Ethnic variations in the prevalence of diabetic retinopathy in people with diabetes attending screening in the United Kingdom (DRIVE UK)

Aims

To compare the prevalence of diabetic retinopathy (DR) in people of various ethnic groups with diabetes in the United Kingdom (UK).

Methods

The Diabetic Retinopathy In Various Ethnic groups in UK (DRIVE UK) Study is a cross-sectional study on the ethnic variations of the prevalence of DR and visual impairment in two multi-racial cohorts in the UK. People on the diabetes register in West Yorkshire and South East London who were screened, treated or monitored between April 2008 to July 2009 (London) or August 2009 (West Yorkshire) were included in the study. Data included age, sex, ethnic group, type of diabetes, presenting visual acuity and the results of grading of diabetic retinopathy. Prevalence estimates for the ethnic groups were age-standardised to the white European population for comparison purposes.

Results

Out of 57,144 people on the two diabetic registers, data were available on 50,285 individuals (88.0%), of these 3,323 had type 1 and 46,962 had type 2 diabetes. In type 2 diabetes, the prevalence of any DR was 38.0% (95% confidence interval(CI) 37.4% to 38.5%) in white Europeans compared to 52.4% (51.2% to 53.6%) in African/Afro-Caribbeans and 42.3% (40.3% to 44.2%) in South Asians. Similarly, sight threatening DR was also significantly more prevalent in Afro-Caribbeans (11.5%, 95% CI 10.7% to 12.3%) and South Asians (10.3%, 9.0% to 11.5%) compared to white Europeans (5.5%, 5.3% to 5.8%). Differences observed in Type 1 diabetes did not achieve conventional levels of statistical significance, but there were lower numbers for these analyses.

Conclusions

Minority ethnic communities with type 2 diabetes in the UK are more prone to diabetic retinopathy, including sight-threatening retinopathy and maculopathy compared to white Europeans.     

SDOCT imaging to identify macular pathology in patients diagnosed with diabetic maculopathy by a digital photographic retinal screening programme

Introduction

Diabetic macular edema (DME) is an important cause of vision loss. England has a national systematic photographic retinal screening programme to identify patients with diabetic eye disease. Grading retinal photographs according to this national protocol identifies surrogate markers for DME. We audited a care pathway using a spectral-domain optical coherence tomography (SDOCT) clinic to identify macular pathology in this subset of patients.

Methods

A prospective audit was performed of patients referred from screening with mild to moderate non-proliferative diabetic retinopathy (R1) and surrogate markers for diabetic macular edema (M1) attending an SDOCT clinic. The SDOCT images were graded by an ophthalmologist as SDOCT positive, borderline or negative. SDOCT positive patients were referred to the medical retina clinic. SDOCT negative and borderline patients were further reviewed in the SDOCT clinic in 6 months.

Results

From a registered screening population of 17 551 patients with diabetes mellitus, 311 patients met the inclusion criteria between (March 2008 and September 2009). We analyzed images from 311 patients’ SDOCT clinic episodes. There were 131 SDOCT negative and 12 borderline patients booked for revisit in the OCT clinic. Twenty-four were referred back to photographic screening for a variety of reasons. A total of 144 were referred to ophthalmology with OCT evidence of definite macular pathology requiring review by an ophthalmologist.

Discussion

This analysis shows that patients with diabetes, mild to moderate non-proliferative diabetic retinopathy (R1) and evidence of diabetic maculopathy on non-stereoscopic retinal photographs (M1) have a 42.1% chance of having no macular edema on SDOCT imaging as defined by standard OCT definitions of DME when graded by a retinal specialist. SDOCT imaging is a useful adjunct to colour fundus photography in screening for referable diabetic maculopathy in our screening population.     

Human Papillomavirus Genotype Distribution in Czech Women and Men with Diseases Etiologically Linked to HPV

Background

The HPV prevalence and genotype distribution are important for the estimation of the impact of HPV-based cervical cancer screening and HPV vaccination on the incidence of diseases etiologically linked to HPVs. The HPV genotype distribution varies across different geographical regions. Therefore, we investigated the type-specific HPV prevalence in Czech women and men with anogenital diseases.

Methods

We analyzed 157 squamous cell carcinoma samples, 695 precancerous lesion samples and 64 cervical, vulvar and anal condylomata acuminate samples. HPV detection and typing were performed by PCR with GP5+/6+ primers, reverse line blot assay and sequencing.

Results

Thirty different HPV genotypes were detected in our study, HPV 16 being the most prevalent type both in precancerous lesions (45%) and squamous cell carcinomas (59%). In benign lesions, HPV 6 (72%) was the most common type. Altogether, 61% of carcinoma samples and 43% of precancerous lesion samples contained HPV 16 and/or 18. The presence of HPV types related to the vaccinal ones (HPV 31, 45, 33, 52, 58) were detected in 16% of carcinoma samples and 18% of precancerous lesion samples. HPV 16 and/or 18 were present in 76% of cervical cancer samples, 33% of CIN1, 43% CIN2 and 71% of CIN3 samples. HPV types 6 and/or 11 were detected in 84% samples of condylomata acuminate samples.

Conclusions

The prevalence of vaccinal and related HPV types in patients with HPV-associated diseases in the Czech Republic is very high. We may assume that the implementation of routine vaccination against HPV would greatly reduce the burden of HPV-associated diseases in the Czech Republic.     

Extracting diagnoses and investigation results from unstructured text in electronic health records by semi-supervised machine learning

Background

Electronic health records are invaluable for medical research, but much of the information is recorded as unstructured free text which is time-consuming to review manually.

Aim

To develop an algorithm to identify relevant free texts automatically based on labelled examples.

Methods

We developed a novel machine learning algorithm, the ‘Semi-supervised Set Covering Machine’ (S3CM), and tested its ability to detect the presence of coronary angiogram results and ovarian cancer diagnoses in free text in the General Practice Research Database. For training the algorithm, we used texts classified as positive and negative according to their associated Read diagnostic codes, rather than by manual annotation. We evaluated the precision (positive predictive value) and recall (sensitivity) of S3CM in classifying unlabelled texts against the gold standard of manual review. We compared the performance of S3CM with the Transductive Vector Support Machine (TVSM), the original fully-supervised Set Covering Machine (SCM) and our ‘Freetext Matching Algorithm’ natural language processor.

Results

Only 60% of texts with Read codes for angiogram actually contained angiogram results. However, the S3CM algorithm achieved 87% recall with 64% precision on detecting coronary angiogram results, outperforming the fully-supervised SCM (recall 78%, precision 60%) and TSVM (recall 2%, precision 3%). For ovarian cancer diagnoses, S3CM had higher recall than the other algorithms tested (86%). The Freetext Matching Algorithm had better precision than S3CM (85% versus 74%) but lower recall (62%).

Conclusions

Our novel S3CM machine learning algorithm effectively detected free texts in primary care records associated with angiogram results and ovarian cancer diagnoses, after training on pre-classified test sets. It should be easy to adapt to other disease areas as it does not rely on linguistic rules, but needs further testing in other electronic health record datasets.     

Neuropathic pain and psychological morbidity in patients with treated leprosy: a cross-sectional prevalence study in Mumbai

Background

Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated.

Methodology/Principal Findings

Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity.

Conclusions/Significance

One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity.     

Microbleed detection using automated segmentation (MIDAS): a new method applicable to standard clinical MR images

Background

Cerebral microbleeds, visible on gradient-recalled echo (GRE) T2* MRI, have generated increasing interest as an imaging marker of small vessel diseases, with relevance for intracerebral bleeding risk or brain dysfunction.

Methodology/Principal Findings

Manual rating methods have limited reliability and are time-consuming. We developed a new method for microbleed detection using automated segmentation (MIDAS) and compared it with a validated visual rating system. In thirty consecutive stroke service patients, standard GRE T2* images were acquired and manually rated for microbleeds by a trained observer. After spatially normalizing each patient''s GRE T2* images into a standard stereotaxic space, the automated microbleed detection algorithm (MIDAS) identified cerebral microbleeds by explicitly incorporating an “extra” tissue class for abnormal voxels within a unified segmentation-normalization model. The agreement between manual and automated methods was assessed using the intraclass correlation coefficient (ICC) and Kappa statistic. We found that MIDAS had generally moderate to good agreement with the manual reference method for the presence of lobar microbleeds (Kappa = 0.43, improved to 0.65 after manual exclusion of obvious artefacts). Agreement for the number of microbleeds was very good for lobar regions: (ICC = 0.71, improved to ICC = 0.87). MIDAS successfully detected all patients with multiple (≥2) lobar microbleeds.

Conclusions/Significance

MIDAS can identify microbleeds on standard MR datasets, and with an additional rapid editing step shows good agreement with a validated visual rating system. MIDAS may be useful in screening for multiple lobar microbleeds.     

Seeking clarity within cloudy effluents: differentiating fungal from bacterial peritonitis in peritoneal dialysis patients

Background

Fungal peritonitis is a serious complication of peritoneal dialysis (PD) therapy with the majority of patients ceasing PD permanently. The aims of this study were to identify risk factors and clinical associations that may discriminate between fungal from bacterial peritonitis.

Methods

We retrospectively identified episodes of fungal peritonitis from 2001–2010 in PD patients at Liverpool and Westmead Hospitals (Australia). Fungal peritonitis cases were matched in a 1∶2 ratio with patients with bacterial peritonitis from each institution''s dialysis registry, occurring closest in time to the fungal episode. Patient demographic, clinical and outcome data were obtained from the medical records.

Results

Thirty-nine episodes of fungal peritonitis (rate of 0.02 episodes per patient-year of dialysis) were matched with 78 episodes of bacterial peritonitis. Candida species were the commonest pathogens (35/39; 90% episodes) with Candida albicans (37%), Candida parapsilosis (32%) and Candida glabrata (13%) the most frequently isolated species. Compared to bacterial peritonitis, fungal peritonitis patients had received PD for significantly longer (1133 vs. 775 catheter-days; p = 0.016), were more likely to have had previous episodes of bacterial peritonitis (51% vs. 10%; p = 0.01), and to have received prior antibacterial therapy (51% vs. 10%; p = 0.01). Patients with fungal peritonitis were less likely to have fever and abdominal pain on presentation, but had higher rates of PD catheter removal (79% vs. 22%; p<0.005), and permanent transfer to haemodialysis (87% vs. 24%; p<0.005). Hospital length of stay was significantly longer in patients with fungal peritonitis (26.1 days vs. 12.6 days; p = 0.017), but the all-cause 30-day mortality rate was similar in both groups. Fluconazole was a suitable empiric antifungal agent; with no Candida resistance detected.

Conclusion

Prompt recognition of clinical risk factors, initiation of antifungal therapy and removal of PD catheters are key considerations in optimising outcomes.     

Mechanisms of esophago-pharyngeal acid regurgitation in human subjects

Esophago-pharyngeal regurgitation is implicated in various otolaryngologic and respiratory disorders. The pathophysiological mechanisms causing regurgitation are still largely unknown.

Aim

To determine the principal mechanisms behind esophago-pharyngeal regurgitation.

Methods

We studied 11 patients with extra-esophageal GORD symptoms in whom esophago-pharyngeal acid regurgitation had previously been demonstrated using ambulatory, dual (pharyngo-esophageal) pH metry (>2 episodes/day using previously validated pH-metric criteria). Patients underwent continuous, 24 hr, stationary monitoring of pharyngo-esophageal manometry and dual (pharyngeal and esophageal) pH recordings. They were intubated with a 14-channel manometric assembly incorporating 2 sleeve sensors monitoring the upper and lower esophageal sphincters simultaneously. A dual pH catheter recorded pH signals 2 cm above the UES midpoint and 7 cm above the LES midpoint.

Results

A total of 32 episodes of spontaneous esophago-pharyngeal acid regurgitation were recorded. All episodes occurred in the upright posture and 91% occurred within 3 hrs post-prandium. All regurgitation events were associated with a relaxation of the UES, which were classified as transient non-swallow related relaxations in 29 (91%) and swallow-related in the remaining 3 (9%). Straining was an additional associated factor in 41% of regurgitation events, but strain alone was not sufficient to cause esophago-pharyngeal regurgitation.

Conclusion

Some form of active UES relaxation is necessary for regurgitation to occur. The dominant mechanism underlying esophago-pharyngeal acid regurgitation is the non-swallow related, transient UES relaxation.

Level of Evidence

N/A     

Trends in breast cancer mortality in Sweden before and after implementation of mammography screening

Background

Incidence-based mortality modelling comparing the risk of breast cancer death in screened and unscreened women in nine Swedish counties has suggested a 39% risk reduction in women 40 to 69 years old after introduction of mammography screening in the 1980s and 1990s.

Objective

We evaluated changes in breast cancer mortality in the same nine Swedish counties using a model approach based on official Swedish breast cancer mortality statistics, robust to effects of over-diagnosis and treatment changes. Using mortality data from the NordCan database from 1974 until 2003, we estimated the change in breast cancer mortality before and after introduction of mammography screening in at least the 13 years that followed screening start.

Results

Breast mortality decreased by 16% (95% CI: 9 to 22%) in women 40 to 69, and by 11% (95% CI: 2 to 20%) in women 40 to 79 years of age.

Discussion

Without individual data it is impossible to completely separate the effects of improved treatment and health service organisation from that of screening, which would bias our results in favour of screening. There will also be some contamination of post-screening mortality from breast cancer diagnosed prior to screening, beyond our attempts to adjust for delayed benefit. This would bias against screening. However, our estimates from publicly available data suggest considerably lower benefits than estimates based on comparison of screened versus non-screened women.     

Screening for future cardiovascular disease using age alone compared with multiple risk factors and age

Background

Risk factors such as blood pressure and serum cholesterol are used, with age, in screening for future cardiovascular disease (CVD) events. The value of using these risk factors with age compared with using age alone is not known. We compared screening for future CVD events using age alone with screening using age and multiple risk factors based on regular Framingham risk assessments.

Methods

Ten-year CVD risk was estimated using Framingham risk equations in a hypothetical sample population of 500,000 people aged 0–89 years. Risk estimates were used to identify individuals who did and did not have a CVD event over a ten-year period. For screening using age alone (age screening) and screening using multiple risk factors and age (Framingham screening) we estimated the (i) detection rate (sensitivity); (ii) false–positive rate; (iii) proportion of CVD-free years of life lost in affected individuals with positive results (person-years detection rate); and (iv) cost per CVD-free life year gained from preventive treatment.

Results

Age screening using a cut-off of 55 years detected 86% of all first CVD events arising in the population every year and 72% of CVD-free years of life lost for a 24% false-positive rate; for five yearly Framingham screening the false-positive rate was 21% for the same 86% detection rate. The estimated cost per CVD-free year of life gained was £2,000 for age screening and £2,200 for Framingham screening if a Framingham screen costs £150 and the annual cost of preventive treatment is £200.

Conclusion

Age screening for future CVD events is simpler than Framingham screening with a similar screening performance and cost-effectiveness. It avoids blood tests and medical examinations. The advantages of age screening in the prevention of heart attack and stroke warrant considering its use in preference to multiple risk factor screening.     

Knowledge and acceptability of pap smears, self-sampling and HPV vaccination among adult women in Kenya

Objectives

Our study aimed to assess adult women’s knowledge of human papillomavirus (HPV) and cervical cancer, and characterize their attitudes towards potential screening and prevention strategies.

Methods

Women were participants of an HIV-discordant couples cohort in Nairobi, Kenya. An interviewer-administered questionnaire was used to obtain information on sociodemographic status, and sexual and medical history at baseline and on knowledge and attitudes towards Pap smears, self-sampling, and HPV vaccination at study exit.

Results

Only 14% of the 409 women (67% HIV-positive; median age 29 years) had ever had a Pap smear prior to study enrollment and very few women had ever heard of HPV (18%). Although most women knew that Pap smears detect cervical cancer (69%), very few knew that routine Pap screening is the main way to prevent ICC (18%). Most women reported a high level of cultural acceptability for Pap smear screening and a low level of physical discomfort during Pap smear collection. In addition, over 80% of women reported that they would feel comfortable using a self-sampling device (82%) and would prefer at-home sample collection (84%). Nearly all women (94%) reported willingness to be vaccinated to prevent cervical cancer if offered at no or low cost.

Conclusions

These findings highlight the need to educate women on routine use of Pap smears in the prevention of cervical cancer and demonstrate that vaccination and self-sampling would be acceptable modalities for cervical cancer prevention and screening.     

Screening for acute childhood malnutrition during the National Nutrition Week in mali increases treatment referrals

Objective

To evaluate a pilot intervention designed to integrate mid-upper arm circumference (MUAC) screening for acute malnutrition into the semi-annual Child Nutrition Week (Semaine d''Intensification des Activités de Nutrition, or “SIAN”) activities carried out in June 2008.

Design

A cross-sectional survey was conducted in Kolokani and Nara, two health districts in the Koulikoro region of Mali, 4–5 months after the SIAN, using a population-proportionate, multi-stage random sample of: 1) health centers, and 2) households in communities linked to each of the selected health centers. Caregivers of 1543 children who were 6–59 months of age at the time of the SIAN, 17 community-based volunteers and 45 health center staff members were interviewed.

Results

A total of 1278 children 6–59 months (83% of those studied) reportedly participated in SIAN. Of the participating children, 1258 received vitamin A (98% of SIAN participants; 82% of all eligible children), 945 received anti-helminth tablets (84% of participants; 71% of eligibles), and 669 were screened for acute malnutrition (52% of participants; 43% of eligibles). 186 of the children screened (27%) were reportedly identified as acutely malnourished. SIAN screening covered a significantly greater proportion of children than were examined in both community-based (22% of children) and health center-based screening activities (5% of children) combined during the 4-5 months after the SIAN (P<0.0001). In general, community volunteers and health personnel positively evaluated their experience adding MUAC screening to SIAN.

Conclusion

Integrating MUAC screening for acute malnutrition in SIAN permits the assessment of a large number of children for acute malnutrition, and should be continued.     

Automated detection of external ventricular and lumbar drain-related meningitis using laboratory and microbiology results and medication data

Objective

Monitoring of healthcare-associated infection rates is important for infection control and hospital benchmarking. However, manual surveillance is time-consuming and susceptible to error. The aim was, therefore, to develop a prediction model to retrospectively detect drain-related meningitis (DRM), a frequently occurring nosocomial infection, using routinely collected data from a clinical data warehouse.

Methods

As part of the hospital infection control program, all patients receiving an external ventricular (EVD) or lumbar drain (ELD) (2004 to 2009; n = 742) had been evaluated for the development of DRM through chart review and standardized diagnostic criteria by infection control staff; this was the reference standard. Children, patients dying <24 hours after drain insertion or with <1 day follow-up and patients with infection at the time of insertion or multiple simultaneous drains were excluded. Logistic regression was used to develop a model predicting the occurrence of DRM. Missing data were imputed using multiple imputation. Bootstrapping was applied to increase generalizability.

Results

537 patients remained after application of exclusion criteria, of which 82 developed DRM (13.5/1000 days at risk). The automated model to detect DRM included the number of drains placed, drain type, blood leukocyte count, C-reactive protein, cerebrospinal fluid leukocyte count and culture result, number of antibiotics started during admission, and empiric antibiotic therapy. Discriminatory power of this model was excellent (area under the ROC curve 0.97). The model achieved 98.8% sensitivity (95% CI 88.0% to 99.9%) and specificity of 87.9% (84.6% to 90.8%). Positive and negative predictive values were 56.9% (50.8% to 67.9%) and 99.9% (98.6% to 99.9%), respectively. Predicted yearly infection rates concurred with observed infection rates.

Conclusion

A prediction model based on multi-source data stored in a clinical data warehouse could accurately quantify rates of DRM. Automated detection using this statistical approach is feasible and could be applied to other nosocomial infections.     

Quality of data entry using single entry, double entry and automated forms processing--an example based on a study of patient-reported outcomes

Background

The clinical and scientific usage of patient-reported outcome measures is increasing in the health services. Often paper forms are used. Manual double entry of data is defined as the definitive gold standard for transferring data to an electronic format, but the process is laborious. Automated forms processing may be an alternative, but further validation is warranted.

Methods

200 patients were randomly selected from a cohort of 5777 patients who had previously answered two different questionnaires. The questionnaires were scanned using an automated forms processing technique, as well as processed by single and double manual data entry, using the EpiData Entry data entry program. The main outcome measure was the proportion of correctly entered numbers at question, form and study level.

Results

Manual double-key data entry (error proportion per 1000 fields = 0.046 (95% CI: 0.001–0.258)) performed better than single-key data entry (error proportion per 1000 fields = 0.370 (95% CI: 0.160–0.729), (p = 0.020)). There was no statistical difference between Optical Mark Recognition (error proportion per 1000 fields = 0.046 (95% CI: 0.001–0.258)) and double-key data entry (p = 1.000). With the Intelligent Character Recognition method, there was no statistical difference compared to single-key data entry (error proportion per 1000 fields = 6.734 (95% CI: 0.817–24.113), (p = 0.656)), as well as double-key data entry (error proportion per 1000 fields = 3.367 (95% CI: 0.085–18.616)), (p = 0.319)).

Conclusions

Automated forms processing is a valid alternative to double manual data entry for highly structured forms containing only check boxes, numerical codes and no dates. Automated forms processing can be superior to single manual data entry through a data entry program, depending on the method chosen.     

A randomized open-label trial of artesunate- sulfadoxine-pyrimethamine with or without primaquine for elimination of sub-microscopic P. falciparum parasitaemia and gametocyte carriage in eastern Sudan

Background

In areas of seasonal malaria transmission, treatment of asymptomatic carriers of malaria parasites, whose parasitaemia persists at low densities throughout the dry season, could be a useful strategy for malaria control. We carried out a randomized trial to compare two drug regimens for clearance of parasitaemia in order to identify the optimum regimen for use in mass drug administration in the dry season.

Methodology and Principal Findings

A two-arm open-label randomized controlled trial was conducted during the dry season in an area of distinct seasonal malaria in two villages in Gedarif State in eastern Sudan. Participants were asymptomatic adults and children aged over 6 months, with low-density P. falciparum infection detected by PCR. Participants were randomized to receive artesunate/sulfadoxine-pyrimethamine (AS+SP) combination for three days with or without a dose of primaquine (PQ) on the fourth day. Parasitaemia detected by PCR on days 3, 7 and 14 after the start of treatment and gametocytes detected by RT-PCR on days 7 and 14 were then recorded. 104 individuals who had low density parasitaemia at screening were randomized and treated during the dry season. On day 7, 8.3% were positive by PCR in the AS+SP+PQ group and 6.5% in the AS+SP group (risk difference 1.8%, 95%CI −10.3% to +13.8%). At enrolment, 12% (12/100) were carrying gametocytes. This was reduced to 6.4% and 4.4% by day 14 (Risk difference 1.9% (95%CI −9.3% to +13.2%) in AS+SP+PQ and AS+SP groups, respectively.

Conclusion

Addition of primaquine to artemisinin combination treatment did not improve elimination of parasitaemia and prevention of gametocyte carriage in carriers with low-density parasitaemia in the dry season.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00330902","term_id":"NCT00330902"}}NCT00330902     

Baseline predictors of sputum culture conversion in pulmonary tuberculosis: importance of cavities, smoking, time to detection and W-Beijing genotype

Background

Time to detection (TTD) on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. The M. tuberculosis W-Beijing genotype is spreading globally, indicating a selective advantage. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes.

Aim

To assess baseline predictors of failure of sputum culture conversion, within the first 2 months of antitubercular therapy, in participants with pulmonary tuberculosis.

Design

Between May 2005 and August 2008 we conducted a prospective cohort study of time to sputum culture conversion in ambulatory participants with first episodes of smear and culture positive pulmonary tuberculosis attending two primary care clinics in Cape Town, South Africa. Rifampicin resistance (diagnosed on phenotypic susceptibility testing) was an exclusion criterion. Sputum was collected weekly for 8 weeks for mycobacterial culture on liquid media (BACTEC MGIT 960). Due to missing data, multiple imputation was performed. Time to sputum culture conversion was analysed using a Cox-proportional hazards model. Bayesian model averaging determined the posterior effect probability for each variable.

Results

113 participants were enrolled (30.1% female, 10.5% HIV-infected, 44.2% W-Beijing genotype, and 89% cavities). On Kaplan Meier analysis 50.4% of participants underwent sputum culture conversion by 8 weeks. The following baseline factors were associated with slower sputum culture conversion: TTD (adjusted hazard ratio (aHR) = 1.11, 95% CI 1.02; 1.2), lung cavities (aHR = 0.13, 95% CI 0.02; 0.95), ever smoking (aHR = 0.32, 95% CI 0.1; 1.02) and the W-Beijing genotype (aHR = 0.51, 95% CI 0.25; 1.07). On Bayesian model averaging, posterior probability effects were strong for TTD, lung cavitation and smoking and moderate for W-Beijing genotype.

Conclusion

We found that baseline TTD, smoking, cavities and W-Beijing genotype were associated with delayed 2 month sputum culture. Larger studies are needed to confirm the relationship between the W-Beijing genotype and sputum culture conversion.     

Visual acuity measures do not reliably detect childhood refractive error--an epidemiological study

Purpose

To investigate the utility of uncorrected visual acuity measures in screening for refractive error in white school children aged 6-7-years and 12-13-years.

Methods

The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit children from schools in Northern Ireland. Detailed eye examinations included assessment of logMAR visual acuity and cycloplegic autorefraction. Spherical equivalent refractive data from the right eye were used to classify significant refractive error as myopia of at least 1DS, hyperopia as greater than +3.50DS and astigmatism as greater than 1.50DC, whether it occurred in isolation or in association with myopia or hyperopia.

Results

Results are presented from 661 white 12-13-year-old and 392 white 6-7-year-old school-children. Using a cut-off of uncorrected visual acuity poorer than 0.20 logMAR to detect significant refractive error gave a sensitivity of 50% and specificity of 92% in 6-7-year-olds and 73% and 93% respectively in 12-13-year-olds. In 12-13-year-old children a cut-off of poorer than 0.20 logMAR had a sensitivity of 92% and a specificity of 91% in detecting myopia and a sensitivity of 41% and a specificity of 84% in detecting hyperopia.

Conclusions

Vision screening using logMAR acuity can reliably detect myopia, but not hyperopia or astigmatism in school-age children. Providers of vision screening programs should be cognisant that where detection of uncorrected hyperopic and/or astigmatic refractive error is an aspiration, current UK protocols will not effectively deliver.     

Screening strategies for tuberculosis prevalence surveys: the value of chest radiography and symptoms

Background

We conducted a tuberculosis (TB) prevalence survey and evaluated the screening methods used in our survey, to assess if screening in TB prevalence surveys could be simplified, and to assess the accuracy of screening algorithms that may be applicable for active case finding.

Methods

All participants with a positive screen on either a symptom questionnaire, chest radiography (CXR) and/or sputum smear microscopy submitted sputum for culture. HIV status was obtained from prevalent cases. We estimated the accuracy of modified screening strategies with bacteriologically confirmed TB as the gold standard, and compared these with other survey reports. We also assessed whether sequential rather than parallel application of symptom, CXR and HIV screening would substantially reduce the number of participants requiring CXR and/or sputum culture.

Results

Presence of any abnormality on CXR had 94% (95%CI 88–98) sensitivity (92% in HIV-infected and 100% in HIV-uninfected) and 73% (95%CI 68–77) specificity. Symptom screening combinations had significantly lower sensitivity than CXR except for ‘any TB symptom’ which had 90% (95%CI 84–95) sensitivity (96% in HIV-infected and 82% in HIV-uninfected) and 32% (95%CI 30–34) specificity. Smear microscopy did not yield additional suspects, thus the combined symptom/CXR screen applied in the survey had 100% (95%CI 97–100) sensitivity. Specificity was 65% (95%CI 61–68). Sequential application of first a symptom screen for ‘any symptom’, followed by CXR-evaluation and different suspect criteria depending on HIV status would result in the largest reduction of the need for CXR and sputum culture, approximately 36%, but would underestimate prevalence by 11%.

Conclusion

CXR screening alone had higher accuracy compared to symptom screening alone. Combined CXR and symptom screening had the highest sensitivity and remains important for suspect identification in TB prevalence surveys in settings where bacteriological sputum examination of all participants is not feasible.     

3q26 amplification is an effective negative triage test for LSIL: a historical prospective study

Background

Women with low grade squamous intraepithelial lesions (LSIL) at cervical cancer screening are currently referred for further diagnostic work up despite 80% having no precancerous lesion. The primary purpose of this study is to measure the test characteristics of 3q26 chromosome gain (3q26 gain) as a host marker of carcinogenesis in women with LSIL. A negative triage test may allow these women to be followed by cytology alone without immediate referral to colposcopy.

Methods and Findings

A historical prospective study was designed to measure 3q26 gain from the archived liquid cytology specimens diagnosed as LSIL among women attending colposcopy between 2007 and 2009. 3q26 gain was assessed on the index liquid sample; and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were measured at immediate triage and at 6–16 months after colposcopic biopsy. The sensitivity of 3q26 gain measured at immediate triage from automated and manually reviewed tests in 65 non-pregnant unique women was 70% (95% CI: 35, 93) with a NPV of 89% (95% CI: 78, 96). The sensitivity and NPV increased to 80% (95% CI: 28, 99) and 98% (95% CI: 87, 100), respectively, when only the automated method of detecting 3q26 gain was used.

Conclusions

3q26 gain demonstrates high sensitivity and NPV as a negative triage test for women with LSIL, allowing possible guideline changes to routine surveillance instead of immediate colposcopy. Prospective studies are ongoing to establish the sensitivity, specificity, PPV and NPV of 3q26 gain for LSIL over time.