Establishment and representativeness of the Stockholm Sodium Cohort: A laboratorial and pharmacoepidemiologic database covering 1.6 million individuals in the Stockholm County.

OBJECTIVE: Hyponatremia is associated with considerable morbidity and mortality, but causal links have been difficult to establish. Here, we describe the establishment and representativeness of the Stockholm Sodium Cohort (SSC), designed to study etiologies and outcomes of hyponatremia. STUDY DESIGN AND SETTING: All residents of Stockholm County undertaking at least one serum sodium test between 2005-2018 were included in the SSC. Individual-level test results from over 100 laboratory parameters relevant to hyponatremia were collected and linked to data on demographics, socioeconomic status, healthcare contacts, diagnoses and dispensed prescription medications using national registers. RESULTS: A total of 1,632,249 individuals, corresponding to 64% of the population of Stockholm County, were included in the SSC. Coverage increased with advancing age, ranging from 32% in children and adolescents (≤18 years) to 97% among the oldest (≥80 years). The coverage of SSC included the vast majority of patients in Stockholm County diagnosed with diabetes mellitus (93%), myocardial infarction (98%), ischemic stroke (97%), cancer (85%), pneumonias requiring inpatient care (95%) and deaths (88%). CONCLUSION: SSC is the first cohort specifically designed to investigate sodium levels in a large, population-based setting. It includes a wide range of administrative health data and laboratory analyses. The coverage is high, particularly among elderly and individuals with comorbidities. Consequently, the cohort has a large potential for exploration of various aspects of hyponatremia.

Internet-based cognitive behavioral therapy for bulimic eating disorders in a clinical setting: Results from a randomized trial with one-year follow-up.

Background: Those who suffer from eating disorders often experience serious impairment in quality of life and the majority never receive treatment. Treatment availability may be increased by implementing methods that demand less resources and are more easy accessible such as internet-based treatments, but knowledge about their effects is still insufficient. The study evaluated effects of two types of internet-based cognitive behavioral therapy and a structured day patient program, the latter being a standard treatment at an eating disorder clinic at the time for the study. Methods: 150 participants with bulimic eating disorders randomized to two types of internet based treatments (one pure online treatment and one based on a self-help guide in book-format) or an intensive 16-week day patient program. The number of participants that started treatment was 120 of which 98 in internet treatment and 22 in the day program. Outcome assessments were carried out at baseline, post treatment, and at one-year follow-up. Results: All treatments were associated with significantly improved eating disorder pathology, self-image, and clinical impairment. Although the day program generally showed larger effects, only one significant difference found was in diagnostic remission post treatment; 51 % of the participant was in remission in internet treatment and 88 % in the day program. At one-year follow-up, participants in the internet treatments had continued to improve, whereas in the day patient program the effect sustained. Internet treatment had a 36 % drop out rate, there were no dropouts found in the day program. Conclusions: All treatments were comparable in effect at follow-up, suggesting that internet treatment is a conceivable alternative to standard treatment. Internet treatment in a book-based format was also equally effective as a pure online format. Internet delivered cognitive behavioral treatment forms can make important contributions to achieve increased access to treatment for patients with bulimic eating disorders. Future research and clinical implications for internet delivered treatments in eating disorder services are discussed. Clinical trial registration: ISRCTN registry https://www.isrctn.com/ISRCTN44999017. The study was registered retrospectively.

Fertilizer Type Affects Stable Isotope Ratios of Nitrogen in Human Blood Plasma─Results from Two-Year Controlled Agricultural Field Trials and a Randomized Crossover Dietary Intervention Study.

The stable nitrogen isotope ratio δ15N is used as a marker of dietary protein sources in blood. Crop fertilization strategies affect δ15N in plant foods. In a double-blinded randomized cross-over dietary intervention trial with 33 participants, we quantified the effect of fertilizer type (conventional: synthetic fertilizer and organic: animal or green manure) on δ15N in blood plasma. At study baseline, plasma δ15N was +9.34 ± 0.29‰ (mean ± standard deviation). After 12 days intervention with a diet based on crops fertilized with animal manure, plasma δ15N was shifted by +0.27 ± 0.04‰ (mean ± standard error) compared to synthetic fertilization and by +0.22 ± 0.04‰ compared to fertilization with green manure (both p < 0.0001). Accordingly, differences in the δ15N values between fertilizers are propagated to the blood plasma of human consumers. The results indicate a need to consider agricultural practices when using δ15N as a dietary biomarker.

Trapeziectomy with or without a tendon-based adjunct: a registry-based study of 650 thumbs.

This study aimed to assess the outcomes after simple trapeziectomy and trapeziectomy with ligament reconstruction and/or tendon interposition based on data in the Swedish national healthcare quality registry for hand surgery (HAKIR). Six-hundred and fifty thumbs were included, and 265 were assessed up to 12 months after operation. There was significant and clinically relevant improvement in patient-reported measures (pain on load, pain on motion without load, pain at rest, stiffness, weakness, and ability to perform activities of daily living and the Quick Disabilities of the Arm, Shoulder and Hand score) and objective measures (strength and thumb mobility) at 3 and 12 months for all procedures. The use of the abductor pollicis longus tendon had better improvement in some respects compared with the use of flexor carpi radialis or extensor carpi radialis tendons. However, overall, the use of a tendon adjuncts yielded no better outcomes than simple trapeziectomy.Level of evidence: III.

The effects of partial wrist denervation in wrist osteoarthritis: patient-reported outcomes and objective function.

This prospective longitudinal study aimed to analyse the effect of partial wrist denervation on patient-reported outcomes, quality of life and objective function in symptomatic wrist osteoarthritis during the first year after surgery. Sixty consecutive patients underwent an anterior and posterior interosseous neurectomy during 2018-2020. Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation, EuroQol-5D-3L, pain at rest and on load, and objective function were assessed preoperatively and 3, 6 and 12 months postoperatively. Generalized estimating equations were used to analyse the effect on the outcome variables. Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation and pain scores improved significantly postoperatively with no decline over time, but no patient reported outcome measure reached the minimal clinically important difference. Quality of life, strength and range of motion did not improve. We found no complications. Seventeen patients needed further surgery during the study period. More studies are needed to evaluate whether denervation is truly effective or not.Level of evidence: II.

Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes.

OBJECTIVE: To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes, and to assess the association between sepsis and all-cause mortality in such patients. RESEARCH DESIGN AND METHODS: We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between 1 January 2005 and 31 December 2015. The association between sepsis and death was examined using multivariable Cox regression analysis. RESULTS: Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07-1.24) for HbA1c <43 mmol/mol (6.1%), 0.93 (0.87-0.99) for HbA1c 53-62 mmol/mol (7.0-7.8%), 1.05 (0.97-1.13) for HbA1c 63-72 mmol/mol (7.9-8.7%), 1.14 (1.04-1.25) for HbA1c 73-82 mmol/mol (8.8-9.7%), and 1.52 (1.37-1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73-0.82) per SD; it increased thereafter (P for nonlinearity <0.001). As compared with patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03-4.30). CONCLUSIONS: In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a fourfold increased risk of death among those developing sepsis.

Associations between selective serotonin reuptake inhibitors and violent crime in adolescents, young, and older adults - a Swedish register-based study.

This study identified individuals ever dispensed a selective serotonin reuptake inhibitor (SSRI) aged 15-60 years during 2006-2013, using Swedish national registers. The outcome was violent crime conviction. The main statistical analyses assessed risks of violent crime during periods on compared to off SSRI treatment within individuals. Further analyses investigated risk over time in relation to treatment initiation and discontinuation. The study identified 785,337 individuals (64.2% female), experiencing 32,203 violent crimes in 5,707,293 person-years. Between-individual analyses found statistically significantly elevated Hazard Ratios (HRs) overall (HR = 1.10), and in 15-24 and 25-34 year-olds (HR = 1.19 and 1.16), but non-significant HRs in 35-44 and 45-60-year-olds (HR = 1.02 and 1.04). In within-individual analyses, where 2.6% of SSRI users were informative, hazards were elevated overall (HR = 1.26, 95% CI = 1.19, 1.34), and across age groups (HR of 1.35 [95% CI = 1.19, 1.54] in 25-34-year-olds to 1.15 [95% CI = 0.99, 1.33] in 35-44-year-olds). In the overall cohort, the within-individual HRs were significantly elevated throughout treatment (HRs of 1.24 to 1.35) and for up to 12 weeks post-discontinuation (HRs of 1.37 and 1.20). While questions on causality remain, these results indicate that there may be an increased risk of violent crime during SSRI treatment in a small group of individuals. It may persist throughout medicated periods, across age groups, and after treatment discontinuation. Further confirmation is needed from studies with different designs, and clinical focus should be on high-risk individuals, as a majority of SSRI-users (around 97% in our cohort) will not commit violent crimes.

Inclusion of Endogenous Plasma Dehydroepiandrosterone Sulfate and Mammographic Density in Risk Prediction Models for Breast Cancer.

BACKGROUND: Endogenous hormones and mammographic density are risk factors for breast cancer. Joint analyses of the two may improve the ability to identify high-risk women. METHODS: This study within the KARMA cohort included prediagnostic measures of plasma hormone levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and mammographic density in 629 cases and 1,223 controls, not using menopausal hormones. We evaluated the area under the receiver-operating curve (AUC) for risk of breast cancer by adding DHEA, DHEAS, and mammographic density to the Gail or Tyrer-Cuzick 5-year risk scores or the CAD2Y 2-year risk score. RESULTS: DHEAS and percentage density were independently and positively associated with breast cancer risk (P = 0.007 and P < 0.001, respectively) for postmenopausal, but not premenopausal, women. No significant association was seen for DHEA. In postmenopausal women, those in the highest tertiles of both DHEAS and density were at greatest risk of breast cancer (OR, 3.5; 95% confidence interval, 1.9-6.3) compared with the lowest tertiles. Adding DHEAS significantly improved the AUC for the Gail (+2.1 units, P = 0.008) and Tyrer-Cuzick (+1.3 units, P = 0.007) risk models. Adding DHEAS to the Gail and Tyrer-Cuzick models already including mammographic density further increased the AUC by 1.2 units (P = 0.006) and 0.4 units (P = 0.007), respectively, compared with only including density. CONCLUSIONS: DHEAS and mammographic density are independent risk factors for breast cancer and improve risk discrimination for postmenopausal breast cancer. IMPACT: Combining DHEAS and mammographic density could help identify women at high risk who may benefit from individualized breast cancer screening and/or preventive measures among postmenopausal women.

High-sensitivity C-reactive protein and the risk of chronic kidney disease progression or acute kidney injury in post-myocardial infarction patients.

BACKGROUND: Persistent, low-grade inflammation likely participates in the pathophysiology of both atherosclerosis and kidney disease. Although high-sensitivity C-reactive protein (hsCRP) predicts future cardiovascular risk in patients with chronic kidney disease (CKD), it is unknown whether hsCRP levels predict adverse renal outcomes in patients with cardiovascular disease. METHODS: We studied all myocardial infarction (MI) survivors undergoing hsCRP testing >30 days after their MI during routine health care in Stockholm, Sweden (2006-2011), with available information on estimated glomerular filtration rate (eGFR). HsCRP tests measured during hospitalization/emergency room visits, followed by antibiotics or indicative of acute illness, were excluded, together with patients with ongoing/recent cancer, chronic infections, or immunosuppression. Inflammation was defined over a 3-month baseline window. Study outcomes were CKD progression (composite of doubling plasma creatinine, renal replacement therapy, or renal death) and acute kidney injury (AKI, acute creatinine peaks according to Kidney Disease: Improving Global Outcomes criteria). Multivariable Cox regression was used to adjust for age, sex, eGFR, hemoglobin, time since MI, comorbidities, undertaken procedures, and medications. RESULTS: A total of 12,905 patients (62% men, mean age 73 years and 3 years since MI) were included, of whom 35% had an eGFR<60 mL/min/1.73 m2. The mean (SD) hsCRP was 3.0 (4.4) mg/L. Baseline hsCRP levels were increasingly higher across lower eGFR categories. During a median follow-up of 3.2 years, 1,019 CKD progressions and 1,481 AKI events were recorded. Patients with hsCRP ≥2 mg/L were at higher risk of both CKD progression (adjusted hazard ratio 1.42; 95% CI 1.21-1.66) and AKI (1.29; 1.13-1.47) compared to those with hsCRP <2 mg/L. This association persisted across single CKD severity stages and after further hsCRP categorization into 4 groups (≤1, 1-3, 3-10, >10 mg/L). Results were robust across subgroups of patients and after exclusion of events occurring during the first 6-12 months. CONCLUSIONS: In post-MI patients undergoing routine health care, elevated hsCRP was associated with subsequent risk of AKI and progression of CKD, irrespective of baseline kidney function.

Prevalence of Strongylus vulgaris in horses after ten years of prescription usage of anthelmintics in Sweden.

Strongylus vulgaris is considered the most pathogenic nematode parasite of the horse. Frequent deworming programs since the 1970s have reduced the prevalence of S. vulgaris to low levels, but to the price of widespread benzimidazole resistance in the small strongyles (cyathostominae) and ivermectin resistance especially in the equine roundworm Parascaris spp. To slow down the progression of anthelmintic resistance in Sweden, horse anthelmintics were made prescription only medicine in 2007 and selective therapy principles were introduced. This means that only individuals with high egg excretion or clinical signs of helminth infection were treated instead of blanket treatment of all horses on a farm. The aims of this study were to investigate the prevalence and risk factors associated with S. vulgaris infection in Sweden ten years after the introduction of a selective therapy regime. A total of 529 faecal samples from 106 farms were collected during March to June in 2016 and 2017. A web-based questionnaire was used to collect information about deworming routines. Strongyle faecal egg counts (FEC) were performed by McMaster and presence of S. vulgaris was demonstrated with a specific PCR on individual larval cultures. Results were analysed by mixed logistic (S. vulgaris prevalence) or linear (FEC) regression models, where farm was included as random factor. The overall prevalence of S. vulgaris at individual and farm levels was 28% and 61%, respectively. We observed a 2.9 increased odds risk of S. vulgaris infection on farms that based their treatment on strongyle FEC only as compared to farms that complemented strongyle FECs with larval cultures or dewormed regularly, 1-4 times per year, without prior diagnosis. We found no association between the prevalence of S. vulgaris and strongyle FEC level, horse age, geographical region or signs of colic. The prevalence of S. vulgaris was 25% in horses shedding ≤150 eggs per gram. Thus horses with low strongyle FECs that are left untreated could be an important source of S. vulgaris infection. This may be an important reason for the approximately three-fold increase in S. vulgaris prevalence since 1999 in Sweden. However, our combined results indicate that selective therapy based on a combination of strongyle FECs and larval cultivation was not associated with an increased risk of S. vulgaris infection. Still, S. vulgaris needs to be monitored continuously and should be taken into careful consideration when the treatment frequency is reduced.

Prevalence of Strongylus vulgaris in horses after ten years of prescription usage of anthelmintics in Sweden.

Strongylus vulgaris is considered the most pathogenic nematode parasite of the horse. Frequent deworming programs since the 1970s have reduced the prevalence of S. vulgaris to low levels, but to the price of widespread benzimidazole resistance in the small strongyles (cyathostominae) and ivermectin resistance especially in the equine roundworm Parascaris spp. To slow down the progression of anthelmintic resistance in Sweden, horse anthelmintics were made prescription only medicine in 2007 and selective therapy principles were introduced. This means that only individuals with high egg excretion or clinical signs of helminth infection were treated instead of blanket treatment of all horses on a farm. The aims of this study were to investigate the prevalence and risk factors associated with S. vulgaris infection in Sweden ten years after the introduction of a selective therapy regime. A total of 529 faecal samples from 106 farms were collected during March to June in 2016 and 2017. A web-based questionnaire was used to collect information about deworming routines. Strongyle faecal egg counts (FEC) were performed by McMaster and presence of S. vulgaris was demonstrated with a specific PCR on individual larval cultures. Results were analysed by mixed logistic (S. vulgaris prevalence) or linear (FEC) regression models, where farm was included as random factor. The overall prevalence of S. vulgaris at individual and farm levels was 28% and 61%, respectively. We observed a 2.9 increased odds risk of S. vulgaris infection on farms that based their treatment on strongyle FEC only as compared to farms that complemented strongyle FECs with larval cultures or dewormed regularly, 1-4 times per year, without prior diagnosis. We found no association between the prevalence of S. vulgaris and strongyle FEC level, horse age, geographical region or signs of colic. The prevalence of S. vulgaris was 25% in horses shedding ≤150 eggs per gram. Thus horses with low strongyle FECs that are left untreated could be an important source of S. vulgaris infection. This may be an important reason for the approximately three-fold increase in S. vulgaris prevalence since 1999 in Sweden. However, our combined results indicate that selective therapy based on a combination of strongyle FECs and larval cultivation was not associated with an increased risk of S. vulgaris infection. Still, S. vulgaris needs to be monitored continuously and should be taken into careful consideration when the treatment frequency is reduced.

Methodological aspects of serosurveillance in resource-poor settings.

Animal production is important for the agricultural economy in low-income countries, but is threatened by infectious diseases. Serosurveys are conducted for different reasons such as disease detection, risk factor studies, disease monitoring and establishing disease-free status. Most reports on such serosurveys include some discussion about methodological constraints but still, by necessity, rely on serological results for case definition. This study uses a cross-sectional serosurvey for foot-and-mouth disease (FMD), Rift Valley fever (RVF) and contagious bovine pleuropneumonia (CBPP) in cattle in three districts in Western Uganda to illustrate the limitations of this approach, addressing the questions of what flaws can be expected in sampling and diagnostics and how these influence the results. The target was to collect blood samples from 60 cattle herds per district. To reflect the recent infection history of the herd, young animals (two to five years) were prioritised. The farmers were interviewed about management, cattle trade, cattle health and vaccination. Commercial ELISAs were used for serological analyses: for CBPP the IDEXX CBPP Mycoplasma mycoides subspecies mycoides antibody test kit, for RVF the ID Screen Rift Valley Fever competitive ELISA, and for FMD the PrioCHECK FMDV NS. Apparent prevalence, true prevalence and associations with herd characteristics were assessed. The sampling plans could not be entirely fulfilled, nor the number of tests run in the laboratory. There were reactors to all three diseases with an apparent prevalence of approximately 30 per cent for CBPP, 6 per cent for RVF and 7 per cent for FMD. Calculation of true prevalence based on test sensitivity and specificity resulted in a slightly higher prevalence figure for CBPP and lower figures for RVF and FMD. The study illustrates the importance of considering diagnostic test performance when interpreting results from serosurveys, and the challenge of representative sampling and laboratory work in low-income countries.

Evaluation of Clonostachys rosea for Control of Plant-Parasitic Nematodes in Soil and in Roots of Carrot and Wheat.

Biological control is a promising approach to reduce plant diseases caused by nematodes. We tested the effect of the fungus Clonostachys rosea strain IK726 inoculation on nematode community composition in a naturally nematode infested soil in a pot experiment, and the effect of C. rosea on plant health. The numbers of plant-parasitic nematode genera extracted from soil and plant roots decreased by 40 to 73% when C. rosea was applied, while genera of nonparasitic nematodes were not affected. Soil inoculation of C. rosea increased fresh shoot weight and shoot length of wheat plants by 20 and 24%, respectively, while only shoot dry weight increased by 48% in carrots. Light microscopy of in vitro C. rosea-nematode interactions did not reveal evidence of direct parasitism. However, culture filtrates of C. rosea growing in potato dextrose broth, malt extract broth and synthetic nutrient broth exhibited toxicity toward nematodes and immobilized 57, 62, and 100% of the nematodes, respectively, within 48 h. This study demonstrates that C. rosea can control plant-parasitic nematodes and thereby improve plant growth. The most likely mechanism responsible for the antagonism is antibiosis through production of nematicidal compounds, rather than direct parasitism.