Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus.

BACKGROUND: Patients with severe aortic stenosis and a small aortic annulus are at risk for impaired valvular hemodynamic performance and associated adverse cardiovascular clinical outcomes after transcatheter aortic-valve replacement (TAVR). METHODS: We randomly assigned patients with symptomatic severe aortic stenosis and an aortic-valve annulus area of 430 mm2 or less in a 1:1 ratio to undergo TAVR with either a self-expanding supraannular valve or a balloon-expandable valve. The coprimary end points, each assessed through 12 months, were a composite of death, disabling stroke, or rehospitalization for heart failure (tested for noninferiority) and a composite end point measuring bioprosthetic-valve dysfunction (tested for superiority). RESULTS: A total of 716 patients were treated at 83 sites in 13 countries (mean age, 80 years; 87% women; mean Society of Thoracic Surgeons Predicted Risk of Mortality, 3.3%). The Kaplan-Meier estimate of the percentage of patients who died, had a disabling stroke, or were rehospitalized for heart failure through 12 months was 9.4% with the self-expanding valve and 10.6% with the balloon-expandable valve (difference, -1.2 percentage points; 90% confidence interval [CI], -4.9 to 2.5; P<0.001 for noninferiority). The Kaplan-Meier estimate of the percentage of patients with bioprosthetic-valve dysfunction through 12 months was 9.4% with the self-expanding valve and 41.6% with the balloon-expandable valve (difference, -32.2 percentage points; 95% CI, -38.7 to -25.6; P<0.001 for superiority). The aortic-valve mean gradient at 12 months was 7.7 mm Hg with the self-expanding valve and 15.7 mm Hg with the balloon-expandable valve, and the corresponding values for additional secondary end points through 12 months were as follows: mean effective orifice area, 1.99 cm2 and 1.50 cm2; percentage of patients with hemodynamic structural valve dysfunction, 3.5% and 32.8%; and percentage of women with bioprosthetic-valve dysfunction, 10.2% and 43.3% (all P<0.001). Moderate or severe prosthesis-patient mismatch at 30 days was found in 11.2% of the patients in the self-expanding valve group and 35.3% of those in the balloon-expandable valve group (P<0.001). Major safety end points appeared to be similar in the two groups. CONCLUSIONS: Among patients with severe aortic stenosis and a small aortic annulus who underwent TAVR, a self-expanding supraannular valve was noninferior to a balloon-expandable valve with respect to clinical outcomes and was superior with respect to bioprosthetic-valve dysfunction through 12 months. (Funded by Medtronic; SMART ClinicalTrials.gov number, NCT04722250.).

Effect of the P-Selectin Inhibitor Crizanlizumab on Survival Free of Organ Support in Patients Hospitalized for COVID-19: A Randomized Controlled Trial.

BACKGROUND: COVID-19 has been associated with endothelial injury, resultant microvascular inflammation and thrombosis. Activated endothelial cells release and express P-selectin and von Willebrand factor, both of which are elevated in severe COVID-19 and may be implicated in the disease pathophysiology. We hypothesized that crizanlizumab, a humanized monoclonal antibody to P-selectin, would reduce morbidity and death in patients hospitalized for COVID-19. METHODS: An international, adaptive, randomized controlled platform trial, funded by the National Heart, Lung, and Blood Institute, randomly assigned 422 patients hospitalized with COVID-19 with moderate or severe illness to receive either a single infusion of the P-selectin inhibitor crizanlizumab (at a dose of 5 mg/kg) plus standard of care or standard of care alone in an open-label 1:1 ratio. The primary outcome was organ support-free days, evaluated on an ordinal scale consisting of the number of days alive free of organ support through the first 21 days after trial entry. RESULTS: The study was stopped for futility by the data safety monitoring committee. Among 421 randomized patients with known 21-day outcomes, 163 patients (77%) randomized to the crizanlizumab plus standard-of-care arm did not require any respiratory or cardiovascular organ support compared with 169 (80%) in the standard-of-care-alone arm. The adjusted odds ratio for the effect of crizanlizumab on organ support-free days was 0.70 (95% CI, 0.43-1.16), where an odds ratio >1 indicates treatment benefit, yielding a posterior probability of futility (odds ratio <1.2) of 98% and a posterior probability of inferiority (odds ratio <1.0) of 91%. Overall, there were 37 deaths (17.5%) in the crizanlizumab arm and 27 deaths (12.8%) in the standard-of-care arm (hazard ratio, 1.33 [95% CrI, 0.85-2.21]; [probability of hazard ratio>1] = 0.879). CONCLUSIONS: Crizanlizumab, a P-selectin inhibitor, did not result in improvement in organ support-free days in patients hospitalized with COVID-19. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04505774.

Clinical diagnosis of psychiatric comorbidities, performance of screening tests and pattern of psychotropic medication use in patients with chronic pancreatitis.

BACKGROUND: Psychiatric comorbidity measured by screening instruments is common in patients with chronic pancreatitis (CP) but whether this accurately reflects clinical diagnosis of psychiatric comorbidity is unknown and the prevalence of psychotropic medication prescription in CP remains largely unexplored. METHODS: Adult patients (≥18 years) with definite CP were enrolled and completed the Hospital Anxiety and Depression Scale (HADS). Demographics, clinical characteristics and medications were retrieved from case report forms and the electronic health record (EHR). Clinical diagnosis of depression or anxiety was determined by presence of ICD-10 code or inclusion in the patient's EHR problem list or treatment plan. Comparisons were made between patients with and without clinical psychiatric comorbidity. RESULTS: Total of 81 patients (48, 59.3% male; mean age 57.6 ± 14.3 years) were included. Clinical diagnoses of anxiety and depression were each noted in 47 (58%) patients, with overlap in 42 (51.9%). Compared to clinical diagnoses, the sensitivity and specificity of a positive screen for anxiety (HADS >7) were 76.6% and 91.2%; for depression 55.3% and 88.2%. Patients with anxiety and/or depression were more frequently female (51.9% v 20.7%), younger (53.6 v 64.9 years), and had alcohol etiology (51.9% v 27.6%) (all p < 0.01). In those with psychiatric comorbidity, 42 (80.8%) were prescribed psychotropic medication, most commonly gabapentinoid (24, 57.1%), selective serotonin reuptake inhibitor (n = 22, 52.4%) or benzodiazepine (n = 20, 47.6%). CONCLUSIONS: Psychiatric comorbidities are common among CP patients and many receive psychotropic medications. Further studies are needed to evaluate the impact of these medications on CP symptoms.

Positive Predictive Value of Cirrhosis and Chronic Pancreatitis Diagnoses in Individuals with Alcohol Use Disorder: A Single-Center Study.

BACKGROUND: Although accuracy of diagnosis codes for cirrhosis and chronic pancreatitis (CP) has been evaluated in multiple studies, none have focused on patients with alcohol use disorders (AUD). We evaluated the positive predictive value (PPV) for a verified diagnosis of cirrhosis and CP in AUD patients treated at a tertiary care center. METHODS: We performed a detailed review of electronic health records for AUD patients assigned ICD-9 or 10 codes for alcoholic cirrhosis (ALC) (n = 199), CP (n = 200), or both (n = 200). We calculated PPV for a verified diagnosis of cirrhosis and CP and performed multivariable regression analysis to assess the impact of relevant factors on PPV for a verified diagnosis. RESULTS: PPV of cirrhosis was 81.2% (95% CI 77.0 to 84.9%) which increased to 87.5% (95% CI 83.8 to 90.6%) if the definition was relaxed to include alcohol-related hepatitis. PPV of CP was 54.5% (95% CI 49.5 to 59.5%) which increased to 78% (95% CI 73.6 to 82.0%) when recurrent acute pancreatitis was included in the definition. In multivariable analyses, the odds of a verified diagnosis were significantly higher in individuals aged 65+ years for both cirrhosis (OR 12.23, 95% CI 2.19 to 68.42) and CP (OR 8.84, 95% CI 2.7 to 28.93) and in ever smokers for CP (OR 1.95, 95% CI 1.05 to 3.65). CONCLUSION: PPV for diagnosis codes in AUD patients is high for a verified diagnosis of cirrhosis but only modest for CP. While administrative datasets can provide reliable information for cirrhosis, future studies should focus on ways to boost the diagnostic validity of administrative datasets for CP.

Hope and illness expectations: A cross-sectional study in patients with advanced cancer.

BACKGROUND: The fear of taking away hope hinders clinicians' willingness to share serious news with patients with advanced disease. Unrealistic illness expectations, on the other hand, can complicate decision making and end-of-life care outcomes. Exploration of the association between hope and illness expectations can support clinicians in better communication with their patients. AIM: The aim of this study was to explore whether realistic illness expectations are associated with reduced hope in people with advanced cancer. DESIGN: This is a cross-sectional secondary analysis of baseline data from a primary palliative care cluster-randomized trial CONNECT (data collected from July 2016 to October 2020). Hope was measured by Herth Hope Index. Illness expectations were measured by assessing patients' understanding of their treatment goals, life expectancy, and terminal illness acknowledgement. Multivariable regression was performed, adjusting for demographical and clinical confounders. SETTING/PARTICIPANTS: Adult patients with advanced solid cancers recruited across 17 oncology clinics. RESULTS: Data from 672 patients were included in the study, with mean age of 69.3 years (±10.2), 53.6% were female. Proportion of patients indicating realistic expectations varied based on which question was asked from 10% to 46%. Median level of hope was 39 (IQR = 36-43). Multivariate non-inferiority regression did not find any significant differences in hope between patients with more and less realistic illness expectations. CONCLUSIONS: Our results suggest that hope can be sustained while holding both realistic and unrealistic illness expectations. Communication about serious news should focus on clarifying the expectations as well as supporting people's hopes.

Western diet unmasks transient low-level vinyl chloride-induced tumorigenesis; potential role of the (epi-)transcriptome.

BACKGROUND & AIMS: Vinyl chloride (VC) monomer is a volatile organic compound commonly used in industry. At high exposure levels, VC causes liver cancer and toxicant-associated steatohepatitis. However, lower exposure levels (i.e., sub-regulatory exposure limits) that do not directly damage the liver, enhance injury caused by Western diet (WD). It is still unknown if the long-term impact of transient low-concentration VC enhances the risk of liver cancer development. This is especially a concern given that fatty liver disease is in and of itself a risk factor for the development of liver cancer. METHODS: C57Bl/6 J mice were fed WD or control diet (CD) for 1 year. During the first 12 weeks of feeding only, mice were also exposed to VC via inhalation at sub-regulatory limit concentrations (<1 ppm) or air for 6 h/day, 5 days/week. RESULTS: Feeding WD for 1 year caused significant hepatic injury, which was exacerbated by VC. Additionally, VC increased the number of tumors which ranged from moderately to poorly differentiated hepatocellular carcinoma (HCC). Transcriptomic analysis demonstrated VC-induced changes in metabolic but also ribosomal processes. Epitranscriptomic analysis showed a VC-induced shift of the modification pattern that has been associated with metabolic disease, mitochondrial dysfunction, and cancer. CONCLUSIONS: These data indicate that VC sensitizes the liver to other stressors (e.g., WD), resulting in enhanced tumorigenesis. These data raise concerns about potential interactions between VC exposure and WD. It also emphasizes that current safety restrictions may be insufficient to account for other factors that can influence hepatotoxicity.

Primary Palliative Care Improves Uptake of Advance Care Planning Among Patients With Advanced Cancers.

BACKGROUND: Palliative care specialists are experts in conducting advance care planning (ACP) but are a limited resource. Oncology nurses often have special relationships with their patients and thus may be poised to provide primary palliative care. We sought to determine the impact of a nurse-led primary palliative care intervention on ACP uptake among patients with advanced cancer. METHODS: We performed a secondary analysis of a cluster randomized controlled trial examining the impact of nurse-based primary palliative care. In the parent trial, patients with advanced cancer received either monthly primary palliative care visits with trained nurses within their cancer center or standard care. Nurses in the intervention arm received special training in ACP. ACP uptake was assessed at enrollment and 3 months later evaluating (1) whether an end-of-life conversation (EOLC) occurred with one's oncologist, and (2) completion of an advance directive (AD). Multivariable logistic regression tested differences in ACP uptake by treatment arm adjusted for age, religious importance, education, time with current oncologist, and performance status. RESULTS: Of 672 patients enrolled, 182/336 (54%) patients in the intervention arm and 196/336 (58%) in the standard care arm lacked an EOLC at baseline and completed the 3-month assessment. Of those, 82/182 (45.1%) patients in the intervention arm and 29/196 (14.8%) in the standard care arm reported having an EOLC at 3 months (adjusted odds ratio, 5.28; 95% CI, 3.10-8.97; P<.001). Similarly, 111/336 (33%) patients in the intervention arm and 105/336 (31%) in the standard care arm lacked an AD at baseline and completed the 3-month assessment. Of those, 48/111 (43.2%) patients in the intervention arm and 19/105 (18.1%) in the standard care arm completed an AD over the study period (adjusted odds ratio, 3.68; 95% CI, 1.89-7.16; P<.001). CONCLUSIONS: Nurse-led primary palliative care increased ACP uptake among patients with advanced cancer. Training oncology nurses embedded within community cancer centers to provide primary palliative care may help improve ACP access.

MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC): randomized clinical trial protocol.

BACKGROUND: Peripheral artery disease (PAD) affects over 230 million people worldwide and is due to systemic atherosclerosis with etiology linked to chronic inflammation, hypertension, and smoking status. PAD is associated with walking impairment and mobility loss as well as a high prevalence of coronary and cerebrovascular disease. Intermittent claudication (IC) is the classic presenting symptom for PAD, although many patients are asymptomatic or have atypical presentations. Few effective medical therapies are available, while surgical and exercise therapies lack durability. Metformin, the most frequently prescribed oral medication for Type 2 diabetes, has salient anti-inflammatory and promitochondrial properties. We hypothesize that metformin will improve function, retard the progression of PAD, and improve systemic inflammation and mitochondrial function in non-diabetic patients with IC. METHODS: 200 non-diabetic Veterans with IC will be randomized 1:1 to 180-day treatment with metformin extended release (1000 mg/day) or placebo to evaluate the effect of metformin on functional status, PAD progression, cardiovascular disease events, and systemic inflammation. The primary outcome is 180-day maximum walking distance on the 6-min walk test (6MWT). Secondary outcomes include additional assessments of functional status (cardiopulmonary exercise testing, grip strength, Walking Impairment Questionnaires), health related quality of life (SF-36, VascuQoL), macro- and micro-vascular assessment of lower extremity blood flow (ankle brachial indices, pulse volume recording, EndoPAT), cardiovascular events (amputations, interventions, major adverse cardiac events, all-cause mortality), and measures of systemic inflammation. All outcomes will be assessed at baseline, 90 and 180 days of study drug exposure, and 180 days following cessation of study drug. We will evaluate the primary outcome with linear mixed-effects model analysis with covariate adjustment for baseline 6MWT, age, baseline ankle brachial indices, and smoking status following an intention to treat protocol. DISCUSSION: MOBILE IC is uniquely suited to evaluate the use of metformin to improve both systematic inflammatory responses, cellular energetics, and functional outcomes in patients with PAD and IC. TRIAL REGISTRATION: The prospective MOBILE IC trial was publicly registered (NCT05132439) November 24, 2021.

Dispensary Staff Perceptions About the Benefits, Risks, and Safety of Cannabis for Medical Purposes.

BACKGROUND: Therapeutic use of cannabis is common in the United States (up to 18.7% of Americans aged ≥12), and dispensaries in the US are proliferating rapidly. However, the efficacy profile of medical cannabis is unclear, and customers often rely on dispensary staff for purchasing decisions. The objective was to describe cannabis dispensary staff perceptions of medical cannabis benefits and risks, as well as its safety in high-risk populations. METHODS: Online Survey study conducted using Qualtrics from February 13, 2020 to October 2, 2020 with a national sample of dispensary staff who reportedinteracting with customers in a cannabis dispensary selling tetrahydrocannabinol-containing products. Participants were queried about benefits ("helpfulness") and risks ("worry") about cannabis for a variety of medical conditions, and safety in older adults and pregnant women on a five-point Likert scale. These results were then collapsed into three categories including "neutral" (3/5). "I don't know" (uncertainty) was a response option for helpfulness and safety. RESULTS: Participants (n = 434) were from 29 states and included patient-facing dispensary staff (40%); managers (32%); pharmacists (13%); and physicians, nurse practitioners, or physician assistants (5%). Over 80% of participants perceived cannabis as helpful for post-traumatic stress disorder (88.7%), epilepsy (85.3%) and cancer (83.4%). Generally, participants were not concerned about potential cannabis risks, including increased use of illicit drugs (76.3%), decreases in intelligence (74.4%), disrupted sleep (71.7%), and new/worsening health problems from medical cannabis use (70.7%). Cannabis was considered safe in older adults by 81.3% of participants, though there was much less consensus on safety in pregnancy. CONCLUSIONS: Cannabis dispensary staff generally view medical cannabis as beneficial and low-risk. However, improvements in dispensary staff training, an increased role for certifying clinicians, and interventions to reduce dispensary staff concerns (e.g., cost, judgment) may improve evidence-based staff recommendations to patients seeking medical cannabis.

Recommendations for Statistical Reporting in Cardiovascular Medicine: A Special Report From the American Heart Association.

Statistical analyses are a crucial component of the biomedical research process and are necessary to draw inferences from biomedical research data. The application of sound statistical methodology is a prerequisite for publication in the American Heart Association (AHA) journal portfolio. The objective of this document is to summarize key aspects of statistical reporting that might be most relevant to the authors, reviewers, and readership of AHA journals. The AHA Scientific Publication Committee convened a task force to inventory existing statistical standards for publication in biomedical journals and to identify approaches suitable for the AHA journal portfolio. The experts on the task force were selected by the AHA Scientific Publication Committee, who identified 12 key topics that serve as the section headers for this document. For each topic, the members of the writing group identified relevant references and evaluated them as a resource to make the standards summarized herein. Each section was independently reviewed by an expert reviewer who was not part of the task force. Expert reviewers were also permitted to comment on other sections if they chose. Differences of opinion were adjudicated by consensus. The standards presented in this report are intended to serve as a guide for high-quality reporting of statistical analyses methods and results.

Hope and advance care planning in advanced cancer: Is there a relationship?

BACKGROUND: Clinicians often cite a fear of giving up hope as a reason they defer advance care planning (ACP) among patients with advanced cancer. The objective of this study was to determine whether engagement in ACP affects hope in these patients. METHODS: This was a secondary analysis of a randomized controlled trial of primary palliative care in advanced cancer. Patients who had not completed ACP at baseline were included in the analysis. ACP was assessed in the forms of an end-of-life (EOL) conversation with one's oncologist and completion of a living will or advance directive (AD). Measurements were obtained at baseline and at 3 months. Hope was measured using the Herth Hope Index (HHI) (range, 12-48; higher scores indicate higher hope). Multivariate regression was performed to assess associations between ACP and hope, controlling for baseline HHI score, study randomization, patient age, religious importance, education, marital status, socioeconomic status, time since cancer diagnosis, pain/symptom burden (Edmonton Symptom Assessment System), and anxiety/depression score (Hospital Anxiety and Depression Scale)-all variables known to be associated with ACP and/or hope. RESULTS: In total, 672 patients with advanced cancer were enrolled in the overall study. The mean age was 69 ± 10 years, and the most common cancer types were lung cancer (36%), gastrointestinal cancer (20%) and breast/gynecologic cancers (16%). In this group, 378 patients (56%) had not had an EOL conversation at baseline, of whom 111 of 378 (29%) reported having an EOL conversation by 3 months. Hope was not different between patients who did or did not have an EOL conversation over the study period (mean ± standard deviation ∆HHI, 0.20 ± 5.32 vs -0.53 ± 3.80, respectively; P = .136). After multivariable adjustment, hope was significantly increased in patients who had engaged in an EOL conversation (adjusted mean difference in ∆HHI, 0.95; 95% CI, 0.08-1.82; P = .032). Similarly, of 216 patients (32%) without an AD at baseline, 67 (31%) had subsequently completed an AD. Unadjusted hope was not different between those who did and did not complete an AD (∆HHI, 0.20 ± 3.89 vs -0.91 ± 4.50, respectively; P = .085). After adjustment, hope was significantly higher in those who completed an AD (adjusted mean difference in ∆HHI, 1.31; 95% CI, 0.13-2.49; P = .030). CONCLUSIONS: The current results demonstrate that hope is not decreased after engagement in ACP and indeed may be increased. These findings may provide reassurance to clinicians who are apprehensive about having these important and difficult conversations. LAY SUMMARY: Many oncologists defer advance care planning (ACP) out of concern for giving up hope. This study demonstrates that hope is not decreased in patients who have engaged in ACP either as a conversation with their oncologists or by completing an advance directive. With this information, providers may feel more comfortable having these important conversations with their patients.

Coexistent Alcohol-Related Liver Disease and Alcohol-Related Pancreatitis: Analysis of a Large Health Care System Cohort.

INTRODUCTION: Although coexistence of alcohol-related liver disease (ALD) and pancreatitis (ALP) is seen in clinical practice, a clear understanding of the overlap between these diseases is lacking. Moreover, the relative risks for certain population groups have not been studied. We determined the prevalence and coexistence of ALD and ALP in patients with an alcohol use disorder using retrospective analysis of a large patient cohort from Western Pennsylvania. We specifically emphasized the analysis of underrepresented populations, including women and blacks. METHODS: We identified all unique patients who received care in UPMC health system during 2006-2017 with at least one International Classification of Diseases versions 9 and/or 10 codes for alcohol misuse, ALD and pancreatitis. We noted their sex, race and age of first diagnosis and duration of contact. RESULTS: Among 89,774 patients that fit our criteria, the prevalence of ALD, ALP and coexistent ALD and ALP in patients with alcohol misuse was 11.7%, 7.4% and 2.5%, respectively. Prevalence of ALP in ALD was 16.4%, and ALD in ALP was 33.1%. Prevalence of ALP in ALD was slightly more prevalent in women (18.6% vs. 15.6%, p < 0.001). Prevalence of ALP in ALD was 2-4 folds greater in blacks than other races. DISCUSSION: A sizeable fraction of patients with ALD or ALP has coexistent disease. This is the first study to identify that blacks are at a higher risk for ALP in the presence of ALD. Future studies should define the clinical impact of coexistent disease on clinical presentation and short- and long-term outcomes.

Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD).

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clinical investigation in ADPKD. In this phase 2 two-year trial, we randomly assigned 97 patients, 18-60 years of age, with ADPKD and estimated GFR over 50 ml/min/1.73 m2, in a 1:1 ratio to receive metformin or placebo twice daily. Primary outcomes were medication safety and tolerability. Secondary outcomes included estimated GFR decline, and total kidney volume growth. Thirty-eight metformin and 39 placebo participants still received study product at 24-months. Twenty-one participants in the metformin arm reduced drug dose due to inability to tolerate, compared with 14 in the placebo arm (not significant). Proportions of participants experiencing serious adverse events was similar between the groups. The Gastrointestinal Symptoms Rating Scale score was low at baseline and did not significantly change over time. The annual change for estimated GFR was -1.71 with metformin and -3.07 ml/min/1.73m2 per year with placebo (mean difference 1.37 {-0.70, 3.44} ml/min/1.73m2), while mean annual percent change in height-adjusted total kidney volume was 3.87% in metformin and 2.16% per year in placebo, (mean difference 1.68% {-2.11, 5.62}). Thus, metformin in adults with ADPKD was found to be safe and tolerable while slightly reducing estimated GFR decline but not to a significant degree. Hence, evaluation of efficacy requires a larger trial, with sufficient power to detect differences in endpoints.

Lifetime smoking history and cohort-based smoking prevalence in chronic pancreatitis.

BACKGROUND/OBJECTIVE: Smoking prevalence in patients with chronic pancreatitis [CP] is high. We aimed to understand lifetime history of smoking and cohort trends in CP patients to inform effective strategies for smoking cessation. METHOD: Data on 317 CP patients from the North American Pancreatitis Study 2 [NAPS2] Continuation and Validation Study and the NAPS2 Ancillary Study were analyzed. Smoking history was assessed for each phase of life from the onset of smoking to study enrollment. Data on second-hand smoke and drinking history were also collected. We compared demographic factors, drinking history, pain level and pancreas morphology by smoking status at age 25 (non-smoking, <1 pack per day [PPD], ≥1 PPD). We compared smoking prevalence by birth cohorts: 1930-1949, 1950-1969, 1970-1989. RESULT: Fifty-one percent of CP patients reported smoking at the time of enrollment. Those who smoked ≥1 PPD at age 25 smoked a cumulative total of 30.3 pack-years of cigarettes over a lifetime. Smoking at age 25 was associated with greater lifetime drinking and greater exposure to second-hand smoke at home and at workplace. Pancreatic atrophy and pseudocysts were more common among smokers. Pancreatic pain was more severe among smokers, and 12-13% of smokers reported smoking to alleviate pain. Male CP patients born in 1950-1969 reported the highest peak prevalence of smoking, and female CP patients born in 1970-1989 reported highest peak prevalence of smoking. CONCLUSION: CP patients exhibit intense and sustained smoking behavior once established in the 20s. Regardless, cohort analyses demonstrate that the behaviors could potentially be altered by policy changes.

Natural course of pain in chronic pancreatitis is independent of disease duration.

OBJECTIVES: Pain burn-out during the course of chronic pancreatitis (CP), proposed in the 1980s, remains controversial, and has clinical implications. We aimed to describe the natural course of pain in a well-characterized cohort. METHODS: We constructed the clinical course of 279 C P patients enrolled from 2000 to 2014 in the North American Pancreatitis Studies from UPMC by retrospectively reviewing their medical records (median observation period, 12.4 years). We assessed abdominal pain at different time points, characterized pain pattern (Type A [short-lived pain episodes] or B [persistent pain and/or clusters of recurrent severe pain]) and recorded information on relevant covariates. RESULTS: Pain at any time, at the end of follow-up, Type A pain pattern or B pain pattern was reported by 89.6%, 46.6%, 34% and 66% patients, respectively. In multivariable analyses, disease duration (time from first diagnosis of pancreatitis to end of observation) did not associate with pain - at last clinical contact (OR, 1.0, 95% CI 0.96-1.03), at NAPS2 enrollment (OR 1.02, 95% CI 0.96-1.07) or Type B pain pattern (OR 1.01, 95% CI 0.97-1.04). Patients needing endoscopic or surgical therapy (97.8 vs. 75.2%, p < 0.001) and those with alcohol etiology (94.7 vs. 84.9%, p = 0.007) had a higher prevalence of pain. In multivariable analyses, invasive therapy associated with Type B pain and pain at last clinical contact. CONCLUSIONS: Only a subset of CP patients achieve durable pain relief. There is urgent need to develop new strategies to evaluate and manage pain, and to identify predictors of response to pain therapies for CP.

Groove pancreatitis has a spectrum of severity and can be managed conservatively.

BACKGROUND & AIMS: The natural history of groove pancreatitis is incompletely characterized. Published literature suggests a high rate of surgery. We describe the short- and long-term outcomes in a cohort of patients with groove pancreatitis treated at our institution. METHODS: Medical records of patients hospitalized in the University of Pittsburgh Medical Center system from 2000 to 2014 and diagnosed with groove pancreatitis based on imaging were retrospectively reviewed. Clinical presentation and outcomes during index admission and follow-up were recorded. RESULTS: Forty-eight patients with groove pancreatitis were identified (mean age 53.2 years, 79% male). Seventy-one percent were alcohol abusers and an equal number were cigarette smokers. Prior histories of acute and chronic pancreatitis were noted in 30 (62.5%) and 21 (43.8%), respectively. Forty-four (91.7%) met criteria for acute pancreatitis during their index admission. Alcohol was the most common etiology (68.8%). No patient experienced organ failure. The most frequent imaging findings were fat stranding in the groove (83.3%), duodenal wall thickening (52.1%), and soft tissue mass/thickening in the groove (50%). Over a mean follow-up of 5.0 years, seven (14.6%) required a pancreas-related surgery. Patients had a high burden of pancreatitis-related readmissions (68.8%, 69.4/100 patient-years). Incident diabetes and chronic pancreatitis were diagnosed in 5 (13.9% of patients at risk) and 8 (29.6% of patients at risk) respectively. CONCLUSIONS: Groove pancreatitis has a wide spectrum of severity; most patients have mild disease. These patients have a high burden of readmissions and progression to chronic pancreatitis. A small minority requires surgical intervention.

Mechanical circulatory support in acute myocardial infarction and cardiogenic shock: Challenges and importance of randomized control trials.

BACKGROUND: Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is associated with significant morbidity and mortality. METHODS: We provide an overview of previously conducted studies on the use of mechanical circulatory support (MCS) devices in the treatment of AMI-CS and difficulties which may be encountered in conducting such trials in the United States. RESULTS: Well powered randomized control trials are difficult to conduct in a critically ill patient population due to physician preferences, perceived lack of equipoise and challenges obtaining informed consent. CONCLUSIONS: With growth in utilization of MCS devices in patients with AMI-CS, efforts to perform well-powered, randomized control trials must be undertaken.

Stronger therapeutic alliance is associated with better quality of life among patients with advanced cancer.

OBJECTIVE: Patient-oncologist therapeutic alliance is a foundation of quality cancer care, although there is limited research demonstrating its relationship with patient outcomes. We investigated the relationship between therapeutic alliance and patient quality of life with a secondary goal of determining whether the association varied by patients' baseline level of psychological distress. METHODS: Cross-sectional analysis of baseline data from a randomized clinical trial of 672 patients with advanced cancer participating in a primary palliative care intervention trial. Patients completed baseline self-reported measures of therapeutic alliance (The Human Connection Scale, range: 16-64), overall quality of life (Functional Assessment of Cancer Therapy-Palliative Care, range: 0-184), and psychological distress (Hospital Anxiety and Depression Scale, range: 0-42). First, we determined the relationship between therapeutic alliance and quality of life using multivariable regression adjusting for confounders. We then examined if psychological distress was an effect modifier in this relationship by adding interaction effects of depression and anxiety symptoms on therapeutic alliance into the regression model. RESULTS: Patients reported high levels of therapeutic alliance (56.4 ± 7.4) and moderate quality of life (130.3 ± 25.5). Stronger therapeutic alliance was associated with better quality of life after adjusting for other confounding factors (ß = 3.7, 95% confidence interval = 2.1, 5.3, p < 0.01). The relationship between therapeutic alliance and quality of life was generally consistent regardless of psychological distress. CONCLUSIONS: Collaborative, trusting relationships between patients with advanced cancer and their oncologists are associated with better patient quality of life. Future research should investigate the causal, longitudinal nature of these relationships.

Nucleic Acid Amplification Testing Compared With Cultures, Gram Stain, and Microscopy in the Diagnosis of Vaginitis.

OBJECTIVE: The aim of the study was to evaluate the performance of nucleic acid amplification testing (NAAT) for the diagnosis of vulvovaginal candidiasis (VVC), bacterial vaginosis, and Trichomonas vaginalis. METHODS: A cross-sectional analysis of women with (n = 200) and without (n = 100) vulvovaginal symptoms was enrolled from outpatient gynecology offices and a vulvovaginal referral clinic. Vaginal swabs were analyzed by wet mount microscopy, yeast culture, Gram stain, T. vaginalis culture, and NAAT. Sensitivity and specificity analyses were performed. RESULTS: Among symptomatic women, the sensitivity of microscopy was 48.5% for VVC and 75% for T. vaginalis. Sensitivities of NAAT and culture for diagnosing VVC were 92.4% and 83.3%, respectively, whereas these methods were 100% and 93.8% for T. vaginalis. The sensitivity for bacterial vaginosis diagnosis by clinical criteria ("Amsel criteria"), Gram stain, and NAAT were 98.7%, 82.7%, and 78.7%, respectively. Test concordance rates were high between culture and NAAT for Candida species (91%) and between Gram stain and NAAT for the detection of bacterial vaginosis (88%). Among asymptomatic women, 20%-21% tested positive for bacterial vaginosis by Gram stain or NAAT, and 8%-13% were colonized with Candida species based on culture or NAAT. CONCLUSIONS: Given the limitations of wet mount sensitivity for VVC and T. vaginalis, culture or NAAT testing should be considered when evaluating women with symptoms of vaginitis who test negative by microscopy. Although Amsel criteria accurately diagnosed bacterial vaginosis, NAAT is preferred for detection of T. vaginalis and performed similarly to culture for the diagnosis of VVC.

Coexistence of alcohol-related pancreatitis and alcohol-related liver disease: A systematic review and meta-analysis.

BACKGROUND: Available estimates of coexistent alcohol-related pancreatitis (ALP) and alcohol-related liver disease (ALD) vary widely, and factors that determine coexistent disease are largely unknown. We performed a systematic review of published literature with the primary aim to generate robust estimates for coexistent alcohol-related chronic pancreatitis (ACP) and alcohol-related cirrhosis (ALC). METHODS: We searched PubMed, EMBASE, and Web of Science databases from inception until February 2018. Studies included were those in English-language, sample size ≥25 and allowed calculation of the coexistent disease. Pooled estimates were calculated using a random-effects model approach. RESULTS: Twenty-nine (including 5 autopsy studies) of 2000 eligible studies met inclusion criteria. Only 6.9% included patients were female. Fifteen studies enabled calculation of ACP in ALC, and 11 for ALC in ACP. Pooled prevalence of ACP in ALC was 16.2% (95% CI 10.4-24.5) overall, and 15.5% (95% CI 8.0-27.7) when data were limited to clinical studies. Corresponding prevalence for ALC in ACP was 21.5% (95% CI 12.0-35.6) and 16.9% (95% CI 11.5-24.3), respectively. There was significant heterogeneity among studies (I2 - 65-92%). Pooled prevalence for ALP in ALD or ALD in ALP in clinical studies were 15.2% and 39%, respectively. None of the studies reported outcomes in patients with coexistent disease. CONCLUSION: A sizeable fraction of patients with ACP or ALC have coexistent disease. Future studies should define the prevalence of coexistent disease in women and minority populations, and the consequences of coexistent disease on clinical presentation and short- and long-term outcomes.