Cancer suspicion in general practice, urgent referral, and time to diagnosis: a population-based GP survey nested within a feasibility study using information technology to flag-up patients with symptoms of colorectal cancer

Background: Patients with symptoms of possible colorectal cancer are not always referred for investigation. Aim: To ascertain barriers and facilitators to GP referral of patients meeting the National Institute for Health and Care Excellence (NICE) guidelines for urgent referral for suspected colorectal cancer. Design & setting: Qualitative study in the context of a feasibility study using information technology in GP practices to flag-up patients meeting urgent referral criteria for colorectal cancer. Method: Semi-structured interview with 18 GPs and 12 practice managers, focusing on early detection of colorectal cancer, issues in the use of information technology to identify patients and GP referral of these patients for further investigation were audiotaped, transcribed verbatim, and analysed according to emergent themes. Results: There were two main themes: wide variation in willingness to refer and uncertainty about whether to refer; and barriers to referral. Three key messages emerged: there was a desire to avoid over-referral, lack of knowledge of guidelines, and the use of individually-derived decision rules for further investigation or referral of symptoms. Some GPs were unaware that iron deficiency anaemia or persistent diarrhoea are urgent referral criteria. Alternatives to urgent referral included undertaking no investigations, trials of iron therapy, use of faecal occult blood tests (FOBt) and non-urgent referral. In minority ethnic groups (South Asians) anaemia was often accepted as normal. Concerns about over-referral were linked to financial pressures and perceived criticism by healthcare commissioners, and a reluctance to scare patients by discussing suspected cancer. Conclusion: GPs’ lack of awareness of referral guidelines and concerns about over-referral are barriers to early diagnosis of colorectal cancer

Transcatheter aortic valve implantation for aortic stenosis in high surgical risk patients: A systematic review and meta-analysis

Background Symptomatic aortic stenosis has a poor prognosis. Many patients are considered inoperable or at high surgical risk for surgical aortic valve replacement (SAVR), reflecting their age, comorbidities and frailty. The clinical effectiveness and safety of TAVI have not been reviewed systematically for these high levels of surgical risk. This systematic review compares mortality and other important clinical outcomes up to 5 years post treatment following TAVI or other treatment in these risk groups. Methods A systematic review protocol was registered on the PROSPERO database (CRD42016048396). The Cochrane Library, Centre for Reviews and Dissemination Databases, MEDLINE, EMBASE, and ZETOC were searched from January 2002 to August 2016. Clinical trials or matched studies comparing TAVI with other treatments for AS in patients surgically inoperable or operable at a high risk were included. Data extraction and quality assessment were conducted by two reviewers. Data were pooled using random-effects meta-analysis. The main outcomes were all-cause mortality, efficacy and major complications. Results Three good quality randomised controlled trials (RCTs) were included. Patients’ mean age ranged from 83- 85 years, around half were female and New York Heart Association (NYHA) functional class III or IV ranged from 83.8% to 94.2% with frequent comorbidities. In 358 surgically inoperable patients from one RCT, TAVI was superior to medical therapy for all-cause mortality at 1 year (hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.36−0.92), 2 years (HR 0.50, 95% CI 0.39−0.65), 3 years (HR 0.53, 95% CI 0.41to 0.68) and 5 years (HR 0.50, 95% CI 0.39−0.65), and NYHA class III or IV at 2 years (TAVI 16.8% (16/95), medical therapy 57.5% (23/40), p In a meta-analysis including 1,494 high risk surgically operable patients from two non-inferiority RCTs TAVI showed no significant differences from SAVR in all-cause mortality at two years (HR 1.03, 95% CI 0.82−1.29) and up to 5 years (HR 0.83, 95% CI 0.83−1.12). There were no statistically significant differences in major vascular complications and myocardial infarction at any time point, discrepant results for major bleeding on variable definitions and no differences in stroke rate at any time point. Using the GRADE tool, this evidence was considered of low quality. Conclusions Symptomatic aortic stenosis can be lethal without intervention but surgical resection is contraindicated for some patients and high risk for others. We found that all-cause mortality up to 5 years of follow-up did not differ significantly between TAVI and SAVR in patients surgically operable at a high risk, but favoured TAVI over medical therapy in patients surgically inoperable. TAVI is a viable life-extending treatment option in these surgical high risk groups.</p

A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease

Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers

Hemodialysis vascular access options in pediatrics: considerations for patients and practitioners

Recent data indicate that the incidence of end-stage renal disease (ESRD) in pediatric patients (age 0–19 years) has increased over the past two decades. Similarly, the prevalence of ESRD has increased threefold over the same period. Hemodialysis (HD) continues to be the most frequently utilized modality for renal replacement therapy in incident pediatric ESRD patients. The number of children on HD exceeded the sum total of those on peritoneal dialysis and those undergoing pre-emptive renal transplantation. Choosing the best vascular access option for pediatric HD patients remains challenging. Despite a national initiative for fistula first in the adult hemodialysis population, the pediatric nephrology community in the United States of America utilizes central venous catheters as the primary dialysis access for most patients. Vascular access management requires proper advance planning to assure that the best permanent access is placed, seamless communication involving a multidisciplinary team of nephrologists, nurses, surgeons, and interventional radiologists, and ongoing monitoring to ensure a long life of use. It is imperative that practitioners have a long-term vision to decrease morbidity in this unique patient population. This article reviews the various types of pediatric vascular accesses used worldwide and the benefits and disadvantages of these various forms of access

Systematic review of effect of community-level interventions to reduce maternal mortality

<p>Abstract</p> <p>Background</p> <p>The objective was to provide a systematic review of the effectiveness of community-level interventions to reduce maternal mortality.</p> <p>Methods</p> <p>We searched published papers using Medline, Embase, Cochrane library, CINAHL, BNI, CAB ABSTRACTS, IBSS, Web of Science, LILACS and African Index Medicus from inception or at least 1982 to June 2006; searched unpublished works using National Research Register website, metaRegister and the WHO International Trial Registry portal. We hand searched major references.</p> <p>Selection criteria were maternity or childbearing age women, comparative study designs with concurrent controls, community-level interventions and maternal death as an outcome. We carried out study selection, data abstraction and quality assessment independently in duplicate.</p> <p>Results</p> <p>We found five cluster randomised controlled trials (RCT) and eight cohort studies of community-level interventions. We summarised results as odds ratios (OR) and confidence intervals (CI), combined using the Peto method for meta-analysis. Two high quality cluster RCTs, aimed at improving perinatal care practices, showed a reduction in maternal mortality reaching statistical significance (OR 0.62, 95% CI 0.39 to 0.98). Three equivalence RCTs of minimal goal-oriented versus usual antenatal care showed no difference in maternal mortality (1.09, 95% CI 0.53 to 2.25). The cohort studies were of low quality and did not contribute further evidence.</p> <p>Conclusion</p> <p>Community-level interventions of improved perinatal care practices can bring about a reduction in maternal mortality. This challenges the view that investment in such interventions is not worthwhile. Programmes to improve maternal mortality should be evaluated using randomised controlled techniques to generate further evidence.</p