The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice: An Ex Vivo and In Vivo Investigation.

BACKGROUND: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1). METHODS: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination. RESULTS: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth. CONCLUSION: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.

Real-world treatment patterns, resource use and costs of treating uncontrolled carcinoid syndrome and carcinoid heart disease: a retrospective Swedish study.

OBJECTIVES: To quantify healthcare resource use (HRU) and costs in relation to carcinoid syndrome (CS) and carcinoid heart disease (CHD) in a real-world setting, and to provide perspective on treatment patterns. MATERIALS AND METHODS: Patient data and HRU were collected retrospectively from three Swedish healthcare registers. Adult patients diagnosed with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) grade 1 or 2 and CS who purchased somatostatin analogs (SSAs), and experienced controlled (defined by SSAs use) and uncontrolled (defined by SSAs dose escalation) CS for ≥8 months during the study period were included. Patients diagnosed with CHD from the date of the GEP-NET diagnosis were included in the CHD study group. RESULTS: Overall, total HRU cost increased with uncontrolled CS and CHD. Total resource cost was 15,500€/patient during controlled CS (8 months), rising to 21,700€/patient during uncontrolled CS (8 months), representing an increase of ∼40% (6200€/patient). Costs/patient were driven mainly by SSA use, tumor-related medical interventions and examinations. The total mean cost/year of disease was 1100€/patient without CHD, compared to 4600€/patient with CHD, a difference of 3500€/patient. Excluding SSA cost burden, the main drivers of increased cost in CHD patients were surgical interventions and echocardiography. CONCLUSIONS: This study provides a comprehensive overview of the treatment patterns and burden of uncontrolled CS symptoms and CHD using Swedish national register data. Increases in medical interventions and examinations HRU and increased SSA use suggest that SSA dose escalation alone may not effectively control the symptoms associated with uncontrolled CS, highlighting an unmet treatment need in this patient group.

Health Economic Analysis of Open and Robot-assisted Laparoscopic Surgery for Prostate Cancer Within the Prospective Multicentre LAPPRO Trial.

BACKGROUND: The rapid adoption of robot-assisted laparoscopy in radical prostatectomy has preceded data regarding associated costs. Qualitative evidence regarding cost outcomes is lacking. OBJECTIVE: This study assessed how costs were affected by robot-assisted laparoscopic prostatectomy (RALP) compared with open surgery. DESIGN, SETTING, AND PARTICIPANTS: Cost analysis was based on the dataset of the LAPPRO (Laparoscopic Prostatectomy Robot Open) clinical trial, which is a prospective controlled, nonrandomised trial of patients who underwent prostatectomy at 14 centres in Sweden between September 2008 and November 2011. Currently, data are available from a follow-up period of 24 mo. INTERVENTION: In the LAPPRO trial, RALP was compared with radical retropubic prostatectomy (RRP). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Costs per surgical technique were assessed based on resource variable data from the LAPPRO database. The calculation of average costs was based on mean values; Swedish currency was converted to purchasing power parity US dollar (PPP$). All tests were two-tailed and conducted at α=0.05 significance level. RESULTS AND LIMITATIONS: The cost analysis comprised 2638 men. Based on the LAPPRO trial data, RALP was associated with an increased cost/procedure of PPP$ 3837 (95% confidence interval: 2747-4928) compared with RRP. The result was sensitive to variations in caseload. Main drivers of overall cost were robotic system cost, operation time, length of stay, and sick leave. Limitations of the study include the uneven distribution between RALP and RRP regarding procedures in public/for-profit hospitals and surgeon/centre procedural volume. CONCLUSIONS: Based on the LAPPRO trial data, this study showed that RALP was associated with an increased cost compared with RRP in Swedish health care. There are many factors influencing the costs, making the absolute result dependent on the specific setting. However, by identifying the main cost drivers and/or most influential parameters, the study provides support for informed decisions and predictions. PATIENT SUMMARY: In this study, we looked at the cost outcome when performing prostatectomies by robot-assisted laparoscopic technique compared with open surgery in Sweden. We found that the robot-assisted procedure was associated with a higher mean cost.

Decreasing mortality and changes in treatment patterns in patients with acromegaly from a nationwide study.

CONTEXT: New therapeutic strategies have developed for the management of acromegaly over recent decades. Whether this has improved mortality has not been fully elucidated. OBJECTIVE: The primary aim was to investigate mortality in a nationwide unselected cohort of patients with acromegaly. Secondary analyses included time trends in mortality and treatment patterns. DESIGN: A total of 1089 patients with acromegaly were identified in Swedish National Health Registries between 1987 and 2013. To analyse time trends, the cohort was divided into three periods (1987-1995, 1996-2004 and 2005-2013) based on the year of diagnosis. MAIN OUTCOME MEASURES: Using the Swedish population as reference, standardized mortality ratios (SMRs) were calculated with 95% confidence intervals (CIs). RESULTS: Overall SMR was 2.79 (95% CI: 2.43-3.15) with 232 observed and 83 expected deaths. Mortality was mainly related to circulatory diseases (SMR: 2.95, 95% CI: 2.35-3.55), including ischemic heart disease (2.00, 1.35-2.66) and cerebrovascular disease (3.99, 2.42-5.55) and malignancy (1.76, 1.27-2.26). Mortality decreased over time, with an SMR of 3.45 (2.87-4.02) and 1.86 (1.04-2.67) during the first and last time period, respectively (P = .015). During the same time periods, the frequency of pituitary surgery increased from 58% to 72% (P < 0.001) and the prevalence of hypopituitarism decreased from 41% to 23% (P < 0.001). CONCLUSIONS: Excess mortality was found in this nationwide cohort of patients with acromegaly, mainly related to circulatory and malignant diseases. Although still high, mortality significantly declined over time. This could be explained by the more frequent use of pituitary surgery, decreased prevalence of hypopituitarism and the availability of new medical treatment options.

Secular changes in at-risk drinking in Sweden: birth cohort comparisons in 75-year-old men and women 1976-2006.

BACKGROUND: little is known about the prevalence of at-risk drinking in older adults. OBJECTIVE: to compare rates of at-risk drinking in 75-year-olds examined in 1976-77 and in 2005-06. DESIGN: cross-sectional survey. SETTING: two samples representative of the general population in Gothenburg, Sweden. PARTICIPANTS: 75-year-olds born in 1901-02 (n = 303) and in 1930 (n = 753). METHODS: participants took part in a multidisciplinary study on health and ageing. Protocols regarding alcohol consumption were identical for both cohorts. Total weekly alcohol intake was estimated and at-risk drinking was defined as ≥100 g alcohol/week. RESULTS: the proportion abstaining differed significantly between birth cohorts (18% in 1976-77 versus 9% in 2005, P < 0.001). Frequencies of drinking beer and liquor were similar in the two cohorts for men, but were lower for women in the later-born cohort. Proportions drinking wine were higher in the later-born cohort for both sexes. Total weekly alcohol intake was higher for both men and women. At-risk drinking was observed in 19.3% of the men in the earlier-born cohort, and in 27.4% in the later-born cohort (P = 0.117). Corresponding figures for women were 0.6 and 10.4% (P < 0.001). At-risk drinking was significantly associated with birth cohort in women (OR: 13.77, CI: 1.82-104.0, P = 0.011) and the occupational group in men (OR: 1.60, CI: 1.13-2.26, P = 0.008). CONCLUSIONS: alcohol consumption in 75-year-olds has changed markedly, especially in women. Studies need to be carried out in varied settings in order to evaluate the clinical and public health implications of changing trends in alcohol consumption.

Western Ontario Osteoarthritis Shoulder (WOOS) index: a cross-cultural adaptation into Swedish, including evaluation of reliability, validity, and responsiveness in patients with subacromial pain.

BACKGROUND: The aim of the present study was to translate the Western Ontario Osteoarthritis Shoulder (WOOS) index into Swedish and to test its validity, reliability, and responsiveness in patients with subacromial pain. METHODS: The validity of the WOOS translation was tested in 54 patients who completed the WOOS and the Shoulder Rating Questionnaire, Swedish version (SRQs). Of these patients, 46 were retested to assess reliability. Responsiveness was evaluated in 29 subjects who completed the WOOS and SRQs before surgery and again at 3 months after surgery, when they also rated perceived change in shoulder function. The relationship between the questionnaires and patient-perceived improvement was assessed. RESULTS: A high correlation was found between the Swedish version of WOOS and the SRQs. The correlations were similar in a group of working patients (r = -0.832) and in all patients (r = -0.843; P < .001). A high degree of agreement between WOOS at test and retest was also observed. A Bland-Altman plot showed a small mean difference and no trend across the range of WOOS values. A strong significant agreement was also shown by a κ value of 0.649 (P < .001) and an intraclass correlation coefficient of 0.95 (95% confidence interval, 0.92-0.97, P < .001) as well as by a low difference between the test and retest means. Responsiveness, calculated by standardized response mean, was excellent (1.02). CONCLUSION: The results of the present study provide evidence that the Swedish version of WOOS is valid, reliable, and responsive in patients with subacromial pain and performs similarly to the original Canadian version.

A patient survey of out-of-hours care provided by Emergency Care Practitioners.

BACKGROUND: Emergency Care Practitioners (ECPs) have recently been deployed to provide out-of-hours primary care home visits - a practice development that has been supported by policy makers. The aim of the study was to evaluate the care provided to patients receiving out-of-hours home visits from ECPs in London from the patients' perspective and to assess their wellbeing following the visit. METHODS: A bespoke telephone-administered questionnaire was designed to survey all patients who had received out-of-hours care in Bromley Primary Care Trust from ECPs during a ten week period in 2005 (n = 174). RESULTS: Sixty three patients (36.2%) were excluded because: no telephone number was available; they had a diagnosis of dementia; or had not received a study information sheet. The remainder (n = 111) were contacted 3-5 days after the home visit, and 81 of these (73.0%) completed the survey. Of those respondents treated at home who gave unequivocal answers (n = 60), all but one (8.3%) reported that they felt that their treatment had been 'right' and/or had followed any advice given. However, overall only 86.4% reported that they had been clear about their ECP's assessment, and only 58.0% reported that their health was now 'better'. Those who reported that they were not clear about their assessment were less likely to report that their health was 'better' (p = 0.03) and more likely to have subsequently used hospital-based health services (p = 0.03). CONCLUSION: Most patients treated at home by ECPs appeared satisfied and compliant with the care provided, according to the measures used in this study. However, it appears that a sizeable minority of patients were unclear about ECP assessments and it remains to be seen whether these patients had pre-existing health complaints which made them less likely to recover and more likely to seek hospital care, or whether the lack of clarity about their assessment undermined their subsequent recovery and necessitated hospital care. Further research is required to establish if the assessments provided by ECPs are less clear than those provided by other practitioners, and whether it is possible to ensure that all such assessments are clear to all patients. Patients hold a mainly positive view of out-of-hours home visit care provided by ECPs, although a lack of clarity about their assessment was evident, with a possible impact on their continuing health.