Sisters of Providence Health System

Sixty-one evaluable patients, 19 with advanced aplastic anemia and 42 with end stage hematological malignancies, were conditioned for marrow grafting with total body irradiation or cyclophosphamide, or a combination of both. Marrow graft donors were siblings matched at the HL-A region and nonreactive in mixed leukocyte culture. All patients received methotrexate postgrafting to modify anticipated graft-versus-host disease (GVHD). Forty-three of the 61 patients developed clinically recognizable GVHD. In seven GVHD was limited to the skin. In the remaining patients, skin involvement was more severe and was followed by gastrointestinal involvement manifested by anorexia, nausea, diarrhea, abdominal pain, and malabsorption and/or liver involvement manifested by hepatomegaly, rises in serum glutamic oxaloacetic acid transaminase, and bilirubin. The severity of GVHD showed no correlation with the underlying disease, the conditioning regimen, or the day of onset after grafting. Fourteen of 25 patients without GVHD or with only skin involvement are alive. By contrast, only 5 of 36 with severe GVHD are alive. Twenty-six of the 36 patients with severe GVHD succumbed to infection, whereas only 4 of 25 without GVHD or with only skin involvement did so. The results show that despite histocompatibility matching and methotrexate therapy, GVHD remains a serious and often fatal complication of marrow transplantation.

CONTEXT: Current treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients. OBJECTIVE: To confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy. DESIGN, SETTING, AND PATIENTS: Open-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N = 106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy. INTERVENTION: Repeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle. MAIN OUTCOME MEASURES: Assessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate (complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians (investigator assessment). RESULTS: All 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months (95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively. CONCLUSION: The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00077974.

<b>Background:</b> Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of autonomic testing, nerve biopsy, and skin biopsy for the assessment of polyneuropathy. <b>Methods:</b> A literature review using MEDLINE, EMBASE, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based upon the level of evidence. <b>Results and Recommendations:</b> 1) Autonomic testing should be considered in the evaluation of patients with polyneuropathy to document autonomic nervous system dysfunction (Level B). Such testing should be considered especially for the evaluation of suspected autonomic neuropathy (Level B) and distal small fiber sensory polyneuropathy (SFSN) (Level C). A battery of validated tests is recommended to achieve the highest diagnostic accuracy (Level B). 2) Nerve biopsy is generally accepted as useful in the evaluation of certain neuropathies as in patients with suspected amyloid neuropathy, mononeuropathy multiplex due to vasculitis, or with atypical forms of chronic inflammatory demyelinating polyneuropathy (CIDP). However, the literature is insufficient to provide a recommendation regarding when a nerve biopsy may be useful in the evaluation of DSP (Level U). 3) Skin biopsy is a validated technique for determining intraepidermal nerve fiber density and may be considered for the diagnosis of DSP, particularly SFSN (Level C). There is a need for additional prospective studies to define more exact guidelines for the evaluation of polyneuropathy. <b>AAN</b> = American Academy of Neurology; <b>AANEM</b> = American Academy of Neuromuscular and Electrodiagnostic Medicine; <b>AAPM&amp;R</b> = American Academy of Physical Medicine and Rehabilitation; <b>ART</b> = autonomic reflex testing; <b>BRSI</b> = baroreflex sensitivity index; <b>CASS</b> = composite autonomic scoring scale; <b>CIDP</b> = chronic inflammatory demyelinating polyneuropathy; <b>DSFN</b> = distal small fiber neuropathy; <b>DSP</b> = distal symmetric polyneuropathy; <b>EDx</b> = electrodiagnosis; <b>EFNS</b> = European Federation of Neurological Societies; <b>HRV</b> = heart rate variability; <b>IAN</b> = idiopathic autonomic neuropathy; <b>IENF</b> = intraepidermal nerve fibers; <b>MSNA</b> = muscle sympathetic nerve activity; <b>NCSs</b> = nerve conduction studies; <b>PGP 9.5</b> = protein-gene-product 9.5; <b>PN</b> = peripheral neuropathy; <b>PRT</b> = blood pressure recovery time; <b>QAE</b> = quantitative autonomic examination; <b>QSART</b> = quantitative sudomotor axon reflex test; <b>QSS</b> = Quality Standards Subcommittee; <b>QST</b> = quantitative sensory testing; <b>SFSN</b> = small fiber sensory polyneuropathy; <b>TST</b> = thermoregulatory sweat testing.

BACKGROUND: Physician-assisted suicide was legalized in Oregon in October 1997. There are data on patients who have received prescriptions for lethal medications and died after taking the medications. There is little information, however, on physicians' experiences with requests for assistance with suicide. METHODS: Between February and August 1999, we mailed a questionnaire to physicians who were eligible to prescribe lethal medications under the Oregon Death with Dignity Act. RESULTS: Of 4053 eligible physicians, 2649 (65 percent) returned the survey. Of the respondents, 144 (5 percent) had received a total of 221 requests for prescriptions for lethal medications since October 1997. We received information on the outcome in 165 patients (complete information for 143 patients and partial for on an additional 22). The mean age of the patients was 68 years; 76 percent had an estimated life expectancy of less than six months. Thirty-five percent requested a prescription from another physician. Twenty-nine patients (18 percent) received prescriptions, and 17 (10 percent) died from administering the prescribed medication. Twenty percent of the patients had symptoms of depression; none of these patients received a prescription for a lethal medication. In the case of 68 patients, including 11 who received prescriptions and 8 who died by taking the prescribed medication, the physician implemented at least one substantive palliative intervention, such as control of pain or other symptoms, referral to a hospice program, a consultation, or a trial of antidepressant medication. Forty-six percent of the patients for whom substantive interventions were made changed their minds about assisted suicide, as compared with 15 percent of those for whom no substantive interventions were made (P<0.001). CONCLUSIONS: Our data indicate that in Oregon, physicians grant about 1 in 6 requests for a prescription for a lethal medication and that 1 in 10 requests actually result in suicide. Substantive palliative interventions lead some--but not all--patients to change their minds about assisted suicide.

BACKGROUND: Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of laboratory and genetic tests for the assessment of DSP. METHODS: A literature review using MEDLINE, EMBASE, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based upon the level of evidence. RESULTS AND RECOMMENDATIONS: 1) Screening laboratory tests may be considered for all patients with polyneuropathy (Level C). Those tests that provide the highest yield of abnormality are blood glucose, serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis (Level C). If there is no definite evidence of diabetes mellitus by routine testing of blood glucose, testing for impaired glucose tolerance may be considered in distal symmetric sensory polyneuropathy (Level C). 2) Genetic testing should be conducted for the accurate diagnosis and classification of hereditary neuropathies (Level A). Genetic testing may be considered in patients with cryptogenic polyneuropathy who exhibit a hereditary neuropathy phenotype (Level C). Initial genetic testing should be guided by the clinical phenotype, inheritance pattern, and electrodiagnostic features and should focus on the most common abnormalities which are CMT1A duplication/HNPP deletion, Cx32 (GJB1), and MFN2 mutation screening. There is insufficient evidence to determine the usefulness of routine genetic testing in patients with cryptogenic polyneuropathy who do not exhibit a hereditary neuropathy phenotype (Level U).

Since quantitative and qualitative alterations in plasma lipoproteins may provide insights into mechanism(s) of altered lipid transport in renal failure, whole plasma triglyceride (TG) and cholesterol (Chol) concentrations and lipoprotein neutral lipids and composition were examined in patients with chronic renal failure (undialyzed and dialyzed) and following successful renal transplantation. Both uremic groups demonstrated increased TG (p less than 0.001) and normal Chol in whole plasma and increased total TG and Chol in the very low-density lipoprotein fraction (VLDL). All hyperlipidemic subjects showed a Type IV phenotype. The percentage triglyceride in VLDL was slightly higher than control in the dialysis patients, and significantly increased in LDL in both undialyzed (p less than 0.001) and dialyzed (p less than 0.005) uremic groups. Transplant patients had significant increases (p less than 0.001) in both TG and Chol in whole plasma, and increased total TG and Chol in both the low-density lipoproteins (LDL) and VLDL fractions. Transplant patients with hyperlipidemia showed a variety of phenotypes and an enrichment of triglyceride in VLDL and LDL. These findings indicate that abnormalities in lipoprotein metabolism in renal failure patients are not appreciably affected by chronic dialysis treatment and continue following successful transplantation. The tendency toward increased VLDL and LDL triglyceride content in these patients resembles the lipoprotein neutral lipid composition found in nonrenal patients with similarly elevated plasma lipids. These alterations could result from primary disturbances in VLDL production and/or removal.

BACKGROUND: Treatment of hypertension is difficult in chronic kidney disease (CKD), and blood pressure goals remain controversial. The association between each blood pressure component and end-stage renal disease (ESRD) risk is less well known. METHODS: We studied associations of systolic and diastolic blood pressure (SBP and DBP, respectively) and pulse pressure (PP) with ESRD risk among 16,129 Kidney Early Evaluation Program (KEEP) participants with an estimated glomerular filtration rate of 60 mL/min/1.73 m(2) using Cox proportional hazards. We estimated the prevalence and characteristics associated with uncontrolled hypertension (SBP ≥ 150 or DBP ≥ 90 mm Hg). RESULTS: The mean (SD) age of participants was 69 (12) years; 25% were black, 6% were Hispanic, and 43% had diabetes mellitus. Over 2.87 years, there were 320 ESRD events. Higher SBP was associated with higher ESRD risk, starting at SBP of 140 mm Hg or higher. After sex and age adjustment, compared with SBP lower than 130 mm Hg, hazard ratios (HRs) were 1.08 (95% CI, 0.74-1.59) for SBP of 130 to 139 mm Hg, 1.72 (95% CI, 1.21-2.45) for SBP of 140 to 149 mm Hg, and 3.36 (95% CI, 2.51-4.49) for SBP of 150 mm Hg or greater. After full adjustment, HRs for ESRD were 1.27 (95% CI, 0.88-1.83) for SBP of 140 to 149 mm Hg and 1.36 (95% CI, 1.02-1.85) for SBP of 150 mm Hg or higher. Persons with DBP of 90 mm Hg or higher were at higher risk for ESRD compared with persons with DBP of 60 to 74 mm Hg (HR, 1.81; 95% CI, 1.33-2.45). Higher PP was also associated with higher ESRD risk (HR, 1.44 [95% CI, 1.00-2.07] for PP ≥ 80 mm Hg compared with PP < 50 mm Hg). Adjustment for SBP attenuated this association. More than 33% of participants had uncontrolled hypertension (SBP ≥ 150 mm Hg or DBP ≥ 90 mm Hg), mostly due to isolated systolic hypertension (54%). CONCLUSIONS: In this large, diverse, community-based sample, we found that high SBP seemed to account for most of the risk of progression to ESRD. This risk started at SBP of 140 mm Hg rather than the currently recommended goal of less than 130 mm Hg, and it was highest among those with SBP of at least 150 mm Hg. Treatment strategies that preferentially lower SBP may be required to improve BP control in CKD.

Objective: Chronic diseases are the leading causes of death and disability in the U.S., and disease management largely falls onto patients' family caregivers. The long-term burden and stress of caregiving negatively impact caregivers' well-being and ability to provide care. Digital health interventions have the potential to support caregivers. This article aims to provide an updated review of interventions using digital health tools to support family caregivers and the scope of the Human-Centered Design (HCD) approaches. Methods: We conducted a systematic search on July 2019 and January 2021 in PubMed, CINAHL, Embase, Cochrane Library, PsycINFO, ERIC, and ACM Digital Library, limiting to 2014-2021 to identify family caregiver interventions assisted by modern technologies. The Mixed Methods Appraisal Tool and the Grading of Recommendations Assessment, Development and Evaluation were used to evaluate the articles. Data were abstracted and evaluated using Rayyan and Research Electronic Data Capture. Results: We identified and reviewed 40 studies from 34 journals, 10 fields, and 19 countries. Findings included patients' conditions and relationships with family caregivers, how the technology is used to deliver the intervention, HCD methods, theoretical frameworks, components of the interventions, and family caregiver health outcomes. Conclusion: This updated and expanded review revealed that digitally enhanced health interventions were robust at providing high-quality assistance and support to caregivers by improving caregiver psychological health, self-efficacy, caregiving skills, quality of life, social support, and problem-coping abilities. Health professionals need to include informal caregivers as an essential component when providing care to patients. Future research should include more marginalized caregivers from diverse backgrounds, improve the accessibility and usability of the technology tools, and tailor the intervention to be more culturally and linguistically sensitive.

Measuring the success of major surgeries such as total hip and total knee replacement is important for both case selection and public policy. Patients, purchasers, and practitioners must choose among clinical scoring systems, health status measures, and patient satisfaction ratings to monitor performance and ensure appropriate use of costly procedures. The present study compares results from the Medical Outcomes Study Short Form 36 (SF-36) Health Status Survey and clinical scoring systems to direct patient ratings of success. Data come from a study of 128 total knee-replacement procedure and 211 total hip replacements. Analyses indicate that for both hip and knee patients, success is related closely to posttreatment physical function and bodily pain. Patient ratings of success also are related to the clinical scores used by physicians. Success is related less to change from pretreatment function for knee patients than for hip patients. Although patient ratings of success are generally consistent with other outcome measures, their relationship to patient expectations, satisfaction, and attributions need to be understood before they can become a useful tool for performance monitoring and case selection.

This report describes an innovative HCV Peer Educator Program that facilitates education, support, and engagement in HCV treatment among patients in an opioid treatment program. Integrating peer educators in a collaborative manner with close supervision holds promise as a model to reduce barriers to HCV treatment among drug users.

Aortic homograft valves are accepted as excellent valve substitutes in the aortic position. Compared to stented bioprostheses, they are considered to have better hemodynamics and a zero or negligible thrombogenicity. Their perceived major single shortcoming is limited durability, but there is apparent broad variation within published data in this respect. Study of the relevant literature reveals important differences between procurement, sterilization and preservation of the individual series refuting any attempt at making a scientifically valid comparison of overall performances. Surgical method and patient selection are further sources of variation among reported long term results. Nevertheless, it appears that (a) cryopreservation produces results at least as good as those of other preservation methods, and (b) the worst results are those of series with the longest follow up. However, the good results with cryopreserved valves are reported in series with limited length of follow up. Because of the many variable factors associated with the use of homograft valves, a comprehensive set of definitions should be introduced, accepted and adhered to in reporting results.

Although contributing greatly to current criminological theory and research on crime and desistance, Sampson and Laub's theory of age-graded informal social control is limited in explaining gender differences in desistance. The authors addressed this limitation by comparing how adult institutions such as marriage, family, and employment affect illicit drug use for women compared with men. The authors analyzed logistic panel models with fixed effects using National Youth Survey data and found gender differences in the predictors of changes in illicit substance use. Although marriage reduced the odds of drug use for men, it was the importance or strength of a relationship that altered illicit drug use for women. The authors also found other gender differences regarding children and the emphasis placed on employment and family by respondents. This research adds to the existing literature on desistance and furthers knowledge about the gendered nature of Sampson and Laub's theory.

BACKGROUND AND AIM OF THE STUDY: The study aim was to update an analysis of the long-term survival of heart valve replacement using the Starr-Edwards prosthesis. METHODS: Cases of isolated aortic (AVR, n = 2,247) and mitral (MVR, n = 1,406) valve replacement with Starr-Edwards prostheses implanted between 1960 and 1997, with follow up to 2003, were reviewed. Introduced in 1965, the Models A1200/1260, M6120 are still in use (Current), while other models have been discontinued (Discontinued). For AVR, 938 valves were Discontinued, with a total follow up of 8,506 patient-years (pt-yr) and a maximum of 41 years; by comparison, 1,309 valves were Current, with a total follow up of 11,586 pt-yr and a maximum of 36.1 MVR, were Discontinued, with a total follow up of 6,454 pt-yr and maximum of 37.2 years; and 771 valves were Current, with a total follow up of 6,211 pt-yr and maximum of 37.0 years. RESULTS: Kaplan-Meier (KM) survival at 10 years was 53% for AVR and 51% for MVR; KM survival at 20 years was 23% for both AVR and MVR; KM survival at 30 years was 8% for both AVR and MVR; KM survival at 40 years was 4% for AVR. The standard error for all KM percentages was 1%. Four patients are currently alive with their original valves, more than 40 years after implantation. CONCLUSION: This series of patients, who underwent valve replacement with the Starr-Edwards valve, now have a follow up extending beyond 40 years, thereby confirming the excellent durability of this valve.

BACKGROUND AND AIMS OF THE STUDY: Having performed our first heart valve replacement in 1960, we began a prospective lifetime follow up service for all patients, contacting them at least annually to determine survivorship and heart valve complications. METHODS: We reviewed isolated aortic (AVR) and mitral (MVR) valve replacements from 1960 to 1993, with follow up to 1998. In total, 2,942 AVR and 1,579 MVR were performed, with 21,742 and 12,142 patient-years of follow up, respectively. Analysis of the results affords an opportunity to demonstrate the usefulness and necessity of certain statistical methods, including multivariable event-free analyses and cumulative incidence functions. RESULTS: The survival rate was 8% at 30 years for both valve positions. However, an overall survival curve is an artificial composite of patients of increasingly higher risk being served during increasingly safer years of calendar time. One result is that, for AVR, age is not a significant univariate risk factor for operative mortality, but is highly significant after accounting for date of surgery using logistic regression. Long-term mortality is higher for tissue valves than for mechanical valves; but mean age is greater (74 versus 57 years), and after accounting for age using Cox regression, mortality is similar for both valve types. Kaplan-Meier analysis estimates thromboembolism occurrences of 85% for AVR and 95% for MVR at 35 and 34 years, respectively, but the cumulative incidence estimates are only 32% and 41%, respectively. CONCLUSIONS: Prospective follow up for over 35 years has provided an opportunity to illustrate important statistical issues: Multivariate analyses are essential to avoid being misled by excluding important risk factors or including artifactual ones, and the cumulative incidence estimates the percentage of patients who will actually experience a complication.

After a private general hospital announced plans to ban smoking inside the hospital, the authors initiated a study on the psychiatric units to identify anticipated and actual patient-related problems associated with the ban and to assess staff and patient attitudes toward the ban. Data were obtained through pre- and post-ban surveys of medical and nursing staff and predischarge interviews with patients. The findings showed that staff anticipated more smoking-related problems than actually occurred and that patients who smoked were able to reduce their tobacco use during their hospital stay. No evidence was found to suggest that hospitalized psychiatric patients are less capable of cutting down on smoking than the general population.

Coagulopathy and elevated D-dimer levels were recognized as prognostic factors early in Wuhan, China, as accompanying more severe COVID-19 patient cases. We sought to determine the accuracy of normal versus elevated D-dimer blood levels at presentation, on day 1, and on day 3 for predicting 28-day survival in a large cohort of consecutive PCR-proven COVID-19 patients to help with patient triage, reassurance, and follow-up management. This is an observational study of a cohort of consecutive patients presenting to Affiliated Hospital of Jianghan University, Wuhan, from January 10 through February 28, 2020. Before data collection, we obtained patients' consent and ethical approval from the Medical Ethics Committee of Jianghan University Affiliated Hospital and China-Japan Friendship Hospital (WHSHIRB-K-2020015). D-dimer levels (Nanopia immunoturbidimetric assay, Sekisui Medical; abnormal > 1.0 mg/L) were measured at day 1 presentation in nearly all patients and again on day 3 and afterward in many. Patients without day 1 D-dimer levels were excluded from the analysis. Clinicians delivered care appropriate to the level of illness, including intensive care, assisted ventilation, and circulatory and other support such as hemodialysis. The primary outcome was 28-day survival. Of 761 PCR-confirmed COVID-19 patients admitted, 749 had presenting day 1 D-dimer levels available. Twenty-eight-day mortality was 78 in the 749-patient cohort, 10.4% (95% CI = 8.3% to 12.8%). D-dimer levels on day 1 were normal in 586 of 671 survivors but elevated in 36 of 78 nonsurvivors, for a survival sensitivity of 87% (95% CI = 86% to 89%), positive predictive value of 93% (95% CI = 92% to 95%), specificity of 46% (95% CI = 36% to 57%), and negative predictive value of 30% (95% CI = 23 to 36%). Figure 1 shows 28-day survival for normal versus elevated D-dimer values in this population. Day 3 D-dimer values, available for 598 cohort patients (80%), were normal in 408 of the 28-day survivors and 10 who died. They were elevated in 130 of the 28-day survivors and 50 who died. Thus, a normal value was strongly associated with survival: sensitivity 76% (95% CI = 75% to 77%), positive predictive value 98% (95% CI = 96% to 99%), specificity 83% (95% CI = 72% to 91%), and negative predictive value 28% (95% CI = 24% to 30%). Survival odds with a normal day 1 D-dimer were 5.9 (95% CI = 3.6% to 9.7%); for a normal day 3 D-dimer, survival odds were 15.6 (95% CI = 7.7% to 31.8%). Association of coagulopathy with COVID-19 is now widely reported.1, 2 In the United States and elsewhere, rapid results of PCR coronavirus testing are not widely available and a positive swab result does not inform prognosis. In this cohort of 100% COVID-19 patients, a day 1 and particularly a day 3 normal D-dimer had high precision for predicting 28-day survival. Similar to how D-dimer is used to assist diagnosis of deep vein thrombosis and pulmonary embolism, a normal result supports a decision to triage a patient to watchful waiting as opposed to hospital admission. For symptomatic COVID-19 suspects awaiting swab results but ill enough to require hospitalization, elevated D-dimer levels could be presumptively diagnosed as COVID-19 and triaged as higher risk. Those with normal D-dimer level and without another reason for hospitalization could be managed expectantly as outpatients with reassurance and appointment for follow-up day 3 D-dimer level, while other etiologies were also considered. Evaluation of subjective outpatient deterioration could be assisted by an on-site, real-time, commercially available point-of-care D-dimer determination. While qualitative bedside tests may be somewhat less accurate than quantitative ones,3 real-time D-dimer testing can even be performed in the field and has been reported to be helpful in expediting emergency department evaluation of pulmonary embolism.4, 5 We speculate that field D-dimer testing may be similarly useful to make prehospital decisions about transport of patients with suspected COVID-19. Our results differ from previous reports.6, 7 Because D-dimer assays have different upper limits of normal and a multiple of some level from one assay is not necessarily proportional to that of another,6 we used the upper limit of normal as the cutoff to allow generalization as universally as possible. We assess D-dimer in the largest number of COVID-19 PCR-confirmed consecutive cohort patients yet prospectively reported rather than selecting patients. We include day 3 data, available for 80% of our cohort. These advantages allow tighter precision of the survival positive predictive value and other accuracy values, reduce possible selection bias, and allow insight for day 3 follow-up with interpretation of those D-dimer level results. A normal D-dimer on presentation is highly predictive of survival, and a day 3 normal value even more so. This readily available information can help guide physicians with triage and follow-up, reassure patients and help to bring confidence to identifying those patients warrant closest surveillance.

Arterial distensibility, assessed by the pulse-wave velocity (PWV), is an independent predictor of cardiovascular risk. We investigated whether natriuretic peptides, acting locally, modify conduit artery distensibility in vivo. All studies were conducted in anesthetized sheep (n = 18) by using a validated ovine hindlimb model. In brief, the PWV was calculated, with the use of the foot-to-foot methodology, from two pressure waveforms recorded simultaneously with a high-fidelity dual pressure-sensing catheter placed in the common iliac artery. Drugs were infused either proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath to control for any reflex changes in flow or sympathetic activation. First, the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP) were studied. Second, the role of endogenous ANP was investigated by infusing the natriuretic peptide receptor type A (NPRA)-selective receptor antagonist A71915. Third, A71915 was coinfused with ANP. Fourth, the NPRC-selective agonist cANF was infused. Infusion of CNP or des-[Gln18Ser19Gly20Leu21Gly22]-ANF-(4-23)-NH2 (cANF) had no effect on iliac PWV. However, infusion of ANP, and to a lesser degree BNP, resulted in a reduction in PWV (-9%; P < 0.01 and -6%; P < 0.05, respectively). A71915 increased iliac PWV from 2.97 +/- 0.13 to 3.06 +/- 0.13 m/s; P < 0.01. Coinfusion of A71915 with ANP completely abolished the effects of ANP (P < 0.01). Importantly, ANP-BNP infusion via the sheath did not alter PWV. In conclusion, ANP, and to a lesser extent BNP, modify large artery distensibility via the NPRA receptor. Neither CNP nor cANF altered PWV, suggesting that the NPRB and NPRC receptors do not acutely influence distensibility in vivo.

AIMS: To assess the dose-related effects of sotagliflozin, a novel dual inhibitor of sodium-glucose co-transporters-1 and -2, in type 1 diabetes (T1D). MATERIALS AND METHODS: In this 12-week, multicentre, randomized, double-blind, placebo-controlled dose-ranging trial, adults with T1D were randomized to once-daily placebo (n = 36) or sotagliflozin 75 mg (n = 35), 200 mg (n = 35) or 400 mg (n = 35). Insulin was maintained at baseline doses. The primary endpoint was least squares mean (LSM) change in glycated haemoglobin (HbA1c) from baseline. Other endpoints included proportion of participants with ≥0.5% HbA1c reduction and assessments of 2-hour postprandial glucose (PPG), weight, and urinary glucose excretion (UGE). RESULTS: From a mean baseline of 8.0% ± 0.8% (full study population), placebo-adjusted LSM HbA1c decreased by 0.3% (P = .07), 0.5% (P < .001) and 0.4% (P = .006) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively, at week 12. In the placebo and sotagliflozin 75 mg, 200 mg and 400 mg groups, 33.3%, 37.1%, 80.0% and 65.7% of participants achieved an HbA1c reduction ≥0.5%. Placebo-adjusted PPG decreased by 22.2 mg/dL (P = .28), 28.7 mg/dL (P = .16) and 50.2 mg/dL (P = .013), UGE increased by 41.8 g/d (P = .006), 57.7 g/d (P < .001) and 70.5 g/d (P < .001), and weight decreased by 1.3 kg (P = .038), 2.4 kg (P < .001) and 2.6 kg (P < .001) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively. One case of severe hypoglycaemia occurred in each sotagliflozin group and one case of diabetic ketoacidosis (DKA) occurred with sotagliflozin 400 mg. CONCLUSIONS: Combined with stable insulin doses, sotagliflozin 200 mg and 400 mg improved glycaemic control and weight in adults with T1D. Sotagliflozin 400 mg reduced PPG levels. UGE increased with all sotagliflozin doses. Rates of severe hypoglycaemia and DKA were low (NCT02459899).

Not only will healthcare investments in information technology (IT) continue, they are sure to increase. Just as other industries learned over time how to extract more value from IT investments, so too will the healthcare industry, and for the same reason: because they must. This article explores the types of business value IT has generated in other industries, what value it can generate in healthcare, and some of the barriers encountered in achieving that value. The article ends with management principles for IT investment.

OBJECTIVE: To determine the validity of an electronic health record (EHR) in the identification of patients with left ventricular dysfunction in a primary care setting. DESIGN: A cross-sectional study. SETTING: Nine clinics participating from the Providence Research Network (PRN) comprising 75 physicians serving approximately 200,000 patients. All clinics utilise the Logician EHR for all patient care activities. PATIENTS: The study included all PRN patients with an active chart. INTERVENTIONS: All patients with a heart failure diagnosis in the problem list were identified by database query. Left ventricular ejection fraction (LVEF) data were identified through query of local cardiology and hospital echocardiography databases. Additional LVEF data were sought in a manual search of paper charts. MEASUREMENTS AND MAIN RESULTS: To determine the problem list coding accuracy for a heart failure (HF) diagnosis we evaluated sensitivity, positive predictive value and related derived statistical measures using documented LVEF as the 'gold standard'. Of 205 755 active PRN patients, 1731 were identified with a problem list entry of HF. Based on comparison with documented LVEF, the sensitivity for problem list entry was 43.9% and 54.4% when HF was defined as an LVEF < or = 55% and < or = 40%, respectively. CONCLUSION: The validity of an EHR problem list entry of HF was poor. The problem list validity could be enhanced through reconciliation with other data sources. Inaccurate EHR problem lists may have clinical consequences, including underprescribing of beneficial therapies.