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Showing papers on "Mass screening published in 2011"


Journal ArticleDOI
08 Jun 2011-JAMA
TL;DR: Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality.
Abstract: Context Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality. Objective To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Design, Setting, and Participants Randomized controlled trial of 78 216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39 105) or usual care (n = 39 111) at 10 screening centers across the United States between November 1993 and July 2001. Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median [range], 12.4 years [10.9-13.0 years]) for cancer diagnoses and death until February 28, 2010. Main Outcome Measures Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures. Results Ovarian cancer was diagnosed in 212 women (5.7 per 10 000 person-years) in the intervention group and 176 (4.7 per 10 000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10 000 person-years) in the intervention group and 100 deaths (2.6 per 10 000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10 000 person-years) in the intervention group and 2914 deaths (76.2 per 10 000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06). Conclusions Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. Trial Registration clinicaltrials.gov Identifier: NCT00002540

1,073 citations


Journal ArticleDOI
TL;DR: The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer.
Abstract: The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5% It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest The NLST is such a trial The rationale for and design of the NLST are presented

1,036 citations


Journal ArticleDOI
27 Jan 2011-PLOS ONE
TL;DR: This is the first large series to demonstrate a composition change in the microbiota of colon cancer patients with possible impact on mucosal immune response and 80% of all sequences could be assigned to a total of 819 taxa based on default parameter of Classifier software.
Abstract: The composition of the human intestinal microbiota is linked to health status. The aim was to analyze the microbiota of normal and colon cancer patients in order to establish cancer-related dysbiosis. Patients and Methods: Stool bacterial DNA was extracted prior to colonoscopy from 179 patients: 60 with colorectal cancer, and 119 with normal colonoscopy. Bacterial genes obtained by pyrosequencing of 12 stool samples (6 Normal and 6 Cancer) were subjected to a validated Principal Component Analysis (PCA) test. The dominant and subdominant bacterial population (C. leptum, C. coccoides, Bacteroides/Prevotella, Lactobacillus/Leuconostoc/Pediococcus groups, Bifidobacterium genus, and E. coli, and Faecalibacterium prausnitzii species) were quantified in all individuals using qPCR and specific IL17 producer cells in the intestinal mucosa were characterized using immunohistochemistry. Findings: Pyrosequencing (Minimal sequence 200 nucleotide reads) revealed 80% of all sequences could be assigned to a total of 819 taxa based on default parameter of Classifier software. The phylogenetic core in Cancer individuals was different from that in Normal individuals according to the PCA analysis, with trends towards differences in the dominant and subdominant families of bacteria. Consequently, All-bacteria [log(10) (bacteria/g of stool)] in Normal, and Cancer individuals were similar [11.88 +/- 0.35, and 11.80 +/- 0.56, respectively, (P = 0.16)], according to qPCR values whereas among all dominant and subdominant species only those of Bacteroides/Prevotella were higher (All bacteria-specific bacterium; P = 0.009) in Cancer (-1.04 +/- 0.55) than in Normal (-1.40 +/- 0.83) individuals. IL17 immunoreactive cells were significantly expressed more in the normal mucosa of cancer patients than in those with normal colonoscopy. Conclusion: This is the first large series to demonstrate a composition change in the microbiota of colon cancer patients with possible impact on mucosal immune response. These data open new filed for mass screening and pathophysiology investigations.

699 citations


Journal ArticleDOI
TL;DR: The natural history and cervical carcinogenicity of HPV is summarized, the promise and uncertainties of currently available screening methods are discussed, and the greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment.
Abstract: Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment.

655 citations


Journal ArticleDOI
TL;DR: In many countries, centralization of vascular surgical services has largely been driven by the improved outcomes of elective aneurysm surgery in specialized centers, the widespread adoption of endovascular techniques, and the introduction of screening programs.
Abstract: Abdominal aortic aneurysms (AAAs) are found in up to 8% of men aged >65 years, yet usually remain asymptomatic until they rupture. Rupture of an AAA and its associated catastrophic physiological insult carries overall mortality in excess of 80%, and 2% of all deaths are AAA-related. Pathologically, AAAs are associated with inflammation, smooth muscle cell apoptosis, and matrix degradation. Once thought to be a consequence of advanced atherosclerosis, accruing evidence indicates that AAAs are a focal representation of a systemic disease of the vasculature. Risk factors for AAAs include increasing age, male sex, smoking, and low HDL-cholesterol levels. Familial associations exist and although susceptibility genes have been described on the basis of candidate-gene studies, robust genetic studies have failed to discover causative gene mutations. The surgical management of AAAs has been revolutionized by minimally invasive endovascular repair. Ongoing randomized trials will establish whether endovascular repair confers a survival advantage over open surgery for patients with a ruptured AAA. In many countries, centralization of vascular surgical services has largely been driven by the improved outcomes of elective aneurysm surgery in specialized centers, the widespread adoption of endovascular techniques, and the introduction of screening programs.

644 citations


Journal ArticleDOI
TL;DR: Advances in treatment that have seen the introduction of a new generation of chemotherapy agents, a proven advantage to adjuvant chemotherapy after complete resection for specific stage groups, new techniques for the planning and administration of radiotherapy, and new surgical approaches to assess and reduce the risks of surgical treatment are described.

587 citations


Journal ArticleDOI
TL;DR: The clinical and genetic features of VHL disease are reviewed, the molecular pathogenesis is reviewed and clinical management and tumour surveillance strategies are outlined.
Abstract: The autosomal dominantly inherited disorder von Hippel–Lindau disease (VHL) is caused by germline mutations in the VHL tumour suppressor gene (TSG). VHL mutations predispose to the development of a variety of tumours (most commonly retinal and central nervous system haemangioblastomas, clear cell renal carcinoma and phaeochromocytomas). Here, we review the clinical and genetic features of VHL disease, briefly review the molecular pathogenesis and outline clinical management and tumour surveillance strategies.

553 citations


Journal ArticleDOI
TL;DR: Prostate-specific antigen-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary.
Abstract: This systematic review was conducted to inform an update of U.S. Preventive Services Task Force recommendations on prostate cancer screening. The authors searched MEDLINE and Cochrane databases fro...

524 citations


Journal ArticleDOI
TL;DR: For women aged 30 years and older in routine clinical practice who are negative by co-testing (both HPV and cytology), 3-year screening intervals were safe because a single negative test for HPV was sufficient to reassure against cervical cancer over 5 years.
Abstract: Summary Background Concurrent testing for human papillomavirus (HPV) and cervical cytology (co-testing) is an approved alternative to cytology alone in women aged 30 years and older. We aimed to assess the safety in routine clinical practice of 3-year screening intervals for women testing negative for HPV with normal cytology and to assess if co-testing can identify women at high risk of cervical cancer or cervical intraepithelial neoplasia grade 3 (CIN3) or worse over 5 years. Methods We assessed the 5-year cumulative incidence, starting in 2003–05, of cervical cancer and CIN3 or worse for 331 818 women aged 30 years and older who enrolled in co-testing at Kaiser Permanente Northern California (Berkeley, CA, USA) and had adequate enrolment co-test results. Follow-up continued until Dec 31, 2009. We defined cumulative incidence to include prevalence at enrolment and incidence after enrolment. Prevalence at enrolment was defined as the ratio of women diagnosed with each outcome on the biopsy visit immediately after their enrolment screening visit to the total enrolled women. At screening visits only HPV test and Pap smear samples were collected, and at biopsy visits colposcopically directed biopsies were taken. To estimate post-enrolment incidence, we used Weibull survival models. Findings In 315 061 women negative by HPV testing, the 5-year cumulative incidence of cancer was 3·8 per 100 000 women per year, slightly higher than for the 306 969 who were both negative by HPV and Pap testing (3·2 per 100 000), and half the cancer risk of the 319 177 who were negative by Pap testing (7·5 per 100 000). 313 465 (99·5%) women negative by HPV testing had either normal cytology or equivocal abnormalities. Abnormal cytology greatly increased cumulative incidence of CIN3 or worse over 5 years for the 16 757 positive by HPV testing (12·1% vs 5·9%; p vs 0·16%; p=0·004). 12 208 (73%) of the women positive by HPV testing had no cytological abnormality, and these women had 258 (35%) of 747 CIN3 or adenocarcinoma in situ, 25 (29%) of 87 cancers, and 17 (63%) of 27 adenocarcinomas. Interpretation For women aged 30 years and older in routine clinical practice who are negative by co-testing (both HPV and cytology), 3-year screening intervals were safe because a single negative test for HPV was sufficient to reassure against cervical cancer over 5 years. Incorporating HPV testing with cytology also resulted in earlier identification of women at high risk of cervical cancer, especially adenocarcinoma. Testing for HPV without adjunctive cytology might be sufficiently sensitive for primary screening for cervical cancer. Funding Intramural Research Program of the US National Cancer Institute/NIH/DHHS, and the American Cancer Society.

519 citations



Journal ArticleDOI
TL;DR: The current ACS guidelines are summarized, the anticipated impact of new health care reform legislation on cancer screening is described, and recent public debates over the comparative effectiveness of different colorectal cancer screening tests are discussed.
Abstract: Each year the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, a report on data and trends in cancer screening rates, and select issues related to cancer screening. This article summarizes the current ACS guidelines, describes the anticipated impact of new health care reform legislation on cancer screening, and discusses recent public debates over the comparative effectiveness of different colorectal cancer screening tests. The latest data on the utilization of cancer screening from the National Health Interview Survey is described, as well as several recent reports on the role of health care professionals in adult utilization of cancer screening.

Journal ArticleDOI
TL;DR: On behalf of all coauthors of the safety paper, they apologize to the scientific community, and provide a revised 13-item screening questionnaire, which should replace the previous one.

Journal ArticleDOI
TL;DR: An intervention to promote early intensive management of patients with type 2 diabetes was associated with a small, non-significant reduction in the incidence of cardiovascular events and death.

Journal ArticleDOI
TL;DR: The ATHENA study as mentioned in this paper evaluated the performance of carcinogenic human papillomavirus (HPV) testing and genotyping compared with liquid-based cytology for cervical cancer screening in a large US population aged 21 years and older.
Abstract: Summary Background The ATHENA study was designed to assess the performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping compared with liquid-based cytology for cervical cancer screening in a large US population aged 21 years and older. We did a subanalysis of this population to compare the screening performance of the cobas HPV test versus liquid-based cytology in women aged 25 years and older, and assess management strategies for HPV-positive women. Methods Women aged 25 years or older who were attending routine cervical screening were enrolled from 61 clinical centres in 23 US states. Cervical specimens were obtained for liquid-based cytology and HPV DNA testing with two first-generation assays (Amplicor HPV test and Linear Array HPV genotyping test) and the second-generation cobas HPV test (with individual HPV16 and HPV18 detection). Colposcopy and diagnostic biopsies were done on women with atypical squamous cells of undetermined significance (ASC-US) or worse cytology, those who tested positive with either first-generation HPV test, and a random sample of women who tested negative for HPV and cytology. All women not selected for colposcopy received their results and exited the study. Participants and colposcopists were masked to cytology and HPV test results until the colposcopy visit was completed. The primary endpoint for this substudy was histologically confirmed cervical intraepithelial neoplasia grade 3 (CIN3) or worse. This study is registered with ClinicalTrials.gov, number NCT00709891; the study is in the follow-up phase, which is due to be completed in December, 2012. Findings From May 27, 2008, to Aug 27, 2009, 47 208 women were enrolled, of whom 41 955 met our eligibility criteria. Valid cobas HPV and liquid-based cytology test results were available for 40 901 women (97%), who were included in this analysis. Of these, 4275 women (10%) tested cobas HPV positive and 2617 (6%) had abnormal cytology. 431 women were diagnosed with CIN2 or worse and 274 with CIN3 or worse. In women who had colposcopy, the cobas HPV test was more sensitive than liquid-based cytology for detection of CIN3 or worse (252/274 [92·0%, 95% CI 88·1–94·6] vs 146/274 [53·3%, 95% CI 47·4–59·1]; difference 38·7%, 95% CI 31·9–45·5; p vs 4275/40 901) compared with HPV testing alone. As a triage test to identify CIN3 or worse in HPV-positive women, detection of HPV16, HPV18, or both alone was equivalent to detection of ASC-US or worse alone in terms of sensitivity (150/252 [59·5%] vs 133/252 [52·8%]; p=0·11) and positive predictive value (PPV) (150/966 [15·5%] vs 133/940 [14·1%]; p=0·20). Among HPV-positive women, detection of HPV16, HPV18, or both or low-grade squamous intraepithelial lesion or worse cytology had better sensitivity (182/252 [72·2%]; p Interpretation HPV testing with separate HPV16 and HPV18 detection could provide an alternative, more sensitive, and efficient strategy for cervical cancer screening than do methods based solely on cytology. Funding Roche Molecular Systems.

Journal ArticleDOI
TL;DR: (see Appendix 2, available at [www.cmaj.ca/lookup/suppl/doi:10.1503/cmaja.090313/-/DC1] for summary of recommendations and clinical considerations)
Abstract: (see Appendix 2, available at [www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.090313/-/DC1][1] for summary of recommendations and clinical considerations) There are more than 200 million international migrants worldwide,[1][2] and this movement of people has implications for individual and

Journal ArticleDOI
TL;DR: Offspring of postnatally depressed mothers are at increased risk for depression by 16 years of age, partially explained by within child vulnerability established in infancy and the early years, and by exposure to family adversity.
Abstract: Objective The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers. Method This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702 mothers were screened, and probable cases interviewed. In all, 58 depressed mothers (95% of identified cases) and 42 nondepressed controls were recruited. A total of 93% were assessed through to 16-year follow-up. The main study outcome was offspring lifetime clinical depression (major depression episode and dysthymia) by 16 years, assessed via interview at 8, 13, and 16 years. It was analysed in relation to postnatal depression, repeated measures of child vulnerability (insecure infant attachment and lower childhood resilience), and family adversity. Results Children of index mothers were more likely than controls to experience depression by 16 years (41.5% versus 12.5%; odds ratio=4.99; 95% confidence interval=1.68–14.70). Lower childhood resilience predicted adolescent depression, and insecure infant attachment influenced adolescent depression via lower resilience (model R 2 = 31%). Family adversity added further to offspring risk (expanded model R 2 = 43%). Conclusions Offspring of postnatally depressed mothers are at increased risk for depression by 16 years of age. This may be partially explained by within child vulnerability established in infancy and the early years, and by exposure to family adversity. Routine screening for postnatal depression, and parenting support for postnatally depressed mothers, might reduce offspring developmental risks for clinical depression in childhood and adolescence.

Journal ArticleDOI
TL;DR: A simple, standardized tuberculosis screening rule for resource-constrained settings is reported, to identify people living with HIV who need further investigation for TB disease.
Abstract: Background: The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule. Methods and Findings: We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%–90.9%) and specificity was 49.6% (95% CI 29.2%–70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%–96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%–94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%–98.0%) and 90.0% (95% CI 88.6%–91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%). Conclusions: Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT. Please see later in the article for the Editors’ Summary.

Journal ArticleDOI
TL;DR: This guideline is applicable to both the management of smoking and the use of smoking cessation medications in patients with a history of alcohol or substance abuse.
Abstract: Competing interests: Marcello Tonelli, Michel Joffres, James Dickinson, Harminder Singh, Gabriela Lewin and Richard Birtwhistle have received support for travel to meetings from the Public Health Agency of Canada. Gabriela Lewin is an employee of Kemptville District Hospital. No other competing interests were declared. This article has been peer reviewed. Contributors: All of the authors made substantial contributions to the conception and design of the article, the acquisition, analysis and interpretation of data, drafted the article and revised it critically for important intellectual content and approved the final version submitted for publication. Funding: Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada and the Canadian Institutes of Health Research. The views of the funding bodies have not influenced the content of the guideline; competing interests have been recorded and addressed. The views expressed in this article are those of the authors and do not represent those of the Public Health Agency of Canada. Guidelines writing group: Marcello Tonelli, Sarah Connor Gorber, Michel Joffres, James Dickinson, Harminder Singh, Gabriela Lewin, Richard Birtwhistle. Systematic review writing group: Donna Fitzpatrick-Lewis, Nicole Hodgson, Donna Ciliska, Marcello Tonelli, Mary Gauld, Yan Yun Liu.

Journal ArticleDOI
TL;DR: The epidemiological and biological understanding of the natural history of HPV infection is examined, with an eye toward using these studies to guide the implementation of cervical cancer prevention strategies.
Abstract: The discovery that certain high-risk strains of human papillomavirus (HR-HPV) cause nearly 100% of invasive cervical cancer has spurred a revolution in cervical cancer prevention by promoting the development of viral vaccines. Although the efficacy of these vaccines has already been demonstrated, a complete understanding of viral latency and natural immunity is lacking, and solving these mysteries could help guide policies of cervical cancer screening and vaccine use. Here, we examine the epidemiological and biological understanding of the natural history of HPV infection, with an eye toward using these studies to guide the implementation of cervical cancer prevention strategies.

Journal ArticleDOI
TL;DR: M mammography screening should be personalized on the basis of a woman's age, breast density, history of breast biopsy, family history of Breast Cancer Prevention, and beliefs about the potential benefit and harms of screening.
Abstract: The optimal timing and frequency of screening mammography are controversial. This analysis found that the cost-effectiveness of screening mammography depended on a woman's age, breast density, fami...

Journal ArticleDOI
TL;DR: The results suggest that the PQ-B may be used as an effective, efficient self-report screen for prodromal psychosis syndromes when followed by diagnostic interview, in a two-stage evaluation process in help-seeking populations.

Journal ArticleDOI
TL;DR: The incidence of sudden death of athletes in this study is within the range reported by others, however, mandatory ECG screening of athletes had no apparent effect on their risk for cardiac arrest.

Journal ArticleDOI
TL;DR: It is found that pre-ART screening with Xpert MTB/RIF increased tuberculosis case detection by 45% compared to smear microscopy in HIV-positive patients at high risk of TB risk.
Abstract: Background The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown. Methods and Findings Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/µl; interquartile range, 102–236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%). Conclusions In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal. Please see later in the article for the Editors' Summary

Journal ArticleDOI
TL;DR: Randomised controlled trials of interventions to increase uptake/informed uptake of cervical cancer screening assessed the effectiveness of invitational and educational interventions, counselling, risk factor assessment and procedural interventions.
Abstract: Background This is an update of the Cochrane review published in Issue 5, 2011. Worldwide, cervical cancer is the fourth commonest cancer affecting women. High-risk human papillomavirus (HPV) infection is causative in 99.7% of cases. Other risk factors include smoking, multiple sexual partners, the presence of other sexually transmitted diseases and immunosuppression. Primary prevention strategies for cervical cancer focus on reducing HPV infection via vaccination and data suggest that this has the potential to prevent nearly 90% of cases in those vaccinated prior to HPV exposure. However, not all countries can afford vaccination programmes and, worryingly, uptake in many countries has been extremely poor. Secondary prevention, through screening programmes, will remain critical to reducing cervical cancer, especially in unvaccinated women or those vaccinated later in adolescence. This includes screening for the detection of pre-cancerous cells, as well as high-risk HPV. In the UK, since the introduction of the Cervical Screening Programme in 1988, the associated mortality rate from cervical cancer has fallen. However, worldwide, there is great variation between countries in both coverage and uptake of screening. In some countries, national screening programmes are available whereas in others, screening is provided on an opportunistic basis. Additionally, there are differences within countries in uptake dependent on ethnic origin, age, education and socioeconomic status. Thus, understanding and incorporating these factors in screening programmes can increase the uptake of screening. This, together with vaccination, can lead to cervical cancer becoming a rare disease. Objectives To assess the effectiveness of interventions aimed at women, to increase the uptake, including informed uptake, of cervical screening. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 6, 2020. MEDLINE, Embase and LILACS databases up to June 2020. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) of interventions to increase uptake/informed uptake of cervical screening. Data collection and analysis Two review authors independently extracted data and assessed risk of bias. Where possible, the data were synthesised in a meta-analysis using standard Cochrane methodology. Main results Comprehensive literature searches identified 2597 records; of these, 70 met our inclusion criteria, of which 69 trials (257,899 participants) were entered into a meta-analysis. The studies assessed the effectiveness of invitational and educational interventions, lay health worker involvement, counselling and risk factor assessment. Clinical and statistical heterogeneity between trials limited statistical pooling of data. Overall, there was moderate-certainty evidence to suggest that invitations appear to be an effective method of increasing uptake compared to control (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.49 to 1.96; 141,391 participants; 24 studies). Additional analyses, ranging from low to moderate-certainty evidence, suggested that invitations that were personalised, i.e. personal invitation, GP invitation letter or letter with a fixed appointment, appeared to be more successful. More specifically, there was very low-certainty evidence to support the use of GP invitation letters as compared to other authority sources' invitation letters within two RCTs, one RCT assessing 86 participants (RR 1.69 95% CI 0.75 to 3.82) and another, showing a modest benefit, included over 4000 participants (RR 1.13, 95 % CI 1.05 to 1.21). Low-certainty evidence favoured personalised invitations (telephone call, face-to-face or targeted letters) as compared to standard invitation letters (RR 1.32, 95 % CI 1.11 to 1.21; 27,663 participants; 5 studies). There was moderate-certainty evidence to support a letter with a fixed appointment to attend, as compared to a letter with an open invitation to make an appointment (RR 1.61, 95 % CI 1.48 to 1.75; 5742 participants; 5 studies). Low-certainty evidence supported the use of educational materials (RR 1.35, 95% CI 1.18 to 1.54; 63,415 participants; 13 studies) and lay health worker involvement (RR 2.30, 95% CI 1.44 to 3.65; 4330 participants; 11 studies). Other less widely reported interventions included counselling, risk factor assessment, access to a health promotion nurse, photo comic book, intensive recruitment and message framing. It was difficult to deduce any meaningful conclusions from these interventions due to sparse data and low-certainty evidence. However, having access to a health promotion nurse and attempts at intensive recruitment may have increased uptake. One trial reported an economic outcome and randomised 3124 participants within a national screening programme to either receive the standard screening invitation, which would incur a fee, or an invitation offering screening free of charge. No difference in the uptake at 90 days was found (574/1562 intervention versus 612/1562 control, (RR 0.94, 95% CI: 0.86 to 1.03). The use of HPV self-testing as an alternative to conventional screening may also be effective at increasing uptake and this will be covered in a subsequent review. Secondary outcomes, including cost data, were incompletely documented. The majority of cluster-RCTs did not account for clustering or adequately report the number of clusters in the trial in order to estimate the design effect, so we did not selectively adjust the trials. It is unlikely that reporting of these trials would impact the overall conclusions and robustness of the results. Of the meta-analyses that could be performed, there was considerable statistical heterogeneity, and this should be borne in mind when interpreting these findings. Given this and the low to moderate evidence, further research may change these findings. The risk of bias in the majority of trials was unclear, and a number of trials suffered from methodological problems and inadequate reporting. We downgraded the certainty of evidence because of an unclear or high risk of bias with regards to allocation concealment, blinding, incomplete outcome data and other biases. Authors' conclusions There is moderate-certainty evidence to support the use of invitation letters to increase the uptake of cervical screening. Low-certainty evidence showed lay health worker involvement amongst ethnic minority populations may increase screening coverage, and there was also support for educational interventions, but it is unclear what format is most effective. The majority of the studies were from developed countries and so the relevance of low- and middle-income countries (LMICs), is unclear. Overall, the low-certainty evidence that was identified makes it difficult to infer as to which interventions were best, with exception of invitational interventions, where there appeared to be more reliable evidence.

Journal ArticleDOI
TL;DR: The HADS anxiety subscale performed worse than the total and the depression subscales for both indicators but was consistently superior for depression screening than for screening of any mental disorder.
Abstract: The Hospital Anxiety and Depression Scale (HADS) is the most extensively validated scale for screening emotional distress in cancer patients. However, thresholds for clinical decision making vary widely across studies. A meta-analysis was conducted with the aim of identifying optimal, empirically derived cut-offs. PubMed, Embase, and PsycINFO databases were searched for studies that compared the HADS total and its subscale scores against a semi-structured or structured clinical interview as a reference standard with regard to its screening efficacy for any mental disorders and depressive disorders alone. Separate pooled analyses were conducted for single or two adjacent thresholds. A total of 28 studies (inter-rater agreement, κ = 0.86) were included. The best thresholds for screening for mental disorders were 10 or 11 on the HADS total (sensitivity 0.80; specificity 0.74), 5 on the HADS depression subscale (sensitivity 0.84; specificity 0.50), and 7 or 8 on the HADS anxiety subscale (sensitivity 0.73; specificity 0.65). Respective thresholds for depression screening were 15 for the HADS total (sensitivity 0.87; specificity 0.88), 7 for the HADS depression subscale (sensitivity 0.86; specificity 0.81), and 10 or 11 for the HADS anxiety subscale (sensitivity 0.63; specificity 0.83). The HADS anxiety subscale performed worse than the total and the depression subscales for both indicators. Diagnostic accuracy varied widely by threshold but was consistently superior for depression screening than for screening of any mental disorder.

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TL;DR: In community populations such as the SHHS, high specificities may be more useful in excluding low-risk patients, while avoiding false positives, however, sleep clinicians may prefer to use screening tools with high sensitivities, like the STOP-Bang, in order to avoid missing cases that may lead to adverse health consequences and increased healthcare costs.
Abstract: Study Objective: The Epworth Sleepiness Scale (ESS) has been used to detect patients with potential sleep disordered breathing (SDB). Recently, a 4-Variable screening tool was proposed to identify patients with SDB, in addition to the STOP and STOP-Bang questionnaires. This study evaluated the abilities of the 4-Variable screening tool, STOP, STOP-Bang, and ESS questionnaires in identifying subjects at risk for SDB.

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TL;DR: Despite greater awareness and treatment of depression in primary care settings, the prevalence of depressive Symptoms remains high, treatment levels remain low, and control of depressive symptoms are suboptimal.
Abstract: Background:Depression remains a major public health problem that is most often evaluated and treated in primary care settings. The objective of this study was to examine the prevalence, treatment, and control of depressive symptoms in a national data sample using a common primary care screening tool for depression. Methods:We analyzed a sample of adults (n = 4836) from 2005 to 2008 National Health and Nutrition Examination Survey data. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9) to determine the overall prevalence, rates of treatment, and antidepressant control of mild, moderate, moderately severe, and severe depressive symptoms. Results:Of the sample, 20.1% reported significant depressive symptoms (PHQ-9) score, ≥5), the majority of whom had mild depressive symptoms (PHQ-9) score, 5–9). Even among individuals with severe depressive symptoms, a large percentage (36.9%) received no treatment from a mental health professional or with antidepressant medication. Of those taking antidepressants, 26.4% reported mild depressive symptoms and 18.8% had moderate, moderately severe, or severe depressive symptoms. Conclusions:Despite greater awareness and treatment of depression in primary care settings, the prevalence of depressive symptoms remains high, treatment levels remain low, and control of depressive symptoms are suboptimal. Primary care providers need to continue to focus their efforts on diagnosing and effectively treating this important disease.

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TL;DR: It is found that programs that took a comprehensive approach (i.e., incorporated multiple program components, including institutional support) were successful in increasing IPV screening and disclosure/identification rates, and four program components appeared to increase provider self-efficacy for screening.

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TL;DR: This study shows that dogs can be trained to detect PCa by smelling urine with a significant success rate and suggests that PCa gives an odor signature to urine.

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TL;DR: The Malaria Eradication Research Agenda (malERA) Consultative Group on Diagnoses and Diagnostics outline a research and development agenda to provide the diagnosis and diagnostic tools required for malaria eradication.
Abstract: Many of malaria's signs and symptoms are indistinguishable from those of other febrile diseases. Detection of the presence of Plasmodium parasites is essential, therefore, to guide case management. Improved diagnostic tools are required to enable targeted treatment of infected individuals. In addition, field-ready diagnostic tools for mass screening and surveillance that can detect asymptomatic infections of very low parasite densities are needed to monitor transmission reduction and ensure elimination. Antibody-based tests for infection and novel methods based on biomarkers need further development and validation, as do methods for the detection and treatment of Plasmodium vivax. Current rapid diagnostic tests targeting P. vivax are generally less effective than those targeting Plasmodium falciparum. Moreover, because current drugs for radical cure may cause serious side effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, more information is needed on the distribution of G6PD-deficiency variants as well as tests to identify at-risk individuals. Finally, in an environment of very low or absent malaria transmission, sustaining interest in elimination and maintaining resources will become increasingly important. Thus, research is required into the context in which malaria diagnostic tests are used, into diagnostics for other febrile diseases, and into the integration of these tests into health systems.