tbuckley/cabot-search huggingface dataset:
Iron Intake and the Risk of Type 2 Diabetes in Women
Authors: Swapnil Rajpathak, Jing Ma, JoAnn Manson, Walter C. Willett, Frank B. Hu
Journal: Diabetes Care (2006)

OBJECTIVE—Epidemiological studies suggest that high body iron stores are associated with insulin resistance and type 2 diabetes. The aim of this study was to evaluate the association between dietary intake of iron and the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS—We conducted a prospective cohort study within the Nurses’ Health Study. We followed 85,031 healthy women aged 34–59 years from 1980 to 2000. Dietary data were collected every 4 years, and data on medical history and lifestyle factors were updated biennially. RESULTS—During the 20 years of follow-up, we documented 4,599 incident cases of type 2 diabetes. We found no association between total, dietary, supplemental, or nonheme iron and the risk of type 2 diabetes. However, heme iron intake (derived from animal products) was positively associated with risk; relative risks (RRs) across increasing quintiles of cumulative intake were 1.00, 1.08 (95% CI 0.97–1.19), 1.20 (1.09–1.33), 1.27 (1.14–1.41), and 1.28 (1.14–1.45) (Ptrend &amp;lt; 0.0001) after controlling for age, BMI, and other nondietary and dietary risk factors. In addition, when we modeled heme iron in seven categories, the multivariate RR comparing women who consumed ≥2.25 mg/day and those with intake &amp;lt;0.75 mg/day was 1.52 (1.22–1.88). The association between heme iron and the risk of diabetes was significant in both overweight and lean women. CONCLUSIONS—This large cohort study suggests that higher heme iron intake is associated with a significantly increased risk of type 2 diabetes.
Cost and Utility Analysis of a Store-and-Forward Teledermatology Referral System
Authors: Santanu K. Datta, Erin M. Warshaw, Karen E. Edison, Kush Kapur, Lizy Thottapurathu, Thomas E. Moritz, Domenic J. Reda, John D. Whited
Journal: JAMA Dermatology (2015)

The costs and utility of teledermatology are important features of implementation. Such an analysis requires a description of the perspective of the entity that will bear the cost.To assess the costs and utility of a store-and-forward teledermatology referral process compared with a conventional referral process from the perspectives of the Department of Veterans Affairs (VA) and society.Three hundred ninety-one randomized participants were referred from remote sites of primary care to the dermatology services of 2 VA medical facilities for ambulatory skin conditions from December 2008 through June 2010, and follow-up was completed in March 2011. The time trade-off utility measures and costs were collected during a 9-month period among participants in a 2-site parallel group randomized clinical trial. The perspectives of the VA and society were evaluated. The multiple imputation procedure or weighted means were used for missing data elements. Data were analyzed from January to July 2014.Referrals were managed using store-and-forward teledermatology or a conventional text-based referral process.Total costs from the perspectives of the VA and society incurred during the 9-month follow-up were used to derive per-participant costs. Utility, using the time trade-off method, was the measure of effectiveness.From the VA perspective, the total cost for conventional referrals was $66 145 (minimum, $58 697; maximum, $71 635), or $338 (SD, $291) per participant (196 participants); the total cost for teledermatology referrals was $59 917 (mimimum, $51 794; maximum, $70 398), or $308 (SD, $298) per participant (195 participants). The $30 difference in per-participant cost was not statistically significant (95% CI, -$79 to $20). From the societal perspective, the total cost for conventional referrals was $106 194 (minimum, $98 746; maximum, $111 684), or $542 (SD, $403) per participant (196 participants); the total cost for teledermatology referrals was $89 523 (minimum, $81 400; maximum, $100 400) or $460 (SD, $428) per participant. This $82 difference in per-participant cost was statistically significant (95% CI, -$12 to -$152). From baseline to the 9-month follow-up, the time trade-off utility value improved by 0.02 in the conventional referral group and 0.03 in the teledermatology group. This difference was not statistically significant (P = .50).Compared with conventional referrals, store-and-forward teledermatology referrals were performed at a comparable cost (VA perspective) or at a lower cost (societal perspective) with no evidence of a difference in utility as measured by the time trade-off method.clinicaltrials.gov Identifier: NCT00488293.
Diagnosis of ventilator-associated pneumonia: nonroutine tools for routine practice
Authors: S. Ewig
Journal: European Respiratory Journal (1996)

During the past decade, remarkable efforts have beenmade to establish valid and reliable techniques for thediagnosis of ventilator-associated pneumonia (VAP). Oneof the most important findings consistently reported hasbeen the limited value of traditional clinical criteria forthe definition of pneumonia [1–3]. This has reinforcedthe need for the inclusion of additional diagnostic crite-ria derived from quantitative bacterial culture techniques.A histological diagnosis of pneumonia as independentreference for the calculation of diagnostic indices is onlyavailable in postmortem studies [4]. In fact, studies usingpostmortem histology as gold standard and fulfilling strictmethodological requirements of lung tissue processingsuggest that the diagnosis of VAP may be established ina realistic clinical setting with satisfactory accuracy byquantitative bacterial cultures [5–8]. It is, nevertheless,evident that postmortem studies select cases with ulti-mately fatal outcome, which do not reflect the wholespectrum of VAP. An irrefutable gold standard does notexist. As a result, clinical criteria remain crucial in rou-tine practice as well as in studies evaluating differentdiagnostic techniques in the diagnosis of VAP.It has been suggested that studies evaluating clinicaland radiological criteria in the diagnosis of VAP shouldinclude quantitative scoring, in order to reflect clinicaljudgement more accurately [9]. In support of this view,a clinical pulmonary infection score (CPIS), which atte-mpts to grade the likelihood of the presence of pneumo-nia, was shown to achieve high concordance rates withquantitative culture results [10]. Thus, a clinical estimate(and/or scoring) of the probability of the presence ofpneumonia remains a mainstay for the diagnosis of VAP.In light of the current controversy as to whether quan-titative culture techniques are useful in routine practice[9, 11], two issues should be addressed: firstly, to whatextent does aetiological diagnosis contribute indepen-dently to the diagnosis of VAP?; and secondly, can werely on colony counts for treatment decisions? P
Impact of Cardiac Resynchronization Therapy on Hospitalizations in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial
Authors: Anne M Gillis, Charles R. Kerr, François Philippon, Gary Newton, Mario Talajic, Michael Froeschl, Sandra Froeschl, Elizabeth Swiggum, Elizabeth Yetisir, George A. Wells, Anthony S. Tang
Journal: Circulation (2014)

Background— This study reports the impact of cardiac resynchronization therapy (CRT) on hospitalizations in patients randomized to implantable cardioverter-defibrillator (ICD) or ICD-CRT in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT). Methods and Results— Hospitalization rates and lengths of hospital stay were compared between the 2 groups. At the 18-month follow-up, the numbers of patients hospitalized for any cause were similar in the ICD (n=351, 38.8%) and ICD-CRT (n=331, 30.0%) groups. The number of patients hospitalized for heart failure was significantly lower in the ICD-CRT (n=101, 11.3%) compared with the ICD (n=141, 15.6%; P =0.003) group. The number of patients hospitalized for a device-related indication was similar in the ICD-CRT group (n=147, 16.4%) and ICD group (n=126, 13.9%; P =0.148). The total number of hospitalizations for any cause (n=1448 versus n=1553; P =0.042), any cardiovascular cause (n=667 versus n=790; P =0.017), and any heart failure cause (n=385 versus n=505; P &lt;0.0001) was significantly lower in ICD-CRT group compared with the ICD group, whereas the number of hospitalizations for device-related causes was significantly higher in the ICD-CRT group compared with the ICD group (246 versus 159; P &lt;0.001). Although the reduction in hospitalizations for heart failure in the CRT-ICD group was offset by an increased number of hospitalizations for device-related indications, the length of hospital stay for any cause was significantly shorter in the ICD-CRT group (8.83±13.30 days) compared with the ICD group (9.59±14.40 days; P =0.005). Conclusion— ICD-CRT therapy significantly reduces hospitalizations and total days in hospital in patients with New York Heart Association class II/III heart failure compared with ICD therapy despite increased admissions for device-related indications. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00251251.
Specialist Nurse-Led Intervention to Treat and Control Hypertension and Hyperlipidemia in Diabetes (SPLINT)
Authors: John P. New, James M. Mason, Nick Freemantle, Sue Teasdale, Louise M. Wong, Nick J. Bruce, John A. Burns, John M. Gibson
Journal: Diabetes Care (2003)

OBJECTIVE—To determine the effectiveness of specialist nurse-led clinics for hypertension and hyperlipidemia provided for diabetic patients receiving hospital-based care. RESEARCH DESIGN AND METHODS—This study was a randomized controlled implementation trial at Hope Hospital, Salford, U.K. The subjects consisted of 1,407 subjects presenting for annual review with raised blood pressure (≥140/80 mmHg), raised total cholesterol (≥5.0 mmol/l), or both. Individuals with diabetes were randomized to usual care or usual care with subsequent invitation to attend specialist nurse-led clinics. Nurses provided clinics for participants, with attendance every 4–6 weeks, until targets were achieved. Lifestyle advice and titration of drug therapies were provided according to the locally agreed upon guidelines. Patients with both conditions were eligible for enrollment in either or both clinics. At subsequent annual review, blood pressure and total cholesterol values were obtained from the Salford electronic diabetes register. Data relating to deaths were obtained from the national strategic tracing service. The primary outcome was the odds ratio of achieving targets in hypertension and hyperlipidemia, attributable to the specialist nurse-led intervention. RESULTS—Overall, specialist nurse-led clinics were associated with a significant improvement in patients achieving the target after 1 year (odds ratio [OR] 1.37 [95% CI 1.11–1.69], P = 0.003). This primary analysis revealed a borderline difference in effect between the two types of clinics (test for interaction between groups: P = 0.06). Secondary analysis, consistent with the prior beliefs of the health care professionals involved, suggested that targets were achieved more frequently in patients enrolled in the specialist nurse-led clinic for hyperlipidemia (OR 1.69 [1.25–2.29], P = 0.0007) than for hypertension (OR 1.14 [0.86–1.51], P = 0.37). Intervention (enrolled to either or both clinics) was associated with a reduction in all-cause mortality (OR 0.55 [0.32–0.92], P = 0.02). CONCLUSIONS—This study provides good evidence to support the use of specialist nurse-led clinics as an effective adjunct to hospital-based care of patients with diabetes. If the standards of care recommended in the National Service Framework for Diabetes are to be achieved, then such proven methods for delivering care must be adopted.
Efficacy of budesonide/formoterol maintenance and reliever therapy in mild asthma
Authors: Christine Jenkins, Göran Eriksson, Eric D. Bateman, Helen K. Reddel, Malcolm R. Sears, Malin Fagerås, Magnus B. Lindberg, Paul M. O'Byrne
Journal: European Respiratory Journal (2013)

RATIONALE:  The benefit of budesonide/formoterol maintenance and reliever therapy (BUD/FM MRT) is well documented in GINA Step 3–5 asthma patients. However, its role and efficacy in milder asthma patients needs further investigation.   METHODS:  A  post-hoc  analysis of three studies focused on patients with milder asthma, i.e. those previously treated with low-dose ICS (≤400 µg BUD equivalent [eq]/day) with baseline post-bronchodilator (BD) FEV 1  ≥80% predicted, comparing patients randomised to BUD/FM MRT or higher-dose BUD (HD-BUD) plus SABA as needed. Efficacy was assessed by exacerbation rate, FEV 1  and reliever use for all patients, and according to baseline reliever use (terbutaline Turbuhaler® 0.5 mg):  2 inh/day (Strata 1–3, respectively).   RESULTS:  889 patients (age 36.5 years; men 36.3%; post-BD FEV 1  94.3% predicted; BUD eq 357 µg/day; reliever use 0.59, 1.49, 3.24 inh/day [Strata 1–3]) were included in the analysis. Baseline data were similar for Strata 1–3. In the whole cohort, BUD/FM MRT significantly increased FEV 1  (110 mL) and reduced exacerbation rate (RR 0.62) and reliever use (–0.47 inh/day) vs HD-BUD (p all  1  (100, 90, 130 mL; p all    CONCLUSIONS:  In a milder asthma cohort, BUD/FM MRT improved exacerbations, lung function and reliever use more than HD-BUD plus SABA. The treatment differences were similar for lung function and exacerbations across the range of baseline reliever use, including    FUNDING:  AstraZeneca.
FAILURE OF SECOND-LOOK LAPAROTOMY TO INFLUENCE SURVIVAL IN EPITHELIAL OVARIAN CANCER
Authors: David Luesley, George Blackledge, Krystyna Kelly, Tom Wade-Evans, John Fielding, Frank Lawton, Christopher Hilton, Terence Rollason, Joseph Jordan, Tal Latief, K.K. Chan
Journal: The Lancet (1988)
Prevention of Fatal Arrhythmias in High-Risk Subjects by Fish Oil n-3 Fatty Acid Intake
Authors: Alexander Leaf, Christine M. Albert, Mark Josephson, David Steinhaus, Jeffrey Kluger, Jing X. Kang, Benjamin Cox, Hui Zhang, David Schoenfeld
Journal: Circulation (2005)

Background— The long-chain n-3 fatty acids in fish have been demonstrated to have antiarrhythmic properties in experimental models and to prevent sudden cardiac death in a randomized trial of post–myocardial infarction patients. Therefore, we hypothesized that these n-3 fatty acids might prevent potentially fatal ventricular arrhythmias in high-risk patients. Methods and Results— Four hundred two patients with implanted cardioverter/defibrillators (ICDs) were randomly assigned to double-blind treatment with either a fish oil or an olive oil daily supplement for 12 months. The primary end point, time to first ICD event for ventricular tachycardia or fibrillation (VT or VF) confirmed by stored electrograms or death from any cause, was analyzed by intention to treat. Secondary analyses were performed for “probable” ventricular arrhythmias, “on-treatment” analyses for all subjects who had taken any of their oil supplements, and “on-treatment” analyses only of those subjects who were on treatment for at least 11 months. Compliance with double-blind treatment was similar in the 2 groups; however, the noncompliance rate was high (35% of all enrollees). In the primary analysis, assignment to treatment with the fish oil supplement showed a trend toward a prolonged time to the first ICD event (VT or VF) or of death from any cause (risk reduction of 28%; P =0.057). When therapies for probable episodes of VT or VF were included, the risk reduction became significant at 31%; P =0.033. For those who stayed on protocol for at least 11 months, the antiarrhythmic benefit of fish oil was improved for those with confirmed events (risk reduction of 38%; P =0.034). Conclusions— Although significance was not achieved for the primary end point, this study provides evidence that for individuals at high risk of fatal ventricular arrhythmias, regular daily ingestion of fish oil fatty acids may significantly reduce potentially fatal ventricular arrhythmias.
Mesenchymal Stem Cells and Tooth Engineering
Authors: Li Peng, Ling Ye, Xue‐dong Zhou
Journal: International Journal of Oral Science (2009)

Tooth loss compromises human oral health. Although several prosthetic methods, such as artificial denture and dental implants, are clinical therapies to tooth loss problems, they are thought to have safety and usage time issues. Recently, tooth tissue engineering has attracted more and more attention. Stem cell based tissue engineering is thought to be a promising way to replace the missing tooth. Mesenchymal stem cells (MSCs) are multipotent stem cells which can differentiate into a variety of cell types. The potential MSCs for tooth regeneration mainly include stem cells from human exfoliated deciduous teeth (SHEDs), adult dental pulp stem cells (DPSCs), stem cells from the apical part of the papilla (SCAPs), stem cells from the dental follicle (DFSCs), periodontal ligament stem cells (PDLSCs) and bone marrow derived mesenchymal stem cells (BMSCs). This review outlines the recent progress in the mesenchymal stem cells used in tooth regeneration.
Blockade of Hsp20 Phosphorylation Exacerbates Cardiac Ischemia/Reperfusion Injury by Suppressed Autophagy and Increased Cell Death
Authors: Jiang Qian, Xiaoping Ren, Xiaohong Wang, Pengyuan Zhang, W. Keith Jones, Jeffery D. Molkentin, Guo-Chang Fan, Evangelia G. Kranias
Journal: Circulation Research (2009)

Rationale: The levels of a small heat shock protein (Hsp)20 and its phosphorylation are increased on ischemic insults, and overexpression of Hsp20 protects the heart against ischemia/reperfusion injury. However, the mechanism underlying cardioprotection of Hsp20 and especially the role of its phosphorylation in regulating ischemia/reperfusion–induced autophagy, apoptosis, and necrosis remain to be clarified. Objective: Herein, we generated a cardiac-specific overexpression model, carrying nonphosphorylatable Hsp20, where serine 16 was substituted with alanine (Hsp20 S16A ). By subjecting this model to ischemia/reperfusion, we addressed whether: (1) the cardioprotective effects of Hsp20 are associated with serine 16 phosphorylation; (2) blockade of Hsp20 phosphorylation influences the balance between autophagy and cell death; and (3) the aggregation pattern of Hsp20 is altered by its phosphorylation. Methods and Results: Our results demonstrated that Hsp20 S16A hearts were more sensitive to ischemia/reperfusion injury, evidenced by lower recovery of contractile function and increased necrosis and apoptosis, compared with non-TG hearts. Interestingly, autophagy was activated in non-TG hearts but significantly inhibited in Hsp20 S16A hearts following ischemia/reperfusion. Accordingly, pretreatment of Hsp20 S16A hearts with rapamycin, an activator of autophagy, resulted in improvement of functional recovery, compared with saline-treated Hsp20 S16A hearts. Furthermore, on ischemia/reperfusion, the oligomerization pattern of Hsp20 appeared to shift to higher aggregates in Hsp20 S16A hearts. Conclusions: Collectively, these data indicate that blockade of Ser16-Hsp20 phosphorylation attenuates the cardioprotective effects of Hsp20 against ischemia/reperfusion injury, which may be attributable to suppressed autophagy and increased cell death. Therefore, phosphorylation of Hsp20 at serine 16 may represent a potential therapeutic target in ischemic heart disease.
Histological changes in small bowel mucosa induced by gliadin sensitive T lymphocytes can be blocked by anti-interferon gamma antibody.
Authors: R T Przemioslo, K E Lundin, L M Sollid, J Nelufer, P J Ciclitira
Journal: Gut (1995)

The isolation of gliadin specific HLA-DQ2 restricted T lymphocyte clones from the intestinal mucosa of patients with coeliac disease supports a role for cell mediated immunity in the pathogenesis of this condition. Whether supernatants from immune activated T cell clones could produce histological damage to duodenal mucosa in vitro was studied. Biopsy specimens were obtained from 18 patients without coeliac disease or any other demonstrable abnormality. The tissue was maintained in organ culture for 24 hours with organ culture medium alone, with supernatant from gliadin sensitive T cell clones that had (B) or had not (A) been stimulated with gluten, and compared with the effects caused by the addition of interferon gamma to the organ culture medium. Both the (B) supernatants (1:100) and interferon gamma (100 IU/ml) produced a significant reduction in the enterocyte height (21:5 (3.4) microns and 21.0 (3.2) microns respectively, each p < 0.001) compared with specimens grown in organ culture medium alone (27.3 (2.8) microns). The toxic effects of (B) supernatants could be blocked by pre-incubating them with anti-interferon gamma antibody. These findings support the role of gliadin sensitive T lymphocytes in the immune pathogenesis of coeliac disease and their secretion of interferon gamma may cause the damage to enterocytes observed in this condition.
SNPs and Haplotypes in <i>DPYD</i> and Outcome of Capecitabine–Letter
Authors: Frans L. Opdam, Jesse J. Swen, Judith A.M. Wessels, Hans Gelderblom
Journal: Clinical Cancer Research (2011)

In their recently published article, Deenen and colleagues (1) have shown a strong association between single-nucleotide polymorphisms in DPYD and toxicity of capecitabine in patients with metastatic colorectal cancer treated with capecitabine-based combination chemotherapy. In particular, all patients who were heterozygous for the IVS14+1G>A polymorphism developed “any grade 3–4” toxicity, although this did not significantly differ from the grade 3–4 toxicity incidence rate of 85% in wild-type patients. The authors found a positive predictive value of 71% for experiencing grade 3–4 diarrhea in carriers of the IVS14+1G>A polymorphism and plea for routine screening for this genetic variant before start of therapy.However, in their analysis, the IVS14+1G>A variant was prevalent in only 1% of the patients in the control group, consistent with an estimated prevalence of 1% to 2% by others (2,3). Therefore, although there is a strong association between the IVS14+1G>A variant and toxicity, upfront genotyping for this polymorphism followed by dose reduction to prevent or reduce grade 3–4 toxicity might not be cost-effective.For example, the authors found that 71% of heterozygous carriers of the IVS14+1G>A variant against 24% of the wild-type patients experienced grade 3–4 diarrhea (Table 3 in ref. 1). Consistent with a higher level of toxicity in the variant allele group, an average dose reduction of up to 50% was applied in the group with the IVS14+1G>A polymorphism compared with 10% in wild-type patients (1). Assuming that a 50% dose reduction of capecitabine would reduce this risk from 71% to a “baseline (wild-type)” risk of 24% in the heterozygous variant carriers (Table 3 in ref. 1), one could calculate that by upfront genotyping followed by dose reduction, the incidence of grade 3–4 diarrhea in the overall treated population would be reduced from 24.47% to 24.00% (see the following table). Therefore, the number needed to genotype (NNTG), in this case, the number of patients needed to genotype to prevent one case of grade 3–4 diarrhea, would be 213 (1/0.0047). With an estimated cost of €120.00 for “custom service” genotyping a single polymorphism (4), it would cost €25,560 (213 × 120) to prevent one case of grade 3–4 diarrhea.However, with an estimated cost of €20.00 per single polymorphism for an “in-house” validated test (4), costs would be reduced to €4,260 (213 × 20), which could be cost-effective. Therefore, we agree with the authors that future studies are warranted to resolve whether upfront genotyping followed by dose reduction of capecitabine in colorectal cancer patients is cost-effective. However, from a clinical point of view, considering current availability and application of this technique with the possibility to protect patients from serious harm, costs aspects might be less important.See the Response, p. 5835No potential conflicts of interest were disclosed.