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Objectives: Neuropeptide Y is associated with stress in animal and human laboratory studies. However, data from clinical studies are scarce and no clinical longitudinal studies have been published. The aim of this clinical study was to assess the possible association between changes in the levels of pain, depression, and stress measures, on the one hand, and plasma neuropeptide Y levels, on the other., Methods: Forty-four women with the fibromyalgia syndrome were exposed to a Cognitive Behavioral Therapy intervention. Levels of the plasma neuropeptide Y as well as pain, depression, and stress measures were obtained at the start and at the end of the intervention, and after a further six month follow-up. Based on these data, a before-and-after analysis was performed., Results: Almost all measures of pain, depression, and stress improved during the study; specifically, variables measuring life control (coping), depression, and stress-related time urgency improved significantly. Moreover, during the same time period, the mean plasma neuropeptide Y level was reduced from 93.2 ± 38.8 fmol/mL before the Cognitive Behavioral Therapy to 75.6 ± 42.9 fmol/mL (p<0.001) at the end of the study., Conclusions: After exposure to a Cognitive Behavioral Therapy intervention, levels of most of the pain, depression, and stress measures improved, half of them significantly, as did the levels of neuropeptide Y. This circumstance indicates a possible functional relationship between pain-depression-stress and neuropeptide Y., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Background and aims Substance P (CSF-SP) is known to be elevated in females with fibromyalgia syndrome (FMS). The aims of this study were to evaluate the effect of cognitive behaviour therapy (CBT) on plasma SP levels in women with FMS and to find possible clinical behavioural correlates to plasma SP level changes. Methods Forty-eight women with FMS were randomly allocated into two groups. Group 1 received the CBT treatment intervention over the course of 6 months while group 2 was waitlisted. CBT was given with a protocol developed to diminish stress and pain. After 6 months, group 2 was given the same CBT treatment as well. All were followed up 1 year after the start of CBT treatment. This approach allowed for two analytical designs - a randomised controlled trial (RCT) (n=24 vs. n=24) and a before-and-after treatment design (n=48). All women were repeatedly evaluated by the West Haven-Yale Multidimensional Pain Inventory (MPI) and three other psychometric questionnaires and plasma SP was analysed. Results In the RCT design, the plasma SP level was 8.79 fmol/mL in both groups at the start of the trial, after adjustment for initial differences. At the end of the RCT, the plasma SP level was 5.25 fmol/mL in the CBT intervention group compared to 8.39 fmol/mL in the control group (p=0.02). In the before-and-after design, the plasma SP was reduced by 33% (p<0.01) after CBT, but returned to the pre-treatment level at follow-up 1 year after the start of CBT treatment. Plasma SP was associated with the MPI dimensions experienced "support from spouses or significant others" and "life control". Conclusions Plasma SP might be a marker of the effect of CBT in FMS associated with better coping strategies and reduced stress rather than a biochemical marker of pain.

Background: In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden., Materials and Methods: In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample ( n  = 145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status., Results: The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p  = 0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age ( p  = 0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were ≥57 years old., Conclusion: The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.

Background: Determinants of vitamin D status measured as 25-OH-vitamin D in blood are exposure to sunlight and intake of vitamin D through food and supplements. It is unclear how large the contributions are from these determinants in Swedish primary care patients, considering the low radiation of UVB in Sweden and the fortification of some foods. Asian and African immigrants in Norway and Denmark have been found to have very low levels, but it is not clear whether the same applies to Swedish patients. The purpose of our study was to identify contributors to vitamin D status in Swedish women attending a primary health care centre at latitude 60°N in Sweden., Methods: In this cross-sectional, observational study, 61 female patients were consecutively recruited between January and March 2009, irrespective of reason for attending the clinic. The women were interviewed about their sun habits, smoking, education and food intake at a personal appointment and blood samples were drawn for measurements of vitamin D and calcium concentrations., Results: Plasma concentration of 25-OH-vitamin D below 25 nmol/L was found in 61% (19/31) of immigrant and 7% (2/30) of native women. Multivariate analysis showed that reported sun holiday of one week during the last year at latitude below 40°N with the purpose of sun-bathing and native origin, were significantly, independently and positively associated with 25-OH-vitamin D concentrations in plasma with the strongest association for sun holiday during the past year., Conclusions: Vitamin D deficiency was common among the women in the present study, with sun holiday and origin as main determinants of 25-OH-vitamin D concentrations in plasma. Given a negative effect on health this would imply needs for vitamin D treatment particularly in women with immigrant background who have moved from lower to higher latitudes.

Background: Long-term sickness absence is one of the main risk factors for permanent exit out of the labour market. Early identification of the condition is essential to facilitate return to work. The aim of this study was to analyse possible determinants of return to work and their relative impact., Methods: All 943 subjects aged 18 to 63 years, sickness certified at a Primary Health Care Centre in Sweden from 1 January until 31 August 2004, were followed up for three years. Baseline information on sex, age, sick leave diagnosis, employment status, extent of sick leave, and sickness absence during the year before baseline was obtained, as was information on all compensated days of sick leave, disability pension and death during follow-up., Results: Slightly more than half the subjects were women, mean age was 39 years. Half of the study population returned to work within 14 days after baseline, and after three years only 15 subjects were still on sick leave. In multivariate proportional hazards regression analysis the extent of previous sick leave, age, being on part-time sick leave, and having a psychiatric, musculoskeletal, cardiovascular, nervous disease, digestive system, or injury or poisoning diagnosis decreased the return to work rate, while being employed increased it. Marital status, sex, being born in Sweden, citizenship, and annual salary had no influence. In logistic regression analyses across follow-up time these variables altogether explained 88-90% of return to work variation., Conclusions: Return to work was positively or negatively associated by a number of variables easily accessible in the GP's office. Track record data in the form of previous sick leave was the most influential variable.

Background: Fibromyalgia is characterized by widespread musculoskeletal pain and palpation tenderness. In addition to these classic symptoms, fibromyalgia patients tend to report a number of other complaints. What these other complaints are and how often they are reported as compared with related referents from the general population is not very well known. We therefore hypothesized that subjects with fibromyalgia report more of a wide range of symptoms as compared with referents of the same sex and age from the general population., Methods: 138 women with diagnosed fibromyalgia in primary health care and 401 referents from the general population matched to the cases by sex, age and residential area responded to a postal questionnaire where information on marital status, education, occupational status, income level, immigrant status, smoking habits physical activity, height and weight history and the prevalence of 42 defined symptoms was sought., Results: The cases had lower educational and income levels, were more often unemployed, on sick leave or on disability pension and were more often first generation immigrants than the referents. They were also heavier, shorter and more often had a history of excessive food intake and excessive weight loss. When these differences were taken into account, cases reported not only significantly more presumed fibromyalgia symptoms but also significantly more of general symptoms than the referents. The distribution of symptoms was similar in subjects with fibromyalgia and referents, indicating a generally higher symptom reporting level among the former., Conclusion: Subjects with fibromyalgia had a high prevalence of reported general symptoms than referents. Some of these differences may be a consequence of the disorder while others may reflect etiological processes.

Background: There are conflicting results on the role of cobalamin and folate for epidemiology and carcinogenesis in colorectal cancer patients and the need of supplementation for prevention of chemotherapy toxicity., Patients and Methods: Serum cobalamin, folate, and homocysteine were analysed before and during the treatment of 93 patients with advanced colorectal cancer (ACRC) with first-line chemotherapy treatment. This cohort was compared with a healthy control group of 224 individuals., Results: Patients with ACRC had similar cobalamin, folate, and homocysteine values as the healthy control group. There were no correlations between serum cobalamin, folate, and homocysteine values and objective response. There were no correlations to anaemia or other severe toxicity for cobalamin and homocysteine. A total of 12 patients had folate deficiency, and 10 of those suffered from severe toxicity (grade 3 or more). All patients had markedly increased folate values after 2 months of treatment. Folate and homocysteine did not predict patient outcome; however, patients with subclinically low cobalamin values (<300 pmol/L) had significant better overall survival and time to progression than patients with normal or high cobalamin values., Conclusion: Patients with ACRC seem to have fairly adequate cobalamin and folate status before and during chemotherapy treatment. This study indicates that ACRC patients receiving chemotherapy do not need supplementation with vitamin B12 and folate. A minor portion of the patients had folate deficiency, and most of those patients had severe toxicity. Patients with subclinically low cobalamin values had surprisingly better survival.

Objectives: To study the effects of vitamin B12 and folic acid treatment on haematological measures, reported symptoms and clinical findings over a 3-year period., Design: A longitudinal two-cohort study., Setting: A mid-Swedish community., Subjects: A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey (n = 266). Sixty-nine persons who had serum cobalamin <300 pmol L(-1) and serum methylmalonic acid (MMA) >/=0.37 micromol L(-1) or serum total homocysteine (tHcy) >/=15 micromol L(-1) and who had no vitamin B12 or folic acid substitution were selected for treatment., Main Outcome Measures: Serum cobalamin, folate, MMA and tHcy. Presence of gastrointestinal, neurological, psychiatric and some other symptoms, obtained by questionnaire, and Mini Mental State Examination (MMSE) score, vibration sense measurement and findings at a physical examination., Results: After combined vitamin B12-folic acid treatment, all persons normalized their serum tHcy and MMA levels and the effect remained after 3 years. The study design allowed separation of pure vitamin B12 deficiencies from folate and combined deficiencies. There was a tendency towards improvement of vibration sense, especially in the long nerve paths, and improvement of neurological symptoms and oral mucosa findings. No improvement was seen for other symptoms, reflex activity or MMSE score., Conclusions: Vitamin treatment of elderly people in the early phase of the condition may reverse damage that otherwise would become irreversible. If initiated, the treatment should be combined with vitamin B12 and folic acid.

Objectives: The early stages of tissue B12 or folate deficiency often cause diagnostic problems. In this report, the levels of serum cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy), and their relationships with clinical findings and reported symptoms in a representative random population sample are presented., Design: Cohort study., Setting: A general central Swedish population 70 years or older., Subjects and Methods: A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey. A total of 235 (85%) persons responded, of whom 161 had no interfering diseases or medication. Blood specimens for serum cobalamin, folate, MMA and tHcy analyses were drawn., Main Outcome Measures: Presence of anaemic, gastrointestinal, neurological and psychiatric symptoms, obtained by questionnaire, and vibration sense measurement and findings at a physical and Mini Mental State Examination., Results: Among a large number of symptoms and clinical findings that traditionally have been linked to vitamin B12 or folate tissue deficiency, only changes in the tongue mucosa and mouth angle stomatitis turned out to be significantly associated with abnormal serum tHcy and serum folate levels. There were no relationships to serum cobalamin and serum MMA., Conclusions: Changes in the oral mucosa were the only signs and symptoms found in this study, indicating that these may be the very early markers of metabolic defects. The traditional symptoms of vitamin deficiency may appear later in the course.

Objectives: The possibilities of detecting tissue cobalamin and folate deficiency are under debate. In this report the levels of serum cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy) and their interrelations in a representative random population sample are presented., Design: Cohort study., Setting: A general mid-Swedish population., Subjects: A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey. A total of 235 (85%) persons responded, out of whom 224 had no interfering diseases., Main Outcome Measures: Serum cobalamin, folate, MMA and tHcy., Results: The serum levels of cobalamin, folate, MMA and tHcy were all correlated to cobalamin and folic acid treatment. They were also correlated to the intake of multivitamin preparations. In addition, serum cobalamin was higher in untreated women than in men but not correlated to age. Serum folate was correlated neither to sex nor age. Serum tHcy and MMA were both directly correlated to age but MMA not to sex. MMA was inversely correlated to serum cobalamin but not to serum folate, whereas serum tHcy was inversely correlated to serum cobalamin, folate and creatinine. Neither serum cobalamin, folate, MMA nor tHcy had any significant correlation to haemoglobin, erythrocyte volume fraction (EVF) or mean red cell volume. Half of the study population had abnormal MMA or tHcy levels, suggesting a latent or overt tissue deficiency of cobalamin or folate., Conclusions: A substantial proportion of the elderly general population had signs of low tissue levels of cobalamin or folate. Amongst those who took multivitamin preparations this proportion was much lower.

Objectives: There is uncertainty amongst clinicians about the definitions of cobalamin and folate deficiency and therefore about the indications for treatment. In this report we present the results of systematic cobalamin and folic acid treatment based upon serum cobalamin, total homocysteine (tHcy) and methylmalonic acid (MMA) analyses in a population-based sample., Subjects: A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey (n = 266). Sixty-nine persons who had serum cobalamin < 300 pmol L-1 and serum MMA >/=0.37 micromol L-1 or serum tHcy >/=15 micromol L-1 and who had no cobalamin or folic acid substitution were selected for treatment., Interventions: Initially all 69 patients were given cobalamin orally or intramuscularly. Those who remained high in tHcy were in addition given folic acid treatment., Main Outcome Measures: Serum cobalamin, serum MMA and serum tHcy., Results: After 6 months of cobalamin treatment, serum MMA became normal in 13 out of 15 persons. Mean serum tHcy decreased but was normalized in only 15 out of 56 persons. After 3 months of folic acid treatment added to those who still had an abnormal serum tHcy, serum tHcy had normalized in all but one person., Conclusions: Cobalamin treatment normalizes increased MMA values and combined cobalamin and folic acid treatment normalizes tHcy, suggesting a pretreatment deficiency of tissue cobalamin and folate in spite of normal serum cobalamin and folate values in the majority of cases.