Statin therapy is associated with a slightly increased risk of developing diabetes mellitus and insulin resistance in patients without diabetes. Ezetimibe combined with statins may be considered for ...high-risk patients who do not achieve optimal low-density lipoprotein cholesterol lowering on statin monotherapy or who are statin intolerant. Changes in fasting serum glucose (FSG) levels during ezetimibe, ezetimibe/statin, and statin treatments were assessed using data pooled from clinical trials in hypercholesterolemic and heterozygous familial hypercholesterolemic patients, who were or were not receiving statin therapy. Study types included first-line trials in statin-naive/wash-out patients and second-line add-on and uptitration studies in patients on stable statin therapy. Similar analyses of FSG changes were performed separately for each study type in patients who were nondiabetic at baseline. Across all study types and treatments, mean FSG increases from baseline were small (0.5 to 3.7 mg/dl with ezetimibe/statin; 0.2 to 4.6 mg/dl with statins) and decreased over time; between-treatment differences (0.3 to 1.4 mg/dl) were nonsignificant for all comparisons. Proportions of patients with elevated FSG ≥126 mg/dl during therapy were low and similar for all treatments in the overall cohort (1.2% to 4.3%). Elevations were highest (3.3% to 25.7%) among patients with baseline factors characteristic of metabolic syndrome and prediabetes, including higher FSG, body mass index, and triglyceride levels, and numerically lower baseline high-density lipoprotein cholesterol; however, these factors were not related to FSG increases. Changes in low-density lipoprotein cholesterol, body mass index, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were not significantly correlated with FSG increases. In conclusion, statin therapy was associated with small FSG increases, and the addition of ezetimibe did not further increase FSG levels beyond those of statins when given to patients who are statin naive or those on statin therapy.
BACKGROUND:Randomized trials of supplementation with antioxidant mixtures during infertility treatment show no benefit on pregnancy or live birth rate. However, the roles of individual antioxidants ...are poorly understood. We examined the association of baseline intake of vitamins A, C, E, and carotenoids with outcomes of assisted reproductive technologies (ARTs).
METHODS:We followed 349 women undergoing a total of 588 ART cycles for infertility treatment at the Massachusetts General Hospital. We assessed antioxidant intakes from food and supplements before treatment using a validated food frequency questionnaire. We used generalized linear mixed models to account for multiple ART cycles per woman while adjusting for confounding.
RESULTS:Mean (SD) age and body mass index were 35.1 years (4.0 years) and 24.1 kg/m (4.3 kg/m), respectively. Total intake of vitamins A, C, and E was not associated with the probability of live birth. Women in the highest intake category of β-carotene from foods had a lower probability of live birth than women in the lowest intake quartile (50% vs. 22%; P trend = 0.03); for lutein and zeaxanthin, the probability for the highest intake group was 44% vs. 28% for the lowest. Intake of β-carotene from supplements and intakes of retinol and all other carotenoids were unrelated to live birth rates.
CONCLUSIONS:We found unexpected inverse associations of β-carotene intake from foods and of lutein and zeaxanthin intake with live birth rates. Within the observed intake ranges, total consumption of vitamins A, C, and E before starting infertility treatment with ART was not associated with live birth rates.
ObjectivesTo examine the patterns of fat mass gain in pregnancy and fat loss in the early postpartum period relative to women’s pre-pregnancy body mass index (BMI) and by adherence to Institute of ...Medicine’s gestational weight gain (GWG) recommendations.DesignProspective cohort study with three to four study visits.SettingThis study is a part of the prospective longitudinal birth cohort, ‘The Alberta Pregnancy Outcomes and Nutrition Study’ (APrON) that recruited pregnant women from the cities of Edmonton and Calgary in Alberta.Participants1820 pregnant women were recruited and followed through their pregnancy and at 3 months postpartum.Outcome measuresBody weight and skinfold thicknesses were measured during pregnancy and early postpartum in women. Body density was calculated from sum of skinfold thickness (biceps, triceps, subscapula and suprailiac), and total fat mass accretion during pregnancy was calculated using Van Raaij’s equations and at postpartum using Siri’s equation. Differences in total fat mass gain, fat mass loss and fat retention according to pre-pregnancy BMI categories and GWG categories were tested using two-way analysis of variance and post hoc comparisons.ResultsMost women (64%) had a normal pre-pregnancy BMI, and overall 49% women exceeded the GWG recommendations. Obese women gained significantly less total fat mass, had lower fat mass loss and had lower postpartum fat retention than normal-weight women (p<0.05). Women with excessive GWG gained higher total fat mass and had higher postpartum fat mass retention (p<0.03) than women who met the GWG recommendations. Total GWG was positively correlated with total fat gain (r=0.61, p<0.01) and total fat retention (r=0.31, p<0.05).ConclusionExcessive GWG is the significant risk factor for higher fat mass accretion during pregnancy and higher postpartum fat retention, irrespective of pre-pregnancy BMI.
Primary immunodeficiency disorders are a recognized public health problem worldwide. The prototype of these conditions is X-linked agammaglobulinemia (XLA) or Bruton's disease. XLA is caused by ...mutations in Bruton's tyrosine kinase gene (BTK), preventing B cell development and resulting in the almost total absence of serum immunoglobulins. The genetic profile and prevalence of XLA have not previously been studied in Eastern and Central European (ECE) countries. We studied the genetic and demographic features of XLA in Belarus, Croatia Hungary, Poland, Republic of Macedonia, Romania, Russia, Serbia, Slovenia, and Ukraine. We collected clinical, immunological, and genetic information for 122 patients from 109 families. The BTK gene was sequenced from the genomic DNA of patients with a high susceptibility to infection, almost no CD19(+) peripheral blood B cells, and low or undetectable levels of serum immunoglobulins M, G, and A, compatible with a clinical and immunological diagnosis of XLA. BTK sequence analysis revealed 98 different mutations, 46 of which are reported for the first time here. The mutations included single nucleotide changes in the coding exons (35 missense and 17 nonsense), 23 splicing defects, 13 small deletions, 7 large deletions, and 3 insertions. The mutations were scattered throughout the BTK gene and most frequently concerned the SH1 domain; no missense mutation was detected in the SH3 domain. The prevalence of XLA in ECE countries (total population 145,530,870) was found to be 1 per 1,399,000 individuals. This report provides the first comprehensive overview of the molecular genetic and demographic features of XLA in Eastern and Central Europe.
The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of ...children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA).
The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting.
One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups.
Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.
There is a significant deficiency of national health information for Indigenous peoples in Canada. This manuscript describes the Community Profile Survey (CPS), a community-based, national-level ...survey designed to identify and describe existing healthcare delivery, funding models, and diabetes specific infrastructure and programs in Indigenous communities.
The CPS was developed collaboratively through FORGE AHEAD and the First Nations and Inuit Health Branch of Health Canada. Regional and federal engagement and partnerships were built with Indigenous organizations to establish regionally-tailored distribution of the 8-page CPS to 440 First Nations communities. Results were collected (one survey per community) and reported in strata by region, with descriptive analyses performed on all variables. Results were shared with participating communities and regional/federal partners through tailored reports.
A total of 84 communities completed the survey (19% response rate). The majority of communities had a health centre/office to provide service to their patients with diabetes, with limited on-reserve hospitals for ambulatory or case-sensitive conditions. Few healthcare specialists were located on-site, with patients frequently travelling off-site (> 40 km) for diabetes-related complications. The majority of healthcare professionals on-site were Health Directors, Community Health Nurses, and Home Care Nurses. Many communities had a diabetes registry but few reported a diabetes surveillance system. Regional variation in healthcare services, diabetes programs, and funding models were noted, with most communities engaging in some type of innovative strategy to improve care for patients with diabetes.
The CPS is the first community-based, national-level survey of its kind in Canada. Although the response rate was low, the CPS was distributed and successfully administered across a broad range of First Nations communities, and future considerations would benefit from a governance structure and leadership that strengthens community engagement, and a longitudinal research approach to increase the representativeness of the data. This type of information is important for communities and regions to inform decision making (maintain successes, and identify areas for improvement), strengthen health service delivery and infrastructure, increase accessibility to healthcare personnel, and allocate funding and/or resources to build capacity and foster a proactive chronic disease prevention and management approach for Indigenous communities across Canada.
Current ClinicalTrial.gov protocol ID NCT02234973 . Registered: September 9, 2014.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Statin therapy is associated with a slightly increased risk of developing diabetes mellitus and insulin resistance in non-diabetic patients. Ezetimibe combined with statins may be considered ...for high-risk patients who do not achieve optimal low-density lipoprotein cholesterol (LDL-C)-lowering on statin monotherapy or who are statin-intolerant. Changes in fasting serum glucose (FSG) levels during ezetimibe, ezetimibe/statin and statin treatments were assessed using data pooled from clinical trials in hypercholesterolemic and heterozygous familial hypercholesterolemic patients, who were or were not receiving statin therapy. Study types included 1st -line trials in statin-naïve/wash-out patients and 2nd -line add-on and uptitration studies in patients on stable statin therapy. Similar analyses of FSG changes were performed separately for each study type in patients who were non-diabetic at baseline. Across all study types and treatments, mean FSG increases from baseline were small (0.5 to 3.7 mg/dL with ezetimibe/statin; 0.2 to 4.6 mg/dL with statins) and declined over time; between-treatment differences (0.3 to 1.4 mg/dL) were non-significant for all comparisons. Proportions of patients with elevated FSG ≥126 mg/dL during therapy were low and similar for all treatments in the overall cohort (1.2 to 4.3%). Elevations were highest (3.3 to 25.7%) among patients with baseline factors characteristic of metabolic syndrome and pre-diabetes, including higher FSG, body-mass index (BMI), and triglyceride levels, and numerically-lower baseline high-density lipoprotein cholesterol (HDL-C); however, these factors were not related to FSG increases. Changes in LDL-C, BMI, HDL-C, triglycerides, and ApoB were not significantly correlated with FSG increases. In conclusion, statin therapy was associated with small FSG increases and the addition of ezetimibe did not further increase FSG levels beyond those of statins when given to statin-naïve patients or those on statin therapy.
BACKGROUND Osteoarthritis (OA) of the hip and knee is a common cause of pain and disability in elderly patients. Joint replacement surgery can alleviate pain and restore function but is associated ...with risks and discomfort. METHODS We conducted a prospective cohort study to examine decision making and clinical outcomes for elderly patients (age ≥65 years) with severe OA of the hip or knee with symptoms inadequately controlled with conservative treatments. Osteoarthritis symptoms and functional status were assessed at baseline and at 12 months. Postoperative symptoms and function were assessed 6 weeks, 6 months, and 12 months after surgery. RESULTS For the 174 patients studied (mean age, 75 years; 76% were female, 17% were nonwhite, 69% had knee OA, and 31% had hip OA), the mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was 56 on a 100-point scale. During a 12-month follow-up, 29% had joint replacement surgery. Of patients who had surgery, no patients died, 17% had postoperative complications, and 38% had postoperative pain lasting more than 4 weeks. The median time to recovery of independence in walking was 12 days and to ability to perform household chores was 49 days, with similar times for patients 65 to 74 years old and those 75 years or older. At 12 months, WOMAC scores improved by 24 points in the patients who had surgery and 0.5 point in the patients who did not have surgery (P < .001); improvements were 19 and 0.3 points in patients 75 or older (P < .001). Among patients who did not have surgery, 45% reported that surgery was not offered as a potential treatment option. CONCLUSIONS Elderly patients who had hip or knee replacements for severe OA took several weeks to recover but experienced excellent long-term outcomes. Physicians often do not discuss joint replacement surgery with elderly patients who might benefit.Arch Intern Med. 2008;168(13):1430-1440-->
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