Novartis (Sweden)

BACKGROUND: Recent breakthroughs regarding gastrointestinal stromal tumors (GIST) and their pathogenesis have redefined diagnostic criteria and have led to the development of molecularly targeted drug therapy. New treatment options mandate more accurate information regarding the incidence, prevalence, clinical behavior, and prognostic factors of GIST. METHODS: All patients (n=1460) who potentially had GIST diagnosed from 1983 to 2000 in western Sweden (population, 1.3-1.6 million) were reviewed, and 288 patients with primary GIST were identified. The incidence and prevalence of GIST were determined, and predictive prognostic factors, including current risk-group stratifications, were analyzed statistically. RESULTS: Ninety percent of GISTs were detected clinically due to symptoms (69%) or were incidental findings at surgery (21%); the remaining 10% of GISTs were found at autopsy. Forty-four percent of symptomatic, clinically detected GISTs were categorized as high risk (29%) or overtly malignant (15%), with tumor-related deaths occurring in 63% of patients and 83% of patients, respectively (estimated median survival, of 40 months and 16 months, respectively). Tumor-related deaths occurred in only 2 of 170 of patients (1.2%) with very-low-risk, low-risk, or intermediate-risk tumors. The annual incidence of GIST was 14.5 per million. The prevalence of all GIST risk groups was 129 per million (31 per million for the high-risk group and the overtly malignant group). CONCLUSIONS: GIST has been under recognized: Its incidence, prevalence, and clinical aggressiveness also have been underestimated. Currently existing risk-group stratification systems based on tumor size and mitotic rate delineate GIST patients who have a poor prognosis. Prognostication in patients with GIST can be refined using a proposed risk score based solely on tumor size and proliferative index.

BACKGROUND: Patients who undergo total hip replacement have a high risk of thromboembolic complications. Recombinant hirudin (desirudin), a specific inhibitor of thrombin, represents a new development in antithrombotic therapy. We compared the efficacy and safety of desirudin with those of a low-molecular-weight heparin (enoxaparin) for the prevention of thromboembolic complications in patients undergoing primary total hip replacement. METHODS: Both treatments, which were assigned in a randomized, double-blind manner, were started preoperatively: enoxaparin on the evening before surgery, and desirudin within 30 minutes before the start of surgery. The dose of desirudin was 15 mg subcutaneously twice daily, and the dose of enoxaparin was 40 mg subcutaneously once daily. The duration of treatment was 8 to 12 days. Deep-vein thrombosis was verified by bilateral venography performed at the end of the treatment period or earlier, if there were clinical signs of deep-vein thrombosis. RESULTS: At 31 centers in 10 European countries, 2079 eligible patients were randomly assigned to receive desirudin or enoxaparin. A total of 1587 patients were included in the primary analysis of efficacy. In the desirudin group, as compared with the enoxaparin group, there was a significantly lower rate of proximal deep-vein thrombosis (4.5 vs. 7.5 percent, P=0.01; relative reduction in risk, 40.3 percent) and a lower overall rate of deep-vein thrombosis (18.4 vs. 25.5 percent, P=0.001; relative reduction in risk, 28.0 percent). The safety profiles were similar in the two treatment groups. CONCLUSIONS: When administered 30 minutes before total hip replacement surgery, desirudin is more effective than enoxaparin in preventing deep-vein thrombosis.

Abstract Rationale Post hoc analyses suggest that blood eosinophils have potential as a predictive biomarker of inhaled corticosteroid efficacy in the management of chronic obstructive pulmonary disease (COPD). Objectives We prospectively investigated the value of blood eosinophils as a predictor of responsiveness to an inhaled corticosteroid/long-acting β2-agonist combination versus a long-acting β2-agonist/long-acting muscarinic antagonist combination for exacerbation prevention. Methods We conducted prespecified analyses of data from the FLAME (Effect of Indacaterol Glycopyronium vs Fluticasone Salmeterol on COPD Exacerbations) study, which compared once-daily long-acting β2-agonist/long-acting muscarinic antagonist indacaterol/glycopyrronium 110/50 μg with twice-daily long-acting β2-agonist/inhaled corticosteroid salmeterol/fluticasone combination 50/500 μg in patients with one or more exacerbations in the preceding year. Subsequent post hoc analyses were conducted to address further cutoffs and endpoints. Measurements and Main Results We compared treatment efficacy according to blood eosinophil percentage (<2% and ≥2%, <3% and ≥3%, and <5% and ≥5%) and absolute blood eosinophil count (<150 cells/μl, 150 to <300 cells/μl, and ≥300 cells/μl). Indacaterol/glycopyrronium was significantly superior to salmeterol/fluticasone for the prevention of exacerbations (all severities, or moderate or severe) in the <2%, ≥2%, <3%, <5%, and <150 cells/μl subgroups, and at no cutoff was salmeterol/fluticasone superior to indacaterol/glycopyrronium. Furthermore, the rate of moderate or severe exacerbations did not increase with increasing blood eosinophils. The incidence of pneumonia was higher in patients receiving salmeterol/fluticasone than indacaterol/glycopyrronium in both the <2% and ≥2% subgroups. Conclusions Our prospective analyses indicate that indacaterol/glycopyrronium provides superior or similar benefits over salmeterol/fluticasone regardless of blood eosinophil levels in patients with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01782326).

Abstract The asthmatic inflammatory response can be attenuated by corticosteroids and in part by β2-agonists. We investigated if these effects are accompanied by a downregulation in nuclear factor kappa B (NF- κ B), a transcription factor regulating many of the cytokine and adhesion molecule genes expressed in allergic inflammation. Bronchial biopsies were taken before and after 8 wk treatment with formoterol, budesonide, or placebo from atopic asthmatics. Biopsies were processed into glycol methacrylate and stained immunohistochemically for eosinophils (as an index of inflammation), activated and total NF- κ B, adhesion molecules, and cytokines. After budesonide treatment there was a significant decrease in the number of submucosal cells staining for total NF- κ B, granulocyte macrophage colony–stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF- α), accompanied by a significant decrease in mucosal eosinophils and expression of vascular cell adhesion molecule-1 (VCAM-1) in the endothelium and interleukin-8 (IL-8) in the epithelium. After formoterol treatment there was a significant decrease in eosinophils and the epithelial expression of activated NF- κ B, but these changes were not accompanied by reduced immunoreactivity for adhesion molecules or cytokines. We conclude that at least some of the therapeutic efficacy of inhaled corticosteroids is mediated through inhibition of NF- κ B-regulated gene expression, whereas the reduction in airway eosinophilia by long-acting β2-agonists probably operates through alternative pathways.

Electrochemical degradation using boron-doped diamond (BDD) electrodes has been proven to be a promising technique for the treatment of water contaminated with per- and poly-fluoroalkyl substances (PFAS). Various studies have demonstrated that the extent of PFAS degradation is influenced by the composition of samples and electrochemical conditions. This study evaluated the significance of several factors, such as the current density, initial concentration of PFAS, concentration of electrolyte, treatment time, and their interactions on the degradation of PFAS. A 24 factorial design was applied to determine the effects of the investigated factors on the degradation of perfluorooctanoic acid (PFOA) and generation of fluoride in spiked water. The best-performing conditions were then applied to the degradation of PFAS in wastewater samples. The results revealed that current density and time were the most important factors for PFOA degradation. In contrast, a high initial concentration of electrolyte had no significant impact on the degradation of PFOA, whereas it decreased the generation of F−. The experimental design model indicated that the treatment of spiked water under a current density higher than 14 mA cm−2 for 3–4 h could degrade PFOA with an efficiency of up to 100% and generate an F− fraction of approximately 40–50%. The observed high PFOA degradation and a low concentration of PFAS degradation products indicated that the mineralization of PFOA was effective. Under the obtained best conditions, the degradation of PFOA in wastewater samples was 44–70%. The degradation efficiency for other PFAS in these samples was 65–80% for perfluorooctane sulfonic acid (PFOS) and 42–52% for 6–2 fluorotelomer sulfonate (6-2 FTSA). The presence of high total organic carbon (TOC) and chloride contents was found to be an important factor affecting the efficiency of PFAS electrochemical degradation in wastewater samples. The current study indicates that the tested method can effectively degrade PFAS in both water and wastewater and suggests that increasing the treatment time is needed to account for the presence of other oxidizable matrices.

The possibility of using linkage disequilibrium mapping in natural plant populations was assessed. In studying linkage disequilibrium among 137 mapped AFLP markers in four populations of sea beet (Beta vulgaris ssp. maritima (L.) Arcang.) it was shown that tightly linked loci could be detected by screening for associations. It was hypothesized that the short distances spanned by linkage disequilibrium enable markers that are very tightly linked to a target gene to be identified. The hypothesis was tested by whole-genome screening of AFLP markers for association with the gene for the annual growth habit, the B gene, in a sample of 106 sea beets. Despite the dominant nature of AFLP, two markers showing significant linkage disequilibrium with the B gene were detected. The results indicate the potential use of linkage disequilibrium for gene mapping in natural plant populations.

BACKGROUND: Severe allergic asthma patients may not be controlled even with guideline recommended care, including inhaled corticosteroids, long-acting beta-2 agonists, theophylline, oral steroids and anti-leukotrienes. They experience exacerbations requiring intensive healthcare use and which may be fatal. Omalizumab, a new monoclonal antibody for use in IgE-mediated allergic diseases, reduces exacerbations and daily symptoms in this patient population. The aim of this study is to estimate the cost effectiveness of adding omalizumab to optimized standard therapy (ST) in patients with severe persistent IgE-mediated (allergic) asthma. METHODS: A Markov model comparing lifelong ST with a treatment period of omalizumab add-on therapy followed by ST, was developed based on efficacy data from the INNOVATE trial (28 weeks, N = 419) and Swedish life table and cost data. This model assumes that patients are at risk of having an exacerbation every 2 weeks and are at risk of dying from a clinically significant severe asthma exacerbation. Patients in a steady-state of having no exacerbations are defined to be in an 'optimized asthma control' state. Resource use data and utilities were obtained from INNOVATE and from a UK observational study. Costs from a societal perspective include estimates for drugs, routine care, exacerbations and costs in added years of life; benefits are expressed in QALYs. The response to omalizumab was evaluated after 16 weeks of trial, and non-responders stopped taking omalizumab for the remaining time. RESULTS: Total lifetime discounted costs and QALYs on ST were 52,702 euros and 11.60. Omalizumab add-on therapy cost an additional 42,754 euros for 0.76 additional QALYs, resulting in an incremental cost-effectiveness ratio of 56,091 euros. A probabilistic sensitivity analysis indicates that the 95% CI around the ICER is [31,328 euros; 120,552 euros]. One-way analyses indicate that the results are sensitive to the exacerbation-related mortality rate, the time horizon and the discount rates. CONCLUSIONS: Based on the model and the assumptions used, our results suggest that omalizumab provides cost offsets, improves quality of life and may have an attractive ICER in treating the severe allergic asthma population.

Abstract Background Chronic urticaria ( CU ) is characterized by the recurrence of itchy hives and/or angioedema for more than 6 weeks. AWARE (A World‐wide Antihistamine‐Refractory Chronic Urticaria Patient Evaluation) is a multinational study designed to document the real‐life treatment situation, burden of disease and clinical resource usage of H1‐antihistamine‐refractory CU patients. Objective To examine baseline data from Scandinavian AWARE patients. Methods AWARE is a prospective, non‐interventional, multinational, umbrella design study, which includes adults (≥18 years) with a confirmed CU diagnosis (>2 months) that is refractory to H1‐antihistamines. Baseline patient characteristics, disease activity (urticaria control test [ UCT ]), pharmacological treatment, comorbidities and healthcare usage were documented by the treating physician. Quality of life (QoL; dermatology life quality index [ DLQI ]; chronic urticaria quality of life questionnaire [ CU ‐Q 2 oL; Danish patients only]) and work productivity and activity impairment ( WPAI ) scores were also assessed. Results Overall, 158 CU patients from seven centres in Denmark ( n = 80), Norway ( n = 50) and Sweden ( n = 28) were included in this baseline analysis. Mean age and BMI were 40.3 years and 26.5 kg/m 2 , respectively. The majority of patients were female (69.6%), had uncontrolled CU (75.6%; UCT score <12) and had a ‘spontaneous’ component to their CU (61.4% CSU ; 20.3% both CSU and chronic inducible urticaria). Common comorbidities included asthma (19.6%), allergic rhinitis (16.5%) and food allergies (8.2%). Overall, 60.1% of patients reported using treatments for CU including non‐sedative H1‐antihistamines (40.5%), corticosteroids (19%), montelukast (14.6%) and omalizumab (8.2%). Pharmacological treatment rates increased to 96.2% during the baseline visit. On average, patient QoL was moderately affected (mean DLQI score 7.7) and healthcare resource usage was high. Conclusion Adult Scandinavian H1‐antihistamine‐refractory CU patients reported high rates of healthcare usage and QoL impairment. Rates of pharmacological treatment use were low before study enrolment but increased to almost 100% during the baseline visit.

AIMS: To analyse real-world treatment patterns of sacubitril/valsartan (sac/val) using data from a pharmacy database in Germany. METHODS AND RESULTS: A retrospective cohort study of 26 191 adult patients (aged ≥ 18 years) in the IMS® longitudinal prescriptions database in Germany who were dispensed sac/val from January 2016 to June 2017 was conducted. The analysis included sac/val dose titration assessed in the 6 months from first sac/val prescription; prescriptions of concomitant cardiovascular medications in the 6 months pre- and post-index and compliance and persistence during 12 months post-index. Two-thirds of patients were prescribed the lowest sac/val dose of 50 mg twice daily (b.i.d.) at index and up-titration during the first 6 months was attempted in 41% of these patients. Ten percent of patients prescribed 200 mg b.i.d. at index had to be stably down-titrated; among patients prescribed 50 or 100 mg b.i.d. at index that were up-titrated, > 80% remained on the higher dose. Overall, the mean daily diuretic dose decreased by 25% after initiation of sac/val. High compliance and persistence rates were observed across sac/val doses, increasing with higher sac/val dose at index. Prior dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker had only minor impact on first sac/val dose, compliance and persistence. CONCLUSIONS: Most patients prescribed sac/val are not initiated on the recommended dose nor up-titrated as recommended by the EU Summary of Product Characteristics. Initiation of sac/val was associated with high persistence and compliance and a dose reduction of diuretics. Barriers to up-titration must be explored.

Background: We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting. Patients and methods: Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52 PC centers from 2000 to 2014. Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed. Results: A total of 17,479 patients with COPD and 84,514 reference controls were analyzed. During 2013, direct costs were considerably higher among the COPD patient population (€13,179) versus the reference population (€2,716), largely due to hospital nights unrelated to COPD. Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights. Indirect costs (~€28,000 per patient) were the largest economic burden in COPD patients of working age during 2013. Conclusion: As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease.

The relation between the level of genetic variation and the rate of recombination per physical unit was investigated in sea beet (Beta vulgaris subsp. maritima). The rate of recombination per physical unit was estimated indirectly through marker density in an RFLP linkage map of sugar beet. From this map, we also selected RFLP markers covering two of the nine chromosomes in Beta. The markers were used to estimate the level of genetic variation in three populations of sea beet, two from Italy and one from England. Two estimates of genetic variation were employed, one based on the number of alleles in the sample and the other on heterozygosity. A statistically significant positive correlation was found between recombination rate and genetic variation. Several theoretical explanations for this are discussed, background selection being one. A correlation similar to this has been observed previously in Drosophila, one that was higher than what we obtained for Beta. This is consistent with various biological differences between the two species.

The Swedish Lucentis Quality Registry is a 12-month, open-label, observational, prospective, and retrospective study of ranibizumab administration for wet AMD. Visual acuity (VA) was measured with Snellen or ETDRS chart in 370 patients (66.8% women; age range 46-93 years). In total, a mean of 4.7 ± 1.6 injections per patient (range 1-10) was given to month 12. Mean VA score was 58.3 ± 12.2 letters before treatment, 63.3 ± 12.5 after 3 injections (Δ4.9 ± 10.1 letters from baseline), and 59.3 ± 16.2 at 12 months (Δ1.0 ± 13.6). VA score from baseline to month 12 was stable in 74.4% of patients, improved by 15 letters/3 lines or more in 14.7%, and decreased by ≥15 letters/3 lines in 10.9% of patients. With a mean of 4.7 ranibizumab injections per patient per year, mean VA was stabilised but not increased. To maintain the initial gain seen after the first three injections, an average of 1.8 ± 1.5 additional injections does not appear to be adequate.

Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD. Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000–2014) were collected from Swedish primary care patients with COPD. COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis). Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization. Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P <0.0001). Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83–1.96; P <0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54–1.69; P <0.0001). Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02–1.18; P =0.0095). Late diagnosis was also associated with higher direct costs than early diagnosis. Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis. The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD. Keywords: chronic obstructive pulmonary disease, diagnosis, Sweden, exacerbations, mortality

BACKGROUND: Xylometazoline is a nasal decongestant spray that constricts nasal blood vessels and increases nasal airflow, enabling patients with a blocked nose to breathe more easily. The purpose of this study was to characterize objectively and subjectively the decongestant and additional effects of xylometazoline in the common cold. METHODS: A double-blind, placebo-controlled, parallel group study was performed. Patients with a common cold (n = 61) were treated with xylometazoline 0.1% (n = 29) or placebo (saline solution; n = 32; 1 spray three times a day for up to 10 days). The primary objective was to determine the decongestant effect (nasal conductance); the secondary objectives were to determine the peak subjective effect (visual analog scale), duration of relief of nasal congestion, total and individual cold symptoms and general well-being (patients' daily diary), and adverse events (AEs). RESULTS: The decongestant effect of xylometazoline was significantly greater than placebo, as shown by the nasal conductance at 1 hour (384.23 versus 226.42 cm(3)/s; p <or= 0.0001) and peak subjective effect (VAS, 20.7 mm versus 31.5 mm; p = 0.0298). Nasal conductance was significantly superior for up to 10 hours (p = 0.0009) and there was a trend in favor of xylometazoline for up to 12 hours (not statistically significant). Xylometazoline significantly improved total and some individual common cold symptoms scores (p < 0.05), leading to significantly greater patient general evaluation and satisfaction with treatment (p < 0.05). Nineteen AEs were reported: 8 with xylometazoline (all mild-moderate) and 11 with placebo (1 severe). CONCLUSION: Xylometazoline is an effective and well-tolerated decongestant nasal spray that significantly relieved nasal congestion compared with placebo in the common cold and provided long-lasting relief with just 1 spray, helping patients to breathe more easily for a longer period of time.

BACKGROUND: To date, biological treatments have been assessed in subjects with a long-term history of psoriasis and previous failures to systemic and topical therapies. In rheumatoid arthritis and other immune-mediated inflammatory diseases, early intensive systemic treatment prolongs treatment-free remission. We hypothesize that, by treating patients with psoriasis early with an effective systemic therapy, we may be able to alter the clinical outcome and the natural course of the disease. The STEPIn study (NCT03020199) investigates early intervention with secukinumab versus narrow-band ultraviolet B (nb-UVB) phototherapy in subjects with new-onset psoriasis. OBJECTIVE: To determine whether early intervention with either nb-UVB treatment or secukinumab in subjects with new-onset plaque psoriasis might modify the natural course of the disease. METHODS: One hundred and sixty subjects aged 18-50 years with new-onset (≤12 months) moderate-to-severe plaque psoriasis and naïve to systemic treatment and phototherapy will be randomized to secukinumab 300 mg or nb-UVB. The Main Study has two treatment arms: Arm A1, subcutaneous secukinumab 300 mg at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter until and including Week 52; Arm B1, one/two cycles of nb-UVB for 12 weeks each (maximum 28-week break between cycles). After treatment discontinuation, patients will be followed up and monitored for disease activity up to Week 208. A Mechanistic Sub-study will assess immunological changes and pathogenic tissue-resident memory T cells in skin biopsies. CONCLUSIONS: STEPIn is the first study to investigate whether early intensive treatment in new-onset psoriasis can modify the long-term natural course of the disease and thus become a novel treatment strategy for patients with psoriasis.

BACKGROUND: Breast cancer is the most common cancer among women in Sweden. Whereas survival for the overall breast cancer population is well-documented, survival of patients with metastatic breast cancer (MBC) is harder to quantify due to the lack of reliable data on disease recurrence in national cancer registers. METHODS: This study used machine learning to classify the total MBC population in Sweden diagnosed between 2009 and 2016 using national registers, with the aim to estimate overall survival (OS). RESULTS: The total population consisted of 13,832 patients-2528 (18.3%) had de novo MBC whereas 11,304 (81.7%) were classed as having a recurrent MBC. Median OS for patients with MBC was found to be 29.8 months 95% confidence interval (CI) [28.9, 30.6]. Hormone-receptor (HR)-positive MBC had a median OS of 37.0 months 95% CI [35.9, 38.3] compared to 9.9 months 95% CI [9.1, 11.0] for patients with HR-negative MBC. CONCLUSION: This study covered the entire MBC population in Sweden during the study time and may serve as a baseline for assessing the effect of new treatment strategies in MBC introduced after the study period.

OBJECTIVE: The objective of this retrospective, observational study was to estimate the long-term impact of early treatment of multiple sclerosis (MS) on the risk of disability pension. METHODS: Our cohort comprised patients with MS in Sweden, identified in a nationwide disease-specific register (the Swedish Multiple Sclerosis Registry), who started treatment with a disease-modifying drug (DMD) between January 1, 2002, and December 31, 2012. We analyzed the association between time from onset of MS to treatment initiation and full-time disability pension using survival analysis. RESULTS: Our sample comprised 2477 patients. Unadjusted Kaplan-Meier failure functions showed that patients who started treatment within six months after onset had a lower risk of disability pension across follow-up compared with patients initiating therapy after 12 months. Outcomes from the univariate Cox proportional hazards model showed that time from onset to treatment initiation (in years) was significantly associated with disability pension (HR 1.03, p < 0.001). Outcomes from the multivariable Cox proportional hazards model showed that patients who started treatment within 6 months after onset had, on average, a 36% lower risk (HR 0.74, p = 0.010) of full-time disability pension during follow-up compared with patients starting treatment after 18 months when controlling for age, sex, marital status, university education, and prevalent comorbidities. CONCLUSIONS: We show that early treatment with DMDs of MS is associated with a significantly reduced risk of disability pension. Our findings highlight the potential long-term benefits of early treatment of MS and should be helpful to inform ongoing discussion on the optimum medical management of the disease.

PURPOSE: Family and friends play a pivotal role in caring for patients with heart failure (HF); however, evidence of the impact of caregiving is limited. The objectives of this study were to describe the burden of caregiving on informal caregivers of patients with chronic HF in China. MATERIALS AND METHODS: A cross-sectional survey of cardiologists, their patients with HF, and those patients' caregivers was conducted. Patient record forms were completed by 150 cardiologists for 10 consecutive patients. Caregivers of these patients were invited to complete a questionnaire. RESULTS: Overall, 458 caregivers completed a questionnaire (mean ± standard deviation age 60.1±10.6 years; 60% female; 77% spouses; 74% retired). Caregivers spent a mean of 24.5 (16.9) hours caregiving per week, and a third reported a reduction in their social activity, time for themselves, or time for family. Caregivers in employment took several days off work in the past 3 months owing to caregiving, sometimes resulting in reduced income. Up to 79% of caregivers reported an impact on their physical or emotional well-being, and 57% reported deterioration in their objective health status. Inconsistencies stemming from differences in the three-level five-dimension EuroQol questionnaire and HF Caregiver Questionnaire were observed for the impact of caregiving on caregivers' health-related quality of life. CONCLUSION: Assisting patients with HF is associated with caregiver burden. Addressing the needs of caregivers may help to promote their continued support and improve patient outcomes.

Abstract The inheritance of Cercospora leaf spot resistance in sugar beet was investigated by means of quantitative trait loci (QTL) analysis of a segregating population of 193 individuals, using 110 AFLP and 35 restriction fragment length polymorphism (RFLP) markers. Five QTL were found through composite interval mapping on linkage groups 1, 2, 3, and 9, respectively, two of which were linked on linkage group 3. The significance of these QTL was tested by permutation analysis The QTL had mostly additive, but also certain negative dominance effects; all the resistance alleles came from the Cercospora ‐resistant parent. Each quantitative trait locus accounted for 7‐18% of the phenotypic variation, leaving 37% of the variation unexplained. The results are discussed in relation to the potential use of marker‐assisted breeding for Cercospora leaf spot resistance in sugar beet.

PURPOSE: This study is designed to estimate the prevalence of epilepsy associated with TSC in Sweden and to describe treatment, morbidity, and mortality of TSC patients with epilepsy. METHODS: Register data for 2004-2014 was obtained from the National Board of Health and Welfare in Sweden. Patients with TSC were identified using ICD-10 codes. Epilepsy was identified using ICD-10 codes, interventions aimed to treat epilepsy, or prescriptions for antiepileptic drugs. RESULTS: The prevalence of TSC was 5.38 per 100 000 individuals. We identified 551 unique patients with TSC, of which 386 (70.1%) had epilepsy. The mean study period was 8.82 years. Antiepileptic drugs were dispensed to 97.9% of patients with epilepsy. The most prescribed antiepileptic drug was sodium valproate. Ketogenic diet was used in 6 (1.6%) patients, vagus nerve stimulation in 23 (6.0%) patients, and epilepsy surgery was performed in 25 (6.5%) patients. The mean number of outpatient visits per year was 4.70 (SD 4.17) and the mean number of inpatient days per year was 3.25 (SD 5.61). The mean number of outpatient visits per year with an ICD-10 code for epilepsy was 1.65 (SD 1.95) and the corresponding number of inpatient days was 2.06 (SD 4.50). A total of 30 patients with TSC and epilepsy died during the study period. CONCLUSIONS: The prevalence of epilepsy in this study was in the lower range of previously reported numbers, suggesting that epilepsy may be overestimated in non-population based studies. A substantial part of the healthcare utilization was directly related to epilepsy.