A cluster randomized controlled trial of a clinical pathway for hospital treatment of heart failure: study design and population

<p>Abstract</p> <p>Background</p> <p>The hospital treatment of heart failure frequently does not follow published guidelines, potentially contributing to the high morbidity, mortality and economic cost of this disorder. Consequently the development of clinical pathways has the potential to reduce the current variability in care, enhance guideline adherence, and improve outcomes for patients. Despite enthusiasm and diffusion, the widespread acceptance of clinical pathways remain questionable because very little prospective controlled data demonstrated their effectiveness. The Experimental Prospective Study on the Effectiveness and Efficiency of the Implementation of Clinical Pathways was designed in order to conduct a rigorous evaluation of clinical pathways in hospital treatment of acute heart failure. The primary objective of the trial was to evaluate the effectiveness of the implementation of clinical pathways for hospital treatment of heart failure in Italian hospitals.</p> <p>Methods/design</p> <p>Two-arm, cluster-randomized trial. 14 community hospitals were randomized either to arm 1 (clinical pathway: appropriate use of practice guidelines and supplies of drugs and ancillary services, new organization and procedures, patient education, etc.) or to arm 2 (no intervention, usual care). 424 patients sample (212 in each group), 80% of power at the 5% significance level (two-sided). The primary outcome measure is in-hospital mortality. We will also analyze the impact of the clinical pathways comparing the length and the appropriateness of the stay, the rate of unscheduled readmissions, the customers' satisfaction and the costs treating the patients with the pathways and with the current practice along all the observation period. The quality of the care will be assessed by monitoring the use of diagnostic and therapeutic procedures during hospital stay and by measuring key quality indicators at discharge.</p> <p>Discussion</p> <p>This paper examines the design of the evaluation of a complex intervention. Since clinical pathways are made up of various interconnecting parts we have chosen the cluster-randomized controlled trial because is widely accepted as the most reliable method of determining effectiveness when measuring cost-effectiveness in real practice.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID [NCT00519038]</p

Airflow Dynamics of Human Jets: Sneezing and Breathing - Potential Sources of Infectious Aerosols

10.1371/journal.pone.0059970PLoS ONE84

Intraprostatic Botulinum Toxin Type A injection in patients with benign prostatic enlargement: duration of the effect of a single treatment

<p>Abstract</p> <p>Background</p> <p>Botulinum Toxin Type-A (BoNT/A) intraprostatic injection can induce prostatic involution and improve LUTS and urinary flow in patients with Benign Prostatic Enlargement (BPE). However, the duration of these effects is unknown. The objective of this work was to determine the duration of prostate volume reduction after one single intraprostatic injection of 200U of Botulinum Toxin Type-A.</p> <p>Methods</p> <p>This is an extension of a 6 month study in which 21 frail elderly patients with refractory urinary retention and unfit for surgery were submitted to intraprostatic injection of BoNT/A-200U, by ultrasound guided transrectal approach. In spite of frail conditions, eleven patients could be followed during 18 months. Prostate volume, total serum PSA, maximal flow rate (Qmax), residual volume (PVR) and IPSS-QoL scores were determined at 1, 3, 6, 12 and 18 months post-treatment.</p> <p>Results</p> <p>Mean prostate volume at baseline, 82 ± 16 ml progressively decreased from month one coming to 49 ± 9,5 ml (p = 0,003) at month six. From this moment on, prostate volume slowly recovered, becoming identical to baseline at 18 months (73 ± 16 ml, p = 0.03). Albeit non significant, serum PSA showed a 25% decrease from baseline to month 6. The 11 patients resumed spontaneous voiding at month one. Mean Qmax was 11,3 ± 1,7 ml/sec and remained unchanged during the follow-up period. PVR ranged from 55 ± 17 to 82 ± 20 ml and IPSS score from10 to 12 points.</p> <p>Conclusion</p> <p>Intraprostatic BoNT/A injection is safe and can reduce prostate volume for a period of 18 months. During this time a marked symptomatic improvement can be maintained.</p

Evolution of vaccination rates after the implementation of a free systematic pneumococcal vaccination in Catalonian older adults: 4-years follow-up

BACKGROUND: The systematic vaccination with 23-valent polysaccharide pneumococcal vaccine (PPV) was introduced as a strategic objective of health for all the people over 65 in Catalonia in 1999. We analysed the evolution of the pneumococcal vaccination rates from 2000 to 2003. METHODS: We conducted a retrospective population-based study including all the individuals 65 years or older assigned to 8 Primary Care Centres (PCCs) in Tarragona (Catalonia, Spain), who figured in the administrative population databases on 31 December 2003 (n = 10,410 persons). We assessed whether every person had received PPV during the last four years (2000 to 2003) or whether they had received it before January 2000. Data sources were the computerised clinical records of the 8 participating PCCs, which included adult vaccination registries and diagnoses coded of International Classification of Diseases 9(th )Review RESULTS: The overall vaccination uptake increased to 38.6% at the end of 2000. Global accumulated coverages increased more slowly the following years: 44.4% in 2001, 50.9% in 2002, and 53.1% at the end of 2003. Vaccine uptake varied significantly according to age (46.7% in people 65–74 years-old, 60.9% in people 75 years or more; p < 0.001) and number of diseases or risk factors (DRFs) for pneumonia (47.1% vaccinated in people without DRFs, 56.8% in patients with one DRF, and 62.2% in patients with two or more DRFs; p < 0.001). The highest coverages were observed among those patients with: diabetes (65.9%), active neoplasia (64.8%), history of stroke (63.7%), and chronic lung disease (63.5%). The lowest uptake was observed among smokers (48.7%). DISCUSSION: The pneumococcal vaccination coverage increased quickly after the introduction of the recommendation for free vaccination in all the elderly people (with and without risk factors), but two years after the improvement the coverage became stable and increased slowly

Effects of Interferon-α/β on HBV Replication Determined by Viral Load

Interferons α and β (IFN-α/β) are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV) patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low

Development of a complex intervention to test the effectiveness of peer support in type 2 diabetes

BACKGROUND: Diabetes is a chronic illness which requires the individual to assume responsibility for their own care with the aim of maintaining glucose and blood pressure levels as close to normal as possible. Traditionally self management training for diabetes has been delivered in a didactic setting. In recent times alternatives to the traditional delivery of diabetes care have been investigated, for example, the concept of peer support which emphasises patient rather than professional domination. The aim of this paper is to describe the development of a complex intervention of peer support in type 2 diabetes for a randomised control trial in a primary care setting. METHODS: The Medical Research Council (MRC) framework for the development and evaluation of complex interventions for randomised control trials (RCT) was used as a theoretical guide to designing the intervention. The first three phases (Preclinical Phase, Phase 1, Phase 2) of this framework were examined in depth. The Preclinical Phase included a review of the literature relating to type 2 diabetes and peer support. In Phase 1 the theoretical background and qualitative data from 4 focus groups were combined to define the main components of the intervention. The preliminary intervention was conducted in Phase 2. This was a pilot study conducted in two general practices and amongst 24 patients and 4 peer supporters. Focus groups and semi structured interviews were conducted to collect additional qualitative data to inform the development of the intervention. RESULTS: The four components of the intervention were identified from the Preclinical Phase and Phase 1. They are: 1. Peer supporters; 2. Peer supporter training; 3. Retention and support for peer supporters; 4. Peer support meetings. The preliminary intervention was implemented in the Phase 2. Findings from this phase allowed further modeling of the intervention, to produce the definitive intervention. CONCLUSION: The MRC framework was instrumental in the development of a robust intervention of peer support of type 2 diabetes in primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42541690

Serum Early Prostate Cancer Antigen (EPCA) Level and Its Association with Disease Progression in Prostate Cancer in a Chinese Population

BACKGROUND: Early prostate cancer antigen (EPCA) has been shown a prostate cancer (PCa)-associated nuclear matrix protein, however, its serum status and prognostic power in PCa are unknown. The goals of this study are to measure serum EPCA levels in a cohort of patients with PCa prior to the treatment, and to evaluate the clinical value of serum EPCA. METHODS: Pretreatment serum EPCA levels were determined with an ELISA in 77 patients with clinically localized PCa who underwent radical prostatectomy and 51 patients with locally advanced or metastatic disease who received primary androgen deprivation therapy, and were correlated with clinicopathological variables and disease progression. Serum EPCA levels were also examined in 40 healthy controls. RESULTS: Pretreatment mean serum EPCA levels were significantly higher in PCa patients than in controls (16.84 ± 7.60 ng/ml vs. 4.12 ± 2.05 ng/ml, P<0.001). Patients with locally advanced and metastatic PCa had significantly higher serum EPCA level than those with clinically localized PCa (22.93 ± 5.28 ng/ml and 29.41 ± 8.47 ng/ml vs. 15.17 ± 6.03 ng/ml, P = 0.014 and P<0.001, respectively). Significantly elevated EPCA level was also found in metastatic PCa compared with locally advanced disease (P < 0.001). Increased serum EPCA levels were significantly and positively correlated with Gleason score and clinical stage, but not with PSA levels and age. On multivariate analysis, pretreatment serum EPCA level held the most significantly predictive value for the biochemical recurrence and androgen-independent progression among pretreatment variables (HR = 4.860, P<0.001 and HR = 5.418, P<0.001, respectively). CONCLUSIONS: Serum EPCA level is markedly elevated in PCa. Pretreatment serum EPCA level correlates significantly with the poor prognosis, showing prediction potential for PCa progression

An assessment of air-sea heat fluxes from ocean and coupled reanalyses

Sixteen monthly air–sea heat flux products from global ocean/coupled reanalyses are compared over 1993–2009 as part of the Ocean Reanalysis Intercomparison Project (ORA-IP). Objectives include assessing the global heat closure, the consistency of temporal variability, comparison with other flux products, and documenting errors against in situ flux measurements at a number of OceanSITES moorings. The ensemble of 16 ORA-IP flux estimates has a global positive bias over 1993–2009 of 4.2 ± 1.1 W m−2. Residual heat gain (i.e., surface flux + assimilation increments) is reduced to a small positive imbalance (typically, +1–2 W m−2). This compensation between surface fluxes and assimilation increments is concentrated in the upper 100 m. Implied steady meridional heat transports also improve by including assimilation sources, except near the equator. The ensemble spread in surface heat fluxes is dominated by turbulent fluxes (>40 W m−2 over the western boundary currents). The mean seasonal cycle is highly consistent, with variability between products mostly <10 W m−2. The interannual variability has consistent signal-to-noise ratio (~2) throughout the equatorial Pacific, reflecting ENSO variability. Comparisons at tropical buoy sites (10°S–15°N) over 2007–2009 showed too little ocean heat gain (i.e., flux into the ocean) in ORA-IP (up to 1/3 smaller than buoy measurements) primarily due to latent heat flux errors in ORA-IP. Comparisons with the Stratus buoy (20°S, 85°W) over a longer period, 2001–2009, also show the ORA-IP ensemble has 16 W m−2 smaller net heat gain, nearly all of which is due to too much latent cooling caused by differences in surface winds imposed in ORA-IP

Functional expression of complement factor I following AAV-mediated gene delivery in the retina of mice and human cells.

Funder: NIHR Oxford Biomedical Research CentreDry age-related macular degeneration (AMD) is characterised by loss of central vision and currently has no approved medical treatment. Dysregulation of the complement system is thought to play an important role in disease pathology and supplementation of Complement Factor I (CFI), a key regulator of the complement system, has the potential to provide a treatment option for AMD. In this study, we demonstrate the generation of AAV constructs carrying the human CFI sequence and expression of CFI in cell lines and in the retina of C57BL/6 J mice. Four codon optimised constructs were compared to the most common human CFI sequence. All constructs expressed CFI protein; however, most codon optimised sequences resulted in significantly reduced CFI secretion compared to the non-optimised CFI sequence. In vivo expression analysis showed that CFI was predominantly expressed in the RPE and photoreceptors. Secreted protein in vitreous humour was demonstrated to be functionally active. The findings presented here have led to the formulation of an AAV-vectored gene therapy product currently being tested in a first-in-human clinical trial in subjects with geographic atrophy secondary to dry AMD (NCT03846193)