Pilot Study Of Screening Research Articles

Implementation of Multicolor Melt Curve Analysis for High-Risk Human Papilloma Virus Detection in Low- and Middle-Income Countries: A Pilot Study for Expanded Cervical Cancer Screening in Honduras.

PurposeCervical cancer is a leading cause of cancer-related mortality in low- and middle-income countries (LMICs) and screening in LMICs is extremely limited. We aimed to implement on-site high-risk human papillomavirus (hrHPV) DNA testing in cohorts of women from an urban factory and from a rural village.MethodsA total of 802 women were recruited for this study in partnership with La Liga Contra el Cancer through the establishment of women’s health resource fairs at two locations in Honduras: a textile factory (n = 401) in the city of San Pedro Sula and the rural village of El Rosario (n = 401) in Yoro. Participants received a routine cervical examination during which three sterile cytobrushes were used to collect cervical samples for testing. hrHPV genotyping was performed using a hrHPV genotyping assay and a real-time polymerase chain reaction instrument.ResultshrHPV status across all participants at both sites was 13% hrHPV positive and 67% hrHPV negative. When hrHPV status was compared across all three testing sites, hrHPV-positive rates were approximately equal among the factory (13%), village (12%), and confirmatory testing at Dartmouth-Hitchcock Medical Center (Lebanon, NH; 14%). hrHPV genotype was compared across sites, with HPV16 showing the highest infection rate (15%), followed by HPV59 (12%), and HPV68 (11%). There was a low prevalence of HPV18 observed in both populations compared with the hrHPV-positive population in the United States.ConclusionIn collaboration with oncologists and pathologists from La Liga Contra el Cancer, we were able to provide a continuum of care once health-fair testing was performed. We established a method and implementation plan for hrHPV testing that is sustainable in LMICs.

The AURORA pilot study for molecular screening of patients with advanced breast cancer\u2013a study of the breast international group

Several studies have demonstrated the feasibility of molecular screening of tumour samples for matching patients with cancer to targeted therapies. However, most of them have been carried out at institutional or national level. Herein, we report on the pilot phase of AURORA (NCT02102165), a European multinational collaborative molecular screening initiative for advanced breast cancer patients. Forty-one patients were prospectively enroled at four participating centres across Europe. Metastatic tumours were biopsied and profiled using an Ion Torrent sequencing platform at a central facility. Sequencing results were obtained for 63% of the patients in real-time with variable turnaround time stemming from delays between patient consent and biopsy. At least one clinically actionable mutation was identified in 73% of patients. We used the Illumina sequencing technology for orthogonal validation and achieved an average of 66% concordance of substitution calls per patient. Additionally, copy number aberrations inferred from the Ion Torrent sequencing were compared to single nucleotide polymorphism arrays and found to be 59% concordant on average. Although this study demonstrates that powerful next generation genomic techniques are logistically ready for international molecular screening programs in routine clinical settings, technical challenges remain to be addressed in order to ensure the accuracy and clinical utility of the genomic data.

A single institution pilot study for universal Lynch syndrome screening: A key step towards statewide screening and care

A single institution pilot study for universal Lynch syndrome screening: A key step towards statewide screening and care

Fragile X Newborn Screening: Lessons Learned From a Multisite Screening Study.

Delays in the diagnosis of children with fragile X syndrome (FXS) suggest the possibility of newborn screening as a way to identify children earlier. However, FXS does not have a proven treatment that must be provided early, and ethical concerns have been raised about the detection of infants who are carriers. This article summarizes major findings from a multisite, prospective, longitudinal pilot screening study. Investigators in North Carolina, California, and Illinois collaborated on a study in which voluntary screening for FXS was offered to parents in 3 birthing hospitals. FXS newborn screening was offered to >28 000 families to assess public acceptance and determine whether identification of babies resulted in any measurable harms or adverse events. Secondary goals were to determine the prevalence of FMR1 carrier gene expansions, study the consent process, and describe early development and behavior of identified children. A number of publications have resulted from the project. This article summarizes 10 "lessons learned" about the consent process, reasons for accepting and declining screening, development and evaluation of a decision aid, prevalence of carriers, father participation in consent, family follow-up, and maternal reactions to screening. The project documented public acceptance of screening as well as the challenges inherent in obtaining consent in the hospital shortly after birth. Collectively, the study provides answers to a number of questions that now set the stage for a next generation of research to determine the benefits of earlier identification for children and families.

Faecal occult blood screening for colorectal cancer in Serbia: a pilot study.

Colorectal cancer (CRC) is becoming a major public health problem in the Republic of Serbia. Organized mass screening has been shown to decrease CRC mortality and even its incidence. The aim of this study was to assess the acceptability of a faecal immunochemical test for haemoglobin proposed by primary care physicians. From August to November 2013, a pilot study for CRC screening was organized in individuals aged 50 to 74 years. The study included 50 primary healthcare centres from all 25 administrative regions of Serbia. A qualitative immunochromatographic faecal immunochemical test for human haemoglobin detection was used. Overall, 50 894 individuals were invited. The participation rate was 67.8 and 3.4% of the tests were positive. Among individuals with a positive test, 69.7% agreed to undergo colonoscopy. The positive predictive value was 27.1% for adenoma and 14.6% for carcinoma. This was the first CRC screening project encompassing approximately one-third of primary healthcare facilities in all regions across the country. It showed a good response of the target population and satisfactory cooperation of the healthcare professionals involved.

A new mutation found in newborn screening for Fabry disease evaluated by plasma globotriaosylsphingosine levels

A pilot study of newborn screening for Fabry disease was performed in Okinawa, Japan. A total of 2,443 neonates were screened using dried blood spot samples over 7 years starting in 2007. Of 13 neonates determined to have low α-galactosidase A (GLA) activity, one boy had a new missense mutation, p.G144D of the GLA gene. This mutation was considered to be a late-onset type, as evaluated based on plasma globotriaosylsphingosine levels and family history.

The DanCavas Pilot Study of Multifaceted Screening for Subclinical Cardiovascular Disease in Men and Women Aged 65–74 Years

This pilot study of a large population based randomised screening trial investigated feasibility, acceptability, and relevance (prevalence of clinical and subclinical cardiovascular disease [CVD] and proportion receiving insufficient prevention) of a multifaceted screening for CVD. In total, 2060 randomly selected Danish men and women aged 65–74 years were offered (i) low dose non-contrast computed tomography to detect coronary artery calcification (CAC) and aortic/iliac aneurysms; (ii) detection of atrial fibrillation (AF); (iii) brachial and ankle blood pressure measurements; and (iv) blood levels of cholesterol and hemoglobin A1c. Web based self booking and data management was used to reduce the administrative burden. Attendance rates were 64.9% (n = 678) and 63.0% (n = 640) for men and women, respectively. In total, 39.7% received a recommendation for medical preventive actions. Prevalence of aneurysms was 12.4% (95% confidence interval [CI] 9.9–14.9) in men and 1.1% (95% CI 0.3–1.9) in women, respectively (p < .001). A CAC score > 400 was found in 37.8% of men and 11.3% of women (p < .001), along with a significant increase in median CAC score with age (p = .03). Peripheral arterial disease was more prevalent in men (18.8%, 95% CI 15.8–21.8) than in women (11.2%, 95% CI 8.7–13.6). No significant differences between the sexes were found with regard to newly discovered AF (men 1.3%, women 0.5%), potential hypertension (men 9.7%, women 11.5%), hypercholesterolemia (men 0.9%, women 1.1%) or diabetes mellitus (men 2.1%, women 1.3%). Owing to the higher prevalence of severe conditions, such as aneurysms and CAC ≥ 400, screening for CVD seemed more prudent in men than women. The attendance rates were acceptable compared with other screening programs and the logistical structure of the screening program proved successful.

PSYCHOLOGICAL CHARACTERISTICS IN PATIENTS WITH CHRONIC HEART FAILURE WAITING FOR HEART TRANSPLANTATION

Introduction. Numerous studies have established the role of psychological factors in the development, treatment, prognosis of the cardiovascular diseases, as well as in formation of compliance and the quality of patients’ lives. However, few of any psychological studies of patients with chronic heart failure (CHF) waiting for transplantation were carried out, despite the obvious need for reliable psychosocial assessments in the preoperative period and development of psychological support programs. In view of the foregoing, a pilot screening study aimed at assessing the state of the cognitive and affective spheres, personal characteristics of patients with CHFwaiting for the HTas wellanalyzing the relationship between psychological, medical and biological characteristics of patients. Material and methods. 30 patients withCHF took part in the study at theFederal State-Funded Institution «Federal Almazov North-West Medical Research Centre» (Saint-Petersburg). The authors’ structured interviews and psychodiagnostic methods were used in the study: «The index of well-being», (WHO, 1999), «The Brief Neuropsychological Cognitive Examination» (BNCE), «The Zung Self-Rating Depression Scale» (SDS), «The State-Trait Anxiety Inventory» (STAI), «Test the Big Five» (BIG V). Statistical data processing was performed using the Mann–Whitney U criterion and the Spearman correlation (SPSS v. 20.0). Results . Absence of violations of cognitive functions was revealed in 23 % of respondents, mild degree of cognitive deficiency – in 60 %, average degree – in 17 %. The lowest average scores were obtained in the BNCE subtests, reflecting the success of active attention, visual-spatial memory, psychomotorics, abstract thinking.The average group index of depression was 45.9±7.2 (normative level). A detailed analysis showed that absence of signs of depression occurred in 74 % of patients, subdepression – in 23 %, moderately expressed depression – in 3 %. In the entire sample, the average level of situational anxiety prevailed (42.4±6.8) with personal anxiety (39.7±8.1). According to the averaged scales of the BIG V questionnaire, moderately pronounced extroversion features predominated in the patient’s personality structure. The relationship between BNCE indices and duration of chronic HF (r = –0.676, p &lt;0.001) was revealed. A statistically significant reduction in the overall level of cognitive function in patients with concomitant diabetes mellitus was found in comparison with patients without it (U = 61) at p = 0.033; According to the data of SDS depressive symptoms in patients with IHD are more pronounced in comparison with patients with dilated cardiomyopathy U = 47 (p = 0.019).

Lysosomal storage diseases.

Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage can be caused not by the enzymatic deficiency of one of the hydrolases, but by the deficiency of an activator protein, as occurs in the AB variant of GM2 gangliosidosis. Still other times, the accumulated lysosomal material results from failed egress of a small molecule as a consequence of a deficient transporter, as in cystinosis or Salla disease. In the last couple of decades, enzyme replacement therapy has become available for a number of lysosomal storage diseases. Examples include imiglucerase, taliglucerase and velaglucerase for Gaucher disease, laronidase for Hurler disease, idursulfase for Hunter disease, elosulfase for Morquio disease, galsulfase for Maroteaux-Lamy disease, alglucosidase alfa for Pompe disease, and agalsidase alfa and beta for Fabry disease. In addition, substrate reduction therapy has been approved for certain disorders, such as eliglustat for Gaucher disease. The advent of treatment options for some of these disorders has led to newborn screening pilot studies, and ultimately to the addition of Pompe disease and Hurler disease to the Recommended Uniform Screening Panel (RUSP) in 2015 and 2016, respectively.

Commentary on: “The DanCavas Pilot Study of Multifaceted Screening for Subclinical Cardiovascular Disease in Men and Women Aged 65–74 Years”

Commentary on: “The DanCavas Pilot Study of Multifaceted Screening for Subclinical Cardiovascular Disease in Men and Women Aged 65–74 Years”

The DanCavas Pilot Study of Multifaceted Screening for Subclinical Cardiovascular Disease in Men and Women Aged 65–74 Years

This pilot study of a large population based randomised screening trial investigated feasibility, acceptability, and relevance (prevalence of clinical and subclinical cardiovascular disease [CVD] and proportion receiving insufficient prevention) of a multifaceted screening for CVD. In total, 2060 randomly selected Danish men and women aged 65-74 years were offered (i) low dose non-contrast computed tomography to detect coronary artery calcification (CAC) and aortic/iliac aneurysms; (ii) detection of atrial fibrillation (AF); (iii) brachial and ankle blood pressure measurements; and (iv) blood levels of cholesterol and hemoglobin A1c. Web based self booking and data management was used to reduce the administrative burden. Attendance rates were 64.9% (n=678) and 63.0% (n=640) for men and women, respectively. In total, 39.7% received a recommendation for medical preventive actions. Prevalence of aneurysms was 12.4% (95% confidence interval [CI] 9.9-14.9) in men and 1.1% (95% CI 0.3-1.9) in women, respectively (p<.001). A CAC score > 400 was found in 37.8% of men and 11.3% of women (p<.001), along with a significant increase in median CAC score with age (p=.03). Peripheral arterial disease was more prevalent in men (18.8%, 95% CI 15.8-21.8) than in women (11.2%, 95% CI 8.7-13.6). No significant differences between the sexes were found with regard to newly discovered AF (men 1.3%, women 0.5%), potential hypertension (men 9.7%, women 11.5%), hypercholesterolemia (men 0.9%, women 1.1%) or diabetes mellitus (men 2.1%, women 1.3%). Owing to the higher prevalence of severe conditions, such as aneurysms and CAC≥400, screening for CVD seemed more prudent in men than women. The attendance rates were acceptable compared with other screening programs and the logistical structure of the screening program proved successful.

A pilot study of routine screening for distress by a nurse and psychologist in an outpatient haematological oncology clinic

AimTo explore the: 1) prevalence of distress, type of problems experienced by haematological patients, and referrals for supportive care; 2) effect of demographic and clinical variables on distress, and 3) effect on the time of health professionals conducting the screening in the ambulatory chemotherapy setting. MethodsParticipants completed the National Comprehensive Cancer Network Distress Thermometer and Problem List and had a follow-up screening discussion with a health professional. ResultsOf 68 participants, 40% reported significant distress (≥4) on the Distress Thermometer (mean 3.2, SD 2.4). All patients reported physical problems and 72% reported emotional problems—the major contributors to distress and to time spent with the health professional. Distress was unrelated to age, gender or cancer type. Patients were less likely to have significant distress at the end of treatment than at the beginning (OR=0.15, 95% CI: 0.03; 0.72,). Forty patients (59%) were referred to supportive services. The psychologist spent less time with patients compared to the nurse (18 vs 48min, p<0.001). The more emotional problems reported, the greater the time spent with the patient (rs=0.34, p=0.009). ConclusionsNurses can appropriately screen for distress and address significant distress reported by haematology patients undergoing chemotherapy without over burdening the nurse or patient.

The DANCAVAS Pilot Study of Multifaceted Screening for Subclinical Cardiovascular Disease in Men and Women Aged 65–74

The DANCAVAS Pilot Study of Multifaceted Screening for Subclinical Cardiovascular Disease in Men and Women Aged 65–74

Running ahead of doping: analytical advances and challenges faced by modern laboratories ahead of Rio 2016.

Running ahead of doping: analytical advances and challenges faced by modern laboratories ahead of Rio 2016.

Prescription Opioid Misuse Among Rural Community Pharmacy Patients: Pilot Study for Screening and Implications for Future Practice and Research

Background: Opioid misuse imposes a disproportionately heavy burden on individuals living in rural areas. Community pharmacy has the potential to expand and coordinate with health professionals to identify and intervene with those who misuse opioids. Objective: Rural and urban community pharmacy patients were recruited in this pilot project to describe and compare patterns of opioid misuse. Methods: We administered a health screening survey in 4 community pharmacies among patients filling opioid medications. Univariate statistics were used to assess differences in health characteristics and opioid medication misuse behaviors between rural and urban respondents. Multivariable statistics were used to identify risk factors associated with rural and urban opioid misuse. Results: A total of 333 participants completed the survey. Participants in rural settings had poorer overall health, higher pain levels, lower education, and a higher rate of unemployment compared to patients in urban pharmacies. Rural respondents with illicit drug use (adjustable odds ratio [aOR]: 14.34, 95% confidence interval [CI] = 2.16-95.38), posttraumatic stress disorder (aOR: 5.44, 95% CI = 1.52-19.50), and ≤high school education (aOR: 6.68, 95% CI = 1.06-42.21) had increased risk for opioid misuse. Conclusions: Community pharmacy represents a promising resource for potential identification of opioid misuse, particularly in rural communities. Continued research must extend these findings and work to establish collaborative services in rural settings.

Inborn errors of metabolism detectable by tandem mass spectrometry in Egypt: The first newborn screening pilot study.

To estimate the burden of metabolic disorders detectable by tandem mass spectrometry in Egypt, through a pilot expanded newborn screening programme at Cairo University Children's Hospital in 2008, and examining the results of 3,900 clinically at-risk children, investigated at Cairo University Children's Hospital for the same disorders over the past 7 years using the same technology. Dried blood spots of 25,276 healthy newborns from three governorates in Upper, Middle, and Lower Egypt were screened, to give a representative sample of the Egyptian newborn population. Based on the pilot study outcomes and the results of clinically suspected children, we estimated the total birth prevalence of tandem mass spectrometry detectable metabolic disorders, and the relative frequency of several individual disorders. Among the healthy newborns, 13 metabolic disorder cases (five phenylketonuria [1:5,000], two methylmalonic acidemia, and isovaleric acidemia [1:12,500], one each of maple syrup urine disease, propionic acidemia, β-ketothiolase deficiency, and primary carnitine deficiency [1:25,000]) were confirmed, giving a total birth prevalence of 1:1944 live births. Among the clinically suspected children, 235 cases were diagnosed, representing a much wider disease spectrum. Egypt has one of the highest reported birth prevalence rates for metabolic disorders detectable by tandem mass spectrometry. Early diagnosis and management are crucial for the survival and well-being of affected children. A nationwide NBS programme by tandem mass spectrometry is recommended.

Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry.

BackgroundThere is current expansion of newborn screening (NBS) programs to include lysosomal storage disorders because of the availability of treatments that produce an optimal clinical outcome when started early in life.ObjectiveTo evaluate the performance of a multiplex-tandem mass spectrometry (MS/MS) enzymatic activity assay of 6 lysosomal enzymes in a NBS laboratory for the identification of newborns at risk for developing Pompe, Mucopolysaccharidosis-I (MPS-I), Fabry, Gaucher, Niemann Pick-A/B, and Krabbe diseases.Methods and ResultsEnzyme activities (acid α-glucosidase (GAA), galactocerebrosidase (GALC), glucocerebrosidase (GBA), α-galactosidase A (GLA), α-iduronidase (IDUA) and sphingomyeline phosphodiesterase-1 (SMPD-1)) were measured on ~43,000 de-identified dried blood spot (DBS) punches, and screen positive samples were submitted for DNA sequencing to obtain genotype confirmation of disease risk. The 6-plex assay was efficiently performed in the Washington state NBS laboratory by a single laboratory technician at the bench using a single MS/MS instrument. The number of screen positive samples per 100,000 newborns were as follows: GAA (4.5), IDUA (13.6), GLA (18.2), SMPD1 (11.4), GBA (6.8), and GALC (25.0).DiscussionA 6-plex MS/MS assay for 6 lysosomal enzymes can be successfully performed in a NBS laboratory. The analytical ranges (enzyme-dependent assay response for the quality control HIGH sample divided by that for all enzyme-independent processes) for the 6-enzymes with the MS/MS is 5- to 15-fold higher than comparable fluorimetric assays using 4-methylumbelliferyl substrates. The rate of screen positive detection is consistently lower for the MS/MS assay compared to the fluorimetric assay using a digital microfluidics platform.

A three-tier algorithm for guanidinoacetate methyltransferase (GAMT) deficiency newborn screening.

Guanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine biosynthesis presenting with epilepsy and developmental delay in infancy. Excellent developmental outcomes have been reported for infants treated from birth due to a family history. The BC Newborn Screening Program initiated a 3year pilot screening study for GAMT deficiency to evaluate the performance of a novel three-tiered screening approach. Over 36months all bloodspots submitted for routine newborn screening were included in the pilot study (de-identified). Initial GAA measurement was integrated into the standard acylcarnitine/amino acid first-tier assay. All samples with elevated GAA were subjected to second-tier GAA analysis by LC-MS/MS integrated into an existing branched-chain amino acid (MSUD) method. GAMT gene sequencing was completed on the original bloodspot for all specimens with elevated GAA on the second-tier test. The protocol allowed for re-identification for treatment of any specimen with one or two likely pathogenic GAMT mutations. Over the study period 135,372 specimens were tested with 259 (0.19%) over the first-tier GAA cut-off. The second-tier assay removed an interference falsely elevating GAA levels, and only 3 samples required genotyping. No mutations were identified in any samples, all were deemed negative screens and no follow-up was initiated. A three-tier algorithm for GAMT newborn screening showed excellent test performance with zero false positives. No cases were detected, supporting a low incidence for this disorder. Given the low incremental costs and evidence of positive outcomes with early intervention, GAMT deficiency remains an excellent candidate for newborn screening.

A pilot study for newborn screening of metachromatic leukodystrophy

A pilot study for newborn screening of metachromatic leukodystrophy

Clinical trial to implementation: Cost and effectiveness considerations for scaling up cervical cancer screening in low- and middle-income countries

Cervical cancer is preventable and early diagnosis is possible using low-cost technologies. Despite the strong evidence base for cervical cancer screening programs, their implementation has been slow in limited-resource countries where the cancer burden is high. In this study we provide a framework for systematically evaluating costs and effectiveness in order to translate clinical study findings to guide implementation of screening programs to maximize benefits in the real-world setting. Comparing the total cost of screening can be misleading, as the resources expended on specific program activities can have direct impact across multiple dimensions including access, quality, and adherence to care; these dimensions, in turn, can affect both overall health care cost and program effectiveness. Therefore, it is important to use activity-based costs and detailed performance indicators to evaluate both screening trials and pilot studies to ensure that large-scale implementation projects are designed and optimally resourced to achieve targeted program effectiveness and outcomes.