Does climacteric status impact regulation of the autonomic nervous system at the age of 46 years?

OBJECTIVE: To investigate whether an earlier-onset climacteric phase is associated with autonomic imbalance at the age of 46 years. METHODS: This cross-sectional birth cohort study included 2661 women aged 46 years. Participants were divided into climacteric (n = 359) and preclimacteric (n = 2302) groups based on menstrual history and follicle stimulating hormone values. The mean heart rate (HR), low-frequency (LF) power, high-frequency (HF) power and LF/HF ratio were analyzed from heart rate variability recordings. The variables were compared between the groups using multivariable linear regression models, including body mass index, smoking and physical activity. The effects of hormone therapy and hot flashes on autonomic function were evaluated in sub-analyses. RESULTS: Climacteric women had a lower mean HR in seated (71.9 ± 10.5 vs. 72.6 ± 10.4 bpm, p = 0.015) and standing (81.2 ± 12.8 vs. 83.6 ± 12.1 bpm, p = 0.002) positions compared to preclimacteric women, and the differences remained significant after the adjustments. In the sub-analyses, more frequent hot flashes were associated with a lower LF power and LF/HF ratio in the sitting position. CONCLUSIONS: The present study suggested an association between greater parasympathetic activation in women with more advanced climacteric status at the age of 46 years.

Farm Environment During Pregnancy and Childhood and Polysensitization at the Age of 31: Prospective Birth Cohort Study in Finland.

BACKGROUND AND OBJECTIVE: The farm environment, especially contact with farm animals in early childhood, may prevent allergic sensitization during adulthood. However, prospective associations between exposure to the farm environment and polysensitization have not been studied. Polysensitization is a risk factor for asthma and asthma-related morbidity. Objective: To investigate whether exposure to a farming environment in early childhood, especially exposure to animals, is associated with sensitization to specific allergens and polysensitization at the age of 31. METHODS: In a prospective birth cohort study, 5509 individuals born in northern Finland in 1966 underwent skin prick testing against birch, timothy, cat, and house dust mite at the age of 31. Prenatal exposure to the farming environment was documented at birth, whereas information on childhood exposure to pets was only collected retrospectively at the age of 31. Data were analyzed using logistic regression. RESULTS: Being born to a family with farm animals was associated with a reduced risk of sensitization to birch, timothy, and cat (adjusted odds ratio [aOR], 0.55 [95%CI, 0.43-0.70]; aOR, 0.62 [95%CI, 0.48-0.79]; aOR, 0.60 [95%CI, 0.47-0.75]) and polysensitization at the age of 31 (aOR, 0.62 [95%CI, 0.48-0.80]). The number of animal species present during childhood was dose-dependently associated with a reduced risk of sensitization to birch, timothy, and cat, as well as of polysensitization. No association was found with sensitization to house dust mite. CONCLUSIONS: Growing up on a farm and contact with higher numbers of animal species in childhood are associated with less frequent sensitization to birch, timothy, and cat allergens and polysensitization in adulthood, but not with sensitization to house dust mite.

Farm Environment During Pregnancy and Childhood and Polysensitization at the Age of 31: Prospective Birth Cohort Study in Finland

BACKGROUND: The farm environment, especially contact with farm animals in early childhood, may prevent allergic sensitization during adulthood. However, prospective associations between exposure to the farm environment and polysensitization have not been studied. Polysensitization is a risk factor for asthma and asthma-related morbidity. OBJECTIVE: To investigate whether exposure to a farming environment in early childhood, especially exposure to animals, is associated with sensitization to specific allergens and polysensitization at the age of 31. METHODS: In a prospective birth cohort study, 5509 individuals born in northern Finland in 1966 underwent skin prick testing against birch, timothy, cat, and house dust mite at the age of 31. Prenatal exposure to the farming environment was documented at birth, whereas information on childhood exposure to pets was only collected retrospectively at the age of 31. Data were analyzed using logistic regression. RESULTS: Being born to a family with farm animals was associated with a reduced risk of sensitization to birch, timothy, and cat (adjusted odds ratio [aOR], 0.55 [95%CI, 0.43-0.70]; aOR, 0.62 [95%CI, 0.48-0.79]; aOR, 0.60 [95%CI, 0.47-0.75]) and polysensitization at the age of 31 (aOR, 0.62 [95%CI, 0.48-0.80]). The number of animal species present during childhood was dose-dependently associated with a reduced risk of sensitization to birch, timothy, and cat, as well as of polysensitization. No association was found with sensitization to house dust mite. CONCLUSIONS: Growing up on a farm and contact with higher numbers of animal species in childhood are associated with less frequent sensitization to birch, timothy, and cat allergens and polysensitization in adulthood, but not with sensitization to house dust mite

ANTECEDENTES: El ambiente de granja, especialmente el contacto con animales de granja en la primera infancia, puede prevenir la sensibilización alérgica durante la edad adulta. Sin embargo, no se han estudiado las posibles asociaciones entre la exposición al entorno agrícola y la polisensibilización. La polisensibilización es un factor de riesgo para el asma y su morbilidad. OBJETIVO: Investigar si el entorno agrícola en la primera infancia, especialmente la exposición a animales, está asociado con la sensibilización a alérgenos específicos y la polisensibilización a la edad de 31 años. MÉTODOS: En un estudio prospectivo de cohorte de nacimiento, 5.509 sujetos nacidos en el norte de Finlandia en 1966 se sometieron a pruebas cutáneas a la edad de 31 años con abedul, hierba timotea, gato y ácaros del polvo doméstico. La exposición prenatal al ambiente agrícola se documentó al nacer, mientras que la información sobre la exposición infantil a las mascotas solo se recopiló retrospectivamente a la edad de 31 años. Se utilizó La regresión logística en los análisis estadísticos. RESULTADOS: Nacer en una familia con animales de granja se asoció con un menor riesgo de sensibilización frente a abedul, hierba timotea o gato (odds ratio ajustado, aOR = 0,55 [intervalo de confianza del 95% 0,43-0,70]; aOR = 0,62 [0,48-0,79] ; aOR = 0,60 [0,47-0,75]) y polisensibilización a la edad de 31 años (aOR = 0,62 [0,48-0,80]). La sensibilización frente a abedul, hierba timotea y gato, así como la polisensibilización, se asociaron de forma dependiente e inversa a la dosis con el número de especies animales presentes durante la infancia. No se encontró asociación con la sensibilización frente a los ácaros del polvo doméstico. CONCLUSIONES: Crecer en una granja y el contacto con un mayor número de especies animales en la infancia se asocia con una menor sensibilización frente al abedul, la hierba timotea, alérgenos de gato y polisensibilización en la edad adulta, pero no con sensibilización frente a los ácaros del polvo doméstico

Mortality by diseases and medical conditions in the offspring of parents with severe mental illness.

PURPOSE: The lifespan of people with severe mental illness (SMI) is shorter compared to the general population. There might be common familial pathway leading to a high co-occurrence of somatic disorders and SMI. To study this we explored the long-term mortality for natural causes in the offspring of people with SMI. METHODS: Participants were members of the Northern Finland Birth Cohort 1966 (NFBC1966; N = 11,325). The data on cause of deaths of the members were obtained from the Population Register Center until year 2015. The data on hospital-treated psychiatric disorders of parents were obtained from nationwide Care Register for Health Care. Cumulative incidences by age were calculated in the NFBC1966 members having a parent with SMI and those who did not have. We were able to take into account multiple confounders. RESULTS: Of the total sample of 11,325 offspring, 853 (7.4%) died during the follow-up period, 74 (8.7%) from the study cohort and 779 (91.3%) from the comparison group. These numbers included 160 stillborn children. There were 557 cases of deaths from diseases and medical conditions and 296 deaths from external causes. The adjusted risk ratio for offspring of mothers with SMI was 1.08 (0.72-1.64), and for offspring of fathers with SMI 0.58 (0.36-0.93). CONCLUSIONS: This was the first long-term follow-up study (up to age 49) of all-cause mortality in offspring of parents with SMI. Our findings were contrary to expectations. Offspring of parents with SMI had no increased risk for dying. In fact, the risk for dying in the group of offspring of fathers with SMI was lower than in the comparison group. This study does not support the assumption of common familial pathway leading to a high co-occurrence of somatic disorders and SMI.

Dairy- and supplement-based calcium intake in adulthood and vertebral dimensions in midlife-the Northern Finland Birth Cohort 1966 Study.

Among a representative sample of 1064 Northern Finns, we studied the association of dairy- and supplement-based calcium intake in adulthood with vertebral size in midlife. Inadequate calcium intake (< 800 mg/day) from age 31 to 46 predicted small vertebral size and thus decreased spinal resilience among women but not men. INTRODUCTION: Small vertebral size predisposes individuals to fractures, which are common among aging populations. Although previous studies have associated calcium (Ca) intake with enhanced bone geometry in the appendicular skeleton, few reports have addressed the axial skeleton or the vertebrae in particular. We aimed to investigate the association of dairy- and supplement-based Ca intake in adulthood with vertebral cross-sectional area (CSA) in midlife. METHODS: A sample of 1064 individuals from the Northern Finland Birth Cohort 1966 had undergone lumbar magnetic resonance imaging at the age of 46, and provided self-reported data on diet and Ca intake (dairy consumption and use of Ca supplements) at the ages of 31 and 46. We assessed the association between Ca intake (both continuous and categorized according to local recommended daily intake) and vertebral CSA, using generalized estimating equation and linear regression models with adjustments for body mass index, diet, vitamin D intake, education, leisure-time physical activity, and smoking. RESULTS: Women with inadequate Ca intake (< 800 mg/day) over the follow-up had 3.8% smaller midlife vertebral CSA than women with adequate Ca intake (p = 0.009). Ca intake among men showed no association with vertebral CSA. CONCLUSIONS: Inadequate Ca intake (< 800 mg/day) from the age of 31 to 46 predicts small vertebral size and thus decreased spinal resilience among middle-aged women. Future studies should confirm these findings and investigate the factors underlying the association of low Ca intake in women but not in men with smaller vertebral size.

Association between adolescent sport activities and lumbar disk degeneration among young adults.

The relationship between different sport activities and lumbar intervertebral disk degeneration (DD) is largely unknown. We evaluated whether adolescent participation in different sports is associated with lumbar DD in a population-based birth cohort of young adults. A total of 558 young adults (325 females and 233 males) underwent magnetic resonance imaging (MRI, 1.5-T scanner). A DD sum score, based on the Pfirrmann grading, was calculated for all lumbar levels. The sum score was categorized into no DD, 1, 2, or at least 3. Participation in different sport activities was self-reported by postal surveys at 16, 18, and 19 years, and three groups were formed based on participation frequency in 11 sports: (a) highly active (at least twice a week), (b) moderately active (2-4 times a month), and (c) inactive (maximum once a month). Cumulative odds ratios (COR) and their 95% confidence intervals (CI) were obtained for each sport by ordinal logistic regression, adjusting for gender, body mass index, age, socioeconomic status, smoking, and other sports. Highly active participation in jogging/running and swimming was associated with a higher DD sum score (COR: 3.0; 95% CI: 1.4-6.3 and 5.0; 1.7-15.2, respectively) compared to inactive participation, whereas highly active participation in skating showed low COR. In conclusion, running and swimming at least twice a week in early adulthood are potentially associated with lumbar DD. Follow-up studies with MRI are needed to show whether frequent exposure to running or swimming has further effect on the integrity of lumbar intervertebral disks.

Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus-a prospective, population-based cohort study.

STUDY QUESTION: What are the respective roles of polycystic ovary syndrome (PCOS), long-term weight gain and obesity for the development of prediabetes or Type 2 diabetes mellitus (T2DM) by age 46 years? SUMMARY ANSWER: The risk of T2DM in women with PCOS is mainly due to overweight and obesity, although these two factors have a synergistic effect on the development of T2DM. WHAT IS KNOWN ALREADY: PCOS is associated with an increased risk of prediabetes and T2DM. However, the respective roles of PCOS per se and BMI for the development of T2DM have remained unclear. STUDY DESIGN, SIZE, DURATION: In a prospective, general population-based follow-up birth cohort 1966 (n = 5889), postal questionnaires were sent at ages 14 (95% answered), 31 (80% answered) and 46 years (72% answered). Questions about oligoamenorrhoea and hirsutism were asked at age 31 years, and a question about PCOS diagnosis at 46 years. Clinical examination and blood sampling were performed at 31 years in 3127 women, and at 46 years in 3280 women. A 2-h oral glucose tolerance test (OGTT) was performed at 46 years of age in 2780 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women reporting both oligoamenorrhoea and hirsutism at age 31 years and/or diagnosis of PCOS by 46 years were considered as women with PCOS (n = 279). Women without any symptoms at 31 years and without PCOS diagnosis by 46 years were considered as controls (n = 1577). The level of glucose metabolism was classified according to the results of the OGTT and previous information of glucose metabolism status from the national drug and hospital discharge registers. MAIN RESULTS AND THE ROLE OF CHANCE: PCOS per se significantly increased the risk of T2DM in overweight/obese (BMI ≥ 25.0 kg/m2) women with PCOS when compared to overweight/obese controls (odds ratio: 2.45, 95% CI: 1.28-4.67). Normal weight women with PCOS did not present with an increased risk of prediabetes or T2DM. The increase in weight between ages 14, 31 and 46 years was significantly greater in women with PCOS developing T2DM than in women with PCOS and normal glucose tolerance, with the most significant increase occurring in early adulthood (between 14 and 31 years: median with [25%; 75% quartiles]: 27.25 kg [20.43; 34.78] versus 13.80 kg [8.55; 20.20], P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The diagnosis of PCOS was based on self-reporting, and the questionnaire at 46 years did not distinguish between polycystic ovaries only in ultrasonography and the syndrome. Ovarian ultrasonography was not available to aid the diagnosis of PCOS. WIDER IMPLICATIONS OF THE FINDINGS: These results emphasize weight management already during adolescence and early adulthood to prevent the development of T2DM in women with PCOS, as the period between 14 and 31 years seems to be a crucial time-window during which the women with PCOS who are destined to develop T2DM by 46 years of age experience a dramatic weight gain. Furthermore, our results support the view that, particularly in times of limited sources of healthcare systems, OGTT screening should be targeted to overweight/obese women with PCOS rather than to all women with PCOS. STUDY FUNDING/COMPETING INTERESTS: Finnish Medical Foundation; North Ostrobothnia Regional Fund; Academy of Finland (project grants 104781, 120315, 129269, 1114194, 24300796, Center of Excellence in Complex Disease Genetics and SALVE); Sigrid Juselius Foundation; Biocenter Oulu; University Hospital Oulu and University of Oulu (75617); Medical Research Center Oulu; National Institute for Health Research (UK); National Heart, Lung, and Blood Institute (grant 5R01HL087679-02) through the STAMPEED program (1RL1MH083268-01); National Institute of Health/National Institute of Mental Health (5R01MH63706:02); ENGAGE project and grant agreement HEALTH-F4-2007-201413; EU FP7 EurHEALTHAgeing-277849 European Commission and Medical Research Council, UK (G0500539, G0600705, G1002319, PrevMetSyn/SALVE) and Medical Research Center, Centenary Early Career Award. The authors have no conflicts of interests. TRIAL REGISTRATION NUMBER: N/A.

Psychosocial and lifestyle correlates of musculoskeletal pain patterns in adolescence: a 2-year follow-up study.

BACKGROUND: The prevalence of musculoskeletal (MS) pain has been increasing among adolescents in the last decades. This may be related to either adverse changes in lifestyle and/or the psychosocial environment. Our study analysed the psychosocial and lifestyle correlates of musculoskeletal pain progression in adolescence. METHODS: The study was based on the 1986 Northern Finland Birth Cohort and included 1773 adolescents at the ages of 16 to 18. Latent class analysis was applied to find the homogeneous profiles of MS pains in four body areas (neck, shoulder, low back and limb). We analysed the associations between time spent in sedentary activities and sleeping, physical activity level, body mass index, alcohol consumption, smoking, and emotional and behavioural factors at 16 years, and belonging to pain clusters at 16 and 18 years. RESULTS: We found an association between a higher probability of MS pains between 16 and 18 years and increasing emotional and behavioural problems in both genders. Among boys, a high likelihood of MS pains during follow-up was also associated with a long time spent sitting and insufficient sleeping time. Among girls, alcohol consumption associated with high pain probability. MS pains already co-occur to a large extent in their early course. CONCLUSIONS: The strong overlap of emotional and behavioural problems and MS pains in adolescence requires awareness in both research and clinical work.

Associations of physical activity and inactivity with low back pain in adolescents.

Low back pain (LBP) is a common health problem already in adolescence. Physical activity has been suggested as a risk factor for LBP in adolescents, but the current evidence is conflicting. This study examined the association of physical activity and amount of sitting with LBP. The study population consisted of 5999 boy and girl members of the Northern Finland 1986 birth cohort who responded to mailed questions at the age of 15-16 years. LBP during the past 6 months was classified as "no LBP,""reporting LBP" (not seeking medical help), or "consultation for LBP." Odds ratios and 95% confidence intervals obtained by multinomial logistic regression were adjusted for smoking and body mass index. Being physically very active (more than 6 h of brisk physical activity per week) was associated with increased prevalence of "consultation for LBP" in both sexes, and with "reporting LBP" in girls, compared with being moderately active (2-3 h of brisk physical activity per week). High amount of sitting associated with "consultation for LBP" and "reporting LBP" in girls, but not in boys. We conclude that very active participation in physical activities in both sexes and a high amount of sitting in girls are related to self-reported LBP.

Antidepressant efficacy and quality of life in depression: a double-blind study with moclobemide and fluoxetine.

The efficacy of moclobemide (300-450 mg/day) was compared with fluoxetine (20-40 mg/day) in a double-blind, multicentre study in 209 patients with new episodes of depression selected from 612 consecutive depressed patients representative of those consulting psychiatric services in Finland. Antidepressant efficacy was assessed with the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale and Clinical Global Impression (CGI). The Medical Outcome Study Short-form General Health Survey (SF-20) and 15D Measure of Quality of Life were used to measure effectiveness in terms of health-related quality of life. Efficacy was evident with both drug treatments, with 67% in the moclobemide group and 57% in the fluoxetine group having a reduction in HDRS of more than 50%. Similarly, 77% of the patients in the moclobemide group and 67% in the fluoxetine group were assessed on the CGI as much better or very much better after 6 weeks of treatment. The most commonly reported adverse events were nausea, other gastrointestinal symptoms, nervousness, dizziness and sleep disorders. Nausea was significantly more common in the fluoxetine group and was found especially in women. Premature terminations of treatment were 18% in the moclobemide and 21% in the fluoxetine group. A significant change for the better in quality of life was found in both treatment groups, even at week 2 but especially after 6 weeks of treatment. Improvement was not only seen in dimensions measuring depression or mental health but also in other dimensions.

Do reversed depressive symptoms occur together as a syndrome?

Although the DSM-IIIR diagnostic criteria for major depression include hypersomnia, increase in appetite, and in children and in adolescents irritability, there is no general agreement on the existence of a depressive syndrome with reversed vegetative symptoms. Our findings suggest that these reversed depressive symptoms may not occur together as a syndrome. However, they may share an enhanced responsiveness to moclobemide treatment.

Nitroglycerin ointment effective for seven hours in severe angina pectoris.

The efficacy and tolerability of nitroglycerin (NTG) ointment were studied in 80 male patients with severe angina pectoris. Two symptom-limited exercise tests were performed on successive days after application of an ointment containing 15 mg NTG or a placebo (P) ointment. The patients were assigned to 4 groups. The study was conducted in a double-blind, cross-over manner. The total amount of work performed was higher in all groups on NTG (46-70%) compared to P ointment. The difference was statistically significant (p less than 0.001) at all points of time from 0.5 to 7 hours. The ST segment depression in ECG at the end of the exercise test was slightly greater on P than on NTG, but the difference was statistically significant only in the 3-hour group (p less than 0.01). The frequencies of headache and dizziness were 35% and 16%, respectively, on NTG. Eight patients (10%) reported that headache was severe enough to prevent regular use of NTG ointment. NTG ointment is effective, has a long duration of action and is relatively well tolerated by patients with severe angina pectoris.

The influence of intramuscularly administered pethidine on the amnesic effects of intravenous diazepam during intravenous regional anaesthesia.

Patients undergoing surgery under regional anaesthesia often receive narcotic analgesics for premedication which may modify the sedative and amnesic effects of intravenously administered diazepam. Sixty-two patients scheduled for upper extremity surgery under intravenous regional anaesthesia received 0.15 mg/kg of diazepam intravenously to supplement the local anaesthesia. Thirty-two of the patients received 0.01 mg/kg of atropine plus 1 mg/kg of pethidine and 30 patients only atropine intramuscularly approximately 1 h before injection of diazepam. Another 30 patients received the same atropine-pethidine premedication and saline intravenously, and served as a reference group. Atropine-pethidine premedication followed by saline did not produce any amnesic effects. Sixty-nine and 38% of patients receiving atropine-pethidine premedication followed by diazepam did not remember a picture shown to them 15 min after diazepam injection or the performance of operation, respectively, the respective figures for patients given atropine premedication followed by diazepam being only 23% and 0% (P less than 0.01 - 0.001 between groups). The anti-recall of painful stimulus (exanguination) was significantly (P less than 0.01) more common when diazepam was given after pethidine premedication (31%) when compared to its injection after atropine alone (7%). The drowsiness produced by the drugs was greatest and the overall patient acceptability of the technique used most satisfactory when pethidine was used for premedication and diazepam for sedation. It is concluded that intramuscularly administered pethidine potentiates the amnesic action of intravenous diazepam for painful stimuli, prolongs the amnesic action of diazepam for visual stimuli and improves the patients' acceptability of intravenous regional anesthesia supplemented by intravenous diazepam.

Failure of intramuscularly administered lorazepam and scopolamine-morphine premedication to produce amnesic effects to supplement conduction anaesthesia.

Patients undergoing surgery under regional anaesthesia often prefer to be sedated and do not later want to recall the procedure. One hundred and twenty-one patients scheduled for various surgical procedures under epidural, spinal, sacral, or brachial plexus blockades received 1 mg/kg of pethidine, 0.007 mg/kg of scopolamine, plus 0.14 mg/kg of morphine, or 0.03 mg/kg or 0.06 mg/kg or lorazepam intramuscularly as preanaesthetic medication before the operation. The patients's self-assessments of degree of fatigue and apprehension were similar after each premedication when assessed before operation. Postoperative anxiety and confusion as well as need for postoperative care and supervision were greatest after 0.06mg/kg of lorazepam. Significantly (P smaller than 0.05 to P smaller than 0.01) fewer patients given 0.06 mg/kg or lorazepam remembered different events and procedures carried out on them before and after operation than those given other premedications, but no significant differences were noted in patients' ability to recall the performance of operation when asked on the following day. Seventy-seven, 63, and 57% of patients receiving 0.06 mg/kg of lorazepam remembered the start of blockade, performance of operation, and stay in recovery room, respectively. Intravenous sedation should be preferred to these intramuscularly administered premedications if drug-induced amnesia is sought to supplement local anaesthetic techniques.

Effect of anticonvulsants on plasma haloperidol and thioridazine levels.

Patients who had therapeutic plasma levels of phenobarbital and/or diphenylhydantoin had significantly lower plasma levels of haloperidol and mesoridazine, the active metabolite of thioridazine, than patients who did not receive anticonvulsants. Plasma thioridazine levels per se were not affected by concomitant anticonvulsant treatment. Biperiden, an antimuscarinic, antiparkinsonian agent, did not affect the plasma levels of these three neuroleptics.

Comparison of i.m. lysine acetylsalicylate and oxycodone in the treatment of pain after operation.

Lysine acetylsalicylate (LAS) is a soluble salt of acetylsalicylic acid and can be given parenterally. LAS 12.5 mg kg-1 and 25 mg kg-1 were compared with oxycodone 0.15 mg kg-1 in the treatment of pain after operation in 60 patients undergoing varicose vein surgery. Both treatments almost completely relieved moderate to severe pain for the 3-h observation period. The time until the peak of action was longer after LAS (60-90 min) than after oxycodone (30-60 min). No significant differences were found between the smaller and larger doses of LAS, suggesting a plateau effect. Further clinical experiments with LAS using i.v. mode of administration and other pain models are warranted.