Determining the Role of Thiamine Deficiency in Systolic Heart Failure: A Meta-Analysis and Systematic Review.

BACKGROUND: Approximately 5.7 million Americans carry the diagnosis of systolic heart failure (HF), a major health care burden. HF is a known manifestation of thiamine deficiency (TD). HF patients are at unique risk for developing TD, which may contribute to further altered cardiac function and symptoms. METHODS AND RESULTS: We performed a systematic review of the literature and a meta-analysis to evaluate the prevalence of TD in HF patients, risk factors for and mechanisms of development of TD in HF population, and outcomes of thiamine supplementation in HF patients. We found 54 studies that met our selection criteria, 9 of which were suitable for meta-analysis. TD is more common in HF patients than control subjects (odds ratio 2.53, 95% confidence interval 1.65-3.87). Diuretic use, changes in dietary habits, and altered thiamine absorption and metabolism were identified as possible mechanisms of TD in HF patients. Small observational studies and randomized control trials suggest that thiamine supplementation in HF population may improve ejection fraction and reduce symptoms. CONCLUSIONS: Thiamine deficiency is more prevalent in the HF population, and its supplementation may be beneficial. The therapeutic role of thiamine in HF warrants further study.

Implementation of the national Getting it Right First Time orthopaedic programme in England: a qualitative case study analysis.

OBJECTIVE: To describe the implementation and impact of the Getting it Right First Time (GIRFT) national orthopaedic improvement programme at the level of individual National Health Service (NHS) Trusts. DESIGN: Qualitative case studies conducted at six NHS Trusts, as part of a mixed-methods evaluation of GIRFT. SETTING: NHS elective orthopaedic surgery in England. PARTICIPANTS: 59 NHS staff. INTERVENTION: Improvement bundle, including bespoke routine performance data and improvement recommendations for each organisation, delivered via 'deep-dive' visits to NHS Trusts by a senior orthopaedic clinician. RESULTS: Although all case study sites had made improvements to care, very few of these were reportedly a direct consequence of GIRFT. A range of factors, operating at three different levels, influenced their ability to implement GIRFT recommendations: at the level of the orthopaedic team (micro-eg, how individuals perceived the intervention); the wider Trust (meso-eg, competition for theatre/bed space) and the health economy more broadly (macro-eg, requirements to form local networks). Some sites used GIRFT evidence to support arguments for change which helped cement and formalise existing plans. However, where GIRFT measures were not a Trust priority because of more immediate demands-for example, financial and bed pressures-it was less likely to influence change. CONCLUSION: Dynamic relationships between the different contextual factors, within and between the three levels, can impact the effectiveness of a large-scale improvement intervention and may account for variations in implementation outcomes in different settings. When designing an intervention, those leading future improvement programmes should consider how it sits in relation to these three contextual levels and the interactions that may occur between them.

'Maze' not pathway: focus group exploration of patients' and public experiences of the UK NHS elective total joint arthroplasty pathway.

OBJECTIVE: To explore patient and public perceptions of planned improvements to the National Health Service (NHS) total joint arthroplasty (TJA) pathway. DESIGN: Three qualitative focus groups undertaken March-May 2018, as part of a mixed-methods evaluation of Getting It Right First Time. Transcripts were subject to framework analysis to identify thematic content between October 2018 and October 2021. SETTING: Elective TJA surgery in the English NHS. PARTICIPANTS: Two focus groups including patients who had undergone TJA in the previous 2 years (group 1: n=5; group 2: n=4) and the other individuals who had not but were aged 60+ (group 3: n=5). Participants were recruited via community groups and patient panels. RESULTS: Fourteen individuals took part in the focus groups; all were aged over 60; seven (50%) were female and nine (64%) had undergone TJA surgery. Participants' perspectives were categorised into themes and mapped onto stages of the TJA pathway. Although perioperative care is often the focus of improvement efforts, participants argued that the patient journey begins before individuals present to primary care. Participants had concerns about other aspects of the pathway, such as obtaining a surgical referral, with prereferral interventions aimed at potentially avoiding the need for surgery (ie, physiotherapy) being perceived as a mechanism to restrict access to secondary care. Patient experience was also conceptualised as a 'maze', rather than the logical, sequential process set out in clinical guidelines; exacerbated by a lack of information, knowledge and power imbalances. CONCLUSION: The linear conceptualisation of the TJA pathway is at odds with patient experience. Improvement programmes focused on perioperative care fail to consider patient concerns and priorities. Patients should be directly involved in improvement programmes, to ensure that patient experience is optimised, as well as informing related processes and important outcomes of care.

Mixed methods evaluation of the Getting it Right First Time programme in elective orthopaedic surgery in England: an analysis from the National Joint Registry and Hospital Episode Statistics.

OBJECTIVE: To evaluate the impact of the 'Getting it Right First Time' (GIRFT) national improvement programme in orthopaedics, which started in 2012. DESIGN: Mixed-methods study comprising statistical analysis of linked national datasets (National Joint Registry; Hospital Episode Statistics; Patient-Reported Outcomes); economic analysis and qualitative case studies in six National Health Service (NHS) Trusts. SETTING: NHS elective orthopaedic surgery in England. PARTICIPANTS: 736 088 patients who underwent primary hip or knee replacement at 126 NHS Trusts between 1 April 2009 and 31 March 2018, plus 50 NHS staff. INTERVENTION: Improvement bundle including 'deep dive' visits by senior clinician to NHS Trusts, informed by bespoke set of routine performance data, to discuss how improvements could be made locally. MAIN OUTCOME MEASURES: Number of procedures conducted by low volume surgeons; use of uncemented hip implants in patients >65; arthroscopy in year prior to knee replacement; hospital length of stay; emergency readmissions within 30 days; revision surgery within 1 year; health-related quality of life and functional status. RESULTS: National trends demonstrated substantial improvements beginning prior to GIRFT. Between 2012 and 2018, there were reductions in procedures by low volume surgeons (ORs (95% CI) hips 0.58 (0.53 to 0.63), knees 0.77 (0.72 to 0.83)); uncemented hip prostheses in >65 s (OR 0.56 (0.51 to 0.61)); knee arthroscopies before surgery (OR 0.48 (0.41 to 0.56)) and mean length of stay (hips -0.90 (-1.00 to -0.81), knees -0.74 days (-0.82 to -0.66)). The additional impact of visits was mixed and comprised an overall economic saving of £431 848 between 2012 and 2018, but this was offset by the costs of the visits. Staff reported that GIRFT's influence ranged from procurement changes to improved regional collaboration. CONCLUSION: Nationally, we found substantial improvements in care, but the specific contribution of GIRFT cannot be reliably estimated due to other concurrent initiatives. Our approach enabled additional analysis of the discrete impact of GIRFT visits.

Exogenous exposure to dihydroxyacetone mimics high fructose induced oxidative stress and mitochondrial dysfunction.

Dihydroxyacetone (DHA) is a three-carbon sugar that is the active ingredient in sunless tanning products and a by-product of electronic cigarette (e-cigarette) combustion. Increased use of sunless tanning products and e-cigarettes has elevated exposures to DHA through inhalation and absorption. Studies have confirmed that DHA is rapidly absorbed into cells and can enter into metabolic pathways following phosphorylation to dihydroxyacetone phosphate (DHAP), a product of fructose metabolism. Recent reports have suggested metabolic imbalance and cellular stress results from DHA exposures. However, the impact of elevated exposure to DHA on human health is currently under-investigated. We propose that exogenous exposures to DHA increase DHAP levels in cells and mimic fructose exposures to produce oxidative stress, mitochondrial dysfunction, and gene and protein expression changes. Here, we review cell line and animal model exposures to fructose to highlight similarities in the effects produced by exogenous exposures to DHA. Given the long-term health consequences of fructose exposure, this review emphasizes the pressing need to further examine DHA exposures from sunless tanning products and e-cigarettes.

Prostate minimally invasive procedures: complications and normal vs. abnormal findings on multiparametric magnetic resonance imaging (mpMRI).

Minimally invasive alternatives to traditional prostate surgery are increasingly utilized to treat benign prostatic hyperplasia and localized prostate cancer in select patients. Advantages of these treatments over prostatectomy include lower risk of complication, shorter length of hospital stay, and a more favorable safety profile. Multiparametric magnetic resonance imaging (mpMRI) has become a widely accepted imaging modality for evaluation of the prostate gland and provides both anatomical and functional information. As prostate mpMRI and minimally invasive prostate procedure volumes increase, it is important for radiologists to be familiar with normal post-procedure imaging findings and potential complications. This paper reviews the indications, procedural concepts, common post-procedure imaging findings, and potential complications of prostatic artery embolization, prostatic urethral lift, irreversible electroporation, photodynamic therapy, high-intensity focused ultrasound, focal cryotherapy, and focal laser ablation.

Schizophrenia and borderline personality disorder: similarities and differences in the experience of auditory hallucinations, paranoia, and childhood trauma.

This study investigated similarities and differences in the experience of auditory hallucinations, paranoia, and childhood trauma in schizophrenia and borderline personality disorder (BPD). Patients with clinical diagnoses of schizophrenia or BPD were interviewed using the Structured Clinical Interviews for DSM-IV. Axes 1 and 2 and auditory hallucinations, paranoia, and childhood trauma were assessed. A total of 111 patients participated; 59 met criteria for schizophrenia, 33 for BPD, and 19 for both. The groups were similar in their experiences of voices, including the perceived location of them, but they differed in frequency of paranoid delusions. Those with a diagnosis of BPD, including those with schizophrenia comorbidity, reported more childhood trauma, especially emotional abuse. BPD and schizophrenia frequently coexist, and this comorbidity has implications for diagnostic classification and treatment. Levels of reported childhood trauma are especially high in those with a BPD diagnosis, whether they have schizophrenia or not, and this requires assessment and appropriate management.

High PD-1/PD-L1 Checkpoint Interaction Infers Tumor Selection and Therapeutic Sensitivity to Anti-PD-1/PD-L1 Treatment.

Many cancers are termed immunoevasive due to expression of immunomodulatory ligands. Programmed death ligand-1 (PD-L1) and cluster of differentiation 80/86 (CD80/86) interact with their receptors, programmed death receptor-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), respectively, on tumor-infiltrating leukocytes eliciting immunosuppression. Immunotherapies aimed at blocking these interactions are revolutionizing cancer treatments, albeit in an inadequately described patient subset. To address the issue of patient stratification for immune checkpoint intervention, we quantitatively imaged PD-1/PD-L1 interactions in tumor samples from patients, employing an assay that readily detects these intercellular protein-protein interactions in the less than or equal to 10 nm range. These analyses across multiple patient cohorts demonstrated the intercancer, interpatient, and intratumoral heterogeneity of interacting immune checkpoints. The PD-1/PD-L1 interaction was not correlated with clinical PD-L1 expression scores in malignant melanoma. Crucially, among anti-PD-1-treated patients with metastatic non-small cell lung cancer, those with lower PD-1/PD-L1 interaction had significantly worsened survival. It is surmised that within tumors selecting for an elevated level of PD-1/PD-L1 interaction, there is a greater dependence on this pathway for immune evasion and hence, they exhibit more impressive patient response to intervention. SIGNIFICANCE: Quantitation of immune checkpoint interaction by direct imaging demonstrates that immunotherapy-treated patients with metastatic NSCLC with a low extent of PD-1/PD-L1 interaction show significantly worse outcome.

Allergy and Asthma: Allergic Rhinitis and Allergic Conjunctivitis.

Allergic rhinitis and allergic conjunctivitis are among the most common conditions seen in family medicine practice. Most cases are due to seasonal allergens, such as pollens, or year-round allergens, such as dust mites, mold, and animal dander. The clinical diagnosis can be made when symptoms of nasal congestion, sneezing, rhinorrhea, nasal or ocular pruritus, or eye tearing are present along with physical findings, such as clear rhinorrhea, pale nasal mucosa, or red watery eyes. Patients should be assessed for any comorbid conditions, such as asthma or eczema, and for symptoms that indicate impaired quality of life, such as poor sleep, daytime somnolence, or irritability. Prevention involves allergen avoidance and environmental controls. Monotherapy with oral antihistamines, intranasal steroids, or intranasal antihistamines are the initial management options for nasal and ocular symptoms. Antihistamine eye drops are fast-acting and safe for management of ocular symptoms; intranasal antihistamines are effective for nasal symptoms. Current guidelines recommend against combining intranasal steroids and oral antihistamines, as this provides no additional benefit. Select patients also may benefit from allergy skin testing or consideration for allergen immunotherapy.

Allergy and Asthma: Food Allergies.

Food allergies are immune-mediated allergic adverse reactions that occur after exposure to specific foods. The most commonly recognized food allergies are immunoglobulin E (IgE)-mediated reactions (eg, urticaria, angioedema, anaphylaxis) that result from exposure to milk, egg, peanut, tree nuts, shellfish, fish, wheat, or soy. However, other foods can cause food allergies. Oral allergy syndrome is a common but underrecognized condition characterized by transient oropharyngeal symptoms that result from ingestion of uncooked fruits or vegetables. Non-IgE-mediated food allergies manifest with more delayed symptoms than IgE-mediated food allergies, and predominately cause gastrointestinal symptoms. Food allergies often are overreported because they may be confused with food intolerances or nonimmunologic adverse food reactions (eg, lactose intolerance, food poisoning, caffeine intolerance). Food allergies are diagnosed using IgE skin tests, IgE serum tests, or oral food challenge tests. These allergies are best managed by avoidance of the food or foods related to the allergy because they require ingestion rather than contact to precipitate symptoms. Injectable epinephrine should be prescribed for patients at risk of anaphylaxis. Careful food label reading and food preparation, awareness, and education are keys to prevention.

Left Main Coronary Artery Thrombosis With Acute Myocardial Infarction: A Management Dilemma.

Left main coronary artery (LMCA) thrombosis with acute myocardial infarction is a rare condition with very high mortality. The low incidence of this condition and exclusion of patients with LMCA thrombosis from clinical trials prevent the development of optimal management strategy in these patients. Therefore, there are no clear-cut guidelines describing an evidence-based approach for this condition. We describe a patient with LMCA thrombosis presenting with acute myocardial infarction, who was found to have hypercoagulable state related to homocysteinemia on further work-up. This case highlights the challenges faced during the management of this rare condition due to lack of clear-cut guidelines describing an evidence-based approach.

Prognostic significance of cyclooxygenase-2 (COX-2) expression in patients with surgically resectable adenocarcinoma of the oesophagus.

BACKGROUND: COX-2 expression in tumour cells has been associated with poor prognosis in gastrointestinal and non-gastrointestinal cancers. The aim of our study was to test the hypothesis that higher levels of COX-2 expression are prognostically related to poor clinico-pathologic features in adenocarcinoma of the oesophagus. METHODS: We reviewed the records of 100 consecutive patients undergoing resection for adenocarcinoma of the oesophagus to collect data on T-stage, N-stage, tumour recurrence and survival. T & N-stage was further confirmed by histological examination. COX-2 protein expression was assessed by immunohistochemistry in all patients and COX-2 m-RNA expression was measured by quantitative RT-PCR in a small group of patients. RESULTS: Higher levels of COX-2 expression were associated with higher T stage (p = 0.008), higher N stage (p = 0.049), increased risk of tumour recurrence (p = 0.01) and poor survival (p = <0.001). A COX-2 score of >200 was associated with a median survival of 10 months compared to 26 months with a score of <200 (p = <0.001). CONCLUSION: Higher levels of COX-2 expression are associated with poor clinico-pathologic features and poor survival in patients with oesophageal adenocarcinoma.

In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease.

Chronic kidney disease may progress to end-stage renal disease, which requires dialysis or kidney transplantation. No generally applicable therapies to slow progression of renal disease are available. Bacteriotherapy affords a promising approach to mitigate uremic intoxication by ingestion of live microbes able to catabolize uremic solutes in the gut. The present study evaluates the nonpathogenic soil-borne alkalophilic urease-positive bacterium Sporosarcina pasteurii (Sp) as a potential urea-targeted component for such "enteric dialysis" formulation. Data presented herein suggest that Sp survives through exposure to gastric juice retaining the ability to hydrolyze urea. In vitro, 10 cfu (colony forming units) of Sp removed from 21 +/- 4.7 mg to 228 +/- 6.7 mg urea per hour, depending on pH, urea concentration, and nutrient availability. Beneficial effects of Sp on fermentation parameters in the intestine were demonstrated in vitro in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) inoculated with fecal microbiota. Enumeration of marker organisms suggested that presence of Sp does not disturb microbial community of the SHIME. Additionally, a pilot study in 5/6th nephrectomized rats fed 10 cfu of live Sp daily throughout the study demonstrated that the tested regimen reduced blood urea-nitrogen levels and significantly prolonged the lifespan of uremic animals.

The Use of Evidence-Based, Problem-Oriented Templates as a Clinical Decision Support in an Inpatient Electronic Health Record System.

BACKGROUND: The integration of clinical decision support (CDS) in documentation practices remains limited due to obstacles in provider workflows and design restrictions in electronic health records (EHRs). The use of electronic problem-oriented templates (POTs) as a CDS has been previously discussed but not widely studied. OBJECTIVE: We evaluated the voluntary use of evidence-based POTs as a CDS on documentation practices. METHODS: This was a randomized cohort (before and after) study of Hospitalist Attendings in an Academic Medical Center using EPIC EHRs. Primary Outcome measurement was note quality, assessed by the 9-item Physician Documentation Quality Instrument (PDQI-9). Secondary Outcome measurement was physician efficiency, assessed by the total charting time per note. RESULTS: Use of POTs increased the quality of note documentation [score 37.5 vs. 39.0, P = 0.0020]. The benefits of POTs scaled with use; the greatest improvement in note quality was found in notes using three or more POTs [score 40.2, P = 0.0262]. There was no significant difference in total charting time [30 minutes vs. 27 minutes, P = 0.42]. CONCLUSION: Use of evidence-based and problem-oriented templates is associated with improved note quality without significant change in total charting time. It can be used as an effective CDS during note documentation.