bluuebunny/crossref_metadata_2025_split huggingface dataset:
CaMKII does not control mitochondrial Ca2+ uptake in cardiac myocytes
Authors: Nickel Alexander G. , Kohlhaas Michael , Bertero Edoardo , Wilhelm Daniel , Wagner Michael , Sequeira Vasco , Kreusser Michael M. , Dewenter Matthias , Kappl Reinhard , Hoth Markus , Dudek Jan , Backs Johannes , Maack Christoph 
Published: February 2019

Key points
Mitochondrial Ca2+ uptake stimulates the Krebs cycle to regenerate the reduced forms of pyridine nucleotides (NADH, NADPH and FADH2) required for ATP production and reactive oxygen species (ROS) elimination.
Ca2+/calmodulin‐dependent protein kinase II (CaMKII) has been proposed to regulate mitochondrial Ca2+ uptake via mitochondrial Ca2+ uniporter phosphorylation.
We used two mouse models with either global deletion of CaMKIIδ (CaMKIIδ knockout) or cardiomyocyte‐specific deletion of CaMKIIδ and γ (CaMKIIδ/γ double knockout) to interrogate whether CaMKII controls mitochondrial Ca2+ uptake in isolated mitochondria and during β‐adrenergic stimulation in cardiac myocytes.
CaMKIIδ/γ did not control Ca2+ uptake, respiration or ROS emission in isolated cardiac mitochondria, nor in isolated cardiac myocytes, during β‐adrenergic stimulation and pacing.
The results of the present study do not support a relevant role of CaMKII for mitochondrial Ca2+ uptake in cardiac myocytes under physiological conditions.
AbstractMitochondria are the main source of ATP and reactive oxygen species (ROS) in cardiac myocytes. Furthermore, activation of the mitochondrial permeability transition pore (mPTP) induces programmed cell death. These processes are essentially controlled by Ca2+, which is taken up into mitochondria via the mitochondrial Ca2+ uniporter (MCU). It was recently proposed that Ca2+/calmodulin‐dependent protein kinase II (CaMKII) regulates Ca2+ uptake by interacting with the MCU, thereby affecting mPTP activation and programmed cell death. In the present study, we investigated the role of CaMKII under physiological conditions in which mitochondrial Ca2+ uptake matches energy supply to the demand of cardiac myocytes. Accordingly, we measured mitochondrial Ca2+ uptake in isolated mitochondria and cardiac myocytes harvested from cardiomyocyte‐specific CaMKII δ and γ double knockout (KO) (CaMKIIδ/γ DKO) and global CaMKIIδ KO mice. To simulate a physiological workload increase, cardiac myocytes were subjected to β‐adrenergic stimulation (by isoproterenol superfusion) and an increase in stimulation frequency (from 0.5 to 5 Hz). No differences in mitochondrial Ca2+ accumulation were detected in isolated mitochondria or cardiac myocytes from both CaMKII KO models compared to wild‐type littermates. Mitochondrial redox state and ROS production were unchanged in CaMKIIδ/γ DKO, whereas we observed a mild oxidation of mitochondrial redox state and an increase in H2O2 emission from CaMKIIδ KO cardiac myocytes exposed to an increase in workload. In conclusion, the results obtained in the present study do not support the regulation of mitochondrial Ca2+ uptake via the MCU or mPTP activation by CaMKII in cardiac myocytes under physiological conditions.
Validity of ICD-10-CM codes for determination of diabetes type for persons with youth-onset type 1 and type 2 diabetes
Authors: Chi Gloria C , Li Xia , Tartof Sara Y , Slezak Jeff M , Koebnick Corinna , Lawrence Jean M. 
Published: February 2019

ObjectiveDiagnosis codes might be used for diabetes surveillance if they accurately distinguish diabetes type. We assessed the validity ofInternational Classification of Disease, 10th Revision, Clinical Modification(ICD-10-CM) codes to discriminate between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) among health plan members with youth-onset (diagnosis age <20 years) diabetes.Research design and methods. Diabetes case identification and abstraction of diabetes type was done as part of the SEARCH for Diabetes in Youth Study. The gold standard for diabetes type is the physician-assigned diabetes type documented in patients’ medical records. Using all healthcare encounters with ICD-10-CM codes for diabetes, we summarized codes within each encounter and determined diabetes type using percent of encounters classified as T2DM. We chose 50% as the threshold from a receiver operating characteristic curve because this threshold yielded the largest Youden’s index. Persons with ≥50% T2DM-coded encounters were classified as having T2DM. Otherwise, persons were classified as having T1DM. We calculated sensitivity, specificity, positive and negative predictive values, and accuracy overall and by demographic characteristics.ResultsAccording to the gold standard, 1911 persons had T1DM and 652 persons had T2DM (mean age (SD): 19.1 (6.5) years). We obtained 90.6% (95% CI 88.4% to 92.9%) sensitivity, 96.3% (95% CI 95.4% to 97.1%) specificity, 89.3% (95% CI 86.9% to 91.6%) positive predictive value, 96.8% (95% CI 96.0% to 97.6%) negative predictive value, and 94.8% (95% CI 94.0% to 95.7%) accuracy for discriminating T2DM from T1DM.ConclusionsICD-10-CM codes can accurately classify diabetes type for persons with youth-onset diabetes, showing promise for rapid, cost-efficient diabetes surveillance.
Body image dissatisfaction in patients with inflammatory bowel disease: a systematic review
Authors: Beese Sophie Elizabeth , Harris Isobel Marion , Dretzke Janine , Moore David 
Published: February 2019

Background and aimsLittle is known about the relationship between inflammatory bowel disease (IBD) and body image. The aim of this systematic review was to summarise the evidence on body image dissatisfaction in patients with IBD across four areas: (1) body image tools, (2) prevalence, (3) factors associated with body image dissatisfaction in IBD and (4) association between IBD and quality of life.MethodsTwo reviewers screened, selected, quality assessed and extracted data from studies in duplicate. EMBASE, MEDLINE, PsycINFO and Cochrane CENTRAL were searched to April 2018. Study design–specific critical appraisal tools were used to assess risk of bias. Narrative analysis was undertaken due to heterogeneity.ResultsFifty-seven studies using a body image tool were included; 31 for prevalence and 16 and 8 for associated factors and association with quality of life, respectively. Studies reported mainly mean or median scores. Evidence suggested female gender, age, fatigue, disease activity and steroid use were associated with increased body image dissatisfaction, which was also associated with decreased quality of life.ConclusionThis is the first systematic review on body image in patients with IBD. The evidence suggests that body image dissatisfaction can negatively impact patients, and certain factors are associated with increased body image dissatisfaction. Greater body image dissatisfaction was also associated with poorer quality of life. However, the methodological and reporting quality of studies was in some cases poor with considerable heterogeneity. Future IBD research should incorporate measurement of body image dissatisfaction using validated tools.
Analytical accuracy of the handheld PICO monitoring device during emergencies
Authors: Renier Walter Sylvain , Erard Koen , Sabbe Marc , Hubloue Ives , Verbakel Jan Y , Aertgeerts Bert , Buntinx Frank 
Published: February 2019

IntroductionGeneral practitioners (GP) use few technical devices during emergency situations. They have to recognise which patients have a life-threatening disease in order to treat or refer them appropriately. Monitoring by a wearable device could help GPs while waiting for the emergency physician to arrive. The PICO monitor is a handheld monitoring device, capable of registering five routine parameters and small enough to be carried in the GP’s bag. We aim to determine the analytical accuracy of the PICO monitor in adults, comparing the recorded vital signs and ECGs of the PICO with those of a standard emergency department (ED) monitor.MethodsAdult (≥18 years) patients, admitted on two inpatient university EDs in Belgium, were recruited. We recorded the SpO2, heart rate (HR), respiration rate (RR), temperature (T°) and 5-lead ECGs. We analysed the correlation and agreement between the continuous and dichotomous variables of the PICO and the ED monitors.ResultsWe included 226 patients (84% of 268 approached), mean age 66 years, 61% were men. The Bland and Altman analysis confirmed the good accuracy, giving a nearly perfect agreement for SpO2(difference —0.9%), for HR (−1.5 beats), for RR between the monitors (0.1 breaths), for RR between the manually counted and the PICO or the monitor (respectively 0.2 and 0.0 breaths), also confirmed by the regression analysis (Passing-Bablok). Analysis of 219 ECG records provided a near perfect agreement between the devices (kappa respectively 0.61–0.80 and 0.81–1.00) for the most important ECG abnormalities. In none of the comparisons, differences were clinically relevant.ConclusionWe were able to confirm the analytical accuracy of the PICO monitor in comparison with the ED monitors. The PICO monitor can be considered a reliable device for monitoring patients during emergencies by GPs and even in ambulances or EDs as a mobile alternative.
Telephone announcements encouraging common cold self-management reduce demand for general practice appointments
Authors: Kerr Robin , Grainger Alan , Messer Carol , Kerr Hamish 
Published: February 2019

BackgroundPatients consulting with the common cold contribute to seasonal demand for general practice appointments. Seeing a community pharmacist or using self-management may have been more appropriate options. The study aimed to measure if the use of telephone announcements signposting appropriate patients with the common cold in the direction of community pharmacy or self-management reduced demand for general practice consultations.MethodsPatients telephoning a UK general practice to request an appointment between December 2017 and March 2018 heard announcements regarding management of the common cold. The percentage of callers choosing to continue to speak to a receptionist was compared with baseline data prior to the intervention. The mean waiting time to the third available routine general practice appointment during the intervention was compared with the previous year.ResultsRoutine calls continuing to reception reduced by 5.5 % (p<0.001) when the incidence of the common cold is at its highest and by 3.9% (p<0.001) throughout the intervention. The mean waiting time to the third available routine appointment reduced by 21%.ConclusionThis study has demonstrated that the use of telephone announcements signposting appropriate patients with the common cold in the direction of community pharmacy or self-management reduces calls to reception. This strongly infers that the telephone announcements reduce demand for general practice appointments and is supported by the reduced mean waiting time to the third available routine appointment. Implementation of this intervention could help general practitioners reduce seasonal demand in their own practices.
Does sector matter for the quality of care services? A secondary analysis of social care services regulated by the Care Inspectorate in Scotland
Authors: Bach-Mortensen Anders Malthe , Montgomery Paul 
Published: February 2019

ObjectivesSocial services are increasingly commissioned to third and for-profit sector providers, but little is known about whether and how these changes influence quality indicators. We assessed quality-related outcomes across for-profit, public and third sector organisations delivering social care services.DesignA secondary analysis was conducted on publically available data collected by the independent regulator of social care organisations in Scotland. All outcomes are reported as predicted probabilities derived from multivariate logistic regression coefficients. Generalised ordered logit models are utilised for the quality domains and the risk assessment score and logistic regression for whether complaints or requirements were issued to organisations.SettingOrganisations inspected by the Care Inspectorate in Scotland.Population13 310 social care organisations (eg, nursing homes and day care organisations).Primary outcomesThe quality and risk domains collected by the Care Inspectorate and complaints and requirements issued to organisations within the last 3 years.ResultsControlling for multiple factors, we find that public and third sector providers performed consistently and statistically significantly better than for-profit organisations on most outcomes. For example, for-profit services were the most likely to be rated as high and medium risk (6.9% and 13.2%, respectively), and the least likely to be classified as low risk (79.9%). Public providers had the highest probability of being categorised as low risk (91.1%), and the lowest probability of having their services classified as medium (6.9%) and high risk (2%), followed by third sector providers (86%, 8.5% and 4.5%, respectively). Public providers performed better than third sector providers in some outcomes, but differences were relatively low and inconsistent.ConclusionPublic and third sector providers were rated considerably higher than their for-profit counterparts on most observed outcomes. Regulators might use this information to consider how social care providers across sector are incentivised to manage their resources.
Can a tool developed for industry be used to assess fatigue risk in medical rotas? A pilot study of foundation doctors’ rotas in a tertiary centre
Authors: Cumber Elspeth , Greig Paul Robert 
Published: February 2019

ObjectivesTo determine the feasibility and ease of using a pre-existing health and safety executive fatigue risk calculator to assess doctors’ rotas.DesignObservational.SettingA large tertiary-referral teaching hospital in the UK.Participants95 anonymised foundation years 1 and 2 rotas in General Medicine, General Surgery and Emergency Medicine covering a 4-month period. All rotas provided by rota coordinators were included and assessed.InterventionsRotas were assessed for two indices: relative risk of fatigue-related errors compared with a ‘2-day, two-night, four-off’ shift pattern and percentage chance of a high score on a standardised sleepiness scale.Primary and secondary outcome measuresFatigue index (percentage chance of a high score on a standardised sleepiness scale) and risk index (relative risk of fatigue-related errors compared with a ‘2-day, two-night, four-off’ shift pattern) of all shifts on all rotas.ResultsNearly half of all shifts demonstrated increased risk of fatigue-related errors and increased probability of high levels of sleepiness. There was significant interspeciality variation in both indices. These results are based on rotas as opposed to ‘work as done’ and are therefore likely to slightly universally underestimate actual fatigue risks.ConclusionsThis preliminary study demonstrates that this tool can be used to compare rotas and guide rota design to minimise risk wherever possible. The calculator guidance clearly states there is no ‘ideal risk’ but that values should be minimised, and a maximum fatigue risk agreed which is deemed acceptable given the nature of work undertaken. This study is intended to demonstrate that fatigue can and should be considered during rota design. We do not suggest that it is used to hold either individuals or organisations to account as there is no evidence for it being used in this way. Further work should assess the practicality of designing medical rotas using this tool to minimise fatigue risk.
PROFIT, a PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis: study protocol for a single-blinded trial
Authors: Woodhouse Charlotte Alexandra , Patel Vishal C , Goldenberg Simon , Sanchez-Fueyo Alberto , China Louise , O’Brien Alastair , Flach Clare , Douiri Abdel , Shawcross Debbie 
Published: February 2019

IntroductionPatients with advanced cirrhosis have enteric bacterial dysbiosis and translocation of bacteria and their products across the gut epithelial barrier. This culminates in systemic inflammation and endotoxaemia, inducing innate immune dysfunction which predisposes to infection, and development of complications such as bleeding, sepsis and hepatic encephalopathy. This feasibility study aims to assess the safety of administering faecal microbiota transplantion to patients with cirrhosis and explore the effect of the intervention on their prognosis by achieving restoration of a healthy gut microbiome.Methods and analysisA PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation is a single-centre, randomised, single-blinded, placebo-controlled study evaluating faecal microbiota transplantation (FMT) against placebo. Patients with advanced but stable cirrhosis with a Model for End-Stage Liver Disease score between 10 and 16 will be recruited. Twenty-four patients will be randomised to FMT plus standard of care (as per our institutional practice) and eight patients to placebo in a ratio of 3:1. Patients will be evaluated at baseline before the study intervention is administered and at 7, 30 and 90 days post-intervention to assess safety and adverse events. FMT/placebo will be administered into the jejunum within 7 days of baseline. The primary outcome measure will be safety and feasibility as assessed by recruitment rates, tolerability and safety of FMT treatment. Results will be disseminated via peer-reviewed journals and international conferences. The recruitment of the first patient occurred on 23 May 2018.Ethics and disseminationResearch Ethics approval was given by the London South East Research Ethics committee (ref 17/LO/2081).Trial registration numberNCT02862249 and EudraCT 2017-003629-13.
Performance of biological mesh materials in abdominal wall reconstruction: study protocol for a randomised controlled trial
Authors: Carver David A , Kirkpatrick Andrew W , Eberle Tammy L , Ball Chad G 
Published: February 2019

IntroductionAbdominal wall hernias are a common source of morbidity and mortality. The use of biological mesh has become an important adjunct in successful abdominal wall reconstruction. There are a variety of biological mesh products available; however, there is limited evidence supporting the use of one type over another. This study aims to compare the performance (eg, the rate of hernia recurrence) of either a crosslinked biological mesh product or a non-crosslinked product in patients undergoing abdominal wall reconstruction.Methods and analysisThis is a single-centre, dual arm randomised controlled trial. Patients requiring abdominal wall reconstruction will be assessed for eligibility. Eligible patients will then undergo an informed consent process following by randomisation to either (1) crosslinked porcine dermis mesh (Permacol); or (2) non-crosslinked porcine dermis mesh (Strattice). These groups will be compared for the rate of hernia recurrence at 1 and 2 years as well as the rate of postoperative complications (eg, surgical site infections).Ethics and disseminationThis study has been approved by the institution’s research ethics board and registered with clinicaltrials.gov. All eligible participants will provide informed consent prior to randomization. The results of this study may help guide the choice of biologic mesh for this population. The results of this study will be published in peer-reviewed journals as well as national and international conferences.Trial registration numberNCT02703662.
Impact of repeated hospital accreditation surveys on quality and reliability, an 8-year interrupted time series analysis
Authors: Devkaran Subashnie , O’Farrell Patrick N , Ellahham Samer , Arcangel Randy 
Published: February 2019

ObjectiveTo evaluate whether hospital re-accreditation improves quality, patient safety and reliability over three accreditation cycles by testing the accreditation life cycle model on quality measures.DesignThe validity of the life cycle model was tested by calibrating interrupted time series (ITS) regression equations for 27 quality measures. The change in the variation of quality over the three accreditation cycles was evaluated using the Levene’s test.SettingA 650-bed tertiary academic hospital in Abu Dhabi, UAE.ParticipantsEach month (over 96 months), a simple random sample of 10% of patient records was selected and audited resulting in a total of 388 800 observations from 14 500 records.Intervention(s)The impact of hospital accreditation on the 27 quality measures was observed for 96 months, 1-year preaccreditation (2007) and 3 years postaccreditation for each of the three accreditation cycles (2008, 2011 and 2014).Main outcome measure(s)The life cycle model was evaluated by aggregating the data for 27 quality measures to produce a composite score (YC) and to fit an ITS regression equation to the unweighted monthly mean of the series.ResultsThe results provide some evidence for the validity of the four phases of the life cycle namely, the initiation phase, the presurvey phase, the postaccreditation slump and the stagnation phase. Furthermore, the life cycle model explains 87% of the variation in quality compliance measures (R2=0.87). The best-fit ITS model contains two significant variables (β1and β3) (p≤0.001). The Levene’s test (p≤0.05) demonstrated a significant reduction in variation of the quality measures (YC) with subsequent accreditation cycles.ConclusionThe study demonstrates that accreditation has the capacity to sustain improvements over the accreditation cycle. The significant reduction in the variation of the quality measures (YC) with subsequent accreditation cycles indicates that accreditation supports the goal of high reliability.
Quality of reporting of outcomes in trials of therapeutic interventions for pressure ulcers in adults: a protocol for a systematic survey
Authors: Miranda Jessica Steffany , Abbade Luciana Patricia Fernandes , Deonizio Arthur Pollo , Abbade Joelcio Francisco , Mbuagbaw Lawrence , Thabane Lehana 
Published: February 2019

Pressure ulcers (PUs) have a high incidence, especially in hospital units. Randomised clinical trials (RCTs) of therapeutic interventions for PU should include a clear description of the outcomes and results to enhance transparency and replicability.ObjectivesThe primary objective of this study is to assess the completeness of the descriptions of the outcomes of therapeutic interventions in RCTs in adult patients with PU. The secondary objectives are to evaluate the types of reported primary outcomes, measurement methods or tools used to evaluate the outcomes and the results of reported outcomes.MethodsWe will conduct a systematic survey of RCTs published from January 2006 to April 2018. The selection process of the studies will be done in two stages of screening: title and abstract, and full text revision, always by two researchers independently. The completeness of the outcome will be assessed according to five criteria: domain (outcome title), specific measurement or technique/instrument used, specific metric or format of the outcome data that will be used for analysis, method of aggregation (how data from each group will be summarised) and time-points that will be used for analysis. The quality of the results of the outcome will be classified as either complete, incomplete or unreported. We will conduct a descriptive analysis of the number, type and degrees of outcome specification in the included RCTs. The frequency of categories in each domain of the outcomes will also be reported. The median and IQR will be estimated for each element of the specified outcome (out of five).Ethics and disseminationThis will be the first systematic assessment of the outcomes of therapeutic interventions used for pressure ulcers. After completion, this review will be submitted to a peer-reviewed journals.