The inpatient burden of abdominal and gynecological adhesiolysis in the US

<p>Abstract</p> <p>Background</p> <p>Adhesions are fibrous bands of scar tissue, often a result of surgery, that form between internal organs and tissues, joining them together abnormally. Postoperative adhesions frequently occur following abdominal surgery, and are associated with a large economic burden. This study examines the inpatient burden of adhesiolysis in the United States (i.e., number and rate of events, cost, length of stay [LOS]).</p> <p>Methods</p> <p>Hospital discharge data for patients with primary and secondary adhesiolysis were analyzed using the 2005 Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. Procedures were aggregated by body system.</p> <p>Results</p> <p>We identified 351,777 adhesiolysis-related hospitalizations: 23.2% for primary and 76.8% for secondary adhesiolysis. The average LOS was 7.8 days for primary adhesiolysis. We found that 967,332 days of care were attributed to adhesiolysis-related procedures, with inpatient expenditures totaling $2.3 billion ($1.4 billion for primary adhesiolysis; $926 million for secondary adhesiolysis). Hospitalizations for adhesiolysis increased steadily by age and were higher for women. Of secondary adhesiolysis procedures, 46.3$220 million in attributable costs.</p> <p>Conclusions</p> <p>Adhesiolysis remain an important surgical problem in the United States. Hospitalization for this condition leads to high direct surgical costs, which should be of interest to providers and payers.</p

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac

General practitioner practice-based pharmacist input to medicines optimisation in the UK: pragmatic, multicenter, randomised, controlled trial

BACKGROUND: Changing demographics across the UK has led to general practitioners (GPs) managing increasing numbers of older patients with multi-morbidity and resultant polypharmacy. Through government led initiatives within the National Health Service, an increasing number of GP practices employ pharmacist support. The purpose of this study is to evaluate the impact of a medicines optimisation intervention, delivered by GP practice-based pharmacists, to patients at risk of medication-related problems (MRPs), on patient outcomes and healthcare costs. METHODS: A multi-centre, randomised (normal care or pharmacist supplemented care) study in four regions of the UK, involving patients (n = 356) from eight GP practices, with a 6-month follow-up period. Participants were adult patients who were at risk of MRPs. RESULTS: Median number of MRPs per intervention patient were reduced at the third assessment, i.e. 3 to 0.5 (p < 0.001) in patients who received the full intervention schedule. Medication Appropriateness Index (MAI) scores were reduced (medications more appropriate) for the intervention group, but not for control group patients (8 [4-13] to 5 [0-11] vs 8 [3-13] to 7 [3-12], respectively; p = 0.001). Using the intention-to-treat (ITT) approach, the number of telephone consultations in intervention group patients was reduced and different from the control group (1 [0-3] to 1 [0-2] vs 1 [0-2] to 1 [0-3], p = 0.020). No significant differences between groups were, however, found in unplanned hospital admissions, length of hospital stay, number of A&E attendances or outpatient visits. The mean overall healthcare cost per intervention patient fell from £1041.7 ± 1446.7 to £859.1 ± 1235.2 (p = 0.032). Cost utility analysis showed an incremental cost per patient of - £229.0 (95% CI - 594.6, 128.2) and a mean QALY gained of 0.024 (95% CI - 0.021 to 0.065), i.e. indicative of a health status gain at a reduced cost (2016/2017). CONCLUSION: The pharmacist service was effective in reducing MRPs, inappropriateness of medications and telephone consultations in general practice in a cost-effective manner. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT03241498. Registered 7 August 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03241498

Grassmannian flows and applications to nonlinear partial differential equations

We show how solutions to a large class of partial differential equations with nonlocal Riccati-type nonlinearities can be generated from the corresponding linearized equations, from arbitrary initial data. It is well known that evolutionary matrix Riccati equations can be generated by projecting linear evolutionary flows on a Stiefel manifold onto a coordinate chart of the underlying Grassmann manifold. Our method relies on extending this idea to the infinite dimensional case. The key is an integral equation analogous to the Marchenko equation in integrable systems, that represents the coodinate chart map. We show explicitly how to generate such solutions to scalar partial differential equations of arbitrary order with nonlocal quadratic nonlinearities using our approach. We provide numerical simulations that demonstrate the generation of solutions to Fisher--Kolmogorov--Petrovskii--Piskunov equations with nonlocal nonlinearities. We also indicate how the method might extend to more general classes of nonlinear partial differential systems.Comment: 26 pages, 2 figure

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD) : study protocol for a randomized controlled trial

Background World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. Methods/Design This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control). Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice. or Control group: Standard GP care, with referral to secondary care as required, but no access to ICCD. Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (≤7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients

Self-organization in the olfactory system: one shot odor recognition in insects

We show in a model of spiking neurons that synaptic plasticity in the mushroom bodies in combination with the general fan-in, fan-out properties of the early processing layers of the olfactory system might be sufficient to account for its efficient recognition of odors. For a large variety of initial conditions the model system consistently finds a working solution without any fine-tuning, and is, therefore, inherently robust. We demonstrate that gain control through the known feedforward inhibition of lateral horn interneurons increases the capacity of the system but is not essential for its general function. We also predict an upper limit for the number of odor classes Drosophila can discriminate based on the number and connectivity of its olfactory neurons

Smoke-free legislation and the incidence of paediatric respiratory infections and wheezing/asthma: interrupted time series analyses in the four UK nations

We investigated the association between introduction of smoke-free legislation in the UK (March 2006 for Scotland, April 2007 for Wales and Northern Ireland, and July 2007 for England) and the incidence of respiratory diseases among children. We extracted monthly counts of new diagnoses of wheezing/asthma and RTIs among children aged 0–12 years from all general practices in the Clinical Practice Research Datalink during 1997–2012. Interrupted time series analyses were performed using generalised additive mixed models, adjusting for underlying incidence trends, population size changes, seasonal factors, and pandemic influenza, as appropriate. 366,642 new wheezing/asthma diagnoses and 4,324,789 RTIs were observed over 9,536,003 patient-years. There was no statistically significant change in the incidence of wheezing/asthma after introduction of smoke-free legislation in England (incidence rate ratio (IRR) 0.94, 95% CI 0.81–1.09) or any other UK country (Scotland: IRR 0.99, 95% CI 0.83–1.19; Wales: IRR 1.09, 95% CI 0.89–1.35; Northern Ireland: IRR 0.96, 95% CI 0.76–1.22). Similarly no statistically significant changes in RTI incidence were demonstrated (England: IRR 0.95, 95% CI 0.86–1.06; Scotland: IRR 0.96, 95% CI 0.83–1.11; Wales: IRR 0.97, 95% CI 0.86–1.09; Northern Ireland: IRR 0.90, 95% CI 0.79–1.03). There were no demonstrable reductions in the incidence of paediatric wheezing/asthma or RTIs following introduction of smoke-free legislation in the UK

Implementation by simulation; strategies for ultrasound screening for hip dysplasia in the Netherlands

Background: Implementation of medical interventions may vary with organization and available capacity. The influence of this source of variability on the cost-effectiveness can be evaluated by computer simulation following a carefully designed experimental design. We used this approach as part of a national implementation study of ultrasonographic infant screening for developmental dysplasia of the hip (DDH). Methods: First, workflow and performance of the current screening program (physical examination) was analyzed. Then, experimental variables, i.e., relevant entities in the workflow of screening, were defined with varying levels to describe alternative implementation models. To determine the relevant levels literature and interviews among professional stakeholders are used. Finally, cost-effectiveness ratios (inclusive of sensitivity analyses) for the range of implementation scenarios were calculated. Results: The four experimental variables for implementation were: 1) location of the consultation, 2) integrated with regular consultation or not, 3) number of ultrasound machines and 4) discipline of the screener. With respective numbers of levels of 3,2,3,4 in total 72 possible scenarios were identified. In our model experimental variables related to the number of available ultrasound machines and the necessity of an extra consultation influenced the cost-effectiveness most. Conclusions: Better information comes available for choosing optimised implementation strategies where organizational and capacity variables are important using the combination of simulation models and an experimental design. Information to determine the levels of experimental variables can be extracted from the literature or directly from experts

The influence of blood on the efficacy of intraperitoneally applied phospholipids for prevention of adhesions

<p>Abstract</p> <p>Background</p> <p>The formation of adhesions following abdominal surgery is a well known problem. In previous studies we demonstrated the efficacy and safety of intraperitoneally applied phospholipids in order to prevent adhesion formation. This study evaluates the influence of blood on the efficacy of intraperitoneally applied phospholipids for prevention of adhesions.</p> <p>Methods</p> <p>In 40 Chinchilla rabbits adhesions were induced by median laparotomy, standardized abrasion of the visceral and parietal peritoneum in defined areas of the ventral abdominal wall and the caecum. The animals were randomly divided into four groups. They received either phospholipids 3.0% or normal saline (NaCl 0,9%) (5 ml/kg body weight). In 50% of the rabbits we simulated intraperitoneal bleeding by administration of blood (1,5 ml/kg body weight). The other half served as control group. Ten days following the operation the animals were sacrificed and adhesion formation was assessed by computer aided planimetry and histopathologic examination.</p> <p>Results</p> <p>The median adhesion surface area in the NaCl-group (n = 9) amounted to 68,72 mm², in the NaCl+Blood-group (n = 10) 147,68 mm². In the Phospholipid (PhL)-group (n = 9) the median adhesion surface area measured 9,35 mm², in the PhL+Blood-group (n = 9) 11,95 mm². The phospholipid groups had a significantly smaller adhesion surface area (p < 0.05).</p> <p>Conclusion</p> <p>Again these results confirm the efficacy of phospholipids in the prevention of adhesions in comparison to NaCl (p = 0,04). We also demonstrated the adhesion preventing effect of phospholipids in the presence of intraperitoneal blood.</p