Evaluating the cost-effectiveness of therapy conversion to insulin detemir in patients with type 2 diabetes in Germany: a modelling study of long-term clinical and cost outcomes

OBJECTIVES: To evaluate the long-term cost-effectiveness of transferring type 2 diabetes patients to an insulin detemir regimen after failure to achieve adequate control with oral antidiabetic agents (OADs) alone, or in combination with neutral protamine hagedorn (NPH) insulin, or with insulin glargine in Germany. METHODS: A computer simulation model of diabetes was used to make long-term projections of future clinical outcomes and direct medical costs based on findings from a German subanalysis of the PREDICTIVE trial. The study analysed the impact of converting patients failing their current treatments to an insulin detemir regimen. Therapy conversion to insulin detemir +/- OADs was associated with a significant reduction in glycosylated haemoglobin (HbA(1)c) compared with OADs alone, NPH insulin +/- OADs, and insulin glargine +/- OADs. Across all three groups, hypoglycaemia rates decreased by 80% and patients lost an average of 0.9 kg of body weight during treatment with insulin detemir +/- OADs. RESULTS: Therapy conversion to insulin detemir +/- OADs was projected to improve life expectancy by 0.28 years compared with OADs alone, and by 0.13 years compared with the NPH and glargine regimens. Transfer to insulin detemir was associated with improvements in quality-adjusted life expectancy of 0.21 quality-adjusted life years (QALYs) over OADs alone, 0.28 QALYs over NPH +/- OADs, and 0.29 QALYs over glargine +/- OADs. Insulin detemir was associated with savings over patient lifetimes due to reduced diabetes-related complications in all three comparisons. CONCLUSIONS: Therapy conversion to insulin detemir +/- OADs in type 2 diabetes patients failing OADs alone, NPH or insulin glargine regimens was associated with improvements in life expectancy, quality-adjusted life expectancy and cost savings in all three scenarios evaluated.     

A novel diversion protocol dramatically reduces diversion hours

Introduction

Ambulance diversion is a problem in many communities. When patients are diverted prompt and appropriate medical care may be delayed.

Objective

Compare diversion hours and drop-off times before and after a dramatic change in diversion policy restricting each hospital to 1 hour out of every 8.

Methods

This study was a retrospective study in a county of 600 000 people and 10 hospitals from September 2004 to February 2006. A countywide diversion protocol was implemented in March 2005 that limited diversion hours to 1 hour out of every 8 (maximum of 90 h/mo). No other changes were implemented during the study period. Pretrial (9/04-2/05), interim (3/05-8/05), and posttrial (9/05-2/06) periods were compared. The main outcome measures were ambulance diversion hours and emergency medical service (EMS) drop-off times. Results were compared using analysis of variance and a Tukey post hoc analysis. P < .05 was considered significant.

Results

There was no significant difference in the number of monthly transports comparing the posttrial vs pretrial periods; however, a significant decrease in monthly ambulance diversion hours (difference, 251 hours; 95% CI, 136-368) and significant increase in additional time that EMS crews required to transport patients (drop-off times) (difference, 178 hours; 95% CI, 74-283) were observed. Posttrial diversion hours decreased to 18% of the pretrial values (from 305 to 54).

Conclusion

This novel ambulance diversion protocol dramatically reduced diversion hours at the cost of increasing EMS drop-off times in a large community.     

Cultivating informatics competencies in a community of practice

To move the healthcare industry into the 21st century, nurses must become savvy in the use of informatics to provide optimal care to their patients. However, the relatively few formal nursing informatics programs that exist across the country are simply not adequate to meet the demands of both new and existing nurses. Informatics competencies must be incorporated into nursing curricula at entry-level and via staff development to provide a ready workforce. Creative faculty development strategies that capitalize on the concept of faculty as a community of practice are required to incorporate informatics competencies into nursing curricula.     

Preclinical In Vitro Safety Investigations of Submicron Sized Hemoglobin Based Oxygen Carrier HbMP‐700

Hemoglobin‐based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume‐expanding therapeutics though their potential to promote oxidative tissue injury and nitric oxide (NO) scavenging combined with vasoconstriction has raised safety concerns. Therefore, we focused on these aspects during preclinical studies performed with the recently introduced hemoglobin microparticles (HbMP‐700). Besides oxidative stress, we investigated possible vasoconstrictory influence of HBOCs as well as genetic toxicity. The novel developed HbMP‐700 presented here provides a high oxygen affinity which prevents premature oxygen oversupply and avoids vasoconstriction of small blood vessels in vitro. The size of these particles is 700 nm (larger than 100 nm and smaller than 1000 nm) in order to prevent penetration through the blood vessel's endothelial gaps, NO‐scavenging, and to avoid phagocytosis of large particles. We expect that the HbMP‐700 meets the sophisticated requirements as a universal blood substitute.     

Topography of Prostate Cancer Recurrence After Radiation Therapy: A Detailed Mapping Study of Salvage Radical Prostatectomy Specimens

In men who do not respond to initial radiation therapy, accurate knowledge of the site of cancer recurrence or persistence is necessary to understand treatment failure. We evaluated the pathologic characteristics of recurrent/persistent prostate cancer with tumor maps from the whole-mount slides of salvage radical prostatectomies performed between 2000 and 2014. Of 216 consecutive patients, detailed tumor maps were available for 77. Sixty-nine patients (90%) were found to have tumor in the apex, of which 46% occurred in the most apical 3 mm. Fifty-three patients (69%) had tumors at a distance of ≤5 mm from the urethra. Five patients had tumor directly involving the urethra, all of whom had urethral invasion at the apex. Seminal vesicle involvement was seen in 32 patients (42%), two of whom had tumor only in the seminal vesicles. Sixty-two patients (81%) had tumors in the distal apex, periurethral area, or seminal vesicles, that is, areas that are not routinely biopsied. Targeting these areas could improve the accuracy of biopsy when cancer recurrence is suspected.

Impact of Trauma System Structure on Injury Outcomes: A Systematic Review and Meta-Analysis

Background

The effectiveness of trauma systems in decreasing injury mortality and morbidity has been well demonstrated. However, little is known about which components contribute to their effectiveness. We aimed to systematically review the evidence of the impact of trauma system components on clinically important injury outcomes.

Methods

We searched MEDLINE, EMBASE, Cochrane CENTRAL, and BIOSIS/Web of Knowledge, gray literature and trauma association Web sites to identify studies evaluating the association between at least one trauma system component and injury outcome. We calculated pooled effect estimates using inverse-variance random-effects models. We evaluated quality of evidence using GRADE criteria.

Results

We screened 15,974 records, retaining 41 studies for qualitative synthesis and 19 for meta-analysis. Two recommended trauma system components were associated with reduced odds of mortality: inclusive design (odds ratio [OR] = 0.72 [0.65–0.80]) and helicopter transport (OR = 0.70 [0.55–0.88]). Pre-Hospital Advanced Trauma Life Support was associated with a significant reduction in hospital days (mean difference [MD] = 5.7 [4.4–7.0]) but a nonsignificant reduction in mortality (OR = 0.78 [0.44–1.39]). Population density of surgeons was associated with a nonsignificant decrease in mortality (MD = 0.58 [?0.22 to 1.39]). Trauma system maturity was associated with a significant reduction in mortality (OR = 0.76 [0.68–0.85]). Quality of evidence was low or very low for mortality and healthcare utilization.

Conclusions

This review offers low-quality evidence for the effectiveness of an inclusive design and trauma system maturity and very-low-quality evidence for helicopter transport in reducing injury mortality. Further research should evaluate other recommended components of trauma systems and non-fatal outcomes and explore the impact of system component interactions.

     

A feasibility double-blind randomized placebo-controlled trial of extracorporeal shockwave therapy as a novel treatment for intermittent claudication

Background

Intermittent claudication is the most common symptom of peripheral arterial disease. Previous research has suggested that extracorporeal shockwave therapy (ESWT) may induce angiogenesis in treated tissue. The objective of this feasibility pilot trial was to assess the safety, tolerability, and efficacy of ESWT as a novel treatment.

Response to sirolimus in capillary lymphatic venous malformations and associated syndromes: Impact on symptomatology,quality of life,and radiographic response

Background

Capillary lymphatic venous malformations (CLVM) and associated syndromes, including Klippel–Trenaunay syndrome (KTS) and congenital lipomatous overgrowth, vascular malformation, epidermal nevi, skeletal, and spinal syndrome (CLOVES), are underrecognized disorders associated with high morbidity from chronic pain, recurrent infections, bleeding, and clotting complications. The rarity of these disorders and heterogeneity of clinical presentations make large-scale randomized clinical drug trials challenging. Identification of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [gene]) mutations in CLVM has made targeted medications, such as sirolimus, attractive treatment options. The aim of this study was to investigate the safety and efficacy of sirolimus therapy in CLVM.

Procedure

A combined prospective and retrospective cohort of pediatric and young adult patients with CLVM treated with sirolimus was evaluated for disease response, including symptom improvement, quality of life (QOL), and radiologic response. Sirolimus dosing regimens and toxicities were also assessed.

Results

Twenty-nine patients with CLVM, including KTS and CLOVES, were included. Ninety-three percent of patients reported improved QOL, and 86% had improvement in at least one symptom. Most significantly, improvement was noted in 100% of patients with bleeding and 89% with thrombotic complications with corresponding decreases in mean D-dimer (p = .008) and increases in mean fibrinogen (p = .016). No patients had progressive disease on sirolimus. Most common side effects included neutropenia, lymphopenia, infection, and aphthous ulcers/stomatitis. No toxicities were life-threatening, and none required long-term discontinuation of sirolimus.

Conclusion

Sirolimus appears to be effective at reducing complications and improving QOL in patients with CLVM and associated syndromes. In this patient cohort, sirolimus was well tolerated and resulted in few treatment-related toxicities.     

Decreasing Use of Axillary Dissection in Node-Positive Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Background

Neoadjuvant chemotherapy (NAC) may downstage axillary disease in node-positive breast cancer. Several clinical trials have shown that sentinel lymph node (SLN) surgery after NAC is feasible for these patients. We sought to evaluate the use of SLN surgery and ALND in cN1 patients undergoing NAC.

Methods

We identified all patients with biopsy-proven cN1 breast cancer treated with NAC at our institution between January 2009 and December 2017. Approximated biologic subtype was determined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. Cochran–Armitage trend and Chi square tests were used for statistical analysis.

Results

Of 430 cN1 patients treated with NAC, 93 (22%) underwent SLN surgery only, 100 (23%) underwent SLN and ALND, and 237 (55%) underwent ALND only. The use of SLN surgery (±?ALND) increased from 28% in 2009 to 86% in 2017 (p?<?0.001), while the performance of ALND decreased from 100% in 2009 to 38% in 2017 (p?<?0.001). Among SLN+ patients who underwent ALND, disease was limited to the SLNs in 25/73 (34%) patients. The nodal pathologic complete response rate was 46% and varied by tumor subtype (p?<?0.001). Among patients undergoing SLN surgery, ALND was avoided in 48% of patients overall and varied by biologic subtype: 55% ER?/HER2+, 61% ER+/HER2+, 62% ER?/HER2?, and 31% ER+/HER2? (p?=?0.001). With short-term follow-up, no nodal recurrences have occurred in patients without ALND.

Conclusions

We observed a significant shift in axillary surgery for cN1 breast cancer patients treated with NAC, with increasing use of SLN surgery to assess nodal treatment response, and decreasing use of ALND.