Four-year survival rate in pulmonary sarcoidosis with extensive pulmonary hypertension screening.

BACKGROUND: Sarcoidosis is a systemic disease of unknown aetiology with significant morbidity and mortality. The PULSAR study prospectively performed cardiac analysis including systematic pulmonary hypertension screening in sarcoidosis patients newly referred to a tertiary sarcoidosis center. In this manuscript we studied the four-year mortality of this population. METHODS AND MAIN FINDINGS: Between august 2015 and October 2017, 399 patients (58% male, mean age 49.4 years, 90.5% Caucasian) were included and followed for a mean period of 4.3±0.7 years. In total, 10 patients had died at the time of analysis. 1-, 2-, 3- and 4-year survival rate was 100% (n=399), 99.0% (n=399), 98.2% (n=399) and 94.6% (n=276). Most patients died of respiratory failure, other causes were heterogeneous including cardiac, neurological and non-sarcoidosis origin. A low CPI score or modified Walsh score was associated with higher mortality, similar for high PH probability on echocardiography and elevated right ventricular systolic pressure. CONCLUSION: This study highlights that elevated RVSP and presence of PH on echocardiography and progression of fibrotic disease with subsequent decline in pulmonary function test are important factors for mortality in sarcoidosis patients.

Assessment of pedicle size in patients with scoliosis using EOS 2D imaging: a validity and reliability study.

PURPOSE: Free-hand pedicle screw insertion methods are widely used for screw insertion during scoliosis surgery. Preoperative knowledge about the pedicle size helps to maximize screw containment and minimize the risk of pedicle breach. Radiographs taken by a biplanar low-dose X-ray device (EOS) have no divergence in the vertical plane. The criterion validity and reliability of preoperative EOS images for pedicle size measurements in patients with idiopathic scoliosis (IS) was investigated in this study. METHODS: Sixteen patients who underwent surgical treatment for IS were prospectively included. Intra- and extracortical pedicle height and width measurements on EOS images were compared with reconstructed intra-operative 3D images of the isthmus of included pedicles. Secondly, intra- and interobserver reliability of pedicle size measurements on EOS images was determined. RESULTS: The total number of analyzed pedicles was 203. The correlation between the EOS and 3D scan measurements was very strong for the intra- and extracortical pedicle height and strong for the intra- and extracortical pedicle width. There are, however, significant, but likely clinically irrelevant differences (mean absolute differences < 0.43 mm) between the two measure methods for all four measurements except for extracortical pedicle height. For pedicles classified as Nash-Moe 0, no significant differences in intra- and extracortical pedicle width were observed. Both intra- and interobserver reliability was excellent for all pedicle size measurements on EOS images. CONCLUSION: The results of this study indicate a good validity and reliability for pedicle size measurements on EOS radiographs. Therefore, EOS radiographs may be used for a preoperative estimation of pedicle size and subsequent screw diameter in patients with IS.

Participation rates of Ashkenazi Jews in a colon cancer community-based screening/prevention study.

In a recent colon cancer risk study, genetic assessment and colonoscopy were offered to virtually all of the adult Ashkenazi Jews in an urban community. The present study was designed to examine factors influencing participation and response in the initial study and to suggest strategies for improving participation in future health promotion programs. The study comprised a random sample of three groups of individuals who had been targeted for participation in the previous study: those who had (a) agreed to participate (n = 234); (b) declined participation (n = 179); and (c) failed to respond to a mailed recruitment package (n = 128). All participants completed a brief telephone survey. Key multivariate predictors of both response and participation were individuals' perceptions of the drawbacks of participating in colon cancer screening research and the degree of decisional conflict they experienced. Response was further predicted by the influence of spouses, family history of colon cancer, past knowledge of genetic testing for colon cancer, and education level. Participation was predicted by awareness that the study was supported by the Ashkenazi Jewish community, past experience with genetic testing, individuals' perceptions of the benefits of participating, and whether or not they had children. The degree to which individuals understand the purpose and nature of genetic screening research, along with their levels of decisional conflict and other psychosocial factors, may influence the likelihood of their participation in such research. Results of this study suggest a number of possible strategies for improving participation and response rates in disease prevention and detection studies.

Academic detailing to improve use of broad-spectrum antibiotics at an academic medical center.

BACKGROUND: Antibiotic misuse is common and costly and may promote antibiotic resistance. We tested the efficacy of a targeted one-on-one educational program ("academic detailing") designed to improve the appropriateness of broad-spectrum antibiotic use. METHODS: A randomized controlled trial was conducted in a large US teaching hospital. During an 18-week study period, 17 general medical, oncology, and cardiology services either received academic detailing or did not. The intervention was prompted by an order for either levofloxacin or ceftazidime that led to a computer-based review of data for that patient. Orders for the 2 target antibiotics deemed unnecessary by a priori criteria were included in the study. The primary outcome examined was the number of days that unnecessary levofloxacin or ceftazidime was administered in intervention and control groups. RESULTS: Before the trial, intervention and control services had similar prescribing patterns for the target antibiotics; the drugs were used for similar indications throughout the study period. During the intervention, there was a reduction of 37% in days of unnecessary levofloxacin or ceftazidime use per 2-week interval on services randomized to the educational intervention vs control services (P< .001). In multivariable analyses controlling for baseline prescribing and study interval, the rate of unnecessary use of the 2 target antibiotics was reduced by 41% on the intervention services compared with controls (95% confidence interval, 44%-78%; P< .001). Length of stay, intensive care unit transfers, readmission rates, and in-hospital death rates were similar in both groups (P> or =.10 for all). CONCLUSION: Targeted one-on-one education is a practical, effective, and safe method for reducing excessive broad-spectrum antibiotic use.

Determinants of tapping speed in normal control subjects and subjects with Parkinson's disease: differing effects of brief and continued practice.

BACKGROUND: Alternate tapping speed is widely used as a measure of bradykinesia in Parkinson's disease (PD). Tapping speed in normal control subjects and factors that might influence tapping speed have not been systematically examined. OBJECTIVE: To examine the effects of age, hand dominance, and gender on tapping speed in normal control subjects and to compare the effects of practice on tapping speed in normal and PD control subjects. METHODS: Tapping speed for three sequential trials in the dominant and nondominant hand was examined in 100 normal control subjects and 60 subjects with PD. The effect of hourly practice over 26 hours (19 trials) was investigated in 14 normal and 24 PD subjects. RESULTS: The speed with which normal subjects alternately tapped two counters was negatively correlated with age, was greater in the dominant hand, was not related to gender, and improved with short-term practice (three trials) and with continued practice over 26 hours. Parkinsonian subjects, in general, tapped more slowly than normal control subjects and more slowly in the more affected arm. Parkinsonian subjects benefited from short-term practice as much as normal control subjects but, unlike normal control subjects, did not improve with continued practice over 26 hours. CONCLUSIONS: Alternate tapping speed is influenced by age, hand dominance, Parkinson's disease, and practice. Subjects with PD do not benefit as much from continued practice as do normal subjects, suggesting some limitation or impairment of procedural (motor) learning in PD.

Short- and long-duration responses to levodopa during the first year of levodopa therapy.

We examined the response to 2-hour levodopa infusions in 18 Parkinson's disease subjects before starting long-term levodopa treatment and after 6 and 12 months of treatment using tapping speed as an index of bradykinesia. The long-duration response (LDR), measured as the increase in baseline (overnight without levodopa) tapping speed, increased by 29 +/- 18 at 6 months and by 35 +/- 24 at 12 months. The magnitude of the short-duration response (SDR) to a 2-hour levodopa infusion after an overnight levodopa withdrawal did not differ at 6 and 12 months (16 +/- 8 and 20 +/- 13 taps/min) from that before long-term levodopa (21 +/- taps/min). However, when levodopa was withheld for 3 days, it was evident that the SDR magnitude was increasing in magnitude (19, 23, and 31 taps/min at 0, 6, and 12 months). Duration of SDR did not change. A diurnal motor pattern with faster tapping speeds in the morning and slower in the evening was apparent on the days no levodopa was administered. These observations indicate (1) the LDR is responsible for much of the sustained response to levodopa during the first year of treatment, (2) the SDR magnitude increases but is obscured by the LDR, and (3) a diurnal pattern of motor function is present that may be partially responsible for the poorer motor function in the afternoons and evenings.

Immunoelectrochemical assays for bacteria: use of epifluorescence microscopy and rapid-scan electrochemical techniques in development of an assay for Salmonella.

Immunoelectrochemical sensors in which the sensor surface functions as both analyte capture phase and electrochemical detector have recently been developed for bacteria analysis. The speed and sensitivity of these devices make them very attractive for applications such as the detection of pathogenic microorganisms in food and water. However, the development and optimization of assays utilizing these sensors can be complicated by undesired interactions between the capture and detection functions. Modification of the sensor to achieve improvements in one function can have deleterious effects on the other function, and such effects can be difficult to diagnose and correct. In the course of investigations on immunoelectrochemical detection of Salmonella, we developed a rapid, nondestructive epifluorescence microscopy method to determine bacteria capture efficiency. This method enabled us to study capture and detection functions independently and efficiently identify performance-limiting factors. Rapid-scan electrochemical methods were used to optimize detection sensitivity and to provide diagnostic information on detection performance.

Enzyme-linked immunomagnetic electrochemical detection of Salmonella typhimurium.

There is a need for rapid methods to detect pathogenic bacteria in food products as alternatives to the current laborious and time-consuming culture procedures. We report a microbial detection technique that combines the selectivity of antibody-coated superparamagnetic beads with the rapidity and sensitivity of electrochemical detection in a format termed enzyme-linked immunomagnetic electrochemistry. In it, Salmonella typhimurium were sandwiched between antibody-coated magnetic beads and an enzyme-conjugated antibody. With the aid of a magnet, the beads (with or without bound bacteria) were localized onto the surface of disposable graphite ink electrodes in a multi-well plate format. Enzyme substrate was added and conversion of substrate to an electroactive product was measured using electrochemical detection. The electrochemical response was directly proportional to the number of captured bacteria. Using this technique, a minimum detectable level of 8 x 10(3) cells/ml of Salmonella typhimurium in buffer was achieved in ca. 80 min.

The social context of teenage childbearing: effects on the infant's care-giving environment.

PIP: 50 low-middle socioeconomic status (SES), primiparous, US Caucasian mothers and their full-term healthy infants were included in a study of the effects of maternal age and the social context on the home environment, and maternal behaviors of adolescent and older mothers, as well as the stability of the care-giving environment. At 4 months, support systems and life stress were assessed, as well as the home environment and maternal behaviors. At 2 years, a similar home visit was conducted in a subsample. Adolescent mothers had less education, lower SES, and a different child care support system. They also differed in the home environment and maternal behaviors at 4 months. Some of these differences disappeared when maternal education and SES, or child care support and life stress, were controlled. Moderate correlations were observed between 4 months and 2 years home environment and maternal verbalizations. Thus, a combination of maternal age and other social factors mediate the negative characteristics of the adolescent mother's care-giving environment, which is relatively stable during the infancy period.^ieng

Seasonal variation of aryl hydrocarbon hydroxylase activity in human lymphocytes.

A seasonal variation was observed when aryl hydrocarbon hydroxylase (AHH) activity was measured in the cultured lymphocytes of 977 donors over a period of 2 1/2 years. The variation was strongest in AHH activity induced by 3-methylcholanthrene and was less apparent for AHH activity in lymphocytes grown without any inducer. The period of the seasonal variation is 1 year, and maximal induced AHH activity occurs during late summer and early fall with minimal activity 6 months later. Based on the average of all individuals tested during the highest and lowest weeks, induced AHH activity can be as much as 10-fold higher during the peak season. It is not possible to tell from these experiments whether the seasonal variation is tissue specific, occurring only in lymphocytes, or characteristic of microsomal oxidases in other tissues as well.

Occupational exposure and cancer of the liver.

The relation between occupational exposure and cancer of the liver was investigated. Excess risk was determined for men working in the nonelectrical machinery and primary metal industries.

An investigation of the cause of death from cancer.

Four thousand seven hundred twenty-eight autopsies performed at the Roswell Park Memorial Institute were reviewed to determine causes of death from cancer. The duration of the disease from the date of diagnosis to death, the primary site of the tumor, a detailed description of the presence or absence of metastatic tumor at a series of sites, and an estimate of the total tumor mass were included in the evaluation. Twenty-three common primary sites were selected for investigation. These sites represented 99% of the total series. Nine causes of death were described. These were respiratory failure, infection, toxic drug reaction, hepatic failure, renal failure, shock or heart failure, adrenal gland failure, electrolyte imbalance, and central nervous system failure. Some of these associations were obviuosly due to the direct destruction of the organ in question. There are some differences, however, comparing lung lesions to hepatic lesions. These and other factors are recited in the text.

Aryl hydrocarbon hydroxylase in cultured lymphocytes of twins.

Measurement of aryl hydrocarbon hydroxylase (AHH) in cultured lymphocytes of 18 monozygotic and 30 dizygotic twin pairs showed that basal and induced AHH activity and AHH inducibility are heritable traits. The data are consistent with AHH inducibility being determined by a single or a very few polymorphic genes.

Questionable relation of aryl hydrocarbon hydroxylase to lung-cancer risk.

To test whether the genetically determined trait, aryl hydrocarbon hydroxylase inducibility, affects susceptibility to lung cancer, we measured this trait in cultured lymphocytes from a normal population, patients with lung cancer and progeny of such patients. We found very low aryl hydrocarbon hydroxylase activity (19 per cent of normal) in about half the patients with lung cancer. Only part of this activity can be accounted for by reduced cell growth and by reduced protein synthesis. In an indirect assessment of inducibility, both 57 progeny and 27 matched controls had a mean inducibility of 2.95 and a similar distribution into low, intermediate and high groups (chi-square = 0.3 P = 0.9). No differences in basal or induced activity were observed. Thus, if patients with lung cancer possess altered aryl hydrocarbon hydroxylase inducibility or activity these characteristics are not transmitted to their progeny.

The changing histopathology of lung cancer: a review of 1682 cases.

We have reviewed the histopathology of lung cancer patients seen over the past 13 years at RPMI. Assessment of this data indicates that adenocarcinoma is becoming progressively more prevalent as related to the other forms of lung cancer. Factors which in part may account for this increased prevalence are: 1) changes in criteria for reading histopathology of lung cancer, particularly since 1967; 2) the increased incidence of lung cancer among the female population who have a propensity for adenocarcinoma; and 3) occupational and environmental factors. In 1974 adenocarcinoma for the first time became the most prevalent type of lung cancer at RPMI. Whatever the reason, if our data are truly representative of a national trend, adenocarcinoma will soon become the most prevalent type of lung cancer in the United States. This fact may result in an increasing death rate since the present 18-month survival rate for adenocarcinoma is substantially less than for squamous cell carcinoma, which has in the past been the prevalent form of the disease. As the smoking habits of women more closely approximate those of men, we expect that the incidence and mortality of lung cancer will prove to be quite similar in both sexes.