Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones.

High-grade serous ovarian carcinoma (HGSOC) is genetically unstable and characterised by the presence of subclones with distinct genotypes. Intratumoural heterogeneity is linked to recurrence, chemotherapy resistance, and poor prognosis. Here, we use spatial transcriptomics to identify HGSOC subclones and study their association with infiltrating cell populations. Visium spatial transcriptomics reveals multiple tumour subclones with different copy number alterations present within individual tumour sections. These subclones differentially express various ligands and receptors and are predicted to differentially associate with different stromal and immune cell populations. In one sample, CosMx single molecule imaging reveals subclones differentially associating with immune cell populations, fibroblasts, and endothelial cells. Cell-to-cell communication analysis identifies subclone-specific signalling to stromal and immune cells and multiple subclone-specific autocrine loops. Our study highlights the high degree of subclonal heterogeneity in HGSOC and suggests that subclone-specific ligand and receptor expression patterns likely modulate how HGSOC cells interact with their local microenvironment.

Management of hypertension in obstructive sleep apnea.

Obstructive sleep apnea (OSA) plays an important role in the development of hypertension. Thus, this review summarizes pharmacological and non-pharmacological approaches to blood pressure (BP) control in patients with OSA. Current treatments for OSA, such as continuous positive airway pressure, are effective at lowering BP. However, they only provide a modest BP reduction, and pharmacological treatment remains important for achieving optimal BP control. Furthermore, current guidelines for the treatment of hypertension do not make specific recommendations on pharmacological treatment protocols for controlling BP in patients with OSA. Moreover, the BP-lowering effects of various classes of antihypertensives may be different in hypertensive patients with OSA than in those without OSA due to the underlying mechanisms that promote hypertension in OSA. The acute and chronic increase in sympathetic nerve activity in patients with OSA explain the effectiveness of beta blockers in controlling BP in these patients. As activation of the renin-angiotensin-aldosterone system may also promote hypertension in OSA, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have generally been found effective for lowering BP in hypertensive patients with OSA. The aldosterone antagonist spironolactone also produces a good antihypertensive response in patients with OSA and resistant hypertension. However, there are limited data available that compare the effects of various classes of antihypertensive medication on BP control in those with OSA, and most data have been obtained from small-scale studies. This demonstrates the need for large-scale randomized controlled trials to evaluate a range of BP-lowering regimens in patients with OSA and hypertension.

Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

Asian Pacific Society of Cardiology Consensus Statements on the Diagnosis and Management of Obstructive Sleep Apnoea in Patients with Cardiovascular Disease.

Obstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease (CVD). However, evidence supporting this association in the Asian population is scarce. Given the differences in the epidemiology of CVD and cardiovascular risk factors, as well as differences in the availability of healthcare resources between Asian and Western countries, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the management of OSA in patients with CVD in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of 'agree' or 'neutral.' The resulting statements provide guidance on the assessment and treatment of OSA in patients with CVD in the Asia-Pacific region. The APSC hopes for these recommendations to pave the way for screening, early diagnosis and treatment of OSA in the Asia-Pacific region.

TRACEBACK: Testing of Historical Tubo-Ovarian Cancer Patients for Hereditary Risk Genes as a Cancer Prevention Strategy in Family Members.

PURPOSE: Tubo-ovarian cancer (TOC) is a sentinel cancer for BRCA1 and BRCA2 pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed. We assessed the feasibility of detecting PVs in this population to enable genetic risk reduction in relatives. PATIENTS AND METHODS: In this pilot study, deceased probands were ascertained from research cohort studies, identification by a relative, and gynecologic oncology clinics. DNA was extracted from archival tissue or stored blood for panel sequencing of 10 risk-associated genes. Testing of deceased probands ascertained through clinic records was performed with a consent waiver. RESULTS: We identified 85 PVs in 84 of 787 (11%) probands. Familial contacts of 39 of 60 (65%) deceased probands with an identified recipient (60 of 84; 71%) have received a written notification of results, with follow-up verbal contact made in 85% (33 of 39). A minority of families (n = 4) were already aware of the PV. For many (29 of 33; 88%), the genetic result provided new information and referral to a genetic service was accepted in most cases (66%; 19 of 29). Those who declined referral (4 of 29) were all male next of kin whose family member had died more than 10 years before. CONCLUSION: We overcame ethical and logistic challenges to demonstrate that retrospective genetic testing to identify PVs in previously untested deceased probands with TOC is feasible. Understanding reasons for a family member's decision to accept or decline a referral will be important for guiding future TRACEBACK projects.

Lynch syndrome associated endometrial carcinomas in Western Australia: an analysis of universal screening by mismatch repair protein immunohistochemistry.

BACKGROUND: In 2016 universal screening with mismatch repair protein immunohistochemistry in all newly diagnosed endometrial carcinomas was introduced in Western Australia. OBJECTIVE: To compare the prevalence of Lynch syndrome associated endometrial carcinomas between 2016 and 2019 with a historical control (2015). Additionally, to compare the number of cases appropriately referred for genetic assessment. METHODS: A cross-sectional study of cases presented at the Western Australia gynecologic oncology tumor board was carried out. The primary outcome was the prevalence of Lynch syndrome associated endometrial carcinomas. A secondary outcome was the number of cases appropriately referred for genetic assessment. The following variables were extracted: date of birth; age at diagnosis; vital status; tumor mismatch repair protein expression status (retained or lost) and if lost, the specific mismatch repair protein deficiency; patients who were referred to a genetic clinic; and family history, if recorded. Data were collected from the clinical databases of the Familial Cancer Program at Genetic Services of Western Australia and WOMEN Center, to determine whether patients were appropriately referred for genetic evaluation and to ascertain the results of genetic testing. RESULTS: Between 2016 and 2019, there were 1040 new endometrial carcinomas. Tumors of 883 (85%) patients underwent mismatch repair protein immunohistochemistry compared with 117 of 199 patients (59%) in 2015 (χ2 73.14, p<0.001). Of 883 tumors tested, 242 (27%) showed loss of mismatch repair protein expression. In 2015, 30 (26%) tumors of 117 tested showed loss of mismatch repair protein expression. During the 4 years of universal screening, 13 (1.5%) of 883 patients screened were diagnosed with Lynch syndrome compared with 2 (1.7%) of 117 in 2015 (Fisher's exact test 0.04, p=0.69). In 2015, 11 (37%) of 30 patients with loss of mismatch repair protein expression were not referred for genetic assessment compared with 36 (17%) of 209 patients in the universal screening group (χ2 6.28, p=0.02). No cases of Lynch syndrome were diagnosed in patients aged over 70 years. CONCLUSIONS: Universal immunohistochemical screening did not increase the proportion of Lynch syndrome associated endometrial carcinomas identified, although the study was underpowered to detect small differences. There was an improvement in appropriate referrals for genetic assessment.

Postoperative use of slow-release opioids: The impact of the Australian and New Zealand College of Anaesthetists/Faculty of Pain Medicine position statement on clinical practice.

Dose titration with immediate-release opioids is currently recommended for acute pain. The Australian and New Zealand College of Anaesthetists and the Faculty of Pain Medicine released a statement in March 2018 supporting their use in the treatment of opioid-naïve patients; however, the impact of this statement on clinical practice is currently unknown. This retrospective cohort study was conducted to compare opioid prescribing patterns before and after the release of the recommendations. Data were collected on 184 patients (2017, n = 78; 2018, n = 106) admitted to the Prince of Wales Hospital in November 2017 and 2018, which consisted of demographic data, opioid prescriptions and discharge opioid information. The main outcome is the number of prescriptions of slow-release opioids in 2017 versus 2018 after the recommendations were published. Confounding factors were accounted for using logistic and multiple regression as appropriate. There was a 29% decrease in slow-release opioid prescriptions during hospitalisation (n = 31, 40% versus n = 12, 11%; P < 0.001) and 17% decrease at discharge (n = 20, 26% versus n = 9, 9%; P = 0.02) post-publication. After adjusting for confounders, the odds of slow-release opioids being prescribed postoperatively and at discharge reduced by 86% and 88%, respectively (postoperative period: odds ratio 0.14, P < 0.05; discharge: odds ratio 0.12, P < 0.05). In addition, orthopaedic patients were more likely to receive slow-release opioids, consistent with existing literature. As the use of slow-release opioids has been associated with increased harm and protracted opioid use compared to immediate-release opioids, it is hoped that wider dissemination of these recommendations and a change in prescribing practice can be a step towards overcoming the opioid crisis.

Excisional treatment comparison for in situ endocervical adenocarcinoma (EXCISE): A phase 2 pilot randomized controlled trial to compare histopathological margin status, specimen size and fragmentation after loop electrosurgical excision procedure and cold knife cone biopsy.

OBJECTIVE: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. We aimed to compare margins status, specimen size and fragmentation after loop electrosurgical excision procedure (LEEP) and 'cold knife cone biopsy' (CKC). METHODS: The EXCISE Trial was an investigator-initiated, multicenter, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat. RESULTS: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p = 1·00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p = ·00). There were no differences in grade three complications (p = ·65). CONCLUSIONS: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardized protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted.

A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases.

Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7-/CK20+/CDX2+/PAX8-. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1-50% of tumor cells) and diffuse ( >50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker in distinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice.

Novel diagnostics for point-of-care bacterial detection and identification.

In addition to limiting the effectiveness of antimicrobial agents, antimicrobial resistance (AMR) is a significant global health concern as it is responsible for significant mortality/morbidity and increased economic burdens on healthcare systems. Diagnostic tests have been suggested as a means of prolonging the effectiveness of current antimicrobials; culture and other conventional diagnostics are hindered in their practicality as they are time- and labour intensive to perform. Point-of-care (POC) testing is performed near where the patient is being treated and can provide timely results that allow evidence based clinical interventions to be made. This review aims to outline the chemical principles behind some novel and emerging diagnostic techniques which have the required speed, simplicity, effectiveness and low-cost for incorporation into POC devices which can be used to inform and optimize antimicrobial use.

Peritumoral granulomatous reaction in endometrial carcinoma: association with DNA mismatch repair protein deficiency, particularly loss of PMS2 expression.

AIMS: The observation of peritumoral granulomatous reactions (PGRs) in two endometrial carcinomas (ECs) with a PMS2-deficient/MLH1-intact expression pattern led us to investigate whether PGRs in EC were specifically associated with DNA mismatch repair (MMR) protein deficiency, particularly PMS2 loss. METHODS AND RESULTS: Hysterectomy specimens from 22 MMR protein-intact and 54 MMR protein-deficient ECs were reviewed with specific attention to the presence of a PGR and a tumour-associated lymphoid reaction [including tumour-infiltrating lymphocytes (TILs) and stromal lymphoid infiltrates]. The MMR protein-deficient ECs included 22 cases with combined MLH1/PMS2 loss, 11 with combined MSH2/MSH6 loss, 11 with isolated MSH6 loss, and 10 with PMS2 loss but intact MLH1 staining (including the two 'index' cases). Overall, PGRs were identified in seven of 54 (13%) MMR protein-deficient ECs, five of which showed a PMS2-deficient/MLH1-intact immunophenotype; three of these patients had germline PMS2 mutations and one additional patient had a germline MSH6 mutation. None of the MMR protein-intact tumours showed a PGR. Although five of the seven PGR-positive ECs had a high-grade histological component, six were stage I. Most ECs with PGRs also showed TILs and stromal lymphoid reactions, similarly to MMR protein-deficient ECs in general. CONCLUSIONS: MMR protein-deficient ECs, particularly those with PMS2 loss, occasionally show PGRs in addition to stromal lymphoid infiltrates and TILs. Therefore, PGRs could be considered to constitute a histological prompt for consideration of Lynch syndrome. The potential prognostic significance of PGRs in EC requires further study.

Awareness and knowledge of obstructive sleep apnea among the general population.

BACKGROUND: Obstructive sleep apnea (OSA) is an increasingly prevalent condition that remains largely undiagnosed. We aimed to assess the level of awareness and knowledge of OSA among the general population. METHODS: The Singapore Health 2 was a population-based study that comprised interview and health screening components. Out of 2720 subjects who completed the interview component, 2080 subjects gave consent for further health surveys. We contacted these subjects and conducted a structured telephone interview. RESULTS: We completed 1306 telephone interviews (response rate 62.8%). Two hundred and eighty-one (21.5%) respondents were aware of OSA, but only 170 (13.0%) respondents could define OSA correctly. A total of 77 (5.9%), 158 (12.1%), 150 (11.5%) and 110 (8.4%) respondents were able to correctly list at least one risk factor, symptom, health consequence and treatment options for OSA, respectively. The most common sources of information about OSA were traditional media such as newspapers (42.0%), internet (14.2%) or relatives and friends (14.6%). On multivariate analysis, respondents were more likely to define OSA correctly if they were older (≥61years), (odds ratio of 2.99, 95% Confidence Interval [CI]: 1.66-5.41), were Chinese as compared to Indians (odds ratio 2.63, 95% CI: 1.46-4.72), had higher levels of income (odds ratio 2.18, 95% CI 1.16-4.10) and post-secondary education (odds ratio 2.87, 95% CI: 1.28-6.45). CONCLUSION: Awareness and knowledge of OSA among the general population is currently poor. The effectiveness of ongoing health education campaigns to increase awareness should be monitored by examining temporal trends in public knowledge of sleep apnea.

Prognostic Role of Histological Tumor Regression in Patients Receiving Neoadjuvant Chemotherapy for High-Grade Serous Tubo-ovarian Carcinoma.

OBJECTIVE: Our objective was to validate the prognostic role of the chemotherapy response score (CRS), which has been proposed for measuring tumor response to neoadjuvant chemotherapy in patients with high-grade serous tubo-ovarian carcinoma, in predicting progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective cohort study was conducted of patients with advanced high-grade serous tubo-ovarian carcinoma diagnosed between January 1, 2010, and December 31, 2014, and treated with neoadjuvant chemotherapy. Treatment-related tumor regression was determined according to the 3-tier CRS, and results were compared with standard clinicopathological variables. Survival analysis was performed using Cox proportional hazards models and the log-rank test. RESULTS: Seventy-one patients were eligible for analysis. Median OS was 25.5 months. Fifty-eight patients (82%) had disease recurrence and 32 (45%) had died at study census. Of the 71 patients, 19, 29, and 23 patients had a CRS of 1, 2, and 3, respectively. On univariate analysis, the CRS significantly predicted PFS (hazard ratio [HR], 3.77; 95% confidence interval [CI], 1.83-7.78; P = 0.000) and OS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022). In a multivariate model, the CRS was significantly associated with PFS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022) but not with OS (HR, 2.39; 95% CI, 0.47-3.08; P = 0.079). Patients with CRS of 1 and 2 combined were twice as likely to progress during the study period compared with patients with a CRS of 3 (HR, 2.0; 95% CI, 1.06-3.78; P = 0.032; median PFS, 16 vs 26 months). No significant association was observed for OS (CRS 1/2 vs 3; HR, 1.57; 95% CI, 0.68-3.65; P = 0.291). CONCLUSIONS: In this study, the CRS showed independent prognostic significance for PFS but not for OS.

Validation of NoSAS score for screening of sleep-disordered breathing in a multiethnic Asian population.

PURPOSE: The NoSAS score was developed to identify subjects at high risk of sleep-disordered breathing (SDB). We aimed to validate the NoSAS score in a multiethnic Asian cohort and compare its performance to the STOP-Bang and Berlin questionnaires. METHODS: A sample of 242 subjects selected from a population-based cohort in Singapore completed home-based sleep testing with an Embletta device (type 3 monitor). All subjects were given the STOP-Bang and Berlin questionnaires for self-administration prior to the sleep study. The NoSAS score was subsequently calculated based on available demographic data and Berlin questionnaire responses. RESULTS: The prevalence of severe SDB, defined as an apnea-hypopnea index cutoff of ≥30 events/h, was 10.7%. The number of subjects who were classified as high risk by the NoSAS score and STOP-Bang and Berlin questionnaires were 76 (31.4%), 89 (36.8%), and 79 (32.6%), respectively. The sensitivity, specificity, and negative and positive predictive values of the NoSAS score to predict severe SDB were 69.2, 73.1, 95.2, and 23.7%, respectively. The STOP-Bang and Berlin questionnaires performed similarly to the NoSAS score, with area under the curve (AUC) values of all three questionnaires clustered around 0.682-0.748. Compared to the STOP-Bang (94.8%) and Berlin questionnaires (96.3%), the NoSAS score (95.2%) had equally high negative predictive value in ruling out severe SDB. CONCLUSIONS: The NoSAS score performed similarly to the STOP-Bang and Berlin questionnaires in a multiethnic Asian cohort. All three questionnaires had high negative predictive values in ruling out severe SDB and may have utility as screening tools.

Using the Berlin Questionnaire to Predict Obstructive Sleep Apnea in the General Population.

STUDY OBJECTIVES: The Berlin questionnaire is a self-administered questionnaire that was developed to identify subjects with obstructive sleep apnea (OSA) in primary care settings. This study evaluated the performance of the questionnaire to predict OSA in the general population. METHODS: A sample of 242 subjects in a population-based cohort completed a home-based sleep study with an Embletta device (type 3 monitor). Subjects completed the Berlin questionnaire on the evening just prior to the sleep study. The sleep studies were manually scored according to the 2012 American Academy of Sleep Medicine (AASM) criteria. RESULTS: The prevalence of moderate-to-severe and severe OSA defined as apnea-hypopnea index (AHI) of ≥ 15 and ≥ 30 was 28.1% and 10.7%, respectively. Seventy-nine subjects (32.6%) were classified as high risk according to the Berlin questionnaire. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the questionnaire to predict an AHI ≥ 15 was 58.8%, 77.6%, 82.9%, and 50.6%, respectively. The area under the receiving operator characteristic (ROC) curve for moderate-to-severe OSA was 0.682. When used to predict an AHI ≥ 30, the sensitivity of the questionnaire increased to 76.9% with a small drop in specificity to 72.7%. The corresponding NPV, PPV, and area under the ROC curve of the questionnaire to predict severe OSA were 96.3%, 25.3%, and 0.748, respectively. CONCLUSIONS: The Berlin questionnaire may have utility in the general population setting as a screening tool for OSA in view of its good sensitivity and high NPV in ruling out severe OSA.

Predicting obstructive sleep apnea using the STOP-Bang questionnaire in the general population.

OBJECTIVE: The STOP-Bang questionnaire was developed as a quick and simple screening tool for obstructive sleep apnea (OSA) in preoperative clinics. We aimed to evaluate the validity of the STOP-Bang questionnaire to predict moderate-to-severe and severe OSA in the general population. METHODS: A sample of 242 subjects selected from a population-based cohort in Singapore completed home-based sleep testing with a type 3 monitor. Subjects were asked to complete the STOP questionnaire while body mass index (BMI), age, neck circumference, and sex were recorded. A score of ≥3 on the questionnaire indicated high risk of OSA. RESULTS: A total of 68 subjects (28.1%) and 26 subjects (10.7%) had an apnea-hypopnea index (AHI) of ≥15 and ≥30 events per hour, respectively. Of the subjects, 89 (36.8%) were classified as high risk based on the questionnaire. The sensitivity of a STOP-Bang score of ≥3 was 66.2% to detect AHI ≥15 and 69.2% to detect AHI ≥30. The specificities were 74.7% and 67.1%, respectively. The negative predictive values were 85% for moderate-to-severe OSA and 94.8% for severe OSA. The corresponding positive predictive values were 50.6% and 20.2%, respectively. Using BMI cutoffs of 30 and 27.5 for Asians compared to the original cutoff of 35 did not improve the questionnaire performance significantly. CONCLUSION: The STOP-Bang questionnaire can be used as a screening tool in the general population in view of its moderate sensitivity and high negative predictive value for subjects with moderate-to-severe and severe OSA. The cutoff of BMI >35 can be used in Asians, as lower BMI cutoffs did not improve questionnaire performance.

The Use of Polymerase Chain Reaction Amplification for the Detection of Viruses and Bacteria in Severe Community-Acquired Pneumonia.

BACKGROUND: Pathogens are often not identified in severe community-acquired pneumonia (CAP), and the few studies using polymerase chain reaction (PCR) techniques for virus detection are from temperate countries. OBJECTIVE: This study assesses if PCR amplification improves virus and bacteria detection, and if viral infection contributes to mortality in severe CAP in a tropical setting, where respiratory pathogens have less well-defined seasonality. METHODS: In this cohort study of patients with severe CAP in an intensive care unit, endotracheal aspirates for intubated patients and nasopharyngeal swabs for non-intubated patients were sent for PCR amplification for respiratory viruses. Blood, endotracheal aspirates for intubated patients, and sputum for non-intubated patients were analysed using a multiplex PCR system for bacteria. RESULTS: Out of 100 patients, using predominantly cultures, bacteria were identified in 42 patients; PCR amplification increased this number to 55 patients. PCR amplification identified viruses in 32 patients. In total, only bacteria, only viruses, and both bacteria and viruses were found in 37, 14, and 18 patients, respectively. The commonest viruses were influenza A H1N1/2009 and rhinovirus; the commonest bacterium was Streptococcus pneumoniae. Hospital mortality rates for patients with no pathogens, bacterial infection, viral infection, and bacterial-viral co-infection were 16.1, 24.3, 0, and 5.6%, respectively (p = 0.10). On multivariable analysis, virus detection was associated with lower mortality (adjusted odds ratio 0.12, 95% confidence interval 0.2-0.99; p = 0.049). CONCLUSIONS: Viruses and bacteria were detected in 7 of 10 patients with severe CAP with the aid of PCR amplification. Viral infection appears to be independently associated with lower mortality.