Search

In the recent past, inclusion criteria for cochlear implant surgery expanded to patients with ever more residual acoustic hearing in the low frequencies. By applying the meticulous hearing preservation surgical strategy and specifically designed atraumatic electrode arrays, residual hearing can be preserved to a meaningful extent in a large majority of patients. In this paper, we describe two female patients suffering from mechanically evoked tinnitus after hearing preservation cochlear implantation surgery with MEDEL flex electrodes. The occurrence of audible perceptions through mechanical stimulation in the region of the external ear is believed to be due to the direct transmission of movements via the electrode array to the basilar membrane of the inner ear. In both cases, the mechanically evoked tinnitus led to revision surgery with immobilization of the array in the mastoid cavity. Despite eliminating the tinnitus, the revision surgery led to a loss of residual hearing in one patient, whereas the relatively poor residual hearing in the other revision case remained unchanged. The presence of mechanically evoked tinnitus seems to be associated with increased fragility of inner ear structures and hearing function, possibly due to direct mechanical contact of the electrode array with the basilar membrane. Consequently, the electrode array needs to be carefully immobilized in the mastoid cavity at a distance from soft tissue to prevent mechanical damage of inner ear structures, particularly in female patients with fine muscular tissue.

The objective of this study was to propose prognostic factors and optimal treatment strategies by analyzing the clinicopathological features and programmed death-ligand 1 (PD-L1) expression. We analyzed 31 patients diagnosed with uterine or ovarian melanoma between 1997 and 2017 in the Kansai Clinical Oncology Group/Intergroup. Twenty-four and seven patients with cervical and ovarian melanomas were included, respectively. Immune checkpoint inhibitors were used in seven patients, and the objective response rate was 40%. Notably, two patients with objective responses had a high PD-L1 expression. Ten and four patients with cervical and ovarian melanomas, respectively, had high PD-L1 immunohistochemical expressions. Multivariate analysis revealed that tumor stage was an independent prognostic factor for progression-free survival in patients with cervical melanomas. In patients with ovarian melanomas, the 1-year cumulative progression-free and overall survival rates were 0 and 29%, respectively. Kaplan-Meier analyses revealed that age60 years was associated with poorer progression-free and overall survivals in patients with ovarian melanomas. In patients with cervical melanomas, the 1-, 3-, and 5-year cumulative overall survival rates were 53, 32, and 16%, respectively. Histological atypia was associated with a poorer progression-free survival, but there was no difference in survival between patients who underwent radical hysterectomy and those who did not. The present study is a large cohort study of uterine and ovarian melanomas, which are aggressive tumors with a significantly poor prognosis, even after standard surgery and adjuvant therapy. The use of immune checkpoint inhibitors is a promising and effective treatment option.

Background High workloads generated by a few patients who consult very frequently can become huge burdens for general practitioners (GPs). Patient-related factors have been repeatedly associated with frequent consultations, but there is evidence that GPs can also influence that frequency. We investigated how patients, GPs and their practices’ organisational characteristics were associated with consultation frequency. Methods Data came from the SPAM Prev (Swiss Primary Health Care Active Monitoring, Prevention in primary care) national, cross-sectional survey conducted in 2015–16, including 167 GPs and 1105 patients. GPs completed an online questionnaire focused on practice organisation. Patients randomly recruited in general practices completed a questionnaire with fieldworkers. Factors predicting consultation frequency were investigated using multilevel Poisson regression models. Results Negative associations with consultation frequency were found for females (Incidence Rate Ratio (IRR) 0.94, 95%CI [0.88–1.01]), less compliant patients (IRR 0.91, 95%CI [0.84–0.98]), high self-perceived health status (IRR 0.8, 95%CI [0.75–0.84]) and physical exercise (IRR 0.87, 95%CI [0.81–0.94]). Consultation frequencies were higher among patients with sleeping problems (IRR 1.08, 95%CI [0.96–1.23]), psychological distress (IRR 1.66, 95%CI [1.49–1.86]), chronic diseases (IRR 1.27, 95%CI [1.18–1.37]) and treatment with medication (IRR 1.24, 95%CI [1.12–1.37]). Positive associations with consultation frequency were found among GPs working longer hours (IRR 1.21, 95%CI [1.01–1.46]). Using shared medical records (IRR 0.79, 95%CI [0.67–0.92]) were negatively associated with consultation frequency. Conclusion GPs’ practices’ characteristics, like patients’, are predictive of patients’ consultation frequency, but those associations’ underlying mechanisms require further qualitative investigation. These new findings could help optimise intervention strategies and reduce healthcare costs.

Background As most countries, Switzerland is experiencing a shortage of physicians especially in general practice and new medical education tracks with respective focusses have been started in response. This study investigated Swiss medical students’ career openness and attractiveness of different medical disciplines as well as the concordance of students’ career intentions with assigned medical education tracks. Methods Cross-sectional study surveying first year medical students assigned to four different Swiss medical education tracks with distinctive additional education focuses (ETH Zurich: medical technology and engineering, University of St. Gallen and University of Lucerne: primary healthcare and University of Zurich: no distinctive focus). Results We surveyed 354 medical students (response rate across all included medical education tracks 71.1%), 64.8% female, mean age 20 years. Regarding career openness, we found that 52.8% of medical students had neither a strong commitment nor a strong reservation for any of the proposed career options and 17.0% had a strong commitment. Among medical disciplines, medical subspecialties were attractive to the largest part of students (inpatient subspecialties attractive for 71%, outpatient for 58%), attractiveness of general practice was moderate (30%), academic (22%) and industrial sector (17%) careers were least attractive. Proportions of medical students attracted to general practice were similar at medical education tracks with focus on primary healthcare compared to other medical education tracks (32.2% vs. 25.8%, p = 0.391). Conversely, proportions of medical students attracted to academic or industry careers were significantly higher at the ETH Zurich compared to other medical education tracks (37.2%, vs. 13.1%, p p Conclusion While most first-year medical students were open to careers in many medical disciplines, attractiveness of disciplines varied strongly. Students attracted to academic or industrial careers accumulated at the medical education track with concordant teaching focus but students attracted to general practice did not accumulate at medical education tracks focused on primary healthcare. For medical education tracks with primary care teaching focus this is both a challenge and an opportunity to specifically counteract the shortage of general practitioners in Switzerland.

Background De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). Methods and findings Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors. Conclusions Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D., Fumiaki Imamura and colleagues investigate the association between concentrations of fatty acid involved in de-novo lipogensis and incidence of Type 2 diabetes., Author summary Why was this study done? De novo lipogenesis (DNL) is a metabolic pathway involved in the endogenous synthesis of specific fatty acids, such as 16:0, 16:1n7, 18:0, and 18:1n9, and it is linked to the pathophysiology of cardiometabolic diseases, including type 2 diabetes (T2D). Circulating or tissue concentrations of these fatty acids have been investigated for the associations with T2D incidence in epidemiological research. However, published studies reported inconsistent associations inconsistently and were subject to publication bias. Summary evidence is not available to date for the associations between these fatty acids and T2D incidence. An integration of available cohort studies would increase statistical power and allow assessment of generalizability, standardization of analytical strategies, and evidence synthesis with the potential publication bias minimized. What did the researchers do and find? As a part of the Fatty Acids and Outcomes Research Consortium (FORCE), we conducted new individual-participant data analyses of 17 cohort studies of a total of 65,225 adults free of T2D at baseline, among whom 15,383 developed incident T2D over up to 20 years of follow-up. The cohort studies analyzed the associations between fatty acids (16:0, 16:1n7, 18:0, and 18:1n9) and the risk of developing T2D with standardized analytic strategy. In pooled analyses, each of the fatty acids was positively associated with a higher risk of developing T2D. The associations were independent of major risk factors for T2D, such as age, sex, race/ethnicity, socioeconomic characteristics, smoking status, physical activity, and obesity. What do these findings mean? The findings provide the first summary evidence to date for the positive relationships of concentrations of the DNL-related fatty acids with a risk of T2D, indicating the strong relevance of DNL and its determinants to the development of T2D. These fatty acids potentially reflect the status of DNL activity, which may be stimulated or suppressed by a combination of carbohydrate intake, alcohol intake, polyunsaturated fatty acid intake, and other lifestyle and clinical factors. Therefore, the current findings indicate the need for investigation into determinants and consequences of elevated concentrations of these fatty acids. Despite several advantages of our individual-level data analysis in this pooling project, the results cannot establish whether elevated concentrations of these fatty acids caused the development of T2D or whether underlying peripheral or hepatic insulin resistance, for example, may elevate both the fatty acid concentrations and the risk of T2D independently.

Context Thyroid hormone (TH) is crucial for the adaptation to cold. Objective To evaluate the effect of hyperthyroidism on resting energy expenditure (REE), cold-induced thermogenesis (CIT) and changes in body composition and weight. Methods This was a prospective cohort study at the endocrine outpatient clinic of a tertiary referral center. Eighteen patients with overt hyperthyroidism were included. We measured REE during hyperthyroidism, after restoring euthyroid TH levels and after 3 months of normal thyroid function. In 14 of the 18 patients, energy expenditure (EE) was measured before and after a mild cold exposure of 2 hours and CIT was the difference between EEcold and EEwarm. Skin temperatures at 8 positions were recorded during the study visits. Body composition was assessed by dual X-ray absorption. Results Free thyroxine (fT4) and free triiodothyronine (fT3) decreased significantly over time (fT4, P = .0003; fT3, P = .0001). REE corrected for lean body mass (LBM) decreased from 42 ± 6.7 kcal/24 hour/kg LBM in the hyperthyroid to 33 ± 4.4 kcal/24 hour/kg LBM (–21%, P Conclusion CIT is not increased in patients with overt hyperthyroidism.

Background Chronic kidney disease (CKD) is a common condition in general practice. Data about quality and physician-level variation of CKD care provided by general practitioners is scarce. In this study, we evaluated determinants and variation of achievement of 14 quality indicators for CKD care using electronic medical records data from Swiss general practice during 2013–2019. Methods We defined two patient cohorts from 483 general practitioners, one to address renal function assessment in patients with predisposing conditions (n = 47,201, median age 68 years, 48.7% female) and one to address care of patients with laboratory-confirmed CKD (n = 14,654, median age 80 years, 57.5% female). We investigated quality indicator achievement with mixed-effect logistic regression and expressed physician-level variation as intraclass correlation coefficients (ICCs) and range odds ratios (rORs). Results We observed the highest quality indicator achievement rate for withholding non-steroidal anti-inflammatory drug prescription in patients with CKD staged G2–3b within 12 months of follow-up (82.6%), the lowest for albuminuria assessment within 18 months of follow-up (18.1%). Highest physician-level variation was found for renal function assessment during 18 months of follow-up in patients with predisposing conditions (diabetes: ICC 0.31, rOR 26.5; cardiovascular disease: ICC 0.28, rOR 17.4; hypertension: ICC 0.24, rOR 17.2). Conclusion This study suggests potentially unwarranted variation in general practice concerning RF assessment in patients affected by conditions predisposing for CKD. We further identified potential gaps in quality of CKD monitoring as well as lower quality of CKD care for female patients and patients not affected by comorbidities.

Multiparous, nonlactating pregnant cows are negatively affected by heat stress, but the effect of heat stress on more thermotolerant pregnant heifers has received less attention. Our objective was to characterize the effect of late-gestation heat abatement on thermoregulatory responses and subsequent milk production of nulliparous Holstein heifers. Pregnant heifers, blocked by body condition score (BCS) and predicted transmitting ability (PTA) for milk, were enrolled in either heat stress (HT, shade of freestall barn; n = 16) or cooling (CL, shade of freestall barn, water soakers, and fans; n = 15) environments during the last 60 d of pregnancy (~8 weeks). Rectal temperature (RT; thermometer), respiration rate (RR; breaths/min), sweating rate (SR; VapoMeter, Delfin Technologies, Kuopio, Finland), and skin temperature (ST; infrared thermometer) were measured thrice weekly from enrollment to calving. Vaginal temperature (VT; i-button intravaginal device) was measured every 10 min for 7 consecutive days at wk -8, -6, -4, and -2 relative to calving and averaged hourly. Daily thermoregulatory patterns assessed by SR and ST, were measured every 4 h over a 36-h time interval at wk -6, -4, and -2 relative to calving. Upon calving, milk, protein, and fat yields were recorded twice daily for 15 wk. The average temperature-humidity index (Hobo Pro temperature probe, Onset Computer Corporation, Pocasset, MA) in the barn during the precalving period was 77 (minimum of 72, maximum of 82). Only heifers that gave birth to a female calf (CL = 12, HT = 14) were included in the statistical analysis. In the precalving period, CL heifers had lower RR (44.3 vs. 60.0 ± 1.6 breaths/min), RT (38.7 vs. 38.8 ± 0.04°C), unshaved ST (34.7 vs. 35.3 ± 0.17°C), and unshaved SR (19.0 vs. 35.2 ± 1.9 g/m2h), relative to HT heifers. Additionally, VT was lower in CL heifers during wk -4, and -2, specifically during early morning and early afternoon hours. When measured over a 36-h time interval, ST and SR were lower in CL heifers, when compared with HT heifers for all weeks. Notably, ST was reduced overnight and SR was reduced during the daytime. Cooled heifers had higher milk yield (35.8 vs. 31.9 ± 1.4 kg/d), when compared with HT heifers. Similar to multiparous cows, our data indicate that actively cooling heifers in late pregnancy is effective in promoting thermoregulation and results in elevated milk production postcalving.

BACKGROUND: Approval of hypomethylating agents in patients with chronic myelomonocytic leukaemia is based on trials done in patients with myelodysplastic syndromes. We aimed to investigate whether hypomethylating agents provide a benefit in subgroups of patients with chronic myelomonocytic leukaemia compared with other treatments. METHODS: For this retrospective cohort study, data were retrieved between Nov 30, 2017, and Jan 5, 2019, from 38 centres in the USA and Europe. We included non-selected, consecutive patients diagnosed with chronic myelomonocytic leukaemia, who received chronic myelomonocytic leukaemia-directed therapy. Patients with acute myeloid leukaemia according to 2016 WHO criteria at initial diagnosis (ie, =20% blasts in the bone marrow or peripheral blood) or with unavailability of treatment data were excluded. Outcomes assessed included overall survival, time to next treatment, and time to transformation to acute myeloid leukaemia. Analyses were adjusted by age, sex, platelet count, and Chronic myelomonocytic leukaemia-Specific Prognostic Scoring System (CPSS). Patients were grouped by first received treatment with either hydroxyurea, hypomethylating agents, or intensive chemotherapy, and stratified by risk according to blast count, French-American-British subtype, CPSS, WHO 2016 subtype, and the eligibility criteria of the DACOTA trial (NCT02214407). FINDINGS: 949 patients diagnosed with chronic myelomonocytic leukaemia between April 13, 1981, and Oct 26, 2018, were included. Median follow-up was 23·4 months (IQR 11·5-42·3) from diagnosis and 16·2 months (6·6-31·6) from start of first-line treatment. 412 (43%) of 949 patients received hypomethylating agents as first treatment, 391 (41%) hydroxyurea, and 83 (9%) intensive chemotherapy. Adjusted median overall survival for patients treated with hydroxyurea versus hypomethylating agents was 15·6 months (95% CI 13·1-17·3) versus 20·7 months (17·9-23·4); hazard ratio (HR) 1·39 (1·17-1·65; p=0·0002) and 14·0 months (9·8-17·2) versus 20·7 months (17·9-23·4; HR 1·55 [1·16-2·05]; p=0·0027) for those treated with intensive chemotherapy versus hypomethylating agents. In patients with myeloproliferative chronic myelomonocytic leukaemia (myeloproliferative CMML), median overall survival was 12·6 months (10·7-15·0) versus 17·6 months (14·8-21·5; HR 1·38 [1·12-1·70]; p=0·0027) for patients treated with hydroxyurea versus hypomethylating agents, and 12·3 months (8·4-16·6) versus 17·6 months (14·8-21·5; HR 1·44 [1·02-2·03]; p=0·040) for intensive chemotherapy versus hypomethylating agents. Hypomethylating agents did not confer an overall survival advantage for patients classified as having lower-risk disease (ie, myelodysplastic chronic myelomonocytic leukaemia with

Background: Although assessment of geriatric syndromes is increasingly encouraged in older adults, little evidence exists to support its systematic use by general practitioners (GPs). The aim of this study was to determine whether a systematic geriatric evaluation performed by GPs can prevent functional decline. Methods: We conducted a controlled, open-label, pragmatic cluster-randomized trial in 42 general practices in Switzerland. Participating GPs were expected to enrol an average of 10 community-dwelling adults (aged ≥ 75 yr) who understood French, and had visited their GP at least twice in the previous year. The intervention consisted of yearly assessment by the GP of 8 geriatric syndromes with an associated tailored management plan according to assessment results, compared with routine care. Our primary outcomes were the proportion of patients who lost at least 1 instrumental activity of daily living (ADL) and the proportion who lost at least 1 basic ADL, over 2 years. Our secondary outcomes were quality-of-life scores, measured using the older adult module of the World Health Organization Quality of Life Instrument, and health care use. Results: Forty-two GPs recruited 429 participants (63% women) with a mean age of 82.5 years (standard deviation 4.8 yr) at time of recruitment. Of these, we randomly assigned 217 participants to the intervention and 212 to the control arm. The proportion of patients who lost at least 1 instrumental ADL in the intervention and control arms during the course of the study was 43.6% and 47.6%, respectively (risk difference −4.0%, 95% confidence interval [CI] −14.9% to 6.7%, p = 0.5). The proportion of patients who lost at least 1 basic ADL was 12.4% in the intervention arm and 16.9% in the control arm (risk difference −5.1%, 95% CI −14.3% to 4.1%, p = 0.3). Interpretation: A yearly geriatric evaluation with an associated management plan, conducted systematically in GP practices, does not significantly lessen functional decline among community-dwelling, older adult patients, compared with routine care. Trial registration: ClinicalTrials.gov, NCT02618291.

The glycoprotein IIb/IIIa inhibitor eptifibatide, administered as bolus followed by infusion, is an adjunctive antithrombotic treatment during primary percutaneous coronary intervention (PCI) in selected patients with ST-segment elevation myocardial infarction (STEMI). Whether both bolus and infusion are necessary to improve outcomes is unknown. We hypothesized that primary PCI with eptifibatide bolus only is non-inferior to the conventional treatment (bolus and infusion) with regard to infarct size, while reducing bleeding complications. We analyzed 720 consecutive STEMI patients receiving eptifibatide bolus only or conventional treatment in an observational case-control study utilizing propensity score matching of clinical and intervention-specific confounders. Infarct size was estimated based on myocardial bound creatine kinase, creatine kinase (CK), and CK area under the curve values, with a prespecified non-inferiority margin of 20%. Major bleeding was defined as type 2, 3, or 5 on the Bleeding Academic Research Consortium classification. Eptifibatide bolus only was administered to 147 patients (20%), which were matched 1:1 to patients receiving conventional treatment. Based on peak myocardial bound creatine kinase, CK and CK area under the curve values, infarct size was -8.4% (95% CI [-31.2%, 14.4%]), -11.6% (95% CI [-33.5%, 10.3%]), and -13.9% (95% CI [-34.1%, 6.2%]) after eptifibatide bolus, respectively, reaching prespecified noninferiority compared with conventional treatment. Bolus treatment significantly reduced major bleeding complications (OR 0.48, 95% CI [0.30, 0.79]). In conclusion, eptifibatide given as abbreviated bolus only to selected STEMI patients who underwent primary PCI was noninferior regarding infarct size and resulted in less bleeding complications compared with conventional bolus and infusion treatment.

Levosimendan improves cardiac function in heart failure populations; however, its exact mechanism is not well defined. We analysed the short-term impact of levosimendan in heart failure patients with ischemic and non-ischemic cardiomyopathy (CMP) using multiparametric cardiac magnetic resonance (CMR). We identified 33 patients with ischemic or non-ischemic CMP who received two consecutive CMR scans prior to and within one week after levosimendan administration. Changes in LV ejection fraction (LVEF) and LV volumes, as well as changes in strain rates, were measured prior to and within one week after levosimendan infusion. LV scarring, based on late gadolinium enhancement (LGE), was correlated to changes in LV size and strain rates. Both LV endiastolic (EDV) and endsystolic volumes (ESV) significantly decreased (EDV: p=0,001; ESV: p=0,002) after levosimendan administration, with no significant impact on LVEF (p=0.41), cardiac output (p=0.61), and strain rates. Subgroup analyses of ischemic or non-ischemic CMP showed no significant differences between the groups in terms of short-term LV reverse remodeling. The presence and extent of scarring in LGE did not correlate with changes in LV size and strain rates. CMR is able to monitor cardiac effects of levosimendan infusion. Short-term follow-up of a single levosimendan infusion using CMR shows a significant decrease in LV size, but no impact on LVEF or strain measurements. There was no difference between patients with ischemic or non-ischemic CMP. Quantification of LV scarring in CMR is not able to predict changes in LV size and strain rates in response to levosimendan.

Various disturbances of social behavior, such as autism, depression, or posttraumatic stress disorder, have been associated with an altered steroid hormone homeostasis and a dysregulation of the hypothalamus–pituitary–adrenal axis. A link between steroid hormone antagonists and the treatment of stress-related conditions has been suggested. We evaluated the effects of stress induction on social behavior in the three chambers and its potential reversibility upon specific steroid hormone antagonism in mice. C57BL/6 mice were stressed twice daily for 8 days by chronic swim testing. Social behavior was evaluated by measuring, first, the preference for sociability and, second, the preference for social novelty in the three-chamber approach before and after the chronic swim test. The reversibility of behavior upon stress induction was analyzed after applying steroid hormone antagonists targeting glucocorticoids with etomidate, mineralocorticoids with potassium canrenoate, and androgens with cyproterone acetate and metformin. In the chronic swim test, increased floating time from 0.8 ± 0.2 min up to 4.8 ± 0.25 min was detected (p

The impacts of late gestation heat stress on the dam and her subsequent lactation are well-recognized. However, more recent research has demonstrated the long-lasting and severe negative consequences on the in-utero heat-stressed progeny. Dairy calves born to late gestation heat-stressed dams weigh less at birth and up to one year of age and have compromised metabolism and immune function. In-utero programming of these offspring may coordinate alterations in thermoregulation, mammary development, and milk synthetic capacity at different developmental windows. Thus, prenatally heat-stressed dairy heifers will produce less milk across multiple lactations and have a lower herd survival rate, potentially negatively impacting the U.S. dairy economy. Dry period heat stress abatement strategies should be considered not only for the productivity and welfare of the pregnant dam but also for the developing calf.

Records of late-gestation heat stress studies conducted over 10 consecutive years in Florida were pooled and analyzed to test the hypothesis that maternal hyperthermia during late gestation impairs performance of the offspring across multiple generations and lactations, ultimately impeding the profitability of the US dairy sector. Dry-pregnant multiparous dams were actively cooled (CL; shade of a freestall barn, fans and water soakers, n = 196) or not (HT; shade only, n = 198) during the last 46 d of gestation, concurrent with the entire dry period. After data mining, records of 156 daughters (F1) that were born either to CL (CLF1, n = 77) or HT dams (HTF1, n = 79) and 45 granddaughters (F2) that were born either to CLF1 (CLF2, n = 24) or HTF1 (HTF2, n = 21) were used in the analysis. Life events and daily milk yield for 3 lactations of daughters and granddaughters were obtained. Milk yield, reproductive performance, and productive life data were analyzed using MIXED and GLIMMIX procedures, and lifespan was analyzed using PHREG and LIFETEST procedures of SAS (SAS Institute Inc., Cary, NC). Milk production of HTF1 was reduced in their first (2.2 kg/d), second (2.3 kg/d), and third lactations (6.5 kg/d) compared with CLF1. More HTF1 were culled before first calving, and the productive life and lifespan of HTF1 were reduced relative to CLF1 (4.9 and 11.7 mo, respectively). The granddaughters (HTF2) born to HTF1 produced less milk in their first lactation (1.3 kg/d) relative to granddaughters (CLF2) born to CLF1. More HTF2 were culled before first breeding relative to CLF2; however, productive life and lifespan were not different between HTF2 and CLF2 animals. An economic analysis was then performed based on the number of heat stress days, dry cows per state, and the aforementioned impairments on daughters' lifespans and milk production. Collectively in the United States, the economic losses for additional heifer rearing cost, reduced productive life, and reduced milk yield of the F1 offspring were estimated at $134, $90, and $371 million per year, respectively. In summary, late-gestation heat stress exerts carryover effects on at least 2 generations. Providing heat abatement to dry-pregnant dams is important to rescue milk loss of the dam and to prevent losses in their progeny.

Background Urinary tract infections are one of the most common reasons for prescribing antibiotics in primary care. Current guidelines recommend fosfomycin, nitrofurantoin, or trimethoprim - sulfamethoxazol as empiric first line antimicrobial agents in uncomplicated infections. However, there is evidence that the use of fluoroquinolones, which are no longer recommended, is still inappropriate high. We determined antibiotic prescription patterns, quality and factors affecting antibiotic prescriptions in urinary tract infections in primary care in Switzerland. Methods From June 2017 to August 2018, we conducted a cross-sectional study in patients suffering from a urinary tract infection (UTI). Patient and general practitioners characteristics as well as antibiotic prescribing patterns were analysed. Results Antibiotic prescribing patterns in 1.352 consecutively recruited patients, treated in 163 practices could be analysed. In 950 (84.7%) patients with an uncomplicated UTI the prescriptions were according to current guidelines and therefore rated as appropriate. Fluoroquinolones were prescribed in 13.8% and therefore rated as inappropriate. In multivariable analysis, the age of the general practitioner was associated with increasing odds of prescribing a not guideline recommended antibiotic therapy. Conclusions We found a high degree of guideline conform antibiotic prescriptions in patients with an uncomplicated urinary tract infection in primary care in Switzerland. However, there is still a substantial use of fluoroquinolones in empiric therapy.

Background Women with vulvar neoplasia often complain about physical and psychological distress after surgical treatment. Lack of information and support can influence resilience. Whether an information-related intervention through an advanced practice nurse supports resilience and which other factors affect resilience in women with vulvar neoplasia has never been investigated. Methods The aims of this study were (a) to analyse whether counselling based on the WOMAN-PRO II program causes a significant improvement in the resilience scores of women with vulvar neoplasia compared to written information and (b) to identify the potential predictors of resilience. A randomized controlled trial was conducted in women with vulvar neoplasia (n = 49) 6 months after surgical treatment in four Swiss hospitals and one Austrian hospital. Analyses of resilience and its predictors were performed using a linear mixed model. Results Thirty-six women (intervention I, n = 8; intervention II, n = 28) completed the randomized controlled trial. In total, 13 women (26.5%) dropped out of the trial. The resilience score did not differ significantly between the two interventions three and six months after randomisation (p = 0.759). Age (b = .04, p = 0.001), social support (b = .28, p = 0.009), counselling time (b = .03, p = 0.018) and local recurrence (b = −.56, p = 0.009) were identified as significant predictors of resilience in the linear mixed model analyses. Conclusion The results indicate that the WOMAN-PRO II program as single intervention does not cause a significant change in the resilience scores of women with vulvar neoplasia 6 months after surgery. Predictors that promote or minimise resilience have been identified and should be considered when developing resilience programs for women with vulvar neoplasia. A repetition of the study with a larger sample size is recommended. Trial registration The WOMAN-PRO II program was registered in ClinicalTrials.gov NCT01986725 on 18 November 2013.

Prenatal heat stress during late gestation exerts long-term effects on growth and productivity of the dairy calf. Further, direct exposure to heat stress during the preweaning period impairs calf thermoregulation and performance. We examined the effects of heat stress abatement during the prenatal period, postnatal period, or both on calf performance. We hypothesized that calves exposed to pre- and postnatal heat stress abatement would perform most optimally in terms of thermoregulation, growth, and health responses when compared with calves that are heat-stressed at any time in the pre- or postnatal periods. Holstein calves born to heat-stressed (HT) or cooled (CL) dams during late gestation (44 ± 5 d; prenatal HT or CL) were exposed to heat stress or cooling postnatally for 56 d (postnatal HT or CL), resulting in 4 treatments: HT-HT, HT-CL, CL-HT, and CL-CL; n = 12/treatment. Calves were administered 4 L of pooled colostrum and after 2 d of age allotted 10 L/d milk replacer and up to 3 kg/d concentrate in automatic feeder group pens (n = 6/pen). Postnatal cooling was achieved by 2 fans (average wind speed 2 m/s). Thermoregulatory responses (respiration rate and heart rate; rectal, body, and skin temperature), feed intake, growth parameters including average daily gain and medication events were recorded, and blood samples were collected weekly. Thermoregulatory responses were lower in postnatal CL calves compared with postnatal HT. In the afternoon, HT-HT calves had the highest respiration rate and rectal temperature, HT-CL calves had the lowest respiration rate, and CL-HT calves had the lowest heart rate compared with the other treatment groups. Prenatal CL calves weighed more at birth and weaning with a tendency for greater average daily gain compared with prenatal HT calves, whereas postnatal CL calves had increased milk replacer and concentrate intake and a tendency for reduced fever, infection, and total medication events relative to postnatal HT. Prenatal HT calves were esophageal tube fed more often than prenatal CL. Blood hematocrit and 24-h serum IgG concentration were greater in prenatal CL calves relative to prenatal HT. Prenatal heat stress abatement improves weight gain, hematocrit, and immunoglobulin transfer, whereas postnatal heat stress abatement modulates thermoregulatory responses, feed intake, and calf health. This study is the first to characterize the combined effects of pre- and postnatal heat stress or active cooling on the dairy calf.

Prenatal hyperthermia has immediate and long-term consequences on dairy cattle growth, immunity, and productivity. While changes in the molecular architecture are reported in the mature mammary gland (MG), any influence on early-life mammary development is unknown. Herein, we characterize the impact of late-gestation in utero heat stress on heifer mammary gross and cellular morphology at early-life developmental stages (i.e., birth and weaning). During summer, pregnant dams were exposed to environmental heat stress (shade of a free-stall barn) or offered active cooling (shade, fans, and water soakers) for 54 ± 5 d before parturition (avg. temperature-humidity index = 79). Heifer calves born to these dams were either in utero heat-stressed (IU-HT; n = 36) or in utero cooled (IU-CL; n = 37) and were managed as a single cohort thereafter. A subset of heifers was euthanized at birth (d0; n = 8/treatment; 4.6 ± 2.3 h after birth) and after weaning (d63; n = 8/treatment; 63.0 ± 1.5 d) to harvest the whole MG. An ultrasound of rear mammary parenchyma (MPAR) was taken prior to d63 and correlated to harvested MPAR cross-sectional area and weight. Portions of mammary fat pad (MFP) and MPAR were preserved for compositional and histological analysis, including ductal structure number and cross-sectional area, connective tissue area, and adipocyte number and cross-sectional area. Cellular proliferation in MPAR was assessed via Ki-67 immunohistochemistry. Relative to IU-CL heifers, the MGs of IU-HT heifers were shorter in length at d0 and d63 (P ≤ 0.02). There were moderate correlations between d63 ultrasound and harvest measures. The IU-HT heifers had reduced MG and MFP mass at d0 and d63 (P ≤ 0.05), whereas MPAR mass was reduced only at d0 (P = 0.01). IU-HT heifers had greater MPAR protein and DNA content at d63 (P ≤ 0.04), but there were no MFP compositional differences (P ≥ 0.12). At d0, IU-HT heifers had fewer MPAR ductal structures (P ≤ 0.06), but there were no differences at d63. Yet, MPAR luminal and total ductal structure cross-sectional areas of IU-HT heifers were reduced at both d0 and d63 (P ≤ 0.01). The MFP adipocytes of IU-HT heifers were smaller at d0 (P ≤ 0.01), but differences were not detected at d63. The IU-HT heifers had diminished MPAR total, stromal, and epithelial cellular proliferation at both d0 and d63 (P0.01). Prenatal hyperthermia derails dairy calf early-life mammary development with potential carry-over consequences on future synthetic capacity.Late-gestation in utero heat stress in dairy cattle negatively affects the mammary microstructure and milk yield at maturity, but investigation into early-life windows of mammary development is needed to fully characterize the lifelong consequences of intrauterine heat stress on the mammary gland (MG). The present study quantified mammary gross morphology and mammary fat pad and parenchyma composition, tissue microstructure, and cellular proliferation at birth and after weaning from heifers exposed to late-gestation prenatal hyperthermia. The whole MGs and fat pads of in utero heat-stressed heifers are lighter across early life relative to in utero cooled heifers. The mammary parenchyma is smaller at birth with stunted ductal development and cellular proliferation at birth and after weaning. These impairments may limit later mammary epithelial development and impact long-term productivity.

Embryonic or fetal loss in cattle is associated with problems that occur during oocyte maturation, early embryonic development, conceptus elongation, maternal recognition of pregnancy (MRP), and/or placental attachment and implantation. Many of these problems manifest as inadequate or asynchronous communication between the developing conceptus and endometrium, resulting in pregnancy failure. This review will provide an overview of how various conceptus-endometrial paracrine signaling systems control the fate of early pregnancy in cattle and other ruminants. We begin by summarizing the actions of interferon-tau, the classic MRP signal in ruminates, and then explore how other secretory factors derived from either the conceptus or endometrium influence establishment and maintenance of pregnancy. Insight into how the endometrium responds to male vs. female conceptuses or conceptuses produced by in vitro methods will also be described. Specific focus will be placed on describing how "omic" technologies and other cutting-edge techniques have assisted with identifying novel conceptus and/or endometrial factors and their functions. Recent findings indicate that the endometrial transcriptome and histotroph are altered by conceptus sex, quality, and origin, suggesting that the endometrium is a sensor of conceptus biochemistry. Although the endometrium has a certain level of flexibility in terms of conceptus-maternal interactions, this interplay is not sufficient to retain some pregnancies. However, new information inspires us to learn more and will help develop technologies that mitigate early embryonic loss and reproductive failure in ruminants and other animals.Early pregnancy losses are common in cattle. This review describes how critical the interplay between the developing conceptus (embryo and extraembryonic membranes) and endometrium is to maintaining pregnancies in cattle and other ruminants. The discovery of interferon-tau more than 40 yr ago initiated a new field of reproductive biology focused on describing how the conceptus and endometrium communicate with one another through the secretion of paracrine factors, extracellular vesicles, and other molecules. The use of “omic” and gene editing technologies has assisted with identifying novel functions for many conceptus and endometrial secreted factors. This review provides examples of how conceptus sex, quality, and in vitro vs. in vivo development influences endometrial function. The endometrium appears to have some flexibility in its response to conceptuses, and this insight could be used to our advantage as we work towards developing schemes to rescue conceptuses that are in danger of experiencing pregnancy loss.

Background Financial incentives are often used to improve quality of care in chronic care patients. However, the evidence concerning the effect of financial incentives is still inconclusive. Objective To test the effect of financial incentives on quality measures (QMs) in the treatment of patients with diabetes mellitus in primary care. We incentivized a clinical QM and a process QM to test the effect of financial incentives on different types of QMs and to investigate the spill-over effect on non-incentivized QMs. Design/Participants Parallel cluster randomized controlled trial based on electronic medical records database involving Swiss general practitioners (GPs). Practices were randomly allocated. Intervention All participants received a bimonthly feedback report. The intervention group additionally received potential financial incentives on GP level depending on their performance. Main Measures Between-group differences in proportions of patients fulfilling incentivized QM (process QM of annual HbA1c measurement and clinical QM of blood pressure level below 140/95 mmHg) after 12 months. Key Results Seventy-one GPs (median age 52 years, 72% male) from 43 different practices and subsequently 3838 patients with diabetes mellitus (median age 70 years, 57% male) were included. Proportions of patients with annual HbA1c measurements remained unchanged (intervention group decreased from 79.0 to 78.3%, control group from 81.5 to 81.0%, OR 1.09, 95% CI 0.90–1.32, p = 0.39). Proportions of patients with blood pressure below 140/95 improved from 49.9 to 52.5% in the intervention group and decreased from 51.2 to 49.0% in the control group (OR 1.16, 95% CI 0.99–1.36, p = 0.06). Proportions of non-incentivized process QMs increased significantly in the intervention group. Conclusion GP level financial incentives did not result in more frequent HbA1c measurements or in improved blood pressure control. Interestingly, we could confirm a spill-over effect on non-incentivized process QMs. Yet, the mechanism of spill-over effects of financial incentives is largely unclear. Trial Registration ISRCTN13305645

Background Response guided treatment in breast cancer is highly desirable, but the effectiveness is only established based on residual cellularity from histopathological analysis after surgery. Tubule formation, a key component of grading score, is directly associated with cellularity, with significant implications on prognosis. Peri-tumoural lipid composition, a potential marker, can be rapidly mapped across the entire breast using novel method of chemical shift-encoded imaging, enabling the quantification of spatial distribution. We hypothesise that peri-tumoural spatial distribution of lipid composition is sensitive to tumour cellular differentiation and proliferative activity. Methods Twenty whole tumour specimens freshly excised from patients with invasive ductal carcinoma (9 Score 2 and 11 Score 3 in tubule formation) were scanned on a 3 T clinical scanner (Achieva TX, Philips Healthcare). Quantitative lipid composition maps were acquired for polyunsaturated, monounsaturated, and saturated fatty acids (PUFA, MUFA, SFA). The peri-tumoural spatial distribution (mean, skewness, entropy and kurtosis) of each lipid constituent were then computed. The proliferative activity marker Ki-67 and tumour-infiltrating lymphocytes (TILs) were assessed histologically. Results For MUFA, there were significant differences between groups in mean (p = 0.0119), skewness (p = 0.0116), entropy (p = 0.0223), kurtosis (p = 0.0381), and correlations against Ki-67 in mean (ρ = -0.5414), skewness (ρ = 0.6045) and entropy (ρ = 0.6677), and TILs in mean (ρ = -0.4621). For SFA, there were significant differences between groups in mean (p = 0.0329) and skewness (p = 0.0111), and correlation against Ki-67 in mean (ρ = 0.5910). For PUFA, there was no significant difference in mean, skewness, entropy or kurtosis between the groups. Conclusions There was an association between peri-tumoural spatial distribution of lipid composition with tumour cellular differentiation and proliferation. Peri-tumoural lipid composition imaging might have potential in non-invasive quantitative assessment of patients with breast cancer for treatment planning and monitoring.

Objective: to define the knowledge level among postpartum women affected by gestational diabetes and identify its association with women’s sociodemographic and clinical characteristics. Design and Setting: a cross-sectional comparative study was conducted. Data collection took place in a single university hospital in the German speaking part of Switzerland. Participants: a total of 107 postpartum women diagnosed with gestational diabetes in the current preg- nancy completed a gestational diabetes mellitus specific knowledge questionnaire (GDMKQ) in German or English in their postpartum period. Further, sociodemographic and clinical characteristics were collected. Results: Women were between 24 and 45 years old, 56.1% had an academic degree, 60.7% were migrant women coming mainly from other European countries, 17.8% had a previous history of gestational dia- betes, and 31.8% had a family history of diabetes. As measured with the GDMKQ, women with a higher educational level obtained higher scores and therefore showed a better knowledge level about gesta- tional diabetes compared to women with primary and secondary educational levels ( M 13.3 vs M 11.1 and 12.5; χ2 (2) = 13.003, p = .002). In addition, women with a previous history of gestational diabetes also reached higher scores compared to women with no history of gestational diabetes ( M 13.6 vs M 12.5, Z = −2.278, p = .023). Conclusion and implication for practice: Even if the knowledge status among women attending this single Swiss hospital is presently very good, a lower educational level was associated with a lower knowledge level and identified as the main factor to hinder women’s comprehension of gestational diabetes. More individually tailored consultations by health care professionals may serve to meet women’s needs more adequately and support them better in the understanding of their condition.

Objective We developed 2 intensity levels of a complex intervention for interprofessional supportive care in cancer (IPSC-C) to facilitate resilience and reduce unmet supportive care needs. We aimed to test the feasibility, acceptability, and preliminary effectiveness of both intensity levels in routine practice. Methods In a randomized, noncomparative phase II trial, newly diagnosed patients received either low (LI-IPSC-C) or high (HI-IPSC-C) intensity interventions. Low-intensity-interprofessional supportive care in cancer (LI-IPSC-C) consisted of 3 electronic assessments of resilience, unmet supportive care needs, mood, and coping effort over 16 weeks with an immediate feedback to clinicians including tailored intervention recommendations to facilitate resilience and supportive care. High-intensity-interprofessional supportive care in cancer (HI-IPSC-C) added 5 structured consultations (face-to-face and telephone) provided by specialized nurses. Primary outcome was a change ≥5 in resilience score on the Connor-Davidson Resilience Scale (CD-RISC). Secondary outcomes were unmet supportive care needs, mood, and coping effort. We assessed feasibility by clinician-provided tailored interventions as recommended and acceptability through qualitative interviews with clinicians and patients. Results In the LI-IPSC-C arm, 11 of 41, in the HI-IPSC-C arm 17 of 43, patients increased resilience scores by ≥5. Relatively more patients decreased unmet needs in HI-IPSC-C arm. Mood, in both arms, and coping effort, in HI-IPSC-C arm, improved meaningfully. Feasibility was limited for the LI-IPSC-C arm, mainly due to lack of time; acceptability was high in both arms. Conclusion Neither LI-IPSC-C nor HI-IPSC-C interventions reached the desired threshold. HI-IPSC-C showed positive effects on secondary outcomes and was feasible. Resilience as measured by the CD-RISC may not be the optimal outcome measure for this intervention.

BACKGROUND AND AIMS BougieCap (Ovesco Endoscopy AG, Tübingen, Germany) is a new device that allows optical and tactile feedback during stricture dilation of the upper gastrointestinal tract. We evaluated the technical feasibility, clinical efficacy, and safety of a one-time esophageal stricture dilation using BougieCap in adults with eosinophilic esophagitis (EoE). METHODS EoE patients prospectively included in the Swiss EoE Cohort were dilated with BougieCap in case of the presence of esophageal strictures (esophageal diameter ≤14 mm) and stricture-related symptoms. Symptoms were assessed before and 2 weeks after a single dilation session using the validated Eosinophilic Esophagitis Activity Index Patient Reported Outcomes (EEsAI PRO)instrument (score ranges from 0-100 points). RESULTS Fifty patients (70% male, median age 41 years, median disease duration of 4 years, 50% treated with swallowed topical corticosteroids, 10% with proton pump inhibitors, 14% with combined swallowed topical corticosteroids plus proton pump inhibitors, 14% with elimination diet, 12% without anti-eosinophil therapy) were evaluated. Endoscopic bougienage was technically successful in 100%. Median esophageal diameter increased from 12 mm (IQR 12-13) to 16 mm (IQR 16-16, p

Objective To assess whether point-of care procalcitonin and lung ultrasonography can safely reduce unnecessary antibiotic treatment in patients with lower respiratory tract infections in primary care. Design Three group, pragmatic cluster randomised controlled trial from September 2018 to March 2020. Setting 60 Swiss general practices. Participants One general practitioner per practice was included. General practitioners screen all patients with acute cough; patients with clinical pneumonia were included. Interventions Randomisation in a 1:1:1 of general practitioners to either antibiotics guided by sequential procalcitonin and lung ultrasonography point-of-care tests (UltraPro; n=152), procalcitonin guided antibiotics (n=195), or usual care (n=122). Main outcomes Primary outcome was proportion of patients in each group prescribed an antibiotic by day 28. Secondary outcomes included duration of restricted activities due to lower respiratory tract infection within 14 days. Results 60 general practitioners included 469 patients (median age 53 years (interquartile range 38-66); 278 (59%) were female). Probability of antibiotic prescription at day 28 was lower in the procalcitonin group than in the usual care group (0.40 v 0.70, cluster corrected difference −0.26 (95% confidence interval −0.41 to −0.10)). No significant difference was seen between UltraPro and procalcitonin groups (0.41 v 0.40, −0.03 (−0.17 to 0.12)). The median number of days with restricted activities by day 14 was 4 days in the procalcitonin group and 3 days in the usual care group (difference 1 day (95% confidence interval −0.23 to 2.32); hazard ratio 0.75 (95% confidence interval 0.58 to 0.97)), which did not prove non-inferiority. Conclusions Compared with usual care, point-of-care procalcitonin led to a 26% absolute reduction in the probability of 28 day antibiotic prescription without affecting patients’ safety. Point-of-care lung ultrasonography did not further reduce antibiotic prescription, although a potential added value cannot be excluded, owing to the wide confidence intervals. Trial registration ClinicalTrials.gov NCT03191071 .

OBJECTIVE: To compare the characteristics of and use of the healthcare system by healthy youths depending on whether they had discussed transition to adult health care with their paediatrician or not. METHODS: Data were drawn from the fourth wave of the GenerationFRee study (2018–2019) conducted in the 11 post-mandatory schools of the canton of Fribourg, Switzerland. The sample included 931 young people (mean age 19.4 years). Participants were categorised into three groups: those who had discussed transition with their p ediatrician (n = 176; 19%), those who had not (n = 286; 31%) and those who did not know (n = 469; 50%). Analyses were stratified by gender through bivariate analysis and post-hoc tests with a Bonferroni-type adjustment. RESULTS: The majority of participants did not know whether or not they had discussed transition. Across all groups, it was found that youths met their primary care physician at a higher rate through family. Meeting with the primary care physician through the paediatrician occurred at a higher rate when youths had discussed transition. Girls with a below average socioeconomic status and boys with advanced puberty onset were more likely to have discussed transition. CONCLUSION: Our results show that youths are not well informed about the transition process. However, youths who have discussed transition appear to be more involved with the healthcare system as they are more likely to have a primary care provider. In order to avoid discontinuity of care, professionals should approach transition to adult care systematically with all their patients.

Background Chronic obstructive pulmonary disease (COPD) is a major public health issue affecting approximately 4% to 7% of the Swiss population. According to current inpatient guidelines, systemic corticosteroids are important in the treatment of acute COPD exacerbations and should be given for 5 to 7 days. Several studies suggest that corticosteroids accelerate the recovery of FEV1 (forced expiratory volume in 1 second), enhance oxygenation, decrease the duration of hospitalization, and improve clinical outcomes. However, the additional therapeutic benefit regarding FEV1 recovery appears to be most apparent in the first 3 to 5 days. No data are available on the optimum duration of corticosteroid treatment in primary-care patients with acute COPD exacerbations. Given that many COPD patients are treated as outpatients, there is an urgent need to improve the evidence base on COPD management in this setting. The aim of this study is to investigate whether a 3-day treatment with orally administered corticosteroids is non-inferior to a 5-day treatment in acute exacerbations of COPD in a primary-care setting. Methods/design This study is a prospective double-blind randomized controlled trial conducted in a primary-care setting. It is anticipated that 470 patients with acutely exacerbated COPD will be recruited. Participants are randomized to receive systemic corticosteroid treatment of 40 mg prednisone daily for 5 days (conventional arm, n = 235) or for 3 days followed by 2 days of placebo (experimental arm, n = 235). Antibiotic treatment for 7 days is given to all patients with CRP ≥ 50 mg/l, those with a known diagnosis of bronchiectasis, or those presenting with Anthonisen type I exacerbation. Additional treatment after inclusion is left at the discretion of the treating general practitioner. Follow-up visits are performed on days 3 and 7, followed by telephone interviews on days 30, 90, and 180 after inclusion in the study. The primary endpoint is the time to next exacerbation during the 6-month follow-up period. Discussion The study is designed to assess whether a 3-day course of corticosteroid treatment is not inferior to the conventional 5-day treatment course in outpatients with exacerbated COPD regarding time to next exacerbation. Depending on the results, this trial may lead to a reduction in the cumulative corticosteroid dose in COPD patients. Trial registration ClinicalTrials.gov, NCT02386735. Registered on 12 March 2015.

Objective Access to primary care (PC) is vital, but complex to define and compare between settings. We aimed to generate a typology of patients’ access patterns across countries using a novel inductive approach. Design Cross-sectional surveys. Setting Australia, Canada, New Zealand and Switzerland between 2012 and 2014 as part of the QUALICO-PC project. Participants Data were collected from 1306 general practices and 10 000+ patients, with nine patients per practice. Intervention(s) None. Main Outcome Measure(s) Typology of access. Results Three axes were retained, explaining 23% of the total variance: (i) ‘temporal and geographical access’; (ii) ‘frequency of access and unmet healthcare needs’; and (iii) ‘affordability and frequency of access’. Based on the three axes, we identified four clusters of patients: (i) patients reporting overall good access to PC; (ii) frequent users with unmet healthcare needs; (iii) under-users with financial barriers; and (iv) users with poor time/geographical access. Better access to PC was experienced in Switzerland and New Zealand, while worst access was reported in Canada, where most of the time and geographical barriers were reported. Most financial barriers were observed in Australia and New Zealand. Frequent users with some level of unmet healthcare needs are prevalent in all four countries. Conclusions Four main groups of patients with different patterns of access were identified: (i) good access; (ii) geographical and time barriers; (iii) financial barriers; and (iv) frequent users with unmet healthcare needs. Differences in access between the four countries are substantial.

Background The 16th St. Gallen International Breast Cancer Conference 2019 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Design Treatments were assessed in light of their intensity, duration and side-effects, estimating the magnitude of clinical benefit according to stage and biology of the disease. The Panel acknowledged that for many patients, the impact of adjuvant therapy or the adherence to specific guidelines may have modest impact on the risk of breast cancer recurrence or overall survival. For that reason, the Panel explicitly encouraged clinicians and patients to routinely discuss the magnitude of benefit for interventions as part of the development of the treatment plan. Results The guidelines focus on common ductal and lobular breast cancer histologies arising in generally healthy women. Special breast cancer histologies may need different considerations, as do individual patients with other substantial health considerations. The panelists' opinions reflect different interpretation of available data and expert opinion where is lack of evidence and sociocultural factors in their environment such as availability of and access to medical service, economic resources and reimbursement issues. Panelists encourage patient participation in well-designed clinical studies whenever available. Conclusions With these caveats in mind, the St. Gallen Consensus Conference seeks to provide guidance to clinicians on appropriate treatments for early-stage breast cancer and guidance for weighing the realistic tradeoffs between treatment and toxicity so that patients and clinical teams can make well-informed decisions on the basis of an honest reckoning of the magnitude of clinical benefit.

Leptin receptor (LepR) signaling in neurons of the ventromedial nucleus of the hypothalamus (VMH), specifically those expressing steroidogenic factor-1 (SF1), have been proposed to play a key role in controlling energy balance. By crossing LepR-silenced (LepRloxTB) mice with those expressing SF1-Cre, we unsilenced native LepR specifically in the VMH and tested whether SF1 neurons in the VMH are critical mediators of leptin’s effect on energy homeostasis. LepRloxTB × SF1-Cre [knockout (KO)/Tg+] mice were metabolically phenotyped and compared with littermate controls that either expressed or were deficient in LepRs. Leptin-induced phosphorylated STAT3 was present in the VMH of KO/Tg+ mice and absent in other hypothalamic nuclei. VMH leptin signaling did not ameliorate obesity resulting from LepR deficiency in chow-fed mice. There was no change in food intake or energy expenditure when comparing complete LepR-null mice with KO/Tg+ mice, nor did KO/Tg+ mice show improved glucose tolerance. The presence of functional LepRs in the VMH mildly enhanced sensitivity to the pancreatic hormone amylin. When maintained on a high-fat diet (HFD), there was no reduction in diet-induced obesity in KO/Tg+ mice, but KO/Tg+ mice had improved glucose tolerance after 7 wk on an HFD compared with LepR-null mice. We conclude that LepR signaling in the VMH alone is not sufficient to correct metabolic dysfunction observed in LepR-null mice.

Context Ankle plantarflexion is thought to play an important role in swimming performance; thus, coaches and swimmers often seek ways to increase range of motion (ROM) in the ankles. Objective To assess whether osteopathic manipulative treatment (OMT), specifically applying the muscle energy technique (MET) principle of post–isometric relaxation, increases ankle plantarflexion and therefore improves swimming performance. Methods Healthy young male and female competitive swimmers were randomly assigned to either a control, sham, or MET group. At baseline, ankle plantarflexion was measured via goniometer, and a 25-yard flutter kick swim with a kickboard was timed. After receiving the ascribed intervention, the ankle plantarflexion measurements and timed flutter kick were repeated. The initial plantarflexion measurement was retrospectively used to determine the presence of somatic dysfunction, by way of restricted motion, with reference to expected normal ranges based on age and gender. Paired t tests were used to analyze the pre- to postintervention changes in ROM and flutter kick speed within each group. Results Fifty-five swimmers (32 girls and 23 boys; mean age, 12 years) participated in this study. Sixteen participants were in the control group, 17 in the sham group, and 22 in the MET intervention group. Among participants with restricted ROM, those in the MET group showed a statistically significant increase in ankle plantarflexion for the left and right ankles (P=.041 and P=.011, respectively). There was no significant difference in ROM of the control or sham groups. For flutter kick speed, there was no significant pre- to postintervention difference in any group. Conclusion Although a single application of MET, using post–isometric relaxation, on participants with restricted ROM immediately significantly increased swimmers’ ROM for bilateral ankle plantarflexion, it did not immediately improve their swimming performance.

Background We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses. Methods Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 and August 2017 at single centers in Germany (H10N8) and USA (H7N9). Healthy adults (ages 18–64 years for H10N8 study; 18–49 years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3 weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400 µg and intradermal dose levels of 25 and 50 µg were evaluated. H7N9 IM 10-, 25-, and 50-µg dose levels were evaluated; 2-dose series 6 months apart was also evaluated. Primary endpoints were safety (adverse events) and tolerability. Secondary immunogenicity outcomes included humoral (hemagglutination inhibition [HAI], microneutralization [MN] assays) and cell-mediated responses (ELISPOT assay). Results H10N8 and H7N9 mRNA IM vaccines demonstrated favorable safety and reactogenicity profiles. No vaccine-related serious adverse event was reported. For H10N8 (N = 201), 100-µg IM dose induced HAI titers ≥ 1:40 in 100% and MN titers ≥ 1:20 in 87.0% of participants. The 25-µg intradermal dose induced HAI titers > 1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (N = 156), IM doses of 10, 25, and 50 µg achieved HAI titers ≥ 1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titers ≥ 1:20 were achieved by 100% in the 10- and 25-µg groups and 96.6% in the 50-µg group. Seroconversion rates were 78.3% (HAI) and 87.0% (MN) for H10N8 (100 µg IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50 µg). Significant cell-mediated responses were not detected in either study. Conclusions The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses. ClinicalTrials.gov NCT03076385 and NCT03345043 .

Background Brown adipose tissue (BAT) has been proposed as a target to treat obesity and metabolic disease. Currently, 18 F-Fluordeoxyglucose positron emission tomography (FDG-PET) is the standard for BAT-imaging. MRI might be a promising alternative, as it is not associated with ionizing radiation, offers a high resolution, and allows to discriminate different types of soft tissue. Purpose We sought to evaluate whether supraclavicular BAT (scBAT) volume, fat-fraction (FF), and relaxation rate (R2*) determined by MRI can predict its metabolic activity, which was assessed by measurement of cold-induced thermogenesis (CIT). Study type Prospective cohort study. Subjects Twenty healthy volunteers (9 female, 11 male), aged 18-47 years, with a body mass index (BMI) of 18-30 kg/m2 . Field strength/sequence Multiecho gradient MRI for water-fat separation was used on a 3T device to measure the FF and T2 * of BAT. Assessment Prior to imaging, CIT was determined by measuring the difference in energy expenditure (EE) during warm conditions and after cold exposure. Volume, FF, and R2* of scBAT was assessed and compared with CIT. In 11 participants, two MRI sessions with and without cold exposure were performed and the dynamic changes in FF and R2* assessed. Statistical tests Linear regression was used to evaluate the relation of MRI measurements and CIT. P-values below 0.05 were considered significant; data are given as mean ± SD. Results R2* correlated positively with CIT (r = 0.64, R2 = 0.41 P = 0.0041). Volume and FF did not correlate significantly with CIT. After mild cold exposure EE increased significantly (P = 0.0002), with a mean CIT of 147 kcal/day. The mean volume of scBAT was 72.4 ± 38.4 ml, mean FF was 74.3 ± 5.8%, and the mean R2* (1/T2 *) was 33.5 ± 12.7 s-1 . Data conclusion R2* of human scBAT can be used to estimate CIT. FF of scBAT was not associated with CIT. Level of evidence 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1160-1168.

Background GPs frequently prescribe antidepressants in mild depression. The aim of this study was to examine, how often Swiss GPs recommend antidepressants in various clinical presentations of mild depression and which factors contribute to antidepressant treatment recommendations. Methods We conducted an online survey among Swiss GPs with within-subject effect analysis. Alternating case vignettes described a typical female case of mild depression according to International Classification of Diseases, 10th edition criteria, with and without anxiety symptoms and sleep problems. GPs indicated for each vignette their preferred treatments (several recommendations were possible). Additionally, we assessed GP characteristics, attitudes towards depression treatments, and elements of clinical decision-making. Results Altogether 178 GPs completed the survey. In the initial description of a case with mild depression, 11% (95%-CI: 7%-17%) of GPs recommended antidepressants. If anxiety symptoms were added to the same case, 29% (23%-36%) recommended antidepressants. If sleep problems were mentioned, 47% (40%-55%) recommended antidepressants, and if both sleep problems and anxiety symptoms were mentioned, 63% (56%-70%) recommended antidepressants. Several factors were independently associated with increased odds of recommending antidepressants, specifically more years of practical experience, an advanced training in psychosomatic and psychosocial medicine, self-dispensation, and a higher perceived effectiveness of antidepressants. By contrast, a higher perceived influence of patient characteristics and the use of clinical practice guidelines were associated with reduced odds of recommending antidepressants. Conclusions Consistent with depression practice guidelines, Swiss GPs rarely recommended antidepressants in mild depression if no co-indications (i.e., sleep problems and anxiety symptoms) were depicted. However, presence of sleep problems and anxiety symptoms, many years of practical experience, overestimation of antidepressants’ effectiveness, self-dispensation, an advanced training in psychosomatic and psychosocial medicine, and non-use of clinical practice guidelines may independently lead to antidepressant over-prescribing. Supplementary Information The online version contains supplementary material available at 10.1186/s12875-021-01621-7.

Purpose: Hearing loss is characterized by an extensive genetic heterogeneity and remains a common disorder in children. Molecular diagnosis is of particular benefit in children, and permits the early identification of clinically-unrecognized hearing loss syndromes, which permits effective clinical management and follow-up, including genetic counselling. Methods: We performed whole-exome sequencing with the analysis of a panel of 189 genes associated with hearing loss in a prospective cohort of 61 children and 9 adults presenting mainly with isolated hearing loss. Results: The overall diagnostic rate using exome sequencing was 47.2% (52.5% in children, 22% in adults). In children with confirmed molecular results, 17/32 (53.2%) showed autosomal recessive inheritance patterns, 14/32 (43.75%) showed an autosomal dominant condition, and one case had X-linked hearing loss. In adults, the two patients showed an autosomal dominant inheritance pattern. Among the 32 children, 17 (53.1%) had nonsyndromic hearing loss and 15 (46.7%) had syndromic hearing loss. One adult was diagnosed with syndromic hearing loss and one with nonsyndromic hearing loss. The most common causative genes were STRC (5 cases), GJB2 (3 cases), COL11A1 (3 cases), and ACTG1 (3 cases). Conclusions: Exome sequencing has a high diagnostic yield in children with hearing loss and can reveal a syndromic hearing loss form before other organs/systems become involved, allowing the surveillance of unrecognized present and/or future complications associated with these syndromes.

The optimal approach to feeding preschool children balances expectation setting (demandingness) with responsivity to the child (responsiveness), and ideal feeding practices use environmental structuring and covert, non-directive control strategies while maintaining responsiveness. However, research has not examined the extent to which demandingness and responsiveness in feeding style is concordant with structure, responsiveness and control (directive and non-directive) in feeding practices. We classified the feeding style of 122 parents of preschoolers as authoritative (high demandingness/high responsiveness), authoritarian (high demandingness/low responsiveness), indulgent (low demandingness/high responsiveness), or uninvolved (low demandingness/low responsiveness). Parents reported on their frequency of use of 31 vegetable parenting practices (VPPs), that were classified into the domains of structure, control and responsiveness, and subcategorized as effective (likely to obtain the desired change without increasing child obesity risk) or ineffective (unlikely or increases risk) by expert consensus. We hypothesized that parents with an authoritative feeding style would have the highest effective structure, responsiveness and control VPPs, and the authoritarian style would differ with less responsiveness VPPs. We also hypothesized that the indulgent feeding style would have low levels of structure and control VPPs and high ineffective responsiveness VPPs. As expected, we found that parents with an authoritative feeding style reported using more effective structure and responsiveness VPPs. Surprisingly, parents with an authoritarian feeding style did not have VPPs which differed from those with an authoritative feeding style, and parents with an indulgent feeding style had surprisingly high effective control VPPs. Further research into the similarities and differences between parents' overall approach to feeding and their use of feeding practices related to specific foods is warranted, which may help inform the design of more effective interventions aimed at improving child dietary quality.

Trust in leaders is central to citizen compliance with public policies. One potential determinant of trust is how leaders resolve conflicts between utilitarian and non-utilitarian ethical principles in moral dilemmas. Past research suggests that utilitarian responses to dilemmas can both erode and enhance trust in leaders: sacrificing some people to save many others (‘instrumental harm’) reduces trust, while maximizing the welfare of everyone equally (‘impartial beneficence’) may increase trust. In a multi-site experiment spanning 22 countries on six continents, participants (N = 23,929) completed self-report (N = 17,591) and behavioural (N = 12,638) measures of trust in leaders who endorsed utilitarian or non-utilitarian principles in dilemmas concerning the COVID-19 pandemic. Across both the self-report and behavioural measures, endorsement of instrumental harm decreased trust, while endorsement of impartial beneficence increased trust. These results show how support for different ethical principles can impact trust in leaders, and inform effective public communication during times of global crisis. Protocol Registration Statement: The Stage 1 protocol for this Registered Report was accepted in principle on 13 November 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.13247315.v1.

Background In Switzerland, there is a lack of adequate rehabilitation services, and effective coordination, that take into account the multifactorial health risks of older people. The literature shows that the hospitalisation rate in rehabilitation facilities has increased in recent years and that a gender bias exists. Additionally, there is little or no evidence available on the effect that a post-acute care programme might have over an extended period on functioning, quality of life and the informal network of older people. Therefore, the aim of this trial is to evaluate the sustainability of post-acute care within three nursing homes in Zurich, Canton of Zurich, Switzerland. Methods The Prevention Admission into Nursing homes (PAN) study is a explorative, prospective, longitudinal pilot trial based on a convenience sample of three long-term care facilities in the Swiss Canton of Zurich. The proposed pilot study will examine the effects of a post-acute care programme on people aged ≥65 years with a post-acute care potential ≥ three admitted to any of the three post-acute care units (n = 260). Older people of all sexes admitted to one of the post-acute care units and likely to be discharged to home within 8 weeks will be eligible for participation in the study. The primary endpoint is functionality based on the Barthel Index. The secondary endpoints are independency based on delirium, cognition, mobility, falling concerns, frailty, weight/height/body mass index, post-acute care capability, quality of life, and lastly, the informal network. As part of process evaluation, a qualitative evaluation will be conducted based on constructive grounded theory to specifically analyse how the experience of informal caregivers (n = 30) can contribute to a successful daily life 6 months after discharge. Discussion We expect to observe improved functional status and independence after the post-acute care programme. The qualitative evaluation conducted with caregivers will complement our description of the transition of older people towards living at home. Trial registration This study is registered in the German Clinical Trials Register under DRKS00016647 (registered on 23.05.2019).

Background Reduced fatty acid oxidation (FAO) is a hallmark of metabolic remodeling in heart failure. Enhancing mitochondrial long-chain fatty acid uptake by Acetyl-CoA carboxylase 2 (ACC2) deletion increases FAO and prevents cardiac dysfunction during chronic stresses, but therapeutic efficacy of this approach has not been determined. Methods Male and female ACC2 f/f-MCM (ACC2KO) and their respective littermate controls were subjected to chronic pressure overload by TAC surgery. Tamoxifen injection 3 weeks after TAC induced ACC2 deletion and increased FAO in ACC2KO mice with pathological hypertrophy. Results ACC2 deletion in mice with pre-existing cardiac pathology promoted FAO in female and male hearts, but improved cardiac function only in female mice. In males, pressure overload caused a downregulation in the mitochondrial oxidative function. Stimulating FAO by ACC2 deletion caused unproductive acyl-carnitine accumulation, which failed to improve cardiac energetics. In contrast, mitochondrial oxidative capacity was sustained in female pressure overloaded hearts and ACC2 deletion improved myocardial energetics. Mechanistically, we revealed a sex-dependent regulation of PPARα signaling pathway in heart failure, which accounted for the differential response to ACC2 deletion. Conclusion Metabolic remodeling in the failing heart is sex-dependent which could determine the response to metabolic intervention. The findings suggest that both mitochondrial oxidative capacity and substrate preference should be considered for metabolic therapy of heart failure.

Recently, the World Health Organization confirmed 120 new human cases of avian H7N9 influenza in China resulting in 37 deaths, highlighting the concern for a potential pandemic and the need for an effective, safe, and high-speed vaccine production platform. Production speed and scale of mRNA-based vaccines make them ideally suited to impede potential pandemic threats. Here we show that lipid nanoparticle (LNP)-formulated, modified mRNA vaccines, encoding hemagglutinin (HA) proteins of H10N8 (A/Jiangxi-Donghu/346/2013) or H7N9 (A/Anhui/1/2013), generated rapid and robust immune responses in mice, ferrets, and nonhuman primates, as measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. A single dose of H7N9 mRNA protected mice from a lethal challenge and reduced lung viral titers in ferrets. Interim results from a first-in-human, escalating-dose, phase 1 H10N8 study show very high seroconversion rates, demonstrating robust prophylactic immunity in humans. Adverse events (AEs) were mild or moderate with only a few severe and no serious events. These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles., Potential pandemic influenzas and the need for an effective, safe, and high-speed vaccine production platform have been widely discussed in the scientific community. Bahl et al. report the rapid and robust immune responses achieved against H10N8 and H7N9 viruses from modified mRNA vaccines with an acceptable safety profile.

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).

BACKGROUND SARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world with several million victims in 213 countries. Switzerland was severely hit by the virus, with 43,000 confirmed cases as of 1 September 2020. AIM In cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19, in addition to their mandatory reporting system. METHODS Patients hospitalised for more than 24 hours with a positive polymerase chain-reaction test, from 20 Swiss hospitals, are included. Data were collected in a customised case report form based on World Health Organisation recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms was more than 5 days after the patient’s admission date. RESULTS As of 1 September 2020, 3645 patients were included. Most patients were male (2168, 59.5%), and aged between 50 and 89 years (2778, 76.2%), with a median age of 68 (interquartile range 54–79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported, with hypertension (1481, 61.7%), cardiovascular diseases (948, 39.5%) and diabetes (660, 27.5%) being the most frequent in adults; respiratory diseases and asthma (4, 21.1%), haematological and oncological diseases (3, 15.8%) were the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly respiratory diseases (2470, 93.2% in adults; 16, 55.2% in children), and renal (681, 25.7%) and cardiac (631, 23.8%) complications for adults. The second and third most frequent complications in children affected the digestive system and the liver (7, 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989, 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. A total of 527 (14.5%) deaths were registered, all among adults. CONCLUSION The surveillance system has been successfully initiated and provides a robust set of data for Switzerland by including about 80% (compared with official statistics) of SARS-CoV-2/COVID-19 hospitalised patients, with similar age and comorbidity distributions. It adds detailed information on the epidemiology, risk factors and clinical course of these cases and, therefore, is a valuable addition to the existing mandatory reporting.

Objective To evaluate in vitro oocyte maturation rates in embryonic culture medium after induction by hyperosmotic shock caused by exposure to vitrification solutions. Methods Bilateral oophorectomy was performed on 20 prepubescent female mice (Swiss). Immature (Prophase I) oocytes (N = 400) were obtained by ovarian dissection, divided into 4 groups, and transferred to culture dishes containing fertilization medium (Sydney IVF Fertilization Medium, Cook® Medical). The control group (CG) did not receive treatment, the test groups (G1, G2, G3) were treated with vitrification solution - 2 (VI-2: 14 M sucrose + ethylene glycol and dimethyl sulfoxide) for 30 seconds and subsequently: G1: 30 seconds in devitrification solution - 2 (DV-2: 0.5M sucrose); G2: 60 seconds DV-2; G3: 60 seconds DV-1(1M sucrose) and 180 seconds DV-2. All groups were cultivated for 24 hours in an incubator at 37oC and 5% CO2 (Thermo model 3110). After this period, we checked their maturation status. Results Oocytes exposed to VI-2, DV-1 and DV-2 (G3) showed the highest rate of competence in resuming meiosis and reaching the MII stage; however, there was no statistically significant difference (G3 = 50.5% - 49/97; CG = 27.8% - 10/30). Conclusions Oocyte exposure to vitrification solutions, in order to cause osmotic shock, did not interfere with the resumption of meiosis in mice oocytes.