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Background Interval cancer rates can be used to evaluate whether screening with digital breast tomosynthesis (DBT) contributes to a screening benefit. Purpose To compare interval cancer rates and tumor characteristics in DBT screening to those in a contemporary population screened with digital mammography (DM). Materials and Methods The prospective population-based Malmö Breast Tomosynthesis Screening Trial (MBTST) was designed to compare one-view DBT to two-view DM in breast cancer detection. The interval cancer rates and cancer characteristics in the MBTST were compared with an age-matched contemporary control group, screened with two-view DM at the same center. Conditional logistic regression was used for data analysis. Results There were 14 848 women who were screened with DBT and DM in the MBTST between January 2010 and February 2015. The trial women were matched with two women of the same age and screening occasion at DM screening during the same period. Matches for 13 369 trial women (mean age, 56 years ± 10 [standard deviation]) were found with 26 738 women in the control group (mean age, 56 years ± 10). The interval cancer rate in the MBTST was 1.6 per 1000 screened women (21 of 13 369; 95% CI: 1.0, 2.4) compared with 2.8 per 1000 screened women in the control group (76 of 26 738 [95% CI: 2.2, 3.6]; conditional odds ratio, 0.6 [95% CI: 0.3, 0.9]

Objective This study aimed to compare the effects of two aerobic exercise programs of different intensities on energy expenditure. Methods This was a single‐center randomized controlled trial of patients with severe obesity allocated to a 24‐week moderate‐intensity continuous training (MICT) program or a combined MICT with high‐intensity interval training (HIIT/MICT) program. The primary outcome was energy expenditure during exercise (EEDE). Secondary outcomes included resting metabolic rate, cardiorespiratory fitness, and body composition. Results A total of 82 (56% females) patients were screened, and 71 (55% females) patients were allocated to HIIT/MICT (n = 37) or MICT (n = 34). Per‐protocol analysis showed that EEDE increased by 10% (95% CI: 3%‐17%) in the HIIT/MICT group (n = 16) and 7.5% (95% CI: 4%‐10%) in the MICT group (n = 24), with no differences between groups. In the 8‐ to 16‐ week per‐protocol analysis, the HIIT/MICT group had a significantly larger increase in EEDE compared with the MICT group. Resting metabolic rate remained unchanged in both groups. HIIT/MICT and MICT were associated with significant weight loss of 5 kg and 2 kg, respectively. Conclusions Patients completing a 24‐week combined HIIT/MICT program did not achieve a higher EEDE compared with those who completed a 24‐week MICT program. The HIIT/MICT group experienced, on average, a 3‐kg‐larger weight loss than the MICT group. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

It remains uncertain whether pharmacokinetic changes following Roux‐en‐Y gastric bypass (RYGB) can be attributed to surgery‐induced gastrointestinal alterations per se and/or the subsequent weight loss. The aim was to compare short‐ and long‐term effects of RYGB and calorie restriction on CYP3A‐activity, and cross‐sectionally compare CYP3A‐activity with normal weight to overweight controls using midazolam as probe drug. This three‐armed controlled trial included patients with severe obesity preparing for RYGB (n = 41) or diet‐induced (n = 41) weight‐loss, and controls (n = 18). Both weight‐loss groups underwent a 3‐week low‐energy‐diet (

Mammographic tumour appearance may provide prognostic useful information. For example, spiculation indicates invasiveness, but also better survival compared to tumours with other appearances. We aimed to study the relationship between mammographic tumour appearance and established clinicopathological factors, including surrogate molecular breast cancer subtypes, in the large Malmö Diet and Cancer Study. A total of 1116 women with invasive breast cancer, diagnosed between 1991 and 2014, were included. Mammographic tumour appearance in relation to status for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2, histological grade, Ki67 and molecular subtype was analysed using various regression models. All models were adjusted for relevant confounders, including breast density, which can affect mammographic appearance. The results consistently showed that spiculated tumours are indicative of favourable characteristics, as they are more likely to be ER and PR positive, and more often exhibit lower histological grade and lower Ki67 expression. Furthermore, spiculated tumours tend to be of luminal A-like subtype, which is associated with a good prognosis. The establishment of associations between mammographic tumour appearance and clinico­pathological factors may aid in characterizing breast cancer at an earlier stage. This could contribute to more individualized breast cancer treatment in the future.

Digital breast tomosynthesis is an advancement of the mammographic technique, with the potential to increase detection of lesions during breast cancer screening. The main aim of the Malmö Breast Tomosynthesis Screening Trial (MBTST) was to investigate the accuracy of one-view digital breast tomosynthesis in population screening compared with standard two-view digital mammography.In this prospective, population-based screening study, of women aged 40-74 years invited to attend national breast cancer screening at Skåne University Hospital, Malmö, Sweden, a random sample was asked to participate in the trial (every third woman who was invited to attend regular screening was invited to participate). Participants had to be able to speak English or Swedish and were excluded from the study if they were pregnant. Participants underwent screening with two-view digital mammography (ie, craniocaudal and mediolateral oblique views) followed by one-view digital breast tomosynthesis with reduced compression in the mediolateral oblique view (with a wide tomosynthesis angle of 50°) at one screening visit. Images were read with masked double reading and scoring by two separate reading groups, one for each method, made up of seven radiologists. Any cancer detected with a malignancy probability score of three or higher by any reader in either group was discussed in a consensus meeting of at least two readers, from which the decision of whether or not to recall the woman for further investigation was made. The primary outcome measures were sensitivity and specificity of breast cancer detection. Secondary outcome measures were screening performance measures of cancer detection, recall, and interval cancers (cancers clinically detected between screenings), and positive predictive value for screen recalls and negative predictive value of each method. Outcomes were analysed in the per-protocol population. Follow-up of the participants for at least 2 years allowed for identification of interval cancers. This trial is registered with ClinicalTrials.gov, number NCT01091545.Between Jan 27, 2010, and Feb 13, 2015, of 21 691 women invited, 14 851 (68%) agreed to participate. Three women withdrew consent during follow-up and were excluded from the analyses. 139 breast cancers were detected in 137 (1%) of 14 848 women. Sensitivity was higher for digital breast tomosynthesis than for digital mammography (81·1%, 95% CI 74·2-86·9, vs 60·4%, 52·3-68·0) and specificity was slightly lower for digital breast tomosynthesis than was for digital mammography (97·2%, 95% CI 97·0-97·5, vs 98·1%, 97·9-98·3). The proportion of cancers detected was significantly higher with digital breast tomosynthesis than with digital mammography (8·7 cancers per 1000 women screened, 95% CI 7·3-10·3 vs 6·5 cancers per 1000 screened, 5·2-7·9; p0·0001). The proportion of women recalled after discussion was higher among cancers detected by digital breast tomosynthesis than for those detected by digital mammography after consensus (3·6%, 95% CI 3·3-3·9 vs 2·5%, 2·2-2·8; p0·0001). The positive predictive value for screen recalls was 24·1% (95% CI 20·5-28·0) for digital breast tomosynthesis and 25·9% (21·6-30·7) for digital mammography, and the negative predictive value was 99·8% (99·7-99·9) and 99·6% (99·4-99·7), respectively. The proportion of women who developed interval cancers after trial screening was 1·48 cancers per 1000 women screened (95% CI 0·93-2·24).Breast cancer screening by use of one-view digital breast tomosynthesis with a reduced compression force has higher sensitivity at a slightly lower specificity for breast cancer detection compared with two-view digital mammography and has the potential to reduce the radiation dose and screen-reading burden required by two-view digital breast tomosynthesis with two-view digital mammography.The Swedish Cancer Society, The Swedish Research Council, The Breast Cancer Foundation, The Swedish Medical Society, The Crafoord Foundation, The Gunnar Nilsson Cancer Foundation, The Skåne University Hospital Foundation, Governmental funding for clinical research, The South Swedish Health Care Region, The Malmö Hospital Cancer Foundation and The Cancer Foundation at the Department of Oncology, Skåne University Hospital.

Background Obesity during adolescence is associated with cardiovascular mortality in adulthood. The adverse obesity-related cardiometabolic risk profile is already observed in adolescence. We aimed to examine possible gender differences in cardiometabolic risk factors and lifestyle behaviors among adolescents with severe obesity, hypothesizing that boys would have both a higher prevalence of the metabolic syndrome as well as less healthy lifestyle behaviors than girls. Methods Cross-sectional study of treatment-seeking adolescents with severe obesity who attended the Morbid Obesity Centre at Vestfold Hospital Trust and who were consecutively enrolled in the Vestfold Register of Obese Children between September 2009 and September 2015. A total of 313 adolescents aged 12 to 18 years were recruited, whereof 268 subjects (49% boys) completed a food and activity frequency questionnaire and were included in the analysis. Results Mean (SD) age, BMI and BMI SDS were 15 (1.6) years, 38.6 (5.9) kg/m2 and 3.5 (0.6). Levels of LDL cholesterol, fasting insulin and glucose and diastolic blood pressure (DBP) did not differ between genders. Compared to girls, boys had significantly higher triglycerides (p = 0.037) and systolic blood pressure (SBP) (p = 0.003), as well as lower HDL cholesterol (p = 0.002). The metabolic syndrome was present in 27% of the boys and 19% of the girls (p = 0.140), and the prevalence of high DBP, dyslipidemia and dysglycemia also did not differ significantly between genders. The prevalence of high SBP was higher in boys than in girls (19% vs. 9%, p = 0.021). Gender was associated with a number of lifestyle habits, as a larger proportions of boys had higher screen time (p = 0.032), more regular breakfast eating (p = 0.023), higher intake of sugar sweetened soda (p = 0.036), and lower intake of vegetables than girls (p = 0.011). By contrast, physical activity level and intake of fruit and berries did not differ between genders. Conclusions Male treatment-seeking adolescents with severe obesity had a more unfavorable set of metabolic and behavioral risk factors for cardiovascular disease than girls. Our results indicate that lifestyle behavioral markers should be thoroughly assessed in both genders, and possible gender-related differences in risk profile should be taken into account in future treatment programs.

Background Screening accuracy can be improved with digital breast tomosynthesis (DBT). To further evaluate DBT in screening, it is important to assess the molecular subtypes of the detected cancers. Purpose To describe tumor characteristics, including molecular subtypes, of cancers detected at DBT compared with those detected at digital mammography (DM) in breast cancer screening. Materials and Methods The Malmo Breast Tomosynthesis Screening Trial is a prospective, population-based screening trial comparing one-view DBT with two-view DM. Tumor characteristics were obtained, and invasive cancers were classified according to St Gallen as follows: luminal A-like, luminal B-like human epidermal growth factor receptor (HER)2-negative/HER2-positive, HER2-positive, and triple-negative cancers. Tumor characteristics were compared by mode of detection: DBT alone or DM (ie, DBT and DM or DM alone). χ2 test was used for data analysis. Results Between January 2010 and February 2015, 14 848 women were enrolled (mean age, 57 years ± 10; age range, 40-76 years). In total, 139 cancers were detected; 118 cancers were invasive and 21 were ductal carcinomas in situ. Thirty-seven additional invasive cancers (36 cancers with complete subtypes and stage) were detected at DBT alone, and 81 cancers (80 cancers with complete stage) were detected at DM. No differences were seen between DBT and DM in the distribution of tumor size 20 mm or smaller (86% [31 of 36] vs 85% [68 of 80], respectively; P = .88), node-negative status (75% [27 of 36] vs 74% [59 of 80], respectively; P = .89), or luminal A-like subtype (53% [19 of 36] vs 46% [37 of 81], respectively; P = .48). Conclusion The biologic profile of the additional cancers detected at digital breast tomosynthesis in a large prospective population-based screening trial was similar to those detected at digital mammography, and the majority were early-stage luminal A-like cancers. This indicates that digital breast tomosynthesis screening does not alter the predictive and prognostic profile of screening-detected cancers. © RSNA, 2019.

IntroductionBariatric surgery is increasingly recognised as an effective treatment option for subjects with type 2 diabetes and obesity; however, there is no conclusive evidence on the superiority of Roux-en-Y gastric bypass or sleeve gastrectomy. The Oseberg study was designed to compare the effects of gastric bypass and sleeve gastrectomy on remission of type 2 diabetes and β-cell function.Methods and analysisSingle-centre, randomised, triple-blinded, two-armed superiority trial carried out at the Morbid Obesity Centre at Vestfold Hospital Trust in Norway. Eligible patients with type 2 diabetes and obesity were randomly allocated in a 1:1 ratio to either gastric bypass or sleeve gastrectomy. The primary outcome measures are (1) the proportion of participants with complete remission of type 2 diabetes (HbA1c≤6.0% in the absence of blood glucose-lowering pharmacologic therapy) and (2) β-cell function expressed by the disposition index (calculated using the frequently sampled intravenous glucose tolerance test with minimal model analysis) 1 year after surgery.Ethics and disseminationThe protocol of the current study was reviewed and approved by the regional ethics committee on 12 September 2012 (ref: 2012/1427/REK sør-øst B). The results will be disseminated to academic and health professional audiences and the public via publications in international peer-reviewed journals and conferences. Participants will receive a summary of the main findings.Trial registration numberNCT01778738;Pre-results.

A post hoc analysis of the ATHENA study was performed to determine whether true HPV‐negative cervical lesions occur and whether they have clinical relevance. The ATHENA database was searched for all CIN2 or worse (CIN2+) cases with cobas HPV‐negative results and comparison was made with Linear Array (LA) and Amplicor to detect true false‐negative HPV results. Immunostaining with p16 was performed on these cases to identify false‐positive histology results. H&E slides were re‐reviewed by the study pathologists with knowledge of patient age, HPV test results and p16 immunostaining. Those with positive p16 immunostaining and/or a positive histopathology review underwent whole tissue section HPV PCR by the SPF10/LiPA/RHA system. Among 46,887 eligible women, 497 cases of CIN2+ were detected, 55 of which tested negative by the cobas® HPV Test (32 CIN2, 23 CIN3/ACIS). By LA and/or Amplicor, 32 CIN2+ (20 CIN2, 12 CIN3/ACIS) were HPV positive and categorized as false‐negatives by cobas HPV; nine of 12 false‐negative CIN3/ACIS cases were p16+. There were 23 cases (12 CIN2, 11 CIN3/ACIS) negative by all HPV tests; seven of 11 CIN3/ACIS cases were p16+. H&E slides were available for six cases for re‐review and all were confirmed as CIN3/ACIS. Tissue PCR was performed on the six confirmed CIN3/ACIS cases (and one without confirmation): four were positive for HPV types not considered oncogenic, two were positive for oncogenic genotypes and one was indeterminate. In summary, subanalysis of a large cervical cancer screening study did not identify any true CIN3/ACIS not attributable to HPV., What's new? Human papillomavirus (HPV) testing has a high negative predictive value for detecting histological cervical intraepithelial neoplasia (CIN). False‐negative HPV results can occur, however, though their clinical relevance is little understood. Using data from the U.S.‐based ATHENA study, the authors of the present report show that only a very small percentage of CIN grade 3/adenocarcinoma in situ (ACIS) lesions were missed by the cobas HPV Test, which identifies 14 high‐risk HPV types. False‐negatives by cobas testing were compared with Linear Array and Amplicor testing. Most missed CIN3/ACIS cases were associated with HPV types not included in current tests.

IntroductionRoux-en-Y gastric bypass (GBP) is associated with changes in cardiometabolic risk factors and bioavailability of drugs, but whether these changes are induced by calorie restriction, the weight loss or surgery per se, remains uncertain. The COCKTAIL study was designed to disentangle the short-term (6 weeks) metabolic and pharmacokinetic effects of GBP and a very low energy diet (VLED) by inducing a similar weight loss in the two groups.Methods and analysisThis open, non-randomised, three-armed, single-centre study is performed at a tertiary care centre in Norway. It aims to compare the short-term (6 weeks) and long-term (2 years) effects of GBP and VLED on, first, bioavailability and pharmacokinetics (24 hours) of probe drugs and biomarkers and, second, their effects on metabolism, cardiometabolic risk factors and biomarkers. The primary outcomes will be measured as changes in: (1) all six probe drugs by absolute bioavailability area under the curve (AUCoral/AUCiv) of midazolam (CYP3A4 probe), systemic exposure (AUCoral) of digoxin and rosuvastatin and drug:metabolite ratios for omeprazole, losartan and caffeine, levels of endogenous CYP3A biomarkers and genotypic variation, changes in the expression and activity data of the drug-metabolising, drug transport and drug regulatory proteins in biopsies from various organs and (2) body composition, cardiometabolic risk factors and metabolic biomarkers.Ethics and disseminationThe COCKTAIL protocol was reviewed and approved by the Regional Committee for Medical and Health Research Ethics (Ref: 2013/2379/REK sørøst A). The results will be disseminated to academic and health professional audiences and the public via presentations at conferences, publications in peer-reviewed journals and press releases and provided to all participants.Trial registration numberNCT02386917.

Objective: Arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. This study aimed to compare the 7-week effect of a low-calorie diet (LCD) and an intensive lifestyle intervention program (ILI) on arterial stiffness in morbidly obese individuals. Design and Methods: Nonrandomized clinical trial. The LCD provided 900 kcal/day, and participants in the LCD group were instructed to maintain their habitual physical activity level. The ILI included two 90-min supervised training sessions 3 days a week at moderate to high intensity (4-8 METs) and a caloric restriction of 1000 kcal/day. Results: A total of 179 individuals completed the study, 88 (56 women) in the ILI group and 91 (57 women) in the LCD group. High-fidelity applanation tonometry (Millar®, Sphygmocor®) was used to measure carotid-femoral pulse wave velocity (PWV). After adjustment for relevant confounders, the ILI group had a significantly greater reduction in PWV than the LCD group; −0.4 (−0.6, −0.1) m/s, P = 0.004. When compared to the LCD group, the ILI group showed a larger reduction in systolic and diastolic blood pressure −5 (−9, −1) and −5 (−7, −2) mmHg, P = 0.038 and P ≤ 0.001 respectively, whereas no difference was observed regarding pulse pressure, P = 0.661. No significant differences between groups were found regarding the loss of fat mass, P = 0.259, but the loss of muscle mass was larger in the LCD group, 0.8 (0.5, 1.1) kg, P ≤ 0.001. Conclusion: Despite the limitations of a nonrandomized design, our findings indicate that for morbidly obese individuals a moderate caloric restriction combined with aerobic physical exercise is associated with a greater decline in PWV than a LCD alone.

Obesity is associated with vitamin D deficiency (25-hydroxyvitamin D (25(OH)D)50 nmol/l). We aimed to examine the effect of gender on vitamin D status in severe obesity.Cross-sectional study of 2026 morbidly obese patients examined consecutively at a tertiary care centre between November 2005 and June 2010. Serum 25(OH)D concentration and use of vitamin D supplements were registered in all patients. Total vitamin D intake (μg/day) was assessed in a subgroup of 154 patients using a validated food frequency questionnaire.The male (n=690) and female (n=1336) patients had a mean (s.d.) age of 45.0 (12.1) years and 42.2 (12.2) years (P0.001), body mass index (BMI) of 44.6 (6.0) kg/m(2) and 44.3 (5.9) kg/m(2) (P=0.30) and waist circumference (WC) of 140 (13) cm and 127 (13) cm (P0.001), respectively. Male patients had significantly lower mean 25(OH)D concentrations than female patients 50.0 (22.0) nmol/l versus 53.6 (22.4) nmol/l (P=0.001) and a higher rate of vitamin D deficiency (56% versus 47%; P0.001). Obese men had significantly higher odds of vitamin D deficiency than women (odds ratio=1.41; 95% confidence interval: 1.17-1.70, P0.001), also after adjustment for season, age, current smoking, intake of vitamin D supplements, BMI and WC (odds ratio=1.39; 95% confidence interval: 1.10-1.76).Morbidly obese Norwegian men seeking weight loss treatment have significantly higher odds of vitamin D deficiency than women. Monitoring of 25(OH)D concentrations in obese patients should therefore take gender into account.

ObjectiveWeight reduction improves several obesity-related health conditions. We aimed to compare the effect of bariatric surgery and comprehensive lifestyle intervention on type 2 diabetes and obesity-related cardiovascular risk factors.DesignOne-year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104).MethodsMorbidly obese subjects (19–66 years, mean (s.d.) body mass index 45.1 kg/m2(5.6), 103 women) were treated with either Roux-en-Y gastric bypass surgery (n=80) or intensive lifestyle intervention at a rehabilitation centre (n=66). The dropout rate within both groups was 5%.ResultsAmong the 76 completers in the surgery group and the 63 completers in the lifestyle group, mean (s.d.) 1-year weight loss was 30% (8) and 8% (9) respectively. Beneficial effects on glucose metabolism, blood pressure, lipids and low-grade inflammation were observed in both groups. Remission rates of type 2 diabetes and hypertension were significantly higher in the surgery group than the lifestyle intervention group; 70 vs 33%,P=0.027, and 49 vs 23%,P=0.016. The improvements in glycaemic control and blood pressure were mediated by weight reduction. The surgery group experienced a significantly greater reduction in the prevalence of metabolic syndrome, albuminuria and electrocardiographic left ventricular hypertrophy than the lifestyle group. Gastrointestinal symptoms and symptomatic postprandial hypoglycaemia developed more frequently after gastric bypass surgery than after lifestyle intervention. There were no deaths.ConclusionsType 2 diabetes and obesity-related cardiovascular risk factors were improved after both treatment strategies. However, the improvements were greatest in those patients treated with gastric bypass surgery.

Background The aim of this review was to determine whether dexmedetomidine alone provided satisfactory conditions for children undergoing magnetice resonance imaging (MRI). Methods A retrospective review of 21 patients was undertaken, (age range: 1-8 years, weight 10-27 kg) who received dexmedetomidine to provide deep sedation for an MRI procedure. Results In the initial eight patients who received dexmedetomidine (bolus 0.5-1.5 mg.kg(-1) and infusion rate 1-1.5 mg.kg(-1).h(-1)) by itself, movement occurred in five of them, even when the maximum suggested dose was used (1 microg.kg(-1).h(-1)). Midazolam (0.1 mg.kg(-1)) i.v. was given as an adjunct to the following 13 patients (dexemdetomidine doses were lower: bolus 1 mg.kg(-1), infusion 0.5-1 mg.kg(-1).h(-1)). Only one patient moved within this group. The mean time to discharge postprocedure was 90 min. There were no differences with respect to recovery or discharge times between those who did or did not receive midazolam. No cardiac or respiratory complications were noted. Conclusions The use of dexmedetomidine for MRI sedation by itself was more unpredictable than anticipated from the published case reports of its use.

Both propofol infusions with oxygen delivered through nasal cannula and isoflurane/N2O (nitrous oxide) delivered via a laryngeal mask airway (LMA) are used to provide anesthesia for children undergoing magnetic resonance imaging scans. We compared the incidence of adverse events and perioperative physiologic responses in children anesthetized with these 2 regimens.One hundred-fifty healthy children, ages 1 to 10 years, were randomized to receive either a propofol infusion (starting at 300 µg kg·min) with oxygen via nasal cannula (n = 75) or isoflurane with 70% N2O in oxygen delivered via an LMA (n = 75), both after a sevoflurane/N2O/oxygen induction. Adverse airway events, as well as hemodynamic, respiratory, and other physiologic responses were recorded during the magnetic resonance imaging scans and in the postanesthesia care unit by a single research nurse who was blind to the treatments. All parents were contacted postoperatively to complete a postanesthetic follow-up.All 150 children completed their scans. The frequency of all adverse airway events during emergence and recovery after propofol (12%) was significantly less than that after isoflurane/N2O/LMA (49%) (95% confidence interval for the risk difference was 23%-50%) (P = 0.0001). Hemodynamic responses and recovery times for the 2 treatments were similar. Early recovery, defined as the time interval from admission to the postanesthesia care unit until eye opening and wakefulness (modified Aldrete score5), after propofol was more rapid than that after isoflurane/N2O/LMA (P = 0.0001 and P = 0.0012, respectively). No scans had to be repeated.The frequency of adverse airway events during emergence and recovery after propofol infusion with oxygen by nasal cannula is less than with isoflurane/N2O/LMA in children.

We compared changes in the dietary patterns of morbidly obese patients undergoing either laparoscopic gastric bypass surgery or a comprehensive lifestyle intervention programme. The present 1-year non-randomised controlled trial included fifty-four patients in the lifestyle group and seventy-two in the surgery group. Dietary intake was assessed by a validated FFQ. ANCOVA was used to adjust for between-group differences in sex, age, baseline BMI and baseline values of the dependent variables. Intakes of food groups and nutrients did not differ significantly between the intervention groups at baseline. At 1-year follow-up, the lifestyle group had a significantly higher daily intake of fruits and vegetables (561 (sd 198) v. 441 (sd 213) g, P= 0·002), whole grains (63 (sd 24) v. 49 (sd 16) g, Psd 6) v. 22 (sd 6) g, Psd 3) v. 14 (sd 3) %, PP

The number of bariatric surgical procedures in Norway is increasing. Patients who undergo bariatric surgery may experience surgical, medical and nutritional complications. Follow-up of these patients is therefore important.The article is based on non-systematic literature searches in PubMed and on the clinical experience of the authors.Bariatric surgery induces significant and sustained weight loss and improves obesity-related disorders. Gastric bypass is the most commonly performed bariatric procedure in Norway. This procedure is associated with a 30-day mortality of below 0.5 %, while severe complications occur in approximately 5 % of patients. Late complications include internal herniation, intestinal ulcers and gallbladder disease. After surgery all patients are given iron, vitamin D/calcium and vitamin B12 supplements to prevent vitamin and mineral deficiencies. Gastrointestinal symptoms and postprandial hypoglycaemia after surgery can be improved by dietary modifications, and the need for anti-diabetic and blood pressure lowering medications is reduced. Dose adjustment of other medications may also be necessary. Pregnancy is not recommended during the first year after bariatric surgery. Many patients need plastic surgery after the operation.Complications after bariatric surgery may manifest in the long term. Regular follow-up is required. General practitioners should be responsible for follow-up in the long term, and should be familiar with common and serious complications as well as normal symptomatology after bariatric surgery.

Background & Aims HLA class I alleles are linked to spontaneous control of hepatitis C virus (HCV) and human immunodeficiency virus−1, but for HCV the roles of particular alleles and corresponding CD8 + T-cell responses remain incompletely defined. We aimed to determine the correlations between these alleles and natural outcomes of HCV and determine associated key T-cell responses. Methods In a cohort of HCV individuals, we determined HLA class I alleles, HCV outcomes, T-cell responses, and examined sequence data for mutational changes within key epitopes. Results Carriage of HLA-B*57 was associated with a higher rate of viral clearance (risk ratio=2.0; 95% confidence interval: 1.2−3.4), while HLA-B*08 was associated with a lower rate (risk ratio=0.34; 95% confidence interval: 0.1−0.9]. Two HLA-B*57 −restricted T-cell epitopes were targeted in spontaneous clearance; subjects with chronic viremia expressing HLA-B*57 harbored HCV strains with a high frequency of mutations in key residues. HLA-B*57 −mediated escape was supported by diminished immune recognition of these variants and acute HCV infection revealing viral evolution toward less recognized variants. Analysis of a genotype 1b strain from a single-source HCV outbreak in which HLA-B*57 was not protective revealed sequence variations that interfere with immunogenicity, thereby preventing HLA-B*57 -mediated immune pressure. Conclusions Our data indicate a role of HLA-B*57 −restricted CD8 + T-cell responses in mediating spontaneous clearance and evolution in HCV infection, and viral strains containing epitope variants that are less recognized abrogate the protective effects of HLA-B*57 . The finding that HLA-B*57 −mediated antiviral immunity is associated with control of both human immunodeficiency virus−1 and HCV suggests a common shared mechanism of a successful immune response against persistent viruses.

Bariatric surgery can lead to vitamin deficiencies. We aimed to assess the changes in blood vitamin concentrations in patients who were taking predefined supplements after gastric bypass surgery.A total of 29 patients underwent gastric bypass and 24 unmatched controls underwent lifestyle intervention in a prospective, nonrandomized trial. The patients in the surgical group received multivitamin, iron, calcium, vitamin D, and vitamin B(12) supplements. No supplements were prescribed to the lifestyle group. The median body mass index decreased from 46 to 32 kg/m(2) after surgery and from 40 to 39 kg/m(2) after lifestyle intervention.Of the 53 included patients, 50 completed the 1-year follow-up examination (94%). Compared with the lifestyle patients, the surgical patients had increased vitamin B(6), folic acid, vitamin B(12), and lipid-adjusted vitamin E (P.02 for each) concentrations but decreased vitamin A concentrations (P.01) during follow-up. No significant difference between the 2 groups was found for vitamin B(1), vitamin C, or 25-hydroxyvitamin D. Most surgical patients reported taking their supplements.Gastric bypass patients adhering to a set of dietary supplements had mostly stable or increased vitamin concentrations compared with both their baseline values and the changes in a nonsurgical control group.

We sought to use data captured in the electronic health record (EHR) to develop and validate a prediction rule for virologic failure among patients being treated for infection with human immunodeficiency virus (HIV).We used EHRs at 2 Boston tertiary care hospitals, Massachusetts General Hospital and Brigham and Women's Hospital, to identify HIV-infected patients who were virologically suppressed (HIV RNA levelor = 400 copies/mL) on antiretroviral therapy (ART) during the period from 1 January 2005 through 31 December 2006. We used a multivariable logistic model with data from Massachusetts General Hospital to derive a 1-year virologic failure prediction rule. The model was validated using data from Brigham and Women's Hospital.We then simplified the scoring scheme to develop a clinical prediction rule.The 1-year virologic failure prediction model, using data from 712 patients from Massachusetts General Hospital, demonstrated good discrimination (C statistic, 0.78) and calibration (chi(2)= 6.6; P= .58). The validation model, based on 362 patients from Brigham and Women's Hospital, also showed good discrimination (C statistic, 0.79) and calibration (chi(2)= 1.9; P= .93). The clinical prediction rule included 7 predictors (suboptimal adherence, CD4 cell count100 cells/microL, drug and/or alcohol abuse, highly ART experienced, missedor = 1 appointment, prior virologic failure, and suppressedor = 12 months) and appropriately stratified patients in the validation data set into low-, medium-, and high-risk groups, with 1-year virologic failure rates of 3.0%, 13.0%, and 28.6%, respectively.A risk score based on 7 variables available in the EHR predicts HIV virologic failure at 1 year and could be used for targeted interventions to improve outcomes in HIV infection.

BACKGROUND: Dexmedetomidine is an 2 agonist that is currently being investigated for its suitability to provide anesthesia for children. We compared the pharmacodynamic responses to dexmedetomidine-midazolam and propofol in children anesthetized with sevoflurane undergoing magnetic resonance imaging (MRI). METHODS: Forty ASA 1 or 2 children, 1–10 yr of age, were randomized to receive either dexmedetomidine-midazolam or propofol for maintenance of anesthesia for MRI after a sevoflurane induction. Dexmedetomidine was administered as an initial loading dose (1 g/kg) followed by a continuous infusion (0.5 g kg 1 h 1 ). Midazolam (0.1 mg/kg) was administered IV when the infusion commenced. Propofol was administered as a continuous infusion (250–300 g kg 1 min 1 ). Recovery times and hemodynamic responses were recorded by one nurse who was blinded to the treatments. RESULTS: We found that the times to fully recover and to discharge from the ambulatory unit after dexmedetomidine administration were significantly greater (by 15 min) than those after propofol. Analysis of variance demonstrated that heart rate was slower and systolic blood pressure was greater with dexmedetomidine than propofol. Respiratory indices for the two treatments were similar. During recovery, hemodynamic responses were similar. Cardiorespiratory indices during anesthesia and recovery remained within normal limits for the children’s ages. No adverse events were recorded. CONCLUSION: Dexmedetomidine-midazolam provides adequate anesthesia for MRI although recovery is prolonged when compared with propofol. Heart rate was slower and systolic blood pressure was greater with dexmedetomidine when compared with propofol. Respiratory indices were similar for the two treatments.

Data to support improved patient outcomes from clinical decision-support systems (CDSSs) are lacking in HIV care.To test the efficacy of a CDSS in improving HIV outcomes in an outpatient clinic.Randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00678600)Massachusetts General Hospital HIV Clinic.HIV care providers and their patients.Computer alerts were generated for virologic failure (HIV RNA level400 copies/mL after a previous HIV RNA level ≤400 copies/mL), evidence of suboptimal follow-up, and 11 abnormal laboratory test results. Providers received interactive computer alerts, facilitating appointment rescheduling and repeated laboratory testing, for half of their patients and static alerts for the other half.The primary end point was change in CD4 cell count. Other end points included time to clinical event, 6-month suboptimal follow-up, and severe laboratory toxicity.Thirty-three HIV care providers followed 1011 patients with HIV. In the intervention group, the mean increase in CD4 cell count was greater (0.0053 vs. 0.0032 × 109 cells/L per month; difference, 0.0021 × 109 cells/L per month [95% CI, 0.0001 to 0.004]; P = 0.040) and the rate of 6-month suboptimal follow-up was lower (20.6 vs. 30.1 events per 100 patient-years; P = 0.022) than those in the control group. Median time to next scheduled appointment was shorter in the intervention group than in the control group after a suboptimal follow-up alert (1.71 vs. 3.48 months; P0.001) and after a toxicity alert (2.79 vs.6 months; P = 0.072). More than 90% of providers supported adopting the CDSS as part of standard care.This was a 1-year informatics study conducted at a single hospital subspecialty clinic.A CDSS using interactive provider alerts improved CD4 cell counts and clinic follow-up for patients with HIV. Wider implementation of such systems can provide important clinical benefits.National Institute of Allergy and Infectious Diseases.

Twenty-three of 1006 (2.3%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986 received additional treatment for documented (15 patients) or suspected (eight patients) tumor growth in the irradiated eye. Growth within the initially irradiated volume was documented at Massachusetts Eye and Ear Infirmary in 12 patients. Documented growth occurred in nine of 665 (1.4%) patients with small and intermediate size tumors, at times after treatment ranging from 6 to 48 months (median 16 months), and in three of 341 (.9%) patients with large tumors at 7, 11, and 12 months after treatment. Melanoma growing totally outside the treated volume was also documented in three additional patients at 7, 9, and 45 months; two of these were thought to be "ring melanomas". Eight patients had the treated eye removed elsewhere for suspected tumor growth. The additional treatment in these 23 patients was conservative in nine patients (repeat proton irradiation in five and laser photocoagulation in four). Thirteen underwent immediate enucleation and one had orbital exenteration. Ultimately, 17 of the 23 eyes (74%) were removed. Estimated probability of local control of the melanoma within the irradiated eye at 60 months was 96.3 +/- 1.5%. Dose distributions to the 12 patients with documented local failure within the irradiated volume were analyzed. Ten tumors recurred marginally in an area receiving less than the prescribed dose of 70 CGE (CGE = Cobalt Gray Equivalents = proton Gy X RBE 1.1), whereas only two recurred in the volume receiving full dose. Based on these data, it appears that a dose of 70 CGE in five fractions is associated with very high rates of local control in human uveal melanoma. It is reasonable to consider initiating studies using a lower total dose or a more protracted course, to determine if some of the observed complications are dose-related.