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Primary care physicians' knowledge, attitudes and practices related to cancer screening and cancer prevention clinical trials.

Native Hawaiians have high cancer incidence and mortality rates, thus would benefit from timely cancer screening and opportunities to participate in cancer prevention clinical trials. Two-hundred-fifty-four (254) primary care physicians (PCPs) were surveyed for their knowledge, attitudes, and practices related to cancer screening and prevention, clinical trials and participation of Native Hawaiians in them. More than 90% of responding PCPs follow guidelines for breast and cervical cancer screening and counsel patients on smoking cessation, and 75% or greater follow guidelines for colonoscopy/sigmoidoscopy testing and counsel patients on exercise, diet, and weight management. About 60% reported familiarity with at least one of three prevention trials offered at the time of the survey, and 28% reported having referred or recommended patients to cancer prevention trials in the past. Major barriers to discussing trials with patients included lack of awareness on the part of physicians and patients, limited support staff, and time constraints. Less than 30% of respondents were aware of community resources supporting cancer research. This study indicated that Hawai'i PCPs follow national guidelines for cancer screening, and many are aware of ongoing prevention trials. However, additional participation in cancer screening and prevention activities will require attention to reducing logistical barriers and increasing awareness of cancer information and research services.

Attitude of Health Personnel↗

Women's preferences for reporting of Down syndrome screening results.

OBJECTIVE: The aim of this study was to determine whether women prefer the results of screening for Down syndrome tests to be reported as the risk of Down syndrome in early pregnancy at the time of the screening test or the risk at delivery (which takes into account the number of Down syndrome pregnancies that will be spontaneously lost before birth). DESIGN: A structured questionnaire. SETTING: A tertiary hospital antenatal clinic. SAMPLE: One hundred and fifteen English-speaking women who expressed an interest in having screening tests for Down syndrome performed. METHODS: A structured questionnaire exploring women's preferences for risk reporting was self administered by women attending for their first antenatal visit. MAIN OUTCOME MEASURES: Women's preference for reporting of screening test results as risk at time of test, risk at birth or both, and the reasons for this preference. RESULTS: The majority (n = 82) of women preferred to have both the risk of Down syndrome at the time of screening and at the time of birth reported. The most common reason (n = 60) given for this preference was a desire to have as much information available as possible so that an informed decision regarding further investigations could be made. CONCLUSIONS: The majority of women prefer to receive Down syndrome screening results as both the risk at the time of the test and the risk at birth.

Adolescent↗

Rapid screening with indirect immunotoxin for monoclonal antibodies against human small cell lung cancer.

For the first time, a screening procedure for antitumor monoclonal antibodies (MOABs) has been developed in which the ability of MOABs to mediate the indirect action of another immunotoxin is the primary criterion for selection of hybridomas for expansion and cloning. Use of the indirect immunotoxin makes it possible to screen MOABs for cytotoxic potential without the necessity of covalently coupling toxin to each individual MOAB. Hybridomas derived from spleens of immunized mice were screened for the synthesis of monoclonal antibodies able to participate in the delivery of a pharmacologically active, indirect immunotoxin conjugate to H69 lung cancer cells. The indirect immunotoxin conjugate was goat anti-mouse immunoglobulin disulfide linked to pokeweed antiviral protein. There was no correlation between the results of the screening with the indirect immunotoxin and an enzyme-linked immunosorbent assay screen for binding of MOAB to tumor cell membranes. An indirect immunotoxin prepared from Fab' fragments of goat anti-mouse immunoglobulin was also effective as an indirect immunotoxin conjugate. Each screening of more than 300 hybridomas was performed in 3 days. The indirect immunotoxin screen detected antitumor MOABs which were not detected by the conventional enzyme-linked immunosorbent assay method. A MOAB selected by the indirect immunotoxin screen was conjugated to pokeweed antiviral protein; the conjugate mediated immunocytotoxicity in a standard direct toxicity assay.

Animals↗

Smoking habits and risk of fatal stroke: 18 years follow up of the Oslo Study.

STUDY OBJECTIVE: To examine the risk of fatal stroke in relation to smoking habits in men screened for the Oslo study. DESIGN: The Oslo study is a prospective, cohort study of the epidemiology and preventive aspects of cardiovascular diseases in middle aged men. Screening started in May 1972 and results after 18 years of follow up are reported. PARTICIPANTS: There were 16209 men aged 40-49 years, of whom 16173 had no stroke history. Eighty five men died from stroke, of whom 48 were daily cigarettes smokers, 7 were pipe and cigar smokers, 15 smoked cigarettes and pipe or cigars daily, 11 were previous cigarette smokers, and 4 had never smoked cigarettes. MAIN RESULTS: Results of proportional hazards regression analysis adjusted for age, diastolic blood pressure, and glucose concentration showed the following rate ratios (RR) (95% confidence interval) of smoking groups compared with those who had never smoked or had previously smoked: combined cigarette and cigar or pipe smokers, RR = 6.1 (3.0, 12.5); cigarettes only, RR = 4.1 (2.3,7.4); and pipe and/or cigars only RR = 2.2 (0.9,5.5). The overall, age adjusted risk of smoking cigarettes daily was 3.5 and was found to increase with increasing cigarette consumption. Regardless of their smoking group, stroke cases had increased diastolic (DBP) and systolic blood pressure (SBP) when compared with men who had not had a stroke. The absolute differences in DBP and SBP between stroke cases and others for never and previous cigarette smokers versus daily smokers were twice as large: DBP, 12.1 mmHg versus 6.5 mmHg respectively and SBP, 16.0 mmHg versus 7.1 mmHg respectively. A high BMI increased the risk of fatal stroke of never and previous cigarette smokers. Men being treated for hypertension at the time of screening had three times the crude risk of fatal stroke of men who were not taking hypertensive treatment. CONCLUSIONS: Daily cigarette smoking increased the risk of fatal stroke three and a half times. Combined cigarette and pipe or cigar smoking had a higher risk than smoking cigarettes only. An increased risk was found in relation to increased daily cigarette consumption.

Adult↗

Precise gas chromatography with retention time locking in comprehensive toxicological screening for drugs in blood.

The long-term precision of three retention parameters, the absolute retention time (RT), the relative retention time related to dibenzepin (RRT), and the internal retention index based on the alkylfluoroaniline series (RI), were studied with 14 basic drugs on HP-5 and DB-17 columns with and without the use of the retention time locking option (RTL). Using the constant flow mode in all experiments, the RTL method was found to produce superior precision with all three retention parameters compared to the non-RTL method on each column. The results showed that RTL offers a significant advantage within a single instrument method, not only between methods, with CV<0.1% by RRT. Consequently, a dual-column gas chromatographic procedure with nitrogen-phosphorus detection was described for comprehensive screening for basic drugs in 1-ml whole blood samples. The method consisted of one-step liquid-liquid extraction with butyl acetate, identification using RRT in the RTL mode, and quantification based on single point calibration. The method allowed reliable screening and quantification of 124 basic drugs at therapeutic and toxic concentration levels in autopsy blood.

Chromatography, Gas↗

Metabolic screening.

The time-honored concept of utilization of the laboratory for screening for metabolic diseases has taken on new meaning in the face of the extensive heterogeneity of genetic diseases that has been revealed by DNA research. Some of the conditions for which screening was used in the past are now known to produce physically identifiable features so more definitive tests may be utilized for them. There remains a set of diseases that are difficult to characterize physically and it is for these that screening tests are most needed. Initial screening procedures for most of them are available in most general hospitals but comprehensive screening is usually done in biochemical genetics laboratories. Numerous and somewhat arcane bedside screening tests have been replaced by a short list of more modern procedures which are much more accurate and reliable.

Epilepsy↗

Predischarge bilirubin screening in glucose-6-phosphate dehydrogenase-deficient neonates.

OBJECTIVE: To assess the validity of predischarge serum bilirubin values in determining or predicting hyperbilirubinemia in glucose-6-phosphate dehydrogenase (G-6-PD)-deficient neonates, and to facilitate appropriate discharge planning. METHODS: Serum total bilirubin values were determined between 44 and 72 hours of life in a cohort of term, healthy neonates at high-risk for G-6-PD deficiency but with no other risk factors for hyperbilirubinemia. Percentile-based bilirubin nomograms were constructed for G-6-PD-deficient infants and normal infants according to age at sampling. The incidence of hyperbilirubinemia (serum bilirubin value > or =256 micromol/L [15 mg/dL]) for each group was determined according to the percentiles for that group. RESULTS: In both G-6-PD-deficient neonates (n = 108) and control neonates (n = 215) with serum bilirubin values <50th percentile for age, the incidence of hyperbilirubinemia was low in the G-6-PD-deficient neonates, with no measurable incidence in the controls. The incidence of hyperbilirubinemia became clinically consequential, and significantly higher in the G-6-PD-deficient groups, when the percentiles were > or =50: for those in the 50% to 74% range the incidence was moderate (23%) for the G-6-PD-deficient and small (7%) for the control infants (relative risk, 3.29; 95% confidence interval, 1.01-10.67). Among those infants > or =75th percentile, 82% of the G-6-PD-deficient infants, compared with 25% of the control infants, were either already hyperbilirubinemic at the time of screening or subsequently developed hyperbilirubinemia (relative risk, 3.23; 95% confidence interval, 1.99-5.24). CONCLUSIONS: Timed, predischarge serum bilirubin screening can be used to identify G-6-PD-deficient neonates at low, intermediate, or high-risk of developing severe neonatal hyperbilirubinemia, and thus offer a selective approach to the discharge and follow-up surveillance of these infants.

Bilirubin↗

Microalbuminuria in diabetes mellitus: efficacy of a new screening method in comparison with timed overnight urine collection.

Diabetic nephropathy and end-stage renal failure are still a major cause of mortality amongst patients with diabetes mellitus (DM). In this study, we evaluated the Clinitek-Microalbumin (CM) screening test strip for the detection of microalbuminuria (MA) in a random morning spot urine in comparison with the quantitative assessment of albuminuria in the timed overnight urine collection ("gold standard"). One hundred thirty-four children, adolescents, and young adults with insulin-dependent DM Type 1 were studied at 222 outpatient visits. Because of urinary tract infection and/or haematuria, the data of 13 visits were excluded. Finally, 165 timed overnight urine were collected in the remaining 209 visits (79% sample per visit rate). Ten (6.1%) patients presented MA of > or =15 microg/min. In comparison however, 200 spot urine could be screened (96% sample/visit rate) yielding a significant increase in compliance and screening rate (P<.001, McNemar test). Furthermore, at 156 occasions, the gold standard and CM could be directly compared. The sensitivity and the specificity for CM in the spot urine (cut-off > or =30 mg albumin/l) were 0.89 [95% confidence interval (CI) 0.56-0.99] and 0.73 (CI 0.66-0.80), respectively. The positive and negative predictive value were 0.17 (CI 0.08-0.30) and 0.99 (CI 0.95-1.00), respectively. Considering CM albumin-to-creatinine ratio, the results were poorer than with the albumin concentration alone. Using CM instead of quantitative assessment of albuminuria is not cost-effective (35 US dollars versus 60 US dollars/patient/year). In conclusion, to exclude MA, the CM used in the random spot urine is reliable and easy to handle, but positive screening results of > or =30 mg albumin/l must be confirmed by analyses in the timed overnight collected urine. Although the screening compliance is improved, in terms of analysing random morning spot urine for MA, we cannot recommend CM in a paediatric diabetic outpatient setting because the specificity is far too low.

Adolescent↗

Screening for dementia in "real world" settings: the cognitive assessment screening test: CAST.

Among elderly people who do not present with complaints of memory impairment, dementia is often missed by physicians, and time-consuming screening tests requiring expertise to administer and interpret are rarely done. Easily administered, reliable and cost effective dementia screening tests are needed for elderly individuals. The "pencil and paper" Cognitive Assessment Screening Test (CAST) takes minimal examiner time/training, and is both sensitive and specific in discriminating demented patients from healthy controls. The objectives of this study were to: (1) confirm the validity of the CAST in identifying individuals with dementia in a real-world setting (nonassisted living retirement community); (2) compare the sensitivity and specificity with other screening tests and extensive psychometric tests; and (3) assess the reliability of the CAST in test-retest conditions over time. The CAST was both sensitive and specific and showed reliability on retesting. The CAST is both simpler to administer and more accurate than other screening tests for elderly subjects.

Aged↗

[Validity of the five-word screening test for Alzheimer's disease in a population based study].

INTRODUCTION: In general medicine lack of time impairs screening for Alzheimer's disease (AD). The five word test (FWT) enables rapid assessment of verbal episodic memory in accordance with Grober and Buschke neuropsychological concept. The main steps of the FWT are: induce specific semantic processing, control of encoding to avoid attention deficits, free and cued recall. Cued recall helps to distinguish a recall impairment from storage impairment which is evocative of AD. OBJECTIVE: Evaluate FWT total score (sum of free and cued recalls), FWT total weighed score which give a higher coefficient for free recalls than cued recalls and present the ability of these two scores for AD screening. METHOD: Evaluation performed with 4116 subjects (of whom 73 MA) aged from 65 years and more, randomly selected in two French towns for the "Three Cities" Study, a population-based cohort. RESULTS: The total score was more specific than sensitive with a maximal sensitivity (Se) at 63 percent with specificity (Sp) at 91.1 percent. The total weighed score significantly increased Se (83.6 percent) with control of specificity (84.9 percent) and positive predictive value (9.1 percent). CONCLUSION: The FWT allows quick screening of patients for whom further neuropsychological evaluation is needed to diagnose AD. The ability of is simple test to screen for AD is improved by a simple weighting procedure: the total weighted score.

Aged↗

[Mass-screening for ovarian cancer by means of transvaginal ultrasonography].

Since April, 1989 in Aomori Prefecture, mass-screening for ovarian cancer by means of transvaginal ultrasonography has been performed in a mass-screening car at the same time mass-screening for uterine cervical cancer. Subjects for this screening were self referred asymptomatic women 30 years of age or older. Real time ultrasonography was performed with a 5-MHz endovaginal transducer 5 sections for scanning were established by means of a transvaginal probe and all ultrasonic pictures obtained were recorded with an 8mm VTR. For women with abnormal ultrasonic findings, such as an ovary (tumor) over 30mm in size and massive ascites, a second screening or accurate examination was performed by retransvaginal ultrasonography, CT-scan, MRI and a combination assay of tumor markers. The results were as follows: The time required for the first screening, including bimanual examination, collection of Pap smear and ultrasonic examination, was about 60-70 seconds. The total number of screened women was 15,282, and 838 (5.5%) of them needed to receive the follow-up examinations. Laparotomy has been done for 48 women to date and 2 women were found to have premalignant and malignant ovarian tumors.

Adult↗

Reconstruction of composite in-line electron holograms using a small emission cone.

We report a new method that gives atomic resolution in the reconstruction of simulated holograms in theoretical low energy electron point source (LEEPS) microscopy, and that uses a screen size that is commensurate with screen sizes used in experimental LEEPS. The method exploits the spherical symmetry in the electron waves emerging from the source. We compare holograms obtained by rotating the screen about an axis passing through the point source as opposed to rotating the atomic cluster in the opposite sense about the same axis. We show that, by generating and combining simulated holograms obtained by rotating the cluster, with the screen held fixed, a composite hologram, comprised of the individual holograms, captures enough information that atomic resolution in the reconstructions is obtained. A key feature is to choose the rotations to optimize the collective interference pattern on the composite hologram. This results in sharper resolution while using a considerably smaller screen size; results are reported for a screen size about ten times smaller than screen sizes typically used in theoretical LEEPS. The method used gives commensurate or better resolution on comparison to results obtained using the larger screen size. Possible implications for experimental LEEPS are briefly discussed.

Journal Article↗

Is atopic dermatitis predictable?

Atopic dermatitis (AD) is a common skin disease which affects 10 to 20% of the population, usually with onset during infancy. The frequency of AD appears to have increased over the past three decades. Attempts to identify parameters predictive of the development of AD have been made by many investigators during the last decades. Although genetic factors remain unmodifiable, avoidance of relevant trigger factors could modify the development of AD. This paper reviews and discusses findings of the last several years and outlines recent advances in genetic studies of AD. In spite of decades of intensive research and newly developed technology, the parental history of AD appears to be the most valuable predictive parameter. However, the predictive capacity is not sufficient to recommend it as screening instrument. At this time, a perinatal screening with the objective of primary prevention of AD does not seem feasible.

Cytokines↗

Automated auditory brainstem response in neonatal hearing screening.

Severe congenital hearing impairment is an important handicap affecting 0.1% of apparently healthy liveborn infants and 1-2% of graduates of neonatal intensive care units. The prognosis for intellectual, emotional, language and speech development in the hearing-impaired child is improved when the diagnosis is made early and intervention is begun before the age of 6 mo. Universal screening is preferable, since about 50% of infants with hearing loss are not discovered if neonatal hearing screening is restricted to high-risk groups. The automated auditory brainstem response (AABR) screener is a dedicated hearing screening device which provides information not only about the outer/middle ear and cochlea but also about the auditory pathway up to the brainstem. AABR has an agreement with conventional auditory brainstem response up to 98%. It uses a 35 dB near hearing level click. No operator interpretation is needed and it can be used on the ward and during oxygen therapy without disturbance from ambient noise. Reported referral rates in a hospital-based screening programme at the time of discharge vary, with an average of 4%. AABR has also been used in a home-based setting, with the same results. The time necessary for screening varies with the setting, but ranges from 4 to 15 min. Initial costs range from $15 to $25 per test, which is similar to neonatal screening for metabolic diseases. In addition to individual healthcare savings, early diagnosis may lead to savings on costs of intensive speech-language intervention and educational facilities.

Audiometry↗

Should we screen for familial intracranial aneurysm?

BACKGROUND AND PURPOSE: The purpose of this study was to establish whether individuals with a family history of >/=2 first-degree relatives with intracranial aneurysm should be offered screening for aneurysm. METHODS: We derived 3 theoretical models and calculated the outcomes of screening with magnetic resonance angiography (MRA) followed by digital subtraction angiography (DSA) if MRA was positive (model 1), screening with DSA alone (model 2), and not screening (model 3). Screening was repeated at intervals of 10 years, and aneurysms detected were treated surgically. We assumed a prevalence of aneurysm of 9.8% (95% CI, 8.9% to 10.6%) in the population screened, an annual rupture rate of asymptomatic aneurysm of 0.8% (95% CI, 0.4% to 1.5%), and a 75% chance of poor outcome from rupture. We assumed the sensitivity and specificity of MRA were each 90% and the risk of DSA was 0.1%. The risk of surgery was taken as 5.1%. RESULTS: Screening 1000 individuals on 3 occasions with MRA and DSA or with DSA alone followed by surgery resulted in poor outcome in 14 and 18 individuals, respectively, over 30 years. Without screening, poor outcome occurred in 15 individuals over the same period of time. CONCLUSIONS: Screening is not an effective way of reducing morbidity and mortality from ruptured intracranial aneurysm in individuals with a history of >/=2 affected first-degree relatives with ruptured intracranial aneurysm unless the expected incidence of asymptomatic aneurysm is considerably >10%.

Adult↗

Safety of AT-1015, a novel 5-HT2A antagonist, in combination with high-dose aspirin: an open-label study.

OBJECTIVE: To assess the safety of AT-1015 in combination with high-dose aspirin (300 mg daily). Study subjects were 17 healthy male volunteers. METHODS: This was an open-label, single-center study. Subjects received aspirin 300 mg once daily, alone on days 1-4, and together with AT-1015 40 mg twice daily on days 5-11. A follow-up assessment was performed on day 18. The primary outcome measure was bleeding time; secondary outcome measures were vital signs, adverse events, physical examinations, 12-lead electrocardiograms (ECG) and laboratory safety tests. RESULTS: There was a significant increase in bleeding time between screening and the end of the aspirin-only period (mean bleeding time 4.8 vs 7.6 min, p = 0.01), but there were no further significant increases during the combination treatment period. The most common adverse events were dry mouth, epistaxis, gingival bleeding and abdominal pain. All treatment-related adverse events were mild in severity and no major bleeding episodes occurred. There were no clinically significant changes in vital signs, physical examinations, 12-lead ECGs or laboratory safety tests. CONCLUSIONS: AT-1015 was safe and well-tolerated in healthy male volunteers when taken in combination with high-dose aspirin, and did not significantly prolong bleeding time compared with aspirin alone.

Administration, Oral↗

Diabetic retinopathy screening model for rural population: awareness and screening methodology.

CONTEXT: Worldwide, the prevalence of diabetic retinopathy is increasing at an alarming rate. WHO has predicted that in India the number of adults with diabetes will be the highest in the world: from 19 million in 1995 to 80 million in 2030. Although originally thought to be a disease of an urban population, the prevalence of diabetes mellitus is increasing in rural areas as well. The socioeconomic burden resulting from visual impairment or blindness caused by diabetic retinopathy, particularly in the working age group, is a serious concern. ISSUE: In order to combat diabetic retinopathy related blindness, Sankara Nethralaya, the premier eye institute of India, in collaboration with the Lions Clubs International Foundation (LCIF) and the RD Tata Trust, Mumbai, India launched a major diabetic retinopathy screening program in the rural community of South India. The objectives were to create awareness among the rural population of diabetic retinopathy with emphasis on early detection, to conduct diabetes and diabetic retinopathy screening camps, and to bring to the base hospital patients who have sight-threatening diabetic retinopathy, for ancillary investigations such as fluorescein angiography, ultrasound and to perform laser photocoagulation or vitreous surgery, or both. Other objectives included training general ophthalmologists and general physicians in order to develop an integrated diabetic retinopathy model. To address the question as to why certain individuals run the risk of developing sight threatening diabetic retinopathy, biochemical and genetic factors were also studied. The program was launched in June 2003 and 3 rural districts have been screened. To the time of writing, 128 screening camps had been organized, 103 awareness meetings conducted, 23 ophthalmologists trained and 43 general physicians attended the continuing medical education program on diabetic retinopathy. LESSONS: The key elements in the successful implementation of this program have been a team approach, involvement of community leaders and voluntary organizations, and support of the district and state administrators.

Adult↗

[Gestational diabetes: new approaches to an old and growing problem].

Gestational diabetes is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy. Gestational Diabetes generally disappears as soon as the pregnancy is terminated. The prevalence of gestational diabetes is 2% to 13%, depending on the genetic characteristics and environment of the population under study. Classic risk factors identify a population of women at risk of gestational diabetes (obesity, family history of diabetes, or previous poor obstetric history); however, these risk factors identify only 60% of women diagnosed as having gestational diabetes. Therefore, it is necessary to screen all pregnant women, regardless of history, for gestational diabetes. The optimal time to screen for gestational diabetes in pregnancy is between 24 and 28 weeks of gestation. The screening test consist of 50 g of oral glucose followed by a plasma determination at 1 hour. If the plasma glucose 1 hour after the oral load is > or = 140 mg/dl, a glucose tolerance test is indicated. The goal of management (diet, insulin and exercise) of the gestational diabetic women is to maintain normoglycemia, needed to avoid complications for the fetus and mother.

Algorithms↗