The preferences of young adults with Type 1 diabetes at clinics using a discrete choice experiment approach: the D1 Now Study.

AIM: Attending routine outpatient clinic appointments is a central self-management behaviour of individuals living with Type 1 diabetes. A large number of young adults with Type 1 diabetes disengage from diabetes services, which may contribute to poor psychosocial and diabetes outcomes. The aim of this study is to elicit preferences from young adults with Type 1 diabetes regarding clinic-related services to inform service delivery. METHODS: A discrete choice experiment was developed to understand the preferences of young adults with Type 1 diabetes for clinic-related services. RESULTS: Young adults recruited from young adult Type 1 diabetes clinics in 2016 completed the experiment (n = 105). Young adults with Type 1 diabetes showed a preference for shorter waiting times, seeing a nurse and a consultant, relative to a nurse alone, and a flexible booking system compared with fixed appointment times. Results suggest no preference for a nurse and a doctor, relative to a nurse alone, or other optional services (e.g. seeing dietitians or psychologists), type of HbA1c test and digital blood glucose diaries over paper-based diaries. CONCLUSION: This study highlights aspects of routine clinic appointments that are valued by young adults living with Type 1 diabetes, namely shorter waiting times at clinic, the option to see both a nurse and consultant at each visit and a flexible clinic appointment booking system. These findings suggest young adults with Type 1 diabetes value convenience and should help services to restructure their clinics to be more responsive to the needs of young adults.

Strength in Numbers: an international consensus conference to develop a novel approach to care delivery for young adults with type 1 diabetes, the D1 Now Study.

PLAIN ENGLISH SUMMARY: Many young adults with type 1 diabetes struggle with the day-to-day management of their condition. They often find it difficult to find the time to attend their clinic appointments and to meet with their diabetes healthcare team. Young adults living with type 1 diabetes are not routinely involved in research that may help improve health services other than being invited to take part in studies as research participants. A 3-day international conference was held in Galway in June 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". It aimed to bring together people from a broad variety of backgrounds with an interest in young adults with type 1 diabetes. Young people with type 1 diabetes came together with healthcare professionals, researchers, software developers and policy makers to come up with and agree on a new approach for engaging young adults with type 1 diabetes with their health services and to improve how they manage their diabetes.The people involved in the conference aimed to reach agreement (consensus) on a fixed set of outcome measures called a core outcome set (COS) that the group would recommend future studies involving young adults with type 1 diabetes to use, to suggest a new approach (intervention) for providing health services to young adults with type 1 diabetes, and to come up with health technology ideas that could help deliver the new intervention. Over the 3 days, this diverse international group of people that included young adults living with type 1 diabetes, agreed on a COS, 3 key parts of a new intervention and 1 possible health technology idea that could help with how the overall intervention could be delivered.Involving young adults living with type 1 diabetes in a 3-day conference along with other key groups is an effective method for coming up with a new approach to improve health services for young adults with type 1 diabetes and better support their self-management. ABSTRACT: Background A 3-day international consensus meeting was hosted by the D1 Now study team in Galway on June 22-24, 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". The aim of the meeting was to bring together young adults with type 1 diabetes, healthcare providers, policy makers and researchers to reach a consensus on strategies to improve engagement, self-management and ultimately outcomes for young adults living with type 1 diabetes. Methods This diverse stakeholder group participated in the meeting to reach consensus on (i) a core outcome set (COS) to be used in future intervention studies involving young adults with type 1 diabetes, (ii) new strategies for delivering health services to young adults and (iii) potential digital health solutions that could be incorporated into a future intervention. Results A COS of 8 outcomes and 3 key intervention components that aim to improve engagement between young adults with type 1 diabetes and service providers were identified. A digital health solution that could potentially compliment the intervention components was proposed. Conclusion The outputs from the 3-day consensus conference, that held patient and public involvement at its core, will help the research team further develop and test the D1 Now intervention for young adults with type 1 diabetes in a pilot and feasibility study and ultimately in a definitive trial. The conference represents a good example of knowledge exchange among different stakeholders for health research and service improvement.

Proteolysis of plasminogen activator inhibitor-1 by Yersinia pestis remodulates the host environment to promote virulence.

UNLABELLED: Essentials Effect of plasminogen activator inhibitor (PAI)-1 on plague and its Y. pestis cleavage is unknown. An intranasal mouse model of infection was used to determine the role of PAI-1 in pneumonic plague. PAI-1 is cleaved and inactivated by the Pla protease of Y. pestis in the lung airspace. PAI-1 impacts both bacterial outgrowth and the immune response to respiratory Y. pestis infection. Click to hear Dr Bock discuss pathogen activators of plasminogen. SUMMARY: Background The hemostatic regulator plasminogen activator inhibitor-1 (PAI-1) inactivates endogenous plasminogen activators and aids in the immune response to bacterial infection. Yersinia pestis, the causative agent of plague, produces the Pla protease, a virulence factor that is required during plague. However, the specific hemostatic proteins cleaved by Pla in vivo that contribute to pathogenesis have not yet been fully elucidated. Objectives To determine whether PAI-1 is cleaved by the Pla protease during pneumonic plague, and to define the impact of PAI-1 on Y. pestis respiratory infection in the presence or absence of Pla. Methods An intranasal mouse model of pneumonic plague was used to assess the levels of total and active PAI-1 in the lung airspace, and the impact of PAI-1 deficiency on bacterial pathogenesis, the host immune response and plasmin generation following infection with wild-type or ∆pla Y. pestis. Results We found that Y. pestis cleaves and inactivates PAI-1 in the lungs in a Pla-dependent manner. The loss of PAI-1 enhances Y. pestis outgrowth in the absence of Pla, and is associated with increased conversion of plasminogen to plasmin. Furthermore, we found that PAI-1 regulates immune cell recruitment, cytokine production and tissue permeability during pneumonic plague. Conclusions Our data demonstrate that PAI-1 is an in vivo target of the Pla protease in the lungs, and that PAI-1 is a key regulator of the pulmonary innate immune response. We conclude that the inactivation of PAI-1 by Y. pestis alters the host environment to promote virulence during pneumonic plague.

Outcome prediction in mechanically ventilated neurologic patients by junior neurointensivists.

OBJECTIVE: Physician prediction of outcome in critically ill neurologic patients impacts treatment decisions and goals of care. In this observational study, we prospectively compared predictions by neurointensivists to patient outcomes at 6 months. METHODS: Consecutive neurologic patients requiring mechanical ventilation for 72 hours or more were enrolled. The attending neurointensivist was asked to predict 6-month 1) functional outcome (modified Rankin scale [mRS]), 2) quality of life (QOL), and 3) whether supportive care should be withdrawn. Six-month functional outcome was determined by telephone interviews and dichotomized to good (mRS 0-3) and poor outcome (mRS 4-6). RESULTS: Of 187 eligible patients, 144 were enrolled. Neurointensivists correctly predicted 6-month functional outcome in 80% (95% confidence interval [CI], 72%-86%) of patients. Accuracy for a predicted good outcome was 63% (95% CI, 50%-74%) and for poor outcome 94% (95% CI, 85%-98%). Excluding patients who had life support withdrawn, accuracy for good outcome was 73% (95% CI, 60%-84%) and for poor outcome 87% (95% CI, 74%-94%). Accuracy for exact agreement between neurointensivists' mRS predictions and actual 6-month mRS was only 43% (95% CI, 35%-52%). Predicted accuracy for QOL was 58% (95% CI, 39%-74%) for good/excellent and 67% (95% CI, 46%-83%) for poor/fair. Of 27 patients for whom withdrawal of care was recommended, 1 patient survived in a vegetative state. CONCLUSIONS: Prediction of long-term functional outcomes in critically ill neurologic patients is challenging. Our neurointensivists were more accurate in predicting poor outcome than good outcome in patients requiring mechanical ventilation >or=72 hours.

Insulin independence and normalization of oral glucose tolerance test after islet cell allotransplantation.

To achieve permanent normoglycemia in patients with type I diabetes, it is necessary to renew the insulin-producing beta-cells by transplantation of either a vascularized pancreatic graft or isolated islets of Langerhans. Presently, about 10% of patients with type I diabetes undergoing islet allotransplantation achieve insulin independence; however, glucose intolerance remains in the majority of cases. We report a case of long-term insulin independence after islet allotransplantation in a type I diabetic patient. Three years after islet transplantation, the patient remains insulin-independent with a normal oral glucose tolerance test (OGTT). The patient therefore no longer meets the World Health Organization criteria for the diagnosis of diabetes mellitus and demonstrates that islet transplantation can cure diabetes in type I diabetic patients.

Short- and long-term results of total vs subtotal thyroidectomies in the surgical treatment of Graves' disease.

OBJECTIVE: Approximately one out of five patients with Graves' disease (GD) undergoes a thyroidectomy after a mean period of 18 months of medical treatment. This retrospective and non-randomized study from a teaching hospital compares short- and long-term results of total (TT) and subtotal thyroidectomies (ST) for this disease. METHODS: From 1987 to 1997, 94 patients were operated for GD. Thirty-three patients underwent a TT (mostly since 1993) and 61 a ST (keeping 4 to 8 grams of thyroid tissue--mean 6 g). All patients had received propylthiouracil and/or neo-mercazole and were in a euthyroid state at the time of surgery; they also took potassium iodide (lugol) for ten days before surgery. RESULTS: There were no deaths. Transient hypocalcemia (< 3 months) occurred in 32 patients (15 TT and 17 ST) and persistent hypocalcemia in 8 having had TT. Two patients developed transient recurrent laryngeal nerve palsy after ST (< 3 months). After a median follow-up period of seven years (1-15) with five patients lost to follow-up, 41 patients having had a ST are in a hypothyroid state (73%), thirteen are euthyroid (23%), and two suffered recurrent hyperthyroidism, requiring completion of thyroidectomy. All 33 patients having had TT--with follow-ups averaging two years (0.5-8)--are receiving thyroxin substitution. CONCLUSIONS: There were no instances of persistent recurrent laryngeal nerve palsy in either group, but persistent hypoparathyroidism occurred more frequently after TT. Long after ST, hypothyroidism developed in nearly three of four cases, whereas euthyroidy was maintained in only one-fourth; recurrent hyperthyroidy was rare.

Transplantation of islets of Langerhans: new developments.

The clinical results recently reported by the Edmonton group in recipients of allogeneic islet grafts, all of whom achieved at least temporary insulin independence, has rekindled interest in transplantation of islets of Langerhans as a means to cure diabetes. Long-term islet graft survival has been achieved in a non-human primate pre-clinical model with a protocol of T-cell signaling blockade using a new monoclonal antibody. Islet xenotransplantation (namely the use of animal islets, with the aim of transplanting them into humans), or stem cell technology (the controlled differentiation of stem cells to obtain specialised cells for the treatment of diabetes) are other procedures currently being evaluated in animal models. The recent clinical success suggests that, in the near future, diabetes might be treated by islet transplantation early in the clinical course of the disease before the development of complications, and without the risks associated with conventional immunosuppression.

Long-term metabolic results after pancreatic resection for severe chronic pancreatitis.

HYPOTHESIS: Type and extent of pancreatic resection have little effect on long-term development of diabetes in patients with chronic pancreatitis (CP) considering the distinctive relentless progression of the disease. DESIGN: A case series of consecutive patients included over a 10-year period. Median duration of follow-up was 6.3 years. Follow-up of survivors was at least 5 years (median, 7.7 years). SETTING: A referral center in a university hospital. PATIENTS: All 68 patients (57 men and 11 women) who underwent pancreatic resection for CP during the study period were included. Median age of patients was 44 years. Complete follow-up was obtained for all patients. INTERVENTIONS: Resection procedures included 35 proximal pancreatoduodenectomies (51%), 31 distal pancreatectomies (46%), and 2 total pancreatoduodenectomies (3%). Four patients (6%) received autologous intraportal islet transplants. MAIN OUTCOME MEASURES: Time from surgery to introduction of insulin therapy or death, perioperative morbidity and mortality, and pain control. RESULTS: Fifty-one patients (75%) had experienced acute episodes of CP 5 months to 13 years before resection. Perioperative mortality and morbidity were 1.5% and 21.0%, respectively. Satisfactory long-term pain control was achieved in 61 patients (90%). Actuarial survival was 54% at 10 years and was significantly worse for patients with alcoholic CP (48% vs 78%; P =.04). Diabetes-free survival was 26% at 10 years, with no difference according to type or extent of pancreatic resection. CONCLUSIONS: Pancreatic resection for severe CP is safe and has good long-term results on pain control but is performed late in the course of disease. Earlier resection and islet of Langerhans autotransplantation should be considered for patients who are inexorably heading toward diabetes, regardless of type and extent of resection performed.

Human islet allotransplantation: world experience and current status.

Currently type-I diabetes mellitus is treated with exogenous insulin administration, but traditional insulin therapy does not prevent long-term systemic complications and therefore alternatives should be sought. Presently the only option is to substitute the insulin-producing beta cells in order to obtain a more physiological way to deliver insulin. Simultaneous kidney and pancreas transplantation is an established procedure. Pancreas transplantation, however, is a major surgical procedure with a high rate of complications. Transplantation of the isolated insulin-secreting islets of Langerhans is an alternative approach, which is easier and safer than whole organ transplantation. Since 1990, clinical trials of islet transplantation have begun in a few specialized centers worldwide and the International Islet Registry counting 305 human islet allografts at the end of 1995. Insulin independence at 1 year was achieved in 8% of the patients, but 20% of cases showed a graft function with a normal basal C peptide and improved glycemic regulation. We review here the different aspects of human islets of Langerhans allotransplatation, namely historical aspects, indications, isolation and purification procedures and the results obtained.

Increasing clinical use of pulse oximetry.

Changing the system from measuring blood gases through invasive measures to using noninvasive pulse oximetry is a challenge in the Critical Care Unit where invasive techniques are taken for granted. The authors report a project that was successful in increasing the use of noninvasive monitoring techniques by critical care nurses in a Surgical Intensive Care Unit. This clinical project became an important aspect of incorporating the staff in a change to more extensive use of pulse oximetry. This study defines the change in nursing practice with the use of pulse oximetry. The authors discuss three areas: (1) demonstration of the correlation between O2Sat as measured by the pulse oximeter and arterial blood gas saturations; (2) introduction of the pulse oximeter as a reliable alternative to ABGs when monitoring oxygenation; and (3) the establishment of guidelines for using pulse oximetry within the clinical setting.