Persistent neuropathy among early-stage breast cancer survivors in a population-based cohort.

BACKGROUND: The prevalence of persistent peripheral neuropathy (PN) in early-stage breast cancer (ESBC) survivors is largely unknown. We explored the occurrence and risk factors of PN among long-term ESBC survivors treated with taxane chemotherapy. METHODS: A population-based cohort of 884 recurrence-free ESBC survivors diagnosed 2010-2015 in the South East Health Care region, Sweden and 1768 control women without prior cancer received a postal questionnaire that included the European Organisation for Research and Treatment of Cancer chemotherapy-induced peripheral neuropathy (CIPN20) items. Prevalence, relative risks (RRs) (Poisson regression) and risk factors (binomial regression) were calculated. Adjustments were made for confounding factors (e.g. age, body mass index, comorbidities). RESULTS: The response rate was 79% for survivors and 59% for controls. The median time post taxane was 3.6 years (1.5-7.3 years). The adjusted RR was highest (RR 1.8) for "tingling/numbness of toes/feet". Individual sensory symptoms occurred in 8.9-48.4% and motor symptoms in 7.2-61.3% of survivors; the most prevalent symptoms were "difficulty opening jar" and "cramps in feet". Paclitaxel, older age, overweight, diabetes mellitus, vibrating hand tools, autoimmune disease and smoking were independent risk factors. CONCLUSIONS: PN was more common among ESBC survivors than control women and many symptoms persisted over time. Risk factors should be considered when treatment decisions are made.

Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes.

BACKGROUND: A routine invasive (RI) strategy in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been associated with better outcome compared with a selective invasive (SI) strategy in men, but results in women have yielded disparate results. The aim of this study was to assess gender differences in long-term outcome with an SI compared with an RI strategy in NSTE ACS. METHODS: Individual patient data were obtained from the FRISC II trial, ICTUS trial, and RITA 3 trial for a collaborative meta-analysis. RESULTS: Men treated with an RI strategy had significantly lower rate of the primary outcome 5-year cardiovascular (CV) death/myocardial infarction (MI) compared with men treated with an SI strategy (15.6% vs 19.8%, P = .001); risk-adjusted hazards ratio (HR) 0.73 (95% CI 0.63-0.86). In contrast, there was little impact of an RI compared with an SI strategy on the primary outcome among women (16.5% vs 15.1%, P = .324); risk-adjusted HR 1.13 (95% CI 0.89-1.43), interaction P = .01. For the individual components of the primary outcome, a similar pattern was seen with lower rate of MI (adjusted HR 0.69, 95% CI 0.57-0.83) and CV death (adjusted HR 0.71, 95% CI 0.56-0.89) in men but without obvious difference in women in MI (adjusted HR 1.13, 95% CI 0.85-1.50) or CV death (adjusted HR 0.97, 95% CI 0.68-1.39). CONCLUSIONS: In this meta-analysis comparing an SI and RI strategy, benefit from an RI strategy during long-term follow-up was confirmed in men. Conversely, in women, there was no evidence of benefit.

Childhood sleep and obesity risk: A prospective cohort study of 10 000 Swedish children.

OBJECTIVES: To identify factors affecting early childhood sleep, and investigate the relationship between sleep and overweight/obesity in childhood. STUDY DESIGN: Data were collected using parental-completed questionnaires from N = 10.840 one-year-old children in the prospective ABIS-study (All Babies in Southeast Sweden), followed up until 8 years of age. Chi-squared test and Pearson Correlation were used to assess the relationship between covariates affecting the children's sleep. Subsequently, longitudinal mixed model analyses were used to predict the effect of different sleep dimensions (bedtime, sleep duration, sleep quality, and the number of awakenings) on BMI Z-scores. RESULTS: Children to parents born in Sweden, parents with higher education, non-single parents, non-smoking mothers during pregnancy, and children with fewer siblings, were more likely to have appropriate sleep habits at 1 year age. A greater number of awakenings and nocturnal feeds, and particularly later bedtime (ß = -0.544, p < 0.0001) were linked to shorter sleep duration. Sleep duration early in life was negatively associated with BMI Z-scores (adjusted effect estimate [95% CI]: ß = -0.09, [(-0.15) - (-0.03)], p = 0.005) later. In addition, higher birth weight, small size for gestational age, unhealthy food habits, children of mothers who smoked during pregnancy, and higher parental BMI resulted in higher BMI Z-scores. CONCLUSION: The child's BMI Z-score increases by 0.09 units with every hour shorter sleep duration, indicating that short sleep duration might increase the risk of overweight and obesity in children. Parental educational interventions advising appropriate sleeping patterns should be considered when implementing strategies to combat the development of childhood obesity.

Allergic disease in infants up to 2 years of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation in pregnancy and lactation.

We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life. Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of ω-3 PUFAs and the frequency and severity of infant allergic disease. 145 pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid (EPA) and 1.1 g docosahexaenoic acid (DHA) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Clinical examinations, skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed. No difference in the prevalence of allergic symptoms was found between the intervention groups. The cumulative incidence of IgE-associated disease was lower in the ω-3-supplemented group (6/54, 13%) compared with the placebo group (19/62, 30%, p=0.01). Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p=0.01-0.05) in a dose-dependent manner. Higher maternal and infant proportions of DHA and EPA were found if the infants presented none, when compared with multiple allergic symptoms, (p<0.05) regardless of sensitization. In summary, the ω-3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease, but the decrease in cumulative incidence of IgE-associated disease seen during the first year still remained until 2 yr of age. Furthermore, high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE-associated disease and a reduced severity of the allergic phenotype.

Antibiotic resistance among major pathogens compared to hospital treatment guidelines and antibiotic use in Nordic hospitals 2010-2018.

BACKGROUND: The Nordic countries have comparable nationwide antibiotic resistance surveillance systems and individual antibiotic stewardship programmes. The aim of this study was to assess antibiotic resistance among major pathogens in relation to practice guidelines for hospital antibiotic treatment and antibiotic use in Nordic countries 2010-2018. METHODS: Antibiotic resistance among invasive isolates from 2010-2018 and aggregated antibiotic use were obtained from the European Centre for Disease Prevention and Control. Hospital practice guidelines were obtained from national or regional guidelines. RESULTS: Antibiotic resistance levels among Escherichia coli and Klebsiella pneumoniae were similar in all Nordic countries in 2018 and low compared to the European mean. Guidelines for acute pyelonephritis varied; 2nd generation cephalosporin (Finland), 3rd generation cephalosporins (Sweden, Norway), ampicillin with an aminoglycoside or aminoglycoside monotherapy (Denmark, Iceland and Norway). Corresponding guidelines for sepsis of unknown origin were 2nd (Finland) or 3rd (Sweden, Norway, Iceland) generation cephalosporins, carbapenems, (Sweden) combinations of penicillin with an aminoglycoside (Norway, Denmark), or piperacillin-tazobactam (all Nordic countries). Methicillin-resistant Staphylococcus aureus rates were 0-2% and empirical treatment with anti-MRSA antibiotics was not recommended in any country. Rates of penicillin non-susceptibility among Streptococcus pneumoniae were low (<10%) except in Finland and Iceland (<15%), but benzylpenicillin was recommended for community-acquired pneumonia in all countries. CONCLUSION: Despite similar resistance rates among Enterobacteriaceae there were differences in practice guidelines for pyelonephritis and sepsis. National surveillance of antibiotic resistance can be used for comparison and optimization of guidelines and stewardship interventions to preserve the low levels of antibiotic resistance in Nordic countries.

Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy.

UNLABELLED: Maternal intake of omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) during pregnancy has decreased, possibly contributing to a current increased risk of childhood allergy. AIM: To describe the effects of maternal omega-3 long-chain PUFA supplementation during pregnancy and lactation on the incidence of allergic disease in infancy. METHODS: One hundred and forty-five pregnant women, affected by allergy themselves or having a husband or previous child with allergies, were included in a randomized placebo-controlled trial. Daily maternal supplementation with either 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo was given from the 25(th) gestational week to average 3-4 months of breastfeeding. Skin prick tests, detection of circulating specific immunoglobulin E (IgE) antibodies and clinical examinations of the infants were performed. RESULTS: The period prevalence of food allergy was lower in the omega-3 group (1/52, 2%) compared to the placebo group (10/65, 15%, p < 0.05) as well as the incidence of IgE-associated eczema (omega-3 group: 4/52, 8%; placebo group: 15/63, 24%, p < 0.05). CONCLUSION: Maternal omega-3 fatty acid supplementation may decrease the risk of food allergy and IgE-associated eczema during the first year of life in infants with a family history of allergic disease.

Impact of Age of Onset, Puberty, and Glycemic Control Followed From Diagnosis on Incidence of Retinopathy in Type 1 Diabetes: The VISS Study.

OBJECTIVE: To evaluate sex, age at diabetes onset, puberty, and HbA1c, with subjects followed from diabetes diagnosis and during different time periods, as risk factors for developing diabetic simplex and proliferative retinopathy. RESEARCH DESIGN AND METHODS: In a population-based observational study, HbA1c for 451 patients diagnosed with diabetes before 35 years of age during 1983-1987 in southeast Sweden was followed for up to 18-24 years from diagnosis. Long-term mean weighted HbA1c (wHbA1c) was calculated. Retinopathy was evaluated by fundus photography and analyzed in relation to wHbA1c levels. RESULTS: Lower wHbA1c, diabetes onset ≤5 years of age, and diabetes onset before puberty, but not sex, were associated with longer time to appearance of simplex retinopathy. Proliferative retinopathy was associated only with wHbA1c. The time to first appearance of any retinopathy decreased with increasing wHbA1c. Lower wHbA1c after ≤5 years' diabetes duration was associated with later onset of simplex retinopathy but not proliferative retinopathy. With time, most patients developed simplex retinopathy, except for those of the category wHbA1c ≤50 mmol/mol (6.7%), for which 20 of 36 patients were without any retinopathy at the end of the follow-up in contrast to none of 49 with wHbA1c >80 mmol/mol (9.5%). CONCLUSIONS: Onset at ≤5 years of age and lower wHbA1c the first 5 years after diagnosis are associated with longer duration before development of simplex retinopathy. There is a strong positive association between long-term mean HbA1c measured from diagnosis and up to 20 years and appearance of both simplex and proliferative retinopathy.

Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy.

The immunological composition of breast milk differs between mothers. The reasons for these differences and the consequences for the breast-fed infants are poorly understood. The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and eczema in the babies. Total IgA, secretory IgA (SIgA), TGF-beta1, TGF-beta2, IL-10, TNF, soluble CD14 (sCD14), and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri (n = 54) or placebo (n = 55) from gestational week 36 until delivery. Bacteriological analyses of L. reuteri were performed in faecal samples of the mothers. The infants were followed prospectively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and/or circulating allergen-specific IgE antibodies at 6, 12, and 24 months of age. Supplementation of L. reuteri during pregnancy was associated with low levels of TGF-beta2 and slightly increased levels of IL-10 in colostrum. For TGF-beta2, this association was most pronounced in mothers with detectable L. reuteri in faeces. Infants receiving breast milk with low levels of TGF-beta2 were less likely to become sensitized during their first 2 yr of life. A similar trend was observed for development of IgE-associated eczema. The levels of total IgA, SIgA, TGF-beta1, TNF, sCD14, and Na/K ratios in breast milk were not affected by the intake of L. reuteri. None of these parameters correlated with sensitization or development of eczema in the infant, except for high Na/K ratios that associated with increased risk of sensitization. Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF-beta2, and low levels of this cytokine are associated with less sensitization and possibly less IgE-associated eczema in breast-fed infants.

Testosterone correlated to symptoms of partial androgen deficiency in aging men (PADAM) in an elderly Swedish population.

OBJECTIVE: To investigate the prevalence of different symptoms of partial androgen deficiency in aging men (PADAM) and to correlate them with blood concentrations of testosterone and bioavailable testosterone. DESIGN: A total of 370 men, aged 55 to 75 years, were invited to one of three primary healthcare centers in Sweden. They were asked to complete a questionnaire regarding demographic data, medical history, mood status, medication, castration therapy and smoking, exercise and alcohol habits, as well as different symptoms of PADAM. The 10 questions from a previously used questionnaire (the ADAM questionnaire) were included. The men were offered blood tests for analyses of testosterone, follicle stimulating hormone, luteinizing hormone, steroid hormone-binding globulin, and albumin. From these test results, we calculated the bioavailable testosterone. RESULTS: Of the questionnaires sent out, 81.6% were returned and eligible for evaluation. Blood samples were obtained from 85.8% of men answering the questionnaire. Many of the symptoms, including five from the ADAM questionnaire, were more common in older age groups (P < 0.05). Three symptoms, deterioration in work performance, decreased strength and/or endurance, and bothersome hot flushes, were associated with low bioavailable testosterone and/or testosterone (P < 0.05). Testosterone and bioavailable testosterone did not differ between age groups, but bioavailable testosterone was higher in men with three or fewer symptoms on the ADAM questionnaire. CONCLUSIONS: Symptoms associated with PADAM often occur in an elderly population, but we could only find an association between three symptoms and blood testosterone concentrations, one being bothersome hot flushes. It is likely that these symptoms have a more complex background than only PADAM.

Alterations in high-density lipoprotein proteome and function associated with persistent organic pollutants.

There is a growing body of evidence that persistent organic pollutants (POPs) may increase the risk for cardiovascular disease (CVD), but the mechanisms remain unclear. High-density lipoprotein (HDL) acts protective against CVD by different processes, and we have earlier found that HDL from subjects with CVD contains higher levels of POPs than healthy controls. In the present study, we have expanded analyses on the same individuals living in a contaminated community and investigated the relationship between the HDL POP levels and protein composition/function. HDL from 17 subjects was isolated by ultracentrifugation. HDL protein composition, using nanoliquid chromatography tandem mass spectrometry, and antioxidant activity were analyzed. The associations of 16 POPs, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, with HDL proteins/functions were investigated by partial least square and multiple linear regression analysis. Proteomic analyses identified 118 HDL proteins, of which ten were significantly (p<0.05) and positively associated with the combined level of POPs or with highly chlorinated PCB congeners. Among these, cholesteryl ester transfer protein and phospholipid transfer protein, as well as the inflammatory marker serum amyloid A, were found. The serum paraoxonase/arylesterase 1 activity was inversely associated with POPs. Pathway analysis demonstrated that up-regulated proteins were associated with biological processes involving lipoprotein metabolism, while down-regulated proteins were associated with processes such as negative regulation of proteinases, acute phase response, platelet degranulation, and complement activation. These results indicate an association between POP levels, especially highly chlorinated PCBs, and HDL protein alterations that may result in a less functional particle. Further studies are needed to determine causality and the importance of other environmental factors. Nevertheless, this study provides a first insight into a possible link between exposure to POPs and risk of CVD.

Prevalence of symptoms possibly related to PADAM, in a Swedish population aged 55, 65 and 75 years.

OBJECTIVES: With age there is an average decline in the concentration of biologically active testosterone. It is still controversial if this leads to a clinically relevant deficit, "partial androgen deficiency of the ageing man" (PADAM). Our objective was to investigate the prevalence of a series of symptoms possibly associated with PADAM in an assumed normal-population of older men. METHODS: We developed a questionnaire including items about symptoms possibly associated with PADAM as well as background data covering demography, medical history, mood status, medication, castration therapy, as well as smoking, exercise and alcohol habits. The 10 items of the ADAM-questionnaire, designed to predict low bio-available T, were also included. The questionnaire was sent to all 1885 men 55, 65 or 75-years-old, living in Linköping, Sweden. RESULTS: We identified a number of symptoms that differed significantly (P < 0.01) between age groups, e.g., "increased abdominal circumference", "decrease in muscle strength and/or endurance", "decreased libido", "less strong erection" and "lack of energy". From factorial analysis we found that the symptoms co-varied in four different groups. CONCLUSION: The prevalence of a number of symptoms differed significantly between age groups, but we cannot infer that there is a causal connection between an average age-dependent decline in testosterone function and these symptoms. There are several other ways to interpret these results like the existence of concurrent somatic and/or mood disorders or ageing as such. For this purpose further studies including measurements of testosterone concentrations relating to the findings of this study have to be performed.

Hot flushes in a male population aged 55, 65, and 75 years, living in the community of Linköping, Sweden.

OBJECTIVE: Hot flushes are as common in castrated men as in menopausal women. We investigated whether hot flushes exist in a normal aging male population and to what extent. DESIGN: A questionnaire was sent to all men living in Linköping, Sweden, who were 55, 65, and 75 years old ( = 1,885). The questionnaire asked for demographic data, medical history, mood status, medication, castrational therapy, and smoking, exercise, and alcohol habits, among other items. We asked specifically for current hot flushes unrelated to exercise or a warm environment. RESULTS: Of the questionnaires received, 1,381 were eligible for evaluation; 33 were analyzed separately because these men had been castrated. Hot flushes of any frequency were reported by 33.1% of noncastrated men, 4.3% reported flushes at least a few times per week, and 1.3% reported daily flushes. Half of the men reporting flushes were also bothered by them, ie, almost every sixth man in total. We found a relation between occurrence of hot flushes and other symptoms thought to be related to low testosterone concentration, such as decreased muscle strength or endurance, decreased enjoyment of life, sadness or grumpiness, and lack of energy ( < 0.05). CONCLUSIONS: Hot flushes occur in one third of a population of noncastrated older men, approximately half of whom consider flushes as bothersome. Neither the mechanisms nor whether the symptoms would respond to testosterone supplementation is known. Androgen substitution to treat symptoms possibly related to a male climacteric is still controversial. Studies are needed to evaluate the needs for and the effects of androgen treatment on vasomotor symptoms.

Prevalence of symptoms in relation to androgen concentrations in women using estrogen plus progestogen and women using estrogen alone.

OBJECTIVE: Women using estrogen plus progestogen therapy sometimes report difficult to describe symptoms, eg, changes in libido, mood, and memory, that may be related to decreased androgens. To evaluate the prevalence of such symptoms and relate these symptoms to androgen levels in women using estrogen plus progestogen therapy, data from the Women's Health in the Lund Area Study were analyzed. DESIGN: A total of 2,816 women using estrogen plus progestogen therapy were asked to complete a questionnaire consisting of questions concerning sexual well-being and different aspects of quality of life. Serum concentrations of testosterone, androstendione, sex hormone-binding globulin, and estradiol were measured. RESULTS: A total of 2,048 questionnaires were eligible for evaluation. Almost 40% of the women reported decreased libido. Approximately 70% were satisfied with their current sex life. Eight percent reported that intercourse was unpleasant because of vaginal dryness. No evident associations were found between libido and serum hormone concentrations. The most positive effects of estrogen plus progestogen therapy concerning memory and urinary tract and vaginal complaints were found in women with the highest and/or moderate testosterone levels (P < 0.05). CONCLUSIONS: We found no strong association between symptoms related to sexual well-being or quality of life and androgen concentrations in this study. Estrogen plus progestogen therapy did not seem to affect symptoms that might be related to low levels of androgens in the group of climacteric women whom we studied.