An Unsuccessful Randomized Trial of Percutaneous vs Endoscopic Drainage of Suspected Malignant Hilar Obstruction.

Percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiopancreatography (ERCP) are widely accepted but competing approaches for the management of malignant obstruction at the hilum of the liver. ERCP is favored in the United States on the basis of high success rates for non-hilar indications, the perceived safety and superior tissue sampling capability of ERCP relative to PTBD, and the avoidance of external drains that are undesirable to patients. A recent randomized controlled trial (RCT) comparing the 2 modalities in patients with resectable hilar cholangiocarcinoma was terminated prematurely because of higher mortality in the PTBD group.1 In contrast, most observational data suggest that PTBD is superior for achieving complete drainage.2-6 Because the preferred procedure remains uncertain, we aimed to compare PTBD and ERCP as the primary intervention in patients with cholestasis due to malignant hilar obstruction (MHO).

Multicenter Trial of the VenaTech Convertible Vena Cava Filter.

PURPOSE: To demonstrate rates of successful filter conversion and 6-month major device-related adverse events in subjects with converted caval filters. MATERIALS AND METHODS: An investigational device exemption multicenter, prospective, single-arm study was performed at 11 sites enrolling 149 patients. The VenaTech Convertible Vena Cava Filter (B. Braun Interventional Systems, Inc, Bethlehem, Pennsylvania) was implanted in 149 patients with venous thromboembolism and contraindication to or failure of anticoagulation (n = 119), with high-risk trauma (n = 14), and for surgical prophylaxis (n = 16). When the patient was no longer at risk for pulmonary embolism as determined by clinical assessment, an attempt at filter conversion was made. Follow-up of converted patients (n = 93) was conducted at 30 days, 3 months, and 6 months after conversion. Patients who did not undergo a conversion attempt (n = 53) had follow-up at 6 months after implant. RESULTS: All implants were successful. One 7-day migration to the right atrium required surgical removal. Technical success rate for filter conversion was 92.7% (89/96). Mean time from placement to conversion was 130.7 days (range, 15-391 d). No major conversion-related events were reported. The mean conversion procedure time was 30.7 minutes (range, 7-135 min). There were 89 converted and 32 unconverted patients who completed 6-month follow-up with no delayed complications. CONCLUSIONS: The VenaTech Convertible filter has a high conversion rate and low 6-month device-related adverse event rate. Further studies are necessary to determine long-term safety and efficacy in both converted and unconverted patients.

Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene.

Mammalian cytochrome c oxidase (COX) catalyses the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. Mitochondrial DNA (mtDNA) encodes three COX subunits (I-III) and nuclear DNA (nDNA) encodes ten. In addition, ancillary proteins are required for the correct assembly and function of COX (refs 2, 3, 4, 5, 6). Although pathogenic mutations in mtDNA-encoded COX subunits have been described, no mutations in the nDNA-encoded subunits have been uncovered in any mendelian-inherited COX deficiency disorder. In yeast, two related COX assembly genes, SCO1 and SCO2 (for synthesis of cytochrome c oxidase), enable subunits I and II to be incorporated into the holoprotein. Here we have identified mutations in the human homologue, SCO2, in three unrelated infants with a newly recognized fatal cardioencephalomyopathy and COX deficiency. Immunohistochemical studies implied that the enzymatic deficiency, which was most severe in cardiac and skeletal muscle, was due to the loss of mtDNA-encoded COX subunits. The clinical phenotype caused by mutations in human SCO2 differs from that caused by mutations in SURF1, the only other known COX assembly gene associated with a human disease, Leigh syndrome.

The effect of manufacturing variables on radiation doses from porcelain tiles.

Previous studies have focused on the radiological properties of glazed ceramic tiles. This study was conducted to describe the radiological properties of porcelain tiles and how they were affected by variations in the manufacturing parameters. The data showed that the majority of the uranium in the tiles was attributable to the addition of zircon while less than half of the thorium in the tile was attributable to the added zircon, and the remainder came from other minerals in the formulation. The effects of firing temperatures and compressive strengths of the tiles are presented and show that higher firing temperatures increase radon emanation, while higher compressive strengths reduce radon emanation. The study also described how the addition of zircon to the tile formulation affected the radiological exposures that could be received by a member of the public from the use of such porcelain tiles. A dose assessment was conducted based on 23 different types of tile formulation. Screening procedures for building materials have been described in European Commission documents, and these limit the addition of zircon in a porcelain tile to approximately 9% by mass. The dose assessment reported in this study showed that 20% zircon could be added to a porcelain tile without exceeding the prescribed dose limits.

Aviation and Procedural Medicine.

Aviation and medicine are two complex fields involving many interdependent steps where problems can occur. When they inevitably do the outcome can be catastrophic, leading to injury or even loss of life. While both professions have made great strides to reduce error and improve safety, we would suggest medicine can still learn much from the approach aviation has developed. We will show how pilots spend a significant amount of time on planning and early recognition of impending challenges, utilize the concept of crew resource management routinely, and stay much focused during each specific mission. More importantly, they are very open and committed to discussing every event or near event to improve the system, and are supported in this by their superiors without fear of punishment or retribution. By adopting many of these principles, medicine can develop a true culture of safety such as aviation has done, leading to a remarkable improvement in their safety record.

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial.

BACKGROUND: The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). METHODS: The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. DISCUSSION: The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.

Prostate cancer: MR imaging-guided galvanotherapy--technical development and first clinical results.

PURPOSE: To prospectively evaluate the safety and effectiveness of magnetic resonance (MR) imaging-guided galvanotherapy in prostate cancer. MATERIALS AND METHODS: This prospective study was approved and authorized by the institutional review board, and patients gave informed consent. Forty-four men (mean age, 63.1 years) with histologically proved prostate cancer were treated with galvanotherapy. After transgluteal puncture of the prostate with local anesthesia, two MR imaging-compatible electrodes were positioned under MR imaging guidance in the periphery of the right and left lobes of the prostate so that they had direct tumor contact. The patients were treated three times in 1-week intervals, and direct current was applied to the localized cancer in the prostate gland with a total charge of 350 coulombs. Follow-up with laboratory testing (prostate-specific antigen [PSA] levels) and endorectal MR imaging with tumor volume measurement was performed 3, 6, and 12 months after the procedure. The Friedman test was used to compare tumor volumes and PSA levels across the four time points. RESULTS: All patients tolerated MR imaging-guided galvanotherapy well without any major side effects or complications. Six patients had some reversible difficulty with urination, and five reported temporary unilateral leg paresthesia. Tumor volume as determined with MR imaging decreased from a pretherapeutic median of 1.90 to 1.12 cm(3), which corresponded to a significant (P < .01) reduction of 41%. One patient (2%) had complete remission and 18 (41%) had partial remission at follow-up 12 months after therapy. Twenty-three patients (52%) were classified as having stable disease. Two patients (5%) had progressive disease. Median PSA levels decreased in the 12-month control period from 7.05 to 2.4 ng/mL (66%, P < .01). CONCLUSION: MR imaging-guided galvanotherapy is a safe procedure and can result in local control of prostatic carcinoma, with a concomitant reduction in the PSA level. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/245/2/895/DC1.

Screening prescription drugs for possible carcinogenicity: eleven to fifteen years of follow-up.

Using computerized pharmacy records from 1969 to 1973 for a cohort of 143,574 members of the Kaiser Permanente Medical Care Program, we have been testing associations of 215 drugs or drug groups with subsequent incidence of cancer at 56 sites. This paper presents findings with follow-up through 1984. There were 227 statistically significant (P less than 0.05, two-tailed) associations: 170 positive, 57 negative. Some were undoubtedly chance findings; others were likely due to confounding by unmeasured covariables. However, several associations suggested hypotheses for further studies and/or the need for continued observation. Most notable among findings not previously reported were associations of several antibiotics, both oral and topical, with lung cancer. These associations could not be explained by indications for drug use or by differences in smoking habits between users and nonusers, and suggest a possible link between the occurrence of bacterial infections and risk for cancer. In general, our results continue to suggest that most medications used during that period did not affect cancer incidence substantially. However, for less frequently prescribed medications, our power to detect moderate increases in cancer risk was quite low.

Exposure to barbiturates in utero and during childhood risk of intracranial and spinal cord tumors.

Barbiturate exposure during childhood was assessed from medical records of 237 children with intracranial and spinal cord tumors and 474 matched controls in a prepaid health plan. In utero exposure was also examined in a subset of 86 "cases" and 172 controls whose mothers were health plan members during pregnancy. No association of in utero exposure to barbiturates was found [odds ratio (O.R.) = 0.96, 95% confidence interval (C.I.) = 0.47, 1.94]. An association was noted for barbiturate use during childhood (O.R. = 1.80, 95% C.I. = 1.18, 2.74) but was reduced (O.R. = 1.41, 95% C.I. = 0.89, 2.21) when history of epilepsy was taken into account and was no longer significant. An apparent dose-response effect disappeared after adjustment for a history of epilepsy. Although barbiturate use for epilepsy due to preexisting brain tumors clearly explains some of the observed association, the small, residual risk prevents us from ruling out a possible carcinogenic effect of barbiturates. Further study of cohorts of adult as well as childhood users of barbiturates and other anticonvulsants is recommended.

Glycemic control and heart failure among adult patients with diabetes.

BACKGROUND: Glycemic control is associated with microvascular events, but its effect on the risk of heart failure is not well understood. We examined the association between hemoglobin (Hb) A(Ic) and the risk of heart failure hospitalization and/or death in a population-based sample of adult patients with diabetes and assessed whether this association differed by patient sex, heart failure pathogenesis, and hypertension status. METHODS AND RESULTS: A cohort design was used with baseline between January 1, 1995, and June 30, 1996, and follow-up through December 31, 1997 (median 2.2 years). Participants were 25 958 men and 22 900 women with (predominantly type 2) diabetes, >/=19 years old, with no known history of heart failure. There were a total of 935 events (516 among men; 419 among women). After adjustment for age, sex, race/ethnicity, education level, cigarette smoking, alcohol consumption, hypertension, obesity, use of beta-blockers and ACE inhibitors, type and duration of diabetes, and incidence of interim myocardial infarction, each 1% increase in Hb A(Ic) was associated with an 8% increased risk of heart failure (95% CI 5% to 12%). An Hb A(Ic) >/=10, relative to Hb A(Ic) <7, was associated with 1.56-fold (95% CI 1.26 to 1.93) greater risk of heart failure. Although the association was stronger in men than in women, no differences existed by heart failure pathogenesis or hypertension status. CONCLUSIONS: These results confirm previous evidence that poor glycemic control may be associated with an increased risk of heart failure among adult patients with diabetes.

Implications of stroke risk criteria on the anticoagulation decision in nonvalvular atrial fibrillation: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study.

BACKGROUND: Warfarin dramatically reduces the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF) but increases the likelihood of bleeding. Accurately identifying patients who need anticoagulation is critical. We assessed the potential impact of prominent stroke risk classification schemes on this decision in a large sample of patients with NVAF. METHODS AND RESULTS: We used clinical and electrocardiographic databases to identify 13 559 ambulatory patients with NVAF from July 1996 through December 1997. We compared the proportion of patients classified as having a low enough stroke risk to receive aspirin using published criteria from the Atrial Fibrillation Investigators (AFI), American College of Chest Physicians (ACCP), and the Stroke Prevention in Atrial Fibrillation Investigators (SPAF). In this cohort, AFI criteria classified 11% as having a low stroke risk, compared with 23% for ACCP and 29% for SPAF (kappa range, 0.44 to 0.85). This 2- to-3-fold increase in low stroke risk patients by ACCP and SPAF criteria primarily resulted from the inclusion of many older subjects (65 to 75 years+/-men >75 years) with no additional clinical stroke risk factors. CONCLUSIONS: The age threshold for assigning an increased stroke risk has a dramatic impact on whether to recommend warfarin in populations of patients with NVAF. Large, prospective studies with many stroke events are needed to precisely determine the relationship of age to stroke risk in AF and to identify which AF subgroups are at a sufficiently low stroke risk to forego anticoagulation.

Insulin sensitivity and abdominal obesity in African-American, Hispanic, and non-Hispanic white men and women. The Insulin Resistance and Atherosclerosis Study.

Increased abdominal obesity has been related to lower insulin sensitivity (SI), independent of overall obesity, but it has been suggested that this relationship may be weaker in non-whites. In the Insulin Resistance and Atherosclerosis Study (IRAS), SI was estimated using a minimal model analysis of the frequently sampled intravenous glucose tolerance test in 1,625 men and women aged 40-69 years. Subjects included African-Americans, Hispanics, and non-Hispanic whites from Oakland and Los Angeles, CA, San Antonio, TX, and the San Luis Valley, CO. Minimum waist circumference was significantly (P = 0.0001) associated with SI after adjusting for age, sex, height, BMI, glucose tolerance status, ethnicity, and clinic. This relationship was significantly (P = 0.0001) stronger in subjects with normal glucose tolerance (NGT) (beta = -0.030, P = 0.0001) than in those with impaired glucose tolerance (IGT) (beta = -0.010, P = 0.02; NIDDM: beta = -0.013, P = 0.0001). There were no significant ethnic differences in effect size across the spectrum of glucose tolerance. Waist circumference was also positively related to fasting insulin, an indirect measure of insulin sensitivity, in NGT (P = 0.0001), IGT (P = 0.0003), and NIDDM (P = 0.0002). The waist-fasting insulin relationship was significantly weaker in African-Americans, relative to non-Hispanic whites, in NGT and IGT (tests of statistical interaction: P = 0.04 and P = 0.02, respectively). In general, these patterns were similar in models specifying waist-to-hip ratio (WHR), rather than waist circumference, as the independent variable. While some ethnic variability exists, a negative relationship between abdominal obesity and insulin sensitivity was confirmed for all three ethnic groups across the spectrum of glucose tolerance.

Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study.

The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S(I)), glucose effectiveness (S(G)), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n= 288), Hispanics (n= 363), and non-Hispanic whites (n= 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S(I) than non-Hispanic whites. No ethnic difference was observed in S(G). After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S(I) than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in S(I) or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between S(I) and upper body adiposity (waist-to-hip, ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non-Hispanic whites, suggesting that greater insulin resistance may be in large part responsible for the higher prevalence of NIDDM in these minority groups. However, in Hispanics. the greater insulin resistance may be due to greater adiposity and other behavioral factors.

Inferior vena cava filters. Indications, safety, effectiveness.

BACKGROUND: Preventing pulmonary embolization by interrupting vena caval flow has been attempted since 1893. Inferior vena cava (IVC) filters have been available for 20 years, and currently there are five filters commercially available in the United States (Greenfield filter, Titanium Greenfield filter, Simon-Nitinol filter, Bird's Nest filter, and LGM or Vena Tech filter) and two other filters under development (Amplatz filter and Günther filter). Although these devices are widely used, their clinical utility and safety have not been completely evaluated. Controlled clinical trials to determine the clinical role for IVC filters have not been attempted, but numerous case series describing the outcomes of the seven current filters have been published. We have systematically reviewed these studies to clarify what is known about the indications, safety, and effectiveness of IVC filters. METHODS: Using the MEDLINE database, all English-language publications since 1970 that included follow-up clinical information after filter insertion were reviewed and eight methodologic guidelines were employed to assess the scientific quality of the clinical information. RESULTS: Twenty-four case series were reviewed: 16 concerned the Greenfield filter (1632 patients), and eight dealt with newer designs (925 patients). Commonly noted methodologic problems included failure to report the initial extent of thromboembolic disease, incomplete description of the patient assembly process, and incomplete and potentially biased outcome assessment. Recurrent clinical pulmonary embolism was rare after filter placement, and only eight deaths from pulmonary embolism were reported. Filter complications were common but rarely life threatening; four (0.16%) deaths from filter complications were noted among the reviewed studies. Thrombotic complications following filter placement included insertion-site deep vein thrombosis and IVC obstruction. These events were rare, but they occurred with all filter types. CONCLUSIONS: Inferior vena cava filters appear to be effective in preventing recurrent pulmonary embolism. Despite the large published experience with IVC filters, many questions remain about their indications, safety, and effectiveness. Anticoagulant therapy, if not contraindicated, should be used in conjunction with filters. While there is no ideal filter, some situations call for specific filters. Filter selection and insertion require experience, modern angiographic technique, and collaboration between clinicians caring for patients and the interventional radiologists or surgeons inserting the device.

The cost of acquired immunodeficiency syndrome in northern California. The experience of a large prepaid health plan.

We studied the cost of acquired immunodeficiency syndrome (AIDS) in the Kaiser Permanente Medical Care Program (KPMCP), northern California region. We report the costs of care to the KPMCP and introduce an innovative application of survival methods to cost analysis. From the beginning of the AIDS epidemic in 1981 to the end of June 1987, 866 cases of AIDS were recorded among members of the KPMCP. Estimates of the costs of care of these patients were derived from comprehensive chart reviews of a random sample of 71 patients whose conditions were diagnosed from January 1984 through June 1987. Total mean lifetime costs per patient were $32,816 (median, $28,677), whereas the mean hospital per diem cost was $20,446 per patient. As more care was shifted to outpatient services overtime, overall costs dropped, despite marked increases in the cost of outpatient medications such as zidovudine. The overall estimate of cost compared closely with other estimates of the cost of care in San Francisco, Calif, and it is lower than estimates from elsewhere in the United States, probably because of the low proportion of cases associated with intravenous drug use and the well-developed social support networks available to patients with AIDS in the San Francisco Bay Area.

Evaluating hypertension control in a managed care setting.

BACKGROUND: We conducted a retrospective cohort study on a random sample of adult patients with hypertension in a large health maintenance organization to assess the feasibility of documenting blood pressure (BP) control and to compare different measures for defining BP control. METHODS: Three criteria for BP control were assessed: systolic BP less than 140 mm Hg; diastolic BP less than 90 mm Hg; and combined BP control, with systolic BP less than 140 mm Hg and diastolic BP less than 90 mm Hg. Four methods of assessing hypertension control by the above criteria were examined: proportion of patients with BP under control at 75% and 50% or more of their office visits; the mean of all pressures during the study period; and the BP from the last visit during the study period. RESULTS: The proportion of patients meeting each criterion for control was similar whether we used the mean BP for all visits, the last recorded BP, or control at 50% or more of visits. Control rates were substantially lower when the more stringent assessment, 75% of visits, was used. The proportion of patients with combined BP control at 75% or more of their visits was half that of the other methods. CONCLUSIONS: In this health maintenance organization population, results with the use of the simplest approach, the last BP measurement recorded, were similar to results with the mean BP. Our findings indicate that evaluation of BP control in a large health maintenance organization will find substantial room for improvement, and clinicians should be encouraged to be more aggressive in their management of hypertension, especially with regard to the systolic BP, which until recent years has been underemphasized.