twins suggested that these predictive associations were independent of familial confounds, such as family income, structure and parental models. In sum, early-onset depressive disorders predict subsequent involvement of substance use and psychiatric morbidity. A heightened risk for substance use is substantial also among those depressed below categorical diagnosis of MDD. Whether early recognition and interventions among these young people hold potential for substance use prevention further in their lives has potential public health significance and calls for more research. Data from this population-derived sample with balanced representation of boys and girls, suggested that boys and girls with ADHD behaviors may differ from each other in their vulnerability to substance use and depressive disorders: the data suggest more adverse substance use outcome for girls that was not attenuated by conduct disorder or previous substance use. Further, the prospective associations of early-onset depressive disorders and future elevated levels of addictive substance use is not explained by familial factors supporting future substance use, which could have important implications for substance use prevention.
  • Bingham, Clarissa (Helsingin yliopisto, 2012)
    Men at the age of military service are in a transition phase between childhood home and independent adulthood. They are starting to make own decisions about their future and ways of life including also eating habits. In Finland, all men are liable to military service and a majority (nearly 80%) complete service. The increasing prevalence of overweight and obesity also among soldiers has raised concerns about conscripts eating habits. This doctoral dissertation studied eating habits of young men before and during military service, determinants of eating habits and associations between diet and health risk factors, and effects of an intervention promoting healthy eating in military conditions. Two datasets were used. In the first, data on conscripts food use and nutrient intake was collected in garrison, encampment and leave conditions. The second belonged to the VARU intervention study in which the supply of healthy food was increased in military eating environments i.e. garrison canteens and soldier s homes. Study questionnaires were collected before military service and during it at the 8th week and 6th month of service. Conscripts health status was also followed during service through 13 anthropometric and clinical risk factors. Main dietary outcomes were food indexes which were formed specifically for studying young men and to suit military conditions. Prior to military service, the diet was mainly healthy although fruit and vegetable consumption was clearly low. Upper secondary school and healthy behaviour predicted healthy eating. During military service, nutrient intake was adequate although salt intake was high and fibre intake low. Food at garrison met nutrition recommendations most and especially fibre-containing foods belonged to it. At fee-time, nutrient intake was less favourable and sugar consumption high. Nutrient-poor foods, such as soft drinks and pizza, were frequently used. Conscripts health risk factor levels were low. During service, overweight decreased and body composition improved. Blood pressure improved but lipid and glucose levels deteriorated. The intervention succeeded in improving conscripts eating habits. In intervention group, cereal foods were consumed more and several fat- and sugar-containing foods less than in control group. The intervention did not increase fruit and vegetable consumption. Positively, young men s everyday diet contained several healthy foods which consumption increased during military service. On the other hand, consumption of some unhealthy foods increased especially at free-time. Already in early adulthood, young men s eating habits, other health behaviours and health risk factors accumulate. Conscripts healthy eating habits can be supported by promoting the food supply in garrison canteens and soldier s homes. Effective intervening on individual choices, as low fruit and vegetable consumption, remains more challenging.
  • Leivo, Tiina (Helsingin yliopisto, 2001)
  • Sarkola, Taisto (Helsingin yliopisto, 2001)
  • Kausto, Johanna (Helsingin yliopisto, 2014)
    In Finland, partial sickness benefit is used to promote recovery and return to work (RTW) to full-time employment after sickness absence since 2007. This thesis aimed to examine the effectiveness and efficacy of the benefit and related partial sick leave on RTW, work retention and work participation mainly in four diagnostic categories: musculoskeletal diseases, mental disorders and traumas and tumors. The first of the five substudies was a literature review which investigated the empirical evidence on the use and effects of partial sick leave on RTW in the Nordic countries. Three of the substudies were longitudinal register-based studies examining the effects of partial sick leave on return to work, work retention and work participation in working populations with prolonged sickness absence. In addition, it was assessed whether the effects differed between men and women or by age, socioeconomic position or diagnostic category. The fifth study, a randomized controlled trial (RCT), focused on the efficacy of partial sick leave on sustained RTW at an earlier phase of work disability attributable to musculoskeletal diseases. Two register-based samples (n = 38 865 and n = 68 924) of the working population with prolonged sickness absence were drawn from the sickness insurance register of The Social Insurance Institution of Finland (SII). Comprehensive prospective and retrospective register data on work participation were collected from the national registers of the SII and the Finnish Centre for Pensions. There were methodological and analytical challenges in comparing work participation between the studied groups in the register-based substudies, namely the selection of individuals into partial sick leave and the complexity of the context. This was taken into account by investigating the study questions in different study samples, with different study designs and several statistical methods. A contrafactual approach with propensity score and difference-in differences methods were applied. A systematic search of literature was carried out in 2008 and replicated in 2012. A total of five methodologically rigorous studies from other Nordic countries were identified. In four of them, partial sick leave was associated with an increased likelihood of return to regular working hours or a higher subsequent employment rate. Some of the reviewed studies suffered from methodological limitations. The register-based substudies showed that both men and women on partial sick leave when compared with individuals on full sick leave, had their first recurrent sick leave sooner and they also had more periods of sick leaves during the follow up. Approximately 60% of subjects on partial sick leave and 30% of those on full sick leave had at least one recurrent sick leave during the follow up time. The adjusted risks of the first recurrent sick leave were 1.8 and 1.7 for men and women, respectively, when subjects on partial sick leave were compared with those on full sick leave. Partial sickness benefit reduced the risk (change in absolute risk) of full disability pension by 6% but conversely increased the risk of partial disability pension by 8% compared with full sick leave. In men, the use of full disability pension was reduced by 10% and in women by 4%. Corresponding 5% and 9% increases in the use of partial disability pension were detected. The effects were stronger in the group of mental disorders than in the group of musculoskeletal diseases. During a follow-up period of five years, the decline in work participation was 5% smaller among those on partial sick leave than in the comparison group. The favorable effect of partial sick leave on work participation was found in those aged from 45 to 65 years, in those with mental disorders and among those with a higher socioeconomic position. No major difference was found in the effect between men and women. In the RCT, both the intervention and the control group consisted of 31 participants with early work disability due to musculoskeletal diseases. In addition to the clinical data collected by the physicians, the participants filled in six questionnaires during the follow up year. Survey information was linked with register-based data on sickness absences and employment periods, obtained from the registers of the occupational health services and employers. Time to RTW sustained for at least four weeks was found to be shorter in the intervention group (median 12 versus 20 days, p = 0.10) and the fully adjusted hazard ratio of RTW was 1.8 (95% CI 1.2-2.8). Compliance with the intervention was high. Overall, the results were rather consistent across the four substudies revealing beneficial effects of partial sick leave on RTW and work participation irrespective of the methodological differences and varying outcomes. Partial sick leave was found to be an effective and efficient way of enhancing RTW and work participation. The findings of this study suggest that, even if the practice so far has been mainly benefitted by women, the use of partial sick leave can be recommended among men as well. Partial sick leave is a relevant measure both in musculoskeletal and mental disorders, at least in the context of the Finnish societal system. More attention needs to be paid to the implementation of the measure among young workers and individuals in physically strenuous, low pay jobs. To conclude, the overall results suggest that partial sickness benefit - if applied in a larger scale in the future - may prove to be an effective tool in increasing the work participation of working population with long term sickness absence.
  • Snäll, Johanna (Helsingin yliopisto, 2015)
    Background and purpose Short-term glucocorticoids (GCs) are frequently used in association with oral and maxillofacial surgery to prevent postoperative pain, edema, and nausea. However, the influence on tissue repair and the anti-inflammatory and immunosuppressive features of GCs may have an adverse impact on healing of the surgical site. The main aim of this study was to determine the occurrence of disturbance in surgical wound healing (DSWH) and pulp necrosis (PN) after surgical treatment of facial fractures and the influence of perioperative administration of GCs on these complications. Patients This study comprised four populations of patients (Studies I-IV) treated for facial fractures. For Study I, the medical records of 280 consecutive patients who had undergone open reduction of different types of facial fractures or reconstruction of orbital wall fracture were assembled retrospectively. Prospective Studies II-IV consisted of patients with mandibular fractures (n=41) (Study II) and patients with a simple zygomatic complex (ZC) fractures (n=64) (Study III). The fourth population (n=24) (Study IV) was extracted from the population of patients with mandibular fractures recruited for Study II. Methods In the retrospective study (Study I), the outcome variable was DSWH, which was established when any kind of aberrant wound healing and/or sign of infection in the surgical site occurred. The primary predictor variable was the perioperative use of GC. Patients recruited for Studies II and III were randomly assigned to one of two groups. Patients in the study group received dexamethasone (DXE) (Oradexon®), whereas patients in the control group received no GC. The main outcome variables were DSWH (Studies II-III) and PN of teeth in the area of mandibular fracture (Study IV). The primary predictor variable was the perioperative use of DXE. Results In patients with ZC fractures (Study III), DSWH was significantly associated with perioperative use of DXE as well as with intraoral surgical approach. In patients operated on for different types of facial fractures (Study I), DSWH was associated significantly with intraoral surgical approach. DSWH occurred more frequently in patients receiving GCs, however, without statistical significance. In patients undergoing intraoral surgery for mandibular fractures (Study II), DSWH occurred more frequently in the DXE group. Also PN occurred more frequently in the DXE group (Study IV). The delay of DSWH was notably longer in the DXE groups (Study I-III). Particularly PN (Study IV) was observed much later in the DXE group. Conclusions Perioperative DXE cannot be recommended in association with surgery of ZC fractures. Moreover, GCs should be used with caution in association with surgery of other facial fractures as well, particularly when the intraoral approach is used.
  • Hirvonen, Johanna (Helsingin yliopisto, 2007)
    Although the principle of equal access to medically justified treatment has been promoted by official health policies in many Western health care systems, practices do not completely meet policy targets. Waiting times for elective surgery vary between patient groups and regions, and growing problems in the availability of services threaten equal access to treatment. Waiting times have come to the attention of decision-makers, and several policy initiatives have been introduced to ensure the availability of care within a reasonable time. In Finland, for example, the treatment guarantee came into force in 2005. However, no consensus exists on optimal waiting time for different patient groups. The purpose of this multi-centre randomized controlled trial was to analyse health-related quality of life, pain and physical function in total hip or knee replacement patients during the waiting time and to evaluate whether the waiting time is associated with patients health outcomes at admission. This study also assessed whether the length of waiting time is associated with social and health services utilization in patients awaiting total hip or knee replacement. In addition, patients health-related quality of life was compared with that of the general population. Consecutive patients with a need for a primary total hip or knee replacement due to osteoarthritis were placed on the waiting list between August 2002 and November 2003. Patients were randomly assigned to a short waiting time (maximum 3 months) or a non-fixed waiting time (waiting time not fixed in advance, instead the patient followed the hospitals routine practice). Patients health-related quality of life was measured upon being placed on the waiting list and again at hospital admission using the generic 15D instrument. Pain and physical function were evaluated using the self-report Harris Hip Score for hip patients and a scale modified from the Knee Society Clinical Rating System for knee patients. Utilization measures were the use of home health care, rehabilitation and social services, physician visits and inpatient care. Health and social services use was low in both waiting time groups. The most common services used while waiting were rehabilitation services and informal care, including unpaid care provided by relatives, neighbours and volunteers. Although patients suffered from clear restrictions in usual activities and physical functioning, they seemed primarily to lean on informal care and personal networks instead of professional care. While longer waiting time did not result in poorer health-related quality of life at admission and use of services during the waiting time was similar to that at the time of placement on the list, there is likely to be higher costs of waiting by people who wait longer simply because they are using services for a longer period. In economic terms, this would represent a negative impact of waiting. Only a few reports have been published of the health-related quality of life of patients awaiting total hip or knee replacement. These findings demonstrate that, in addition to physical dimensions of health, patients suffered from restrictions in psychological well-being such as depression, distress and reduced vitality. This raises the question of how to support patients who suffer from psychological distress during the waiting time and how to develop strategies to improve patients initiatives to reduce symptoms and the burden of waiting. Key words: waiting time, total hip replacement, total knee replacement, health-related quality of life, randomized controlled trial, outcome assessment, social service, utilization of health services
  • Stenberg, Jan-Henry (Helsingin yliopisto, 2014)
    Schizophrenia is a severe, psychiatric illness with neurocognitive deficits as its major component, and affects about 1% of the world population. Improving impaired neurocognitive function is one of the pivotal treatment goals in this patient population. In the treatment of schizophrenia, only a partial treatment response is typically achieved with dopamine antagonists; i.e., antipsychotics . The antidepressant mirtazapine has a unique mechanism of action with, in theory, an ability to enhance neurocognition and provide added value to antipsychotic treatment. This study explored whether or not adjunctive mirtazapine has the potential to improve neurocognitive performance and alleviate clinical symptoms in patients with schizophrenia who demonstrated a suboptimal treatment response to first-generation antipsychotics (FGAs). This study was a neurocognitive arm of a single-center, randomized, add-on, double-blinded, placebo-controlled study, which was carried out in the Karelian Republic, Petrozavodsk, Russia. Patients with schizophrenia or a depressive type schizoaffective disorder, according to the Diagnostic and Statistical Manual of Mental and Behavioral Disorders 4th edition (DSM-IV) criteria, who received stable doses of FGA with inadequate treatment response were enrolled into the trial. Twenty patients were assigned to mirtazapine and 21 to placebo. After a one-week single-blind placebo run-in period, the participants were randomized to receive either 30 mg of mirtazapine or the placebo four times a day (QID) in a double-blind fashion for 6 weeks. Subsequently, those who were eligible to continue entered the following 6-week open-label phase, where they were treated with mirtazapine 30 mg QID. At study weeks 0, 6, and 12, a senior psychologist performed neuropsychological examinations to evaluate neurocognitive functioning. Verbal and visual memory, visuo-spatial and executive functions, verbal fluency and both general mental and psychomotor speeds were assessed by commonly used, validated neuropsychological tests for different neurocognitive domains. Clinical examinations were conducted at week 1 (screening), week 0 (baseline) and after 1, 2, 4, 6, 7, 8, 10, and 12 weeks of treatment. Within group and between group differences were analyzed on a Modified Intent-to Treat (MITT) basis with Last Observations Carried Forward (LOCF). After 6 weeks of treatment, 5/21 neurocognitive parameters (i.e. Wechsler Adult Intelligence Scale Revised (WAIS-R) Block Design, p=0.021; Wechsler Memory Scale (WMS) Logical Memory, p=0.044; WMS Logical Memory Delayed, p=0.044; Stroop Dots, p=0.044; Trail Making Test Part A (TMT-A), p=0.018) were improved with statistical significance in the mirtazapine group. In contrast, only 1 of the 21 parameters changed significantly (WMS Logical Memory, p=0.039) in the placebo group. Add-on 6-week mirtazapine treatment was superior when compared with placebo in the neuropsychological domains of visuo-spatial ability and general mental speed/attentional control (Block Design mirtazapine group vs. placebo and Stroop dots mirtazapine group vs. placebo, p=0.044 for both comparisons). The enhancing effect on the Block Design-measured visuo-spatial functioning was mediated through changes in positive, depressive symptoms and parkinsonism-like side effects, but not via changes in negative symptoms. Moreover, higher doses of FGAs, longer duration of illness and lower initial Block Design scores predicted this effect. During the 6 weeks extension phase, individuals who continued mirtazapine treatment and those who were switched from placebo to mirtazapine showed significant improvements on several neurocognitive tests. Those who switched from placebo to open label mirtazapine treatment achieved similar results in the 6 following weeks as the mirtazapine group during their first 6 weeks of mirtazapine treatment. From week 0 to week 12, the continuation group demonstrated improvements in 17/21 neurocognitive parameters, while the switch group improved in 8/21 of the measured parameters. Twelve weeks of mirtazapine treatment indicated an advantage over a shorter, 6-week mirtazapine treatment on Stroop Dots time (p=0.035) and Trail Making Test part B (TMT-B), and number of mistakes (p=0.043). During the 6-week open-label phase, significant improvements on several clinical parameters, which included the Positive and Negative Syndrome Scale (PANSS) total score, were observed. In the total population (i.e., pooled switch and continuation groups), the effect size was 0.94 (CI 95%=0.451.43) as determined by the PANSS total score. Conclusions. Adjunctive mirtazapine treatment might offer added value as a neurocognitive enhancer, and may augment the antipsychotic effect in FGA-treated schizophrenia patients with inadequate treatment response. The ability to generalize these results for a larger population may be limited by the small sample size of the present study.