First Dark Matter Search Results from the LUX-ZEPLIN (LZ) Experiment.

The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.

Sociodemographic characteristics associated with a higher wish to complain about health care.

OBJECTIVES: Previous research has shown that patients who are older, less educated, or have lower income are less likely to lodge complaints about health care. This variation may reflect less wish to complain or inequitable access to complaint channels or remedies. We aimed to investigate associations between sociodemographic characteristics and health users' wish to complain. STUDY DESIGN: This was a randomized case vignette survey among 6756 Danish men aged 45-70 years (30% response rate). METHODS: Assuming they received the care in vignettes about prostate cancer (prostate-specific antigen) testing, participants rated their wish to complain on a 5-point Likert scale. Information on sociodemographic characteristics was obtained through self-reports and municipality-level information from national registries. RESULTS: Lower education was associated with an increased wish to complain (mean Likert difference 0.44 [95% CI 0.36-0.51]; P < .001). The wish to complain was higher among unemployed men (difference 0.16 [95% CI 0.04-0.28]; P < .011) and those with a chronic illness (difference 0.06 [95% CI 0.02-0.10]; P < .004). Given the same healthcare scenarios, there was no difference in wish to complain among health users who were retired, living rurally, or from lower income groups. CONCLUSIONS: Health users who are less educated, lower income, elderly, or from rural or minority communities appear to be as likely, or more likely, to wish to complain about health care as others. Yet, younger, well-educated, and higher income citizens are overrepresented in actual complaint statistics. The finding suggests persisting inequalities in the suitability or accessibility of complaint processes for some groups of patients.

Radial scars and complex sclerosing lesions on core needle biopsy of the breast: upgrade rates and long-term outcomes.

PURPOSE: Radial scars and complex sclerosing lesions of the breast are part of a group of "indeterminate" breast lesions, which are excised due to risk of coexistent carcinoma. The aim of this study was to assess rate of upgrade of these lesions to invasive and in situ carcinoma and to quantify the risk of development of subsequent cancer in women diagnosed with these lesions. METHODS: A retrospective review of a prospectively maintained breast screening database was performed. All patients with radial scar identified at either core biopsy or final excision biopsy between January 2006 and July 2012 were identified. Full pathological reports for both core biopsy and final excision biopsy were reviewed. Patient outcomes were followed for a mean of 117.1 months. RESULTS: Of 451 B3 biopsies performed at our screening unit, 95 (22%) were found to have a radial scar or complex sclerosing lesion (CSL) on core needle biopsy. Within this group, 77 had no atypia on CNB, with 7 (9%) upgraded to invasive/in situ carcinoma on final excision. Of nine with definite atypia on CNB, 3 (33%) were upgraded. In those patients without atypia or malignancy on final excision, 7.5% developed cancer during 10-year follow-up. CONCLUSION: Patients with radial scar with atypia have a higher risk of upgrade to malignancy. Further research is needed to identify which patients may safely avoid excision of radial scar. Patients with a diagnosis of radial scar on CNB are at increased subsequent risk of breast cancer and may benefit from additional screening.

Emergency medical admissions and COVID-19: impact on 30-day mortality and hospital length of stay.

BACKGROUND: The COVID-19 pandemic has put considerable strain on healthcare systems. AIM: To investigate the effect of the COVID-19 pandemic on 30-day in-hospital mortality, length of stay (LOS) and resource utilization in acute medical care. METHODS: We compared emergency medical admissions to a single secondary care centre during 2020 to the preceding 18 years (2002-2019). We investigated 30-day in-hospital mortality with a multiple variable logistic regression model. Utilization of procedures/services was related to LOS with zero truncated Poisson regression. RESULTS: There were 132,715 admissions in 67,185 patients over the 19-year study. There was a linear reduction in 30-day in-hospital mortality over time; over the most recent 5 years (2016-2020), there was a relative risk reduction of 36%, from 7.9 to 4.3% with a number needed to treat of 27.7. Emergency medical admissions increased 18.8% to 10,452 in 2020 with COVID-19 admissions representing 3.5%. 18.6% of COVID-19 cases required ICU admission with a median stay of 10.1 days (IQR 3.8, 16.0). COVID-19 was a significant univariate predictor of 30-day in-hospital mortality, 18.5% (95%CI: 13.9, 23.1) vs. 3.0% (95%CI: 2.7, 3.4)-OR 7.3 (95%CI: 5.3, 10.1). ICU admission was the dominant outcome predictor-OR 12.4 (95%CI: 7.7, 20.1). COVID-19 mortality in the last third of 2020 improved-OR 0.64 (95%CI: 0.47, 0.86). Hospital LOS and resource utilization were increased. CONCLUSION: A diagnosis of COVID-19 was associated with significantly increased mortality and LOS but represented only 3.5% of admissions and did not attenuate the established temporal decline in overall in-hospital mortality.

Follow-up prostate cancer treatments after radical prostatectomy: a population-based study.

BACKGROUND: Radical prostatectomy is one of the most commonly used curative procedures for the treatment of localized prostate cancer. The probability that a patient will undergo additional cancer therapy after this procedure is largely unknown. PURPOSE: The objective was to determine the likelihood of additional cancer therapy after radical prostatectomy. METHODS: Data for this study were derived from a linked dataset that combined information from the Surveillance, Epidemiology, and End Results Program and Medicare hospital and physician claims. Records were included in this study if patient histories met the following criteria: (a) residing in Connecticut, Washington (Seattle-Puget Sound), or Georgia (Metropolitan Atlanta); (b) having been diagnosed with prostate cancer during the period from January 1, 1985, through December 31, 1991; (c) undergoing radical prostatectomy by December 31, 1992; and (d) having no evidence of other types of cancer. Patients were considered to have had additional cancer therapy if they had had radiation therapy, orchiectomy, and/or androgen-deprivation therapy by injection after radical prostatectomy. The interval between the initial treatment and any follow-up treatment was calculated from the date of radical prostatectomy to the 1st day of the follow-up cancer therapy. All presented probabilities are based on Kaplan-Meier estimates. RESULTS: The study population consisted of 3494 Medicare patients, 3173 of whom underwent radical prostatectomy within 3 months of prostate cancer diagnosis. Although radical prostatectomy is often reserved for localized cancer, less than 60% (1934) of patients whose records were included in this study had organ-confined disease, according to final surgical pathology. Overall, the 5-year cumulative incidence of having any additional cancer treatment after radical prostatectomy reached 34.9% (95% confidence interval [CI] = 31.5%-38.5%). For patients with pathologically organ-confined cancer, the 5-year cumulative incidence was 24.3% (95% CI = 20.0%-29.3%) overall and ranged from 15.6% (95% CI = 9.7%-24.5%) for well-differentiated cancer (Gleason scores 2-4) to 41.5% (95% CI = 27.9%-58.4%) for poorly differentiated cancer (Gleason scores 8-10). The corresponding figures for pathologically regional cancer were 22.7% (95% CI = 12.0%-40.5%) and 68.1% (95% CI = 58.7%-77.1%). CONCLUSION: Further treatment of prostate cancer was done in about one third of patients who had had a radical prostatectomy with curative intent and in about one quarter of patients who were found to have organ-confined disease. IMPLICATIONS: Given the common requirement for follow-up cancer treatments after radical prostatectomy and the uncertainties about the effectiveness of the various follow-up treatment strategies, further investigation of these treatments is warranted.

Outcomes of external-beam radiation therapy for prostate cancer: a study of Medicare beneficiaries in three surveillance, epidemiology, and end results areas.

PURPOSE: This study was designed to obtain representative estimates of the quality of life and probabilities of possible adverse effects among Medicare-age patients treated with external-beam radiation therapy for prostate cancer. METHODS: Patients treated for local or regional prostate cancer with high-energy external-beam radiation between 1989 and 1991 were sampled from a claims data base of the Surveillance, Epidemiology, and End Results (SEER) program from three regions. Patients were surveyed primarily by mail, with telephone follow-up evaluation of non-respondents. There were 621 respondents (83% response rate). The results were compared with data from a previously published national survey of Medicare-age men who had undergone radical prostatectomy. RESULTS: Although they were older at the time of treatment, radiation patients were less likely than surgical patients to wear pads for wetness (7% v 32%) and had a lower rate of impotence (23% v 56% for men < 70 years), while they were more likely to report problems with bowel dysfunction (10% v 4%). Both groups reported generally positive feelings about their treatments. Radiation and surgical patients reported similar rates of additional subsequent treatment (24% v 26% at 3 years after primary treatment). However, radiation patients were less likely to say they were cancer-free, and they reported more worry about cancer than did surgical patients. CONCLUSION: The health-related quality of life of radiation and surgical patients, on average, is similar, but the pattern of experience with adverse consequences of treatment differs by treatment.

Advance directives. Stability of patients' treatment choices.

BACKGROUND: Advance directives are intended to extend patient autonomy into periods of mental incompetence. However, for advance directives to fulfill this objective, patients' choices must be reasonably consistent over time. Thus, we assessed the stability of the advance treatment decisions of patients and members of the public. METHODS: In a prospective cohort study of 495 outpatients and 102 members of the public, we studied the stability of scenario- and treatment-specific choices. Subjects completed an advance directive, which included four illness scenarios with 11 treatment choices in each, as part of a questionnaire. A second interview was completed by 296 patients and 78 members of the public after 6 to 12 months; 154 patients completed a third interview after a further 6 to 12 months. We assessed stability by comparing each choice between interviews. RESULTS: Stability of choices was moderately high among patients (pooled kappa = 0.39) and members of the public (pooled kappa = 0.48). Stability improved with repeat interview (pooled kappa = 0.47 among patients). Patients who had discussions with their physicians showed more improvement (kappa = 0.57) than others. Patients had a wide range of personal stability levels (0% to 100%), but individuals starting out stable rarely became less so (93% of the patients with 85% to 100% stability maintained this level of stability on the third interview). Hospitalized patients showed no significant difference in stability at the second interview, but their stability was not improved at the third interview. CONCLUSIONS: Our findings generally support the use of advance directives. Most people made moderately stable decisions when using scenario- and treatment-specific directives, and stability improved after they reviewed the decisions, especially among those who had discussions with their physicians. Recent hospitalization did not decrease stability, although it appeared to reduce the improvement that others achieved with repeat interview. These findings suggest that advance directives can be relied on 1 to 2 years after completion to reflect a patient's choices.

Positive therapeutic response to lithium in hypomania secondary to organic brain syndrome.

A 57-year-old man with no personal or family history of manic-depressive disease developed symptoms of hypomania after a cerebrovascular accident and surgical trauma to the brain. The patient responded well to lithium carbonate treatment over a 2-year period. Although this therapy is contraindicated in cases of organic brain syndrome, the authors suggest that it should be considered in the management of hypomanic behavior following organic brain dysfunction.

High rates of prostate-specific antigen testing in men with evidence of benign prostatic hyperplasia.

PURPOSE: Benign prostatic hyperplasia is common among men who may be candidates for prostate cancer screening using prostate-specific antigen (PSA) testing. Patterns of PSA testing among men with evidence of benign prostatic hyperplasia have not been studied. METHODS: We examined the prevalence and correlates of a self-reported history of PSA testing. In 1994, 33,028 US health professionals without prostate cancer aged 47 to 85 years provided information on prior PSA testing, lower urinary tract symptoms characteristic of benign prostatic hyperplasia, history of prostatectomy, and prostate cancer risk factors. In 1995, a subset of 7,070 men provided additional information on diagnosis and treatment of benign prostatic hyperplasia. RESULTS: From 39% of men in their 50s to 53% of men in their 80s reported PSA testing in the prior year (P <0.0001 for trend with age). Men were more likely to report PSA testing if they had lower urinary tract symptoms characteristic of benign prostatic hyperplasia (age-adjusted odds ratio for severe symptoms 2.2, 95% confidence interval 1.8 to 2.6), a prior history of prostatectomy (age-adjusted odds ratio 1.1, 95% confidence interval 1.02 to 1.2), or a physician diagnosis of benign prostatic hyperplasia (odds ratio 1.9, 95% confidence interval 1.7 to 2.2; adjusted for age, signs or symptoms of benign prostatic hyperplasia, and prostate cancer risk factors). CONCLUSIONS: These US health professionals reported preferential use of PSA testing among men least likely to benefit from early cancer detection (older men) and among men most likely to have a false-positive PSA result (men with benign prostatic hyperplasia). Physician and patient education are needed to promote more rational and selective use of this screening test.

Prostate cancer screening and beliefs about treatment efficacy: a national survey of primary care physicians and urologists.

PURPOSE: To describe practice patterns and beliefs of primary care physicians and urologists regarding early detection and treatment of prostate cancer. SUBJECTS AND METHODS: National probability samples of primary care physicians (n=444) and urologists (n=394) completed mail survey instruments in 1995. Physicians were asked about their use of prostate-specific antigen (PSA) testing for men of different ages and their beliefs about the value of radical prostatectomy, external-beam radiation therapy, and watchful waiting for men with differing life expectancies. RESULTS: Most primary care physicians report doing PSA tests during routine examination of men older than 50 years of age. The majority say they continue to do them on patients over 80 years and to refer men with abnormal values for biopsy. In contrast, only a minority of urologists would recommend PSA tests or biopsy for abnormal values for men over 75 years of age. More than 80% of primary care physicians and urologists doubt the value of radical prostatectomy for men with < 10 years of life expectancy; more primary care physicians than urologists see probable survival benefit in radiation therapy for patients with life expectancy < 10 years (48% versus 36%) or > 10 years (67% versus 53%). Thirteen percent of primary care physicians and only 3% of urologists consider watchful waiting to be as appropriate as aggressive therapy for men with > 10 years of life expectancy. CONCLUSIONS: Primary care physicians are more aggressive about PSA testing and referral for biopsy than most urologists recommend. Both groups recommend PSA testing and believe that aggressive treatment is more beneficial than existing evidence indicates.

The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine.

The characterization of the enzymatic step(s) involved in the reduction of 3'-azido-3'-deoxythymidine (zidovudine)(ZDV) to 3'-amino-3'-deoxythymidine (AMT) was pursued. AMT formation by human liver microsomes was NADPH dependent, enhanced under anaerobic conditions, and increased by flavin adenine dinucleotide (FAD) and FMN. Carbon monoxide inhibited AMT formation by up to 80%. The effect of theophylline (CYP1A substrate), tolbutamide (CYP2C substrate), chlorzoxazone, thiobenzamide, p-nitrophenol, mercaptoethanol, isoniazid (CYP2E substrates), cortisol (CYP3A substrate), ketoconazole, itraconazole, fluconazole, cimetidine, micronazole (CYP inhibitors), methimazole (flavin-containing mono-oxygenase inhibitor), chloramphenicol (undergoes nitroreduction), allopurinol (xanthine oxidase inhibitor) and dicoumarol (DT-diaphorase inhibitor) on AMT formation were studied to see if the reduction reaction was mediated by a particular isozyme. The greatest inhibition was observed with ketoconazole (concentration producing 50% inhibition = 78.0 microM). At this concentration ketoconazole acted as a non-selective inhibitor of several CYP isozymes. Overall, these data suggested that ZDV reduction was probably mediated by both cytochrome P450 isozymes and NADPH-cytochrome P450 reductase. Formation of AMT, as measured by intrinsic clearance (Clint), was significantly increased in microsomes from rats pre-treated with phenobarbitone, dexamethasone and clofibrate (inducers of CYP2B, CYP3A and CYP4A, respectively). Pre-treatment of rats with beta-naphthoflavone and ethanol (CYP1A and CYP2E1 inducers, respectively) had no effect on AMT formation.

Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men.

We defined risk factors for a clinical diagnosis of benign prostatic hyperplasia (BPH) among subjects of the population-based Massachusetts Male Aging Study. In 1987-89 1709 men aged 40-70 provided baseline risk factor data and were followed for a mean of 9 years; 1019 men without prostate cancer provided follow-up data. We classified men with clinical BPH at follow-up if they reported (1) frequent or difficulty urinating and were told by a health professional that they had an enlarged or swollen prostate or (2) if they reported having surgery for BPH. At follow-up the prevalence of clinical BPH was 19.4%, increasing from 8.4% of men aged 38-49 years to 33.5% of men aged 60-70 years (P < 0.001 for trend). Elevated free PSA levels (age- and total PSA-adjusted OR, top vs. bottom quartile ng/mL 4.4, 95% CI 1.9-10.5), heart disease (age-adjusted OR 2.1, CI 1.3-3.3), and use of beta-blocker medications (OR 1.8, CI 1.1-3.0) increased odds for BPH, while current cigarette smoking (OR 0.5, CI 0.3-0.8) and high levels of physical activity (top vs. bottom quartile kcals/day OR 0.5, CI 0.3-0.9) decreased odds of BPH. All but the medication effects persisted in fully adjusted multivariable models. Total or fat calorie intake, sexual activity level, alcohol intake, body mass index, waist-hip ratio, diastolic blood pressure, a history of diabetes, hypertension, vasectomy, or serum levels of androgens or estrogens did not individually predict clinical BPH. We conclude that physical exercise and cigarette smoking appear to protect against development of clinical BPH. Elevated free PSA levels predict clinical BPH independent of total PSA levels. Risk associated with heart disease does not appear to be due solely to detection bias or to effects of heart disease medications. A wide variety of other characteristics appear to have no influence on risk for clinical BPH.

The influence of early surface thromboreactivity on long-term arterial graft patency.

The influence of early graft surface thromboreactivity on long-term arterial polyester (Dacron) graft patency was investigated with separate ex vivo and in vivo animal models. First, parallel, flow-regulated external aortocaval fistulae were created in five pigs with use of paired 8 mm X 35 cm crimped, warp-knitted, low-profile filamentous velour Dacron tubes: one tube preclotted with autologous blood, the other autoclaved after being soaked in human albumin. Autologous radiolabeled platelets, red cells, and radiolabeled human fibrinogen were injected at initiation of graft flow, with timed graft samples submitted for isotope gamma well-counting. Flow surface accumulation of radiolabeled blood elements was greater on the preclotted graft limb at-all time intervals studied, greatest after 5 minutes of flow initiation with RBC accumulation on the preclotted limb 5.19 +/- 0.84 (x +/- S.E.), platelet accumulation 5.57 +/- 1.00, and fibrinogen accumulation 1.82 +/- 0.14 times greater than that on the albumin-treated limb. Second, bilateral iliofemoral artery bypass grafts were placed in 12 mongrel dogs using 6 mm X 10 cm externally supported, noncrimped, warp-knitted, low-profile filamentous Dacron tubes. Before implant in each dog, one graft limb was clotted with autologous blood and the other was autoclaved after being soaked in 25% human albumin. Fresh autologous radiolabeled platelets were injected after wound closure in seven of these dogs. Postimplant graft imaging at 24 and 72 hours showed radiolabeled platelet accumulation to be 1.43 +/- 0.21 and 2.05 +/- 0.18 times greater on the preclotted graft limb. Six of 12 preclotted graft limbs and 7 of 12 albumin-treated graft limbs were patent when animals were killed 5 to 6 months after implant (not significant). Heat-denatured albumin-coated Dacron surfaces have a reduced early thromboreactivity but do not appear to greatly potentiate long-term arterial graft patency.

Three-dimensional image reconstruction for planning of a complex cardiovascular procedure.

A rare left subclavian artery aneurysm associated with a congenital arch anomaly was difficult to visualize using standard radiographic techniques. Three-dimensional computer imaging produced a clear depiction of this unusual anatomy and simplified the preoperative planning.

Coronary artery bypass in idiopathic thrombocytopenia without splenectomy.

A patient with coronary artery disease and idiopathic thrombocytopenia purpura underwent coronary artery bypass grafting without splenectomy. Our experience indicates that use of cardiopulmonary bypass in patients with idiopathic thrombocytopenic purpura does not invariably mandate splenectomy.

Transseptal control of the difficult aortic annulus.

Successful control of the aortic root in extensive erosive endocarditis, with or without mycotic ventricular septal defect, frequently depends on secure prosthetic fixation to the interventricular septum. We describe transseptal suture fixation of aortic root prostheses through a pulmonary infundibular approach and recommend its early use to avoid difficult, often injurious, attempts at septal suture from within the left ventricular outflow tract.

The value of computed tomography in staging bronchogenic carcinoma: a changing role for mediastinoscopy.

Forty-one patients underwent operative staging for bronchogenic carcinoma following computed tomography of the mediastinum between August, 1982, and March, 1984. Twenty-seven patients were classified as Stage I preoperatively; in 2 of them, positive mediastinal nodes were found at thoracotomy. For the 14 patients in whom positive nodes had been identified by computed tomographic (CT) scanning, staging was unchanged as a result of the findings at mediastinoscopy or thoracotomy or both. In this series, computed tomography had a sensitivity of 89%, a specificity of 100%, and an overall accuracy rate of 95%. We conclude that mediastinoscopy is not needed in patients without evidence of mediastinal nodal enlargement by CT scan; when performed, it should be guided toward those nodes identified as positive.

Use of a Bayesian statistical model for risk assessment in coronary artery surgery.

A computerized statistical model based on the theorem of Bayes was developed to predict mortality after coronary artery bypass grafting. From January, 1984, to April, 1987, at our hospital, 700 patients underwent isolated coronary artery bypass grafting. The presence or absence of 20 risk factors was determined for each patient. The first 300 patients formed the initial database of the Bayesian predictive model, and the remaining 400 patients were prospectively evaluated in four groups of 100 each. Each group was prospectively evaluated and then incorporated into the database to update the model. There was good agreement between predicted and observed results. Bayesian theory is particularly suited to this task because it (1) accommodates multiple risk factors, (2) is tailored to one's specific practice, (3) determines individual, rather than group, prognosis, and (4) can be updated with time to compensate for a changing patient population. These flexible attributes are especially valuable in light of recent changes in the coronary artery bypass graft patient profile.

True emergency coronary artery bypass surgery.

Previous reports of emergency coronary artery bypass grafting often included cases that were not true surgical emergencies, thereby creating inappropriately favorable results. To accurately investigate this important subgroup of patients, we analyzed our recent experience with truly emergent coronary artery bypass grafting. From January 1984 to January 1989, 117 patients underwent true emergency bypass grafting for acute refractory coronary artery ischemia. Clinical deterioration was associated with failure of percutaneous angioplasty in 37 patients and instability during diagnostic catheterization in 13 patients. Refractory ischemia developed in the remaining patients while on the ward or in the intensive care unit. All operations were performed within four hours of surgical consultation, most within one hour. Overall in-hospital operative mortality was 14.5% (17/117), and 76.5% of deaths (13/17) were due to cardiac-related causes. Major morbidity occurred in 35.9% (42/117). Univariate analysis isolated ejection fraction, extent of coronary artery disease, previous myocardial infarction, hypertension, need for inotropic support, use of an intraaortic balloon pump, and cardiopulmonary resuscitation as risk factors for operative mortality. Stepwise multivariate analysis confirmed that previous myocardial infarction, hypertension, cardiopulmonary resuscitation, and reoperation were independently significant risk factors. Age, sex, diabetes, left main disease, and peripheral vascular disease had no significant impact on the prognosis. The 4% operative mortality (2/50) for patients taken directly to the operating room from the catheterization suite was significantly lower than the 22.4% mortality (15/67) associated with emergencies arising on the ward or intensive care unit (p less than 0.01). A logistic risk equation developed from this population accurately modeled operative mortality.(ABSTRACT TRUNCATED AT 250 WORDS)