Advancing against drug-resistant tuberculosis: an extensive review, novel strategies and patent landscape.

Drug-resistant tuberculosis (DR-TB) represents a pressing global health issue, leading to heightened morbidity and mortality. Despite extensive research efforts, the escalation of DR-TB cases underscores the urgent need for enhanced prevention, diagnosis, and treatment strategies. This review delves deep into the molecular and genetic origins of different types of DR-TB, highlighting recent breakthroughs in detection and diagnosis, including Rapid Diagnostic Tests like Xpert Ultra, Whole Genome Sequencing, and AI-based tools along with latest viewpoints on diagnosis and treatment of DR-TB utilizing newer and repurposed drug molecules. Special emphasis is given to the pivotal role of novel drugs and discusses updated treatment regimens endorsed by governing bodies, alongside innovative personalized drug-delivery systems such as nano-carriers, along with an analysis of relevant patents in this area. All the compiled information highlights the inherent challenges of current DR-TB treatments, discussing their complexity, potential side effects, and the socioeconomic strain they impose, particularly in under-resourced regions, emphasizing the cost-effective and accessible solutions. By offering insights, this review aims to serve as a compass for researchers, healthcare practitioners, and policymakers, emphasizing the critical need for ongoing R&D to improve treatments and broaden access to crucial TB interventions.

Myocardial Blood Flow Quantification Using Stress Cardiac Magnetic Resonance Improves Detection of Coronary Artery Disease.

BACKGROUND: Myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) using stress cardiovascular magnetic resonance (CMR) have been shown to identify epicardial coronary artery disease. However, comparative analysis between quantitative perfusion and conventional qualitative assessment (QA) remains limited. OBJECTIVES: The aim of this multicenter study was to test the hypothesis that quantitative stress MBF (sMBF) and MPR analysis can identify obstructive coronary artery disease (obCAD) with comparable performance as QA of stress CMR performed by experienced physicians in interpretation. METHODS: The analysis included 127 individuals (mean age 62 ± 16 years, 84 men [67%]) who underwent stress CMR. obCAD was defined as the presence of stenosis ≥50% in the left main coronary artery or ≥70% in a major vessel. Each patient, coronary territory, and myocardial segment was categorized as having either obCAD or no obCAD (noCAD). Global, per coronary territory, and segmental MBF and MPR values were calculated. QA was performed by 4 CMR experts. RESULTS: At the patient level, global sMBF and MPR were significantly lower in subjects with obCAD than in those with noCAD, with median values of sMBF of 1.5 mL/g/min (Q1-Q3: 1.2-1.8 mL/g/min) vs 2.4 mL/g/min (Q1-Q3: 2.1-2.7 mL/g/min) (P < 0.001) and median values of MPR of 1.3 (Q1-Q3: 1.0-1.6) vs 2.1 (Q1-Q3: 1.6-2.7) (P < 0.001). At the coronary artery level, sMBF and MPR were also significantly lower in vessels with obCAD compared with those with noCAD. Global sMBF and MPR had areas under the curve (AUCs) of 0.90 (95% CI: 0.84-0.96) and 0.86 (95% CI: 0.80-0.93). The AUCs for QA by 4 physicians ranged between 0.69 and 0.88. The AUC for global sMBF and MPR was significantly better than the average AUC for QA. CONCLUSIONS: This study demonstrates that sMBF and MPR using dual-sequence stress CMR can identify obCAD more accurately than qualitative analysis by experienced CMR readers.

Fatty acid composition MRI of epicardial adipose tissue: Methods and detection of proinflammatory biomarkers in ST-segment elevation myocardial infarction patients.

PURPOSE: To develop a method for quantifying the fatty acid composition (FAC) of human epicardial adipose tissue (EAT) using accelerated MRI and identify its potential for detecting proinflammatory biomarkers in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A multi-echo radial gradient-echo sequence was developed for accelerated imaging during a breath hold using a locally low-rank denoising technique to reconstruct undersampled images. FAC mapping was achieved by fitting the multi-echo images to a multi-resonance complex signal model based on triglyceride characterization. Validation of the method was assessed using a phantom comprised of multiple oils. In vivo imaging was performed in STEMI patients (n = 21; 14 males/seven females). FAC was quantified in EAT, subcutaneous AT, and abdominal visceral AT. RESULTS: Phantom validation demonstrated strong correlations (r > 0.97) and statistical significance (p < 0.0001) between measured and reference proton density fat fraction and FAC values. In vivo imaging of STEMI patients revealed a distinct EAT FAC profile compared to subcutaneous AT and abdominal visceral AT. EAT FAC parameters had significant correlations with left ventricular (LV) end-diastolic volume index (p < 0.05), LV end-systolic volume index (p < 0.05), and LV mass index (p < 0.05). CONCLUSIONS: Accelerated MRI enabled accurate quantification of human EAT FAC. The relationships between the EAT FAC profile and LV structure and function in STEMI patients suggest the potential of EAT FAC MRI as a biomarker for adipose tissue quality and inflammatory status in cardiovascular disease.

Robotic Totally Endoscopic Off-Pump Unroofing of Myocardial Bridge: Early Experience and Midterm Outcomes.

OBJECTIVE: Myocardial bridging (MB) occurs when a coronary artery, commonly the left anterior descending (LAD), has an intramyocardial course. In symptomatic patients who fail medical therapy, surgical unroofing can provide symptomatic relief by improving coronary blood flow. We present a series of patients undergoing robotic totally endoscopic beating-heart MB unroofing. METHODS: There were 34 patients with an LAD-MB who failed medical therapy and underwent robotic totally endoscopic, off-pump unroofing between January 2017 and October 2023. Patients were evaluated by a multidisciplinary team and underwent provocative coronary angiography to confirm hemodynamic significance. We reviewed perioperative outcomes and contacted patients for midterm follow-up, including completion of a modified Seattle Angina Questionnaire (SAQ). RESULTS: The mean age was 48 ± 8 years, and 56% were female patients. One patient had prior septal myectomy via sternotomy. All patients had significant dobutamine Pd/Pa reduction on preoperative coronary angiography. One patient had atrial fibrillation and underwent concomitant ablation with left atrial appendage ligation. The mean procedure time was 140 ± 69 min. All were completed totally endoscopically off-pump without intraoperative conversions. The mean MB length was 4.5 ± 1.4 cm, and the mean depth was 1.6 ± 0.9 cm. Of the patients, 76% were extubated in the operating room. The mean intensive care unit and hospital length of stay were 0.97 ± 0.58 and 1.73 ± 1.1 days, respectively. There were no mortalities or strokes. There was 1 postoperative take-back for bleeding. At midterm follow-up (19 ± 14 months), 28 patients completed the SAQ; 86% reported "much less angina" during activity compared with before surgery, and 93% reported taking no antianginal medication since surgery. CONCLUSIONS: In appropriate patients with hemodynamically significant LAD-MB who fail medical therapy, robotic beating-heart unroofing is possible with good outcomes. Further studies are warranted.

AGA Clinical Practice Update on Integrating Potassium-Competitive Acid Blockers Into Clinical Practice: Expert Review.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to summarize the available evidence and offer expert Best Practice Advice on the integration of potassium-competitive acid blockers (P-CABs) in the clinical management of foregut disorders, specifically including gastroesophageal reflux disease, Helicobacter pylori infection, and peptic ulcer disease. METHODS: This expert review was commissioned and approved by the AGA Institute Governing Board and CPU Committee to provide timely guidance on a topic of high clinical importance to the AGA membership. This CPU expert review underwent internal peer review by the CPU Committee and external peer review through the standard procedures of Gastroenterology. These Best Practice Advice statements were developed based on review of the published literature and expert consensus opinion. Because formal systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Based on nonclinical factors (including cost, greater obstacles to obtaining medication, and fewer long-term safety data), clinicians should generally not use P-CABs as initial therapy for acid-related conditions in which clinical superiority has not been shown. BEST PRACTICE ADVICE 2: Based on current costs in the United States, even modest clinical superiority of P-CABs over double-dose proton pump inhibitors (PPIs) may not make P-CABs cost-effective as first-line therapy. BEST PRACTICE ADVICE 3: Clinicians should generally not use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. BEST PRACTICE ADVICE 4: Although there is currently insufficient evidence for clinicians to use P-CABs as first-line on-demand therapy for patients with heartburn symptoms who have previously responded to antisecretory therapy, their rapid onset of acid inhibition raises the possibility of their utility in this population. BEST PRACTICE ADVICE 5: Clinicians should generally not use P-CABs as first-line therapy in patients with milder erosive esophagitis (EE) (Los Angeles classification of erosive esophagitis grade A/B EE). Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. BEST PRACTICE ADVICE 6: Clinicians may use P-CABs as a therapeutic option for the healing and maintenance of healing in patients with more severe EE (Los Angeles classification of erosive esophagitis grade C/D EE). However, given the markedly higher costs of the P-CAB presently available in the United States and the lack of randomized comparisons with double-dose PPIs, it is not clear that the benefits in endoscopic outcomes over standard-dose PPIs justify the routine use of P-CABs as first-line therapy. BEST PRACTICE ADVICE 7: Clinicians should use P-CABs in place of PPIs in eradication regimens for most patients with H pylori infection. BEST PRACTICE ADVICE 8: Clinicians should generally not use P-CABs as first-line therapy in the treatment or prophylaxis of peptic ulcer disease. BEST PRACTICE ADVICE 9: Although there is currently insufficient evidence for clinicians to use P-CABs as first-line therapy in patients with bleeding gastroduodenal ulcers and high-risk stigmata, their rapid and potent acid inhibition raises the possibility of their utility in this population.

Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

BACKGROUND: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being. METHODS: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied. Metrics correlating with baseline HRQOL and CPET performance were identified. The impact of valsartan treatment on these measures was analyzed in the early stage cohort. RESULTS: Two hundred participants were included: 166 with early stage HCM (mean age, 23±10 years; 40% female; 97% White; and 92% New York Heart Association class I) and 34 subclinical sarcomere variant carriers (mean age, 16±5 years; 50% female; and 100% White). Baseline HRQOL was good in both cohorts, although slightly better in subclinical HCM (composite pediatric quality of life score 84.6±10.6 versus 90.2±9.8; P=0.005). Both cohorts demonstrated mildly reduced functional status (mean percent predicted peak oxygen uptake 73±16 versus 78±12 mL/kg per minute; P=0.18). Percent predicted peak oxygen uptake and peak oxygen pulse correlated with HRQOL. Valsartan improved physical HRQOL in early stage HCM (adjusted mean change in pediatric quality of life score +4.1 versus placebo; P=0.01) but did not significantly impact CPET performance. CONCLUSIONS: Functional capacity can be impaired in young, healthy people with early stage HCM, despite New York Heart Association class I status and good HRQOL. Peak oxygen uptake was similarly decreased in subclinical HCM despite normal left ventricular wall thickness and excellent HRQOL. Valsartan improved physical pediatric quality of life scores but did not significantly impact CPET performance. Further studies are needed for validation and to understand how to improve patient experience. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01912534.

Comparison of dual-bolus versus dual-sequence techniques for determining myocardial blood flow and myocardial perfusion reserve by cardiac magnetic resonance stress perfusion: From the Automated Quantitative analysis of myocardial perfusion cardiac Magnetic Resonance Consortium.

BACKGROUND: Quantitative stress cardiac magnetic resonance (CMR) can be performed using the dual-sequence (DS) technique or dual-bolus (DB) method. It is unknown if DS and DB produce similar results for myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). The study objective is to investigate if there are any differences between DB- and DS-derived MBF and MPR. METHODS: Retrospective observational study with 168 patients who underwent stress CMR. DB and DS methods were simultaneously performed on each patient on the same day. Global and segmental stress MBF and rest MBF values were collected. RESULTS: Using Bland-Altman analysis, segmental and global stress MBF values were higher in DB than DS (0.22 ± 0.60 mL/g/min, p < 0.001 and 0.20 ± 0.48 mL/g/min, p = 0.005, respectively) with strong correlation (r = 0.81, p < 0.001 for segmental and r = 0.82, p < 0.001 for global). In rest MBF, segmental and global DB values were higher than by DS (0.15 ± 0.51 mL/g/min, p < 0.001 and 0.14 ± 0.36 mL/g/min, p = 0.011, respectively) with strong correlation (r = 0.81, p < 0.001 and r = 0.77, p < 0.001). Mean difference between MPR by DB and DS was -0.02 ± 0.68 mL/g/min (p = 0.758) for segmental values and -0.01 ± 0.49 mL/g/min (p = 0.773) for global values. MPR values correlated strongly as well in both segmental and global, both (r = 0.74, p < 0.001) and (r = 0.75, p < 0.001), respectively. CONCLUSION: There is a very good correlation between DB- and DS-derived MBF and MPR values. However, there are significant differences between DB- and DS-derived global stress and rest MBF. While MPR values did not show statistically significant differences between DB and DS methods.

Emerging Pathway to a Precision Medicine Approach for Angina With Nonobstructive Coronary Arteries in Women.

Women are disproportionately affected by symptoms of angina with nonobstructive coronary arteries (ANOCA) which is associated with significant mortality and economic impact. Although distinct endotypes of ANOCA have been defined, it is underdiagnosed and is often incompletely characterized when identified. Patients are often unresponsive to traditional therapeutic options, which are typically antianginal, and the current ability to guide treatment modification by specific pathways is limited. Studies have associated specific genetic loci, transcriptomic features, and biomarkers with ANOCA. Such panomic data, in combination with known imaging and invasive diagnostic techniques, should be utilized to define more precise pathophysiologic subtypes of ANOCA in women, which will in turn help to identify targeted, effective therapies. A precision medicine-based approach to managing ANOCA incorporating these techniques in women has the potential to significantly improve their clinical care.

Automated software-derived supine baseline impedance is highly correlated with manual nocturnal baseline impedance for the diagnosis of GERD.

BACKGROUND: Mean nocturnal baseline impedance (MNBI) can improve diagnostic accuracy for gastroesophageal reflux disease (GERD), but must be manually calculated and is not routinely reported. We aimed to determine how automated software-derived mean supine baseline impedance (MSBI), a potential novel GERD metric, is related to MNBI. METHODS: Consecutively obtained pH-impedance studies were assessed. Manually extracted MNBI was compared to MSBI using paired t-test and Spearman's correlations. KEY RESULTS: The correlation between MNBI and MSBI was very high (ρ = 0.966, p < 0.01). CONCLUSIONS & INFERENCES: The ease of acquisition and correlation with MNBI warrant the routine clinical use and reporting of MSBI with pH-impedance studies.

Training and Verification Requirements for Interpretation of Cardiac CT and MRI: AJR Expert Panel Narrative Review.

The use of cardiac CT and MRI is rapidly expanding based on strong evidence from large international trials. The number of physicians competent to interpret cardiac CT and MRI may be unable to keep pace with the increasing demand. Societies and organizations have prescribed training requirements for interpreting cardiac CT and MRI, with recent updates focusing on the increased breadth of competency that is now required due to ongoing imaging advances. In this AJR Expert Panel Narrative Review, we discuss several aspects of cardiac CT and MRI training, focusing on topics that are uncertain or not addressed in existing society statements and guidelines, including determination of competency in different practice types in real-world settings and the impact of artificial intelligence on training and education. The article is intended to guide updates in professional society training requirements and also inform institutional verification processes.

Association of Adverse Clinical Outcomes With Peri-Infarct Ischemia Detected by Stress Cardiac Magnetic Imaging.

BACKGROUND: Early invasive revascularization guided by moderate to severe ischemia did not improve outcomes over medical therapy alone, underlying the need to identify high-risk patients for a more effective invasive referral. CMR could determine the myocardial extent and matching locations of ischemia and infarction. OBJECTIVES: This study sought to investigate if CMR peri-infarct ischemia is associated with adverse events incremental to known risk markers. METHODS: Consecutive patients were included in an expanded cohort of the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study. Peri-infarct ischemia was defined by the presence of any ischemic segment neighboring an infarcted segment by late gadolinium enhancement imaging. Primary outcome events included acute myocardial infarction and cardiovascular death, whereas secondary events included any primary events, hospitalization for unstable angina, heart failure hospitalization, and late coronary artery bypass surgery. RESULTS: Among 3,915 patients (age: 61.0 ± 12.9 years; 54.7% male), ischemia, infarct, and peri-infarct ischemia were present in 752 (19.2%), 1,123 (28.8%), and 382 (9.8%) patients, respectively. At 5.3 years (Q1-Q3: 3.9-7.2 years) of median follow-up, primary and secondary events occurred in 406 (10.4%) and 745 (19.0%) patients, respectively. Peri-infarct ischemia was the strongest multivariable predictor for primary and secondary events (HRadjusted: 1.72 [95% CI: 1.23-2.41] and 1.71 [95% CI: 1.32-2.20], respectively; both P < 0.001), adjusted for clinical risk factors, left ventricular function, ischemia extent, and infarct size. The presence of peri-infarct ischemia portended to a >6-fold increased annualized primary event rate compared to those with no infarct and ischemia (6.5% vs 0.9%). CONCLUSIONS: Peri-infarct ischemia is a novel and robust prognostic marker of adverse cardiovascular events.

Machine learning of ECG waveforms and cardiac magnetic resonance for response and survival after cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) can lead to marked symptom reduction and improved survival in selected patients with heart failure with reduced ejection fraction (HFrEF); however, many candidates for CRT based on clinical guidelines do not have a favorable response. A better way to identify patients expected to benefit from CRT that applies machine learning to accessible and cost-effective diagnostic tools such as the 12-lead electrocardiogram (ECG) could have a major impact on clinical care in HFrEF by helping providers personalize treatment strategies and avoid delays in initiation of other potentially beneficial treatments. This study addresses this need by demonstrating that a novel approach to ECG waveform analysis using functional principal component decomposition (FPCD) performs better than measures that require manual ECG analysis with the human eye and also at least as well as a previously validated but more expensive approach based on cardiac magnetic resonance (CMR). Analyses are based on five-fold cross validation of areas under the curve (AUCs) for CRT response and survival time after the CRT implant using Cox proportional hazards regression with stratification of groups using a Gaussian mixture model approach. Furthermore, FPCD and CMR predictors are shown to be independent, which demonstrates that the FPCD electrical findings and the CMR mechanical findings together provide a synergistic model for response and survival after CRT. In summary, this study provides a highly effective approach to prognostication after CRT in HFrEF using an accessible and inexpensive diagnostic test with a major expected impact on personalization of therapies.

Ineffective esophageal motility is associated with diabetes mellitus end organ complications.

BACKGROUND: Diabetes Mellitus (DM) is known to induce a wide range of harmful effects on several organs, notably leading to ineffective esophageal motility (IEM). However, the relationship between DM and IEM is not fully elucidated. We aimed to determine the relationship between DM and IEM and to evaluate the impact of DM's end organ complications on IEM severity. METHODS: A multicenter cohort study of consecutive patients undergoing high-resolution esophageal manometry (HREM) was performed. We reviewed medical records of patients diagnosed with IEM using HREM, encompassing data on demographics, DM history, antidiabetic and other medications as well as comorbidities. KEY RESULTS: Two hundred and forty six subjects met the inclusion criteria. There was no significant difference in any of the HREM parameters between diabetics and nondiabetics. Out of 246 patients, 92 were diabetics. Diabetics with neuropathy presented a significantly lower distal contractile integral (DCI) value compared to those without neuropathy (248.2 ± 226.7 mmHg·cm·sec vs. 375.6 ± 232.4 mmHg·cm·sec; p = 0.02) Similarly, the DCI was lower in diabetics with retinopathy compared to those without retinopathy (199.9 ± 123.1 mmHg·cm·sec vs. 335.4 ± 251.7 mmHg·cm·sec; p = 0.041). Additionally, a significant difference was observed in DCI values among DM patients with ≥2 comorbidities compared to those without comorbidities (224.8 ± 161.0 mmHg·cm·sec vs. 394.2 ± 243.6 mmHg·cm·sec; p = 0.025). Around 12.6% of the variation in DCI could be explained by its linear relationship with hemoglobin A1c (HbA1c), with a regression coefficient (ß) of -55.3. CONCLUSION & INFERENCES: DM is significantly associated with IEM in patients with neuropathy, retinopathy, or multiple comorbidities. These results are pivotal for tailoring patient-specific management approaches.

Defining echocardiographic predictors of outcome in cardiac amyloidosis by subtype.

BACKGROUND: Current echocardiographic risk factors for prognosis in cardiac amyloidosis (CA) do not distinguish between the two main subtypes: transthyretin cardiomyopathy (TTR) and immunoglobulin light chain cardiomyopathy (AL), each of which require distinct diagnostic and therapeutic approaches. Additionally, only traditional parameters have been studied with little data on advanced techniques. Accordingly, we sought to determine whether differences exist in 2D transthoracic echocardiography (2DE) predictors of survival between the CA subtypes using a comprehensive approach. METHODS: 220 patients (72±12 years) with confirmed CA (AL=89, TTR=131) who underwent 2DE at the time of CA diagnosis were enrolled. Left ventricular (LV) dimensions, indexed mass (LVMi), global longitudinal strain (LVGLS), apical-sparing ratio (LVASR), diastology, right ventricular (RV) size and function indices including tricuspid annular systolic excursion (TAPSE), RV free-wall (RVFWS) and global (RVGLS) strain, indexed left (LA) and right atrial volumes (LAVi and RAVi), LA strain (reservoir and booster) and RV systolic pressure (RVSP) were measured. A propensity-score weighted stepwise variable selection Cox proportional hazards model derived from NYHA class and renal impairment status at diagnosis was used to determine the associations between 2DE parameters and mortality specific to CA subtype over a median follow-up of 36-months. RESULTS: After adjusting for age, atrial fibrillation and treatment, parameters associated with survival were RVFWS (p=0.003, HR 1.15, 95% CI[1.053,1.245]) and RVSP (p=0.03, HR 1.03, 95% CI[1.004,1.063]) in AL and LVASR (p=0.007, HR 6.68, 95% CI[1.75,25.492]) and RAVi (p=0.049, HR 1.03, 95% CI[1.000,1.052]) in TTR. CONCLUSIONS: Echocardiographic prognosticators for survival are specific to cardiac amyloid subtype. These results potentially provide information critical for clinical decision-making and follow-up in these patients.

A Description and Safety Overview of Irreversible Electroporation for Prostate Tissue Ablation in Intermediate-Risk Prostate Cancer Patients: Preliminary Results from the PRESERVE Trial.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0-72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3-82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.

Assessment of embedded versus remote pharmacist versus remote student pharmacist outreach on statin prescribing.

BACKGROUND: The Statin Use in Persons with Diabetes (SUPD) measure is a Star measure by the Center for Medicare & Medicaid Services. The Duke Population Health Management Office has a team of pharmacists and pharmacy students who conduct targeted outreach to patients at risk of failing statin quality measures. Pharmacy services are embedded in select primary care clinics and other clinics are supported remotely. OBJECTIVES: The primary objective of this review is to compare the initiation rates of recommended statin prescriptions between embedded pharmacist versus remote pharmacist versus remote student pharmacist outreach groups, all of which have different levels of autonomy within pharmacy practice. The secondary objectives are to identify the barriers to the implementation of statin therapy and to assess the statin drugs and intensity of the statins prescribed. METHODS: A single-center, retrospective chart review was performed for SUPD patients with Medicare insurance. SUPD patients included patients between 40 and 75 years of age, diagnosed with type 2 diabetes, and were not dispensed at least 1 statin medication of any intensity during the 6-month measurement period. The primary outcome was the initiation of recommended statin medications prescribed, or pended for the primary care provider to prescribe, for qualifying patients by embedded, remote, and remote student pharmacists. Secondary outcomes included the reasons for the nonimplementation of statin recommendations, reasons statin therapy was not prescribed to patients contributing to the SUPD measure gap, and statin drug and dose prescribed for appropriateness. RESULTS: A total of 189 patients were included in the evaluation. In this study, 34.9% of the patients filled the prescribed or pended statin prescription and 83.3% of patients filled the prescribed or pended statin prescription at the recommended intensity according to the American College of Cardiology/American Hospital Association guidelines, effectively closing the SUPD measure gap. The initiation rates of recommended statin prescriptions between the embedded pharmacist, remote pharmacist, and remote student pharmacist outreach were numerically different at 36.7%, 28.2%, and 36.7%, respectively, even though not statistically different (P = 0.61). CONCLUSION: Remote student pharmacists' performance was equal to that of the embedded pharmacists when comparing the initiation rates of statin medications prescribed or pending the primary care provider's approval. The most common reason for nonimplementation of statin therapy is that the statin was refused by the patient. Atorvastatin and rosuvastatin were the two most commonly prescribed statins.

BSP Implementation of prevention and treatment of peri-implant diseases - The EFP S3 level clinical practice guideline.

OBJECTIVES: to adapt the supranational European Federation of Periodontology (EFP) Prevention and Treatment of Peri-implant Diseases - The EFP S3 Level Clinical Practice Guideline for UK healthcare environment, taking into account a broad range of views from stakeholders and patients. SOURCES: This UK version, based on the supranational EFP guideline [1] published in the Journal of Clinical Periodontology, was developed using S3-level methodology, combining assessment of formal evidence from 13 systematic reviews with a moderated consensus process of a representative group of stakeholders, and accounts for health equality, environmental factors and clinical effectiveness. It encompasses 55 clinical recommendations for the Prevention and Treatment of Peri-implant Diseases, based on the classification for periodontal and peri­implant diseases and conditions [2]. METHODOLOGY: The UK version was developed from the source guideline using a formal process called the GRADE ADOLOPMENT framework. This framework allows for adoption (unmodified acceptance), adaptation (acceptance with modifications) and the de novo development of clinical recommendations. Using this framework, following the S3-process, the underlying evidence was updated and a representative guideline group of 111 delegates from 26 stakeholder organisations was assembled into four working groups. Following the formal S3-process, all clinical recommendations were formally assessed for their applicability to the UK and adoloped accordingly. RESULTS AND CONCLUSION: Using the ADOLOPMENT protocol, a UK version of the EFP S3-level clinical practice guideline for the Prevention and Treatment of Peri-implant Diseases was developed. This guideline delivers evidence- and consensus-based clinical recommendations of direct relevance to the UK healthcare community including the public. CLINICAL SIGNIFICANCE: The S3-level-guidelines combine evaluation of formal evidence, grading of recommendations and synthesis with clinical expertise of a broad range of stakeholders. The international S3-level-guideline was implemented for direct clinical applicability in the UK healthcare system, facilitating a consistent, interdisciplinary, evidence-based approach with public involvement for the prevention and treatment of peri­implant diseases.

Does IPSS-R downstaging before transplantation improve the prognosis of patients with myelodysplastic neoplasms?

ABSTRACT: In patients with myelodysplastic syndrome (MDS), higher revised International Prognostic Scoring System (IPSS-R) scores at transplant are associated with worse transplant outcome and, thus, lowering IPSS-R scores by therapeutic intervention before transplantation may seem beneficial. However, there is no evidence, to date, to support this approach. In a retrospective analysis, a total of 1482 patients with MDS with sufficient data to calculate IPSS-R score at diagnosis and at time of transplantation were selected from the European Society for Blood and Marrow Transplantation transplant registry and analyzed for transplant outcome in a multivariable Cox model including IPSS-R score at diagnosis, treatment intervention, change in IPSS-R score before transplant, and several patient and transplant variables. Transplant outcome was unaffected by IPSS-R score change in untreated patients and moderately superior in patients treated with chemotherapy with improved IPSS-R score at transplant. Improved IPSS-R score after hypomethylating agents (HMAs) or other therapies showed no beneficial effect. However, when IPSS-R score progressed after chemotherapy, HMAs, or other therapies, transplant outcome was worse than without any prior treatment. Similar results were found when reduction or increase in bone marrow (BM) blasts between diagnosis and transplantation was considered. The results show a limited benefit of IPSS-R score downstaging or reduction of BM blasts after chemotherapy and no benefit for HMAs or other treatments and thus question the role of prior therapy in patients with MDS scheduled for transplantation. The model-based survival estimates should help inform decision-making for both doctors and patients.