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PurposeTo evaluate the performance of swept source optical coherence tomography (SS-OCT) to detect gonioscopic angle closure using different classification algorithms.MethodsThis was a cross-sectional study of 2028 subjects without ophthalmic symptoms recruited from a community-based clinic. All subjects underwent gonioscopy and SS-OCT (Casia, Tomey Corporation, Nagoya, Japan) under dark room conditions. For each eye, 8 out of 128 frames (22.5° interval) were selected to measure anterior chamber parameters namely anterior chamber width, depth, area and volume (ACW, ACD, ACA, and ACV), lens vault (LV), iris curvature (IC), iris thickness (IT) from 750 µm and 2000 µm from the scleral spur, iris area and iris volume. Five diagnostic algorithms—stepwise logistic regression, random forest, multivariate adaptive regression splines, recursive partitioning and Naïve Bayes were evaluated for detection of gonioscopic angle closure (defined as ≥2 closed quadrants). The performance of the horizontal frame was compared with that of other meridians.ResultsData from 1988 subjects, including 143 (7.2%) with gonioscopic angle closure, were available for analysis. They were divided into two groups: training (1391, 70%) and validation (597, 30%). The best algorithm for detecting gonioscopic angle closure was stepwise logistic regression with an area under the curve of 0.91 (95% CI 0.88 to 0.93) using all parameters, and 0.88 (95% CI 0.82 to 0.93) using only ACA, LV and IC of the horizontal meridian scan.ConclusionsA stepwise logistic regression model incorporating SS-OCT measurements has a high diagnostic ability to detect gonioscopic angle closure.

Background/aimsAlthough being a more objective tool for assessment and follow-up of angle closure, reliability studies have reported a moderate diagnostic performance for anterior segment optical coherence tomography (OCT) technologies when comparing with gonioscopy as the reference standard. We aim to determine factors associated with diagnostic disagreement in angle closure when assessed by anterior segment swept source OCT (SS-OCT, CASIA SS-1000; Tomey, Nagoya, Japan) and gonioscopy.MethodsCross-sectional study. A total of 2027 phakic subjects aged ≥50 years, with no relevant previous ophthalmic history, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy and SS-OCT (128 radial scans) for the entire circumference of the angle were performed for each subject. A two-quadrant closed gonioscopic definition was used. On SS-OCT images, angle closure was defined as iridotrabecular contact (ITC) to the extent of ≥35%, ≥50% and ≥75% of the circumferential angle. Diagnostic disagreements between both methods, that is, false positives or overcalls and false negatives or undercalls were defined, respectively, as gonioscopic open/closed angles inversely assessed as closed/open by SS-OCT.ResultsTwo hundred and seventy-two (14.7%) resulted in overcall results (false positives) when ≥50% of the angle circumference was closed using SS-OCT. These eyes had significantly wider (anterior chamber width, 11.7 vs 11.6 mm, pConclusionsWe found that anterior chamber dimensions, determined by ACD and LV, were factors significantly associated with diagnostic disagreement between anterior segment SS-OCT and gonioscopy in angle closure assessment.

Background The adaptability of existing recommendations on shared care implementation to Asian settings is unknown. This qualitative study aims to elicit public- and private-sectors primary care practitioners’ (PCPs) perspectives on the sustainable implementation of a shared care model among breast cancer survivors in Singapore. Methods Purposive sampling was employed to engage 70 PCPs from SingHealth Polyclinics, National University Polyclinics, National Healthcare Group Polyclinics, and private practice. Eleven focus groups and six in-depth interviews were conducted between June to November 2018. All sessions were audio-recorded and transcribed verbatim. Guided by the RE-AIM framework, we performed deductive thematic analysis in QSR NVivo 12. Results PCPs identified low-risk breast cancer survivors who demonstrated clear acceptability of PCPs’ involvement in follow-up as suitable candidates for shared care. Engagement with institution stakeholders as early adopters is crucial with adequate support through PCP training, return pathways to oncologists, and survivorship care plans as communication tools. Implementation considerations differed across practices. Selection of participating PCPs could consider seniority and interest for public and private practice, respectively. Proposed adoption incentives included increased renumeration for private PCPs and work recognition for public PCPs. Public PCPs further proposed integrating shared care elements to their existing family medicine clinics. Conclusions PCPs perceived shared care favorably as it echoed principles of primary care to provide holistic and well-coordinated care. Contextual factors should be considered when adapting implementation recommendations to Asian settings like Singapore. With limited competitive pressure, the government is then pivotal in empowering primary care participation in survivorship shared care delivery.

and purpose: Among chronic kidney disease (CKD) patients, manipulative and body-based methods (MBM) have demonstrated efficacy in improving symptoms such as fatigue. This review aims to summarize the efficacy and safety of MBM among CKD patients.A systematic review was performed in PubMed, Embase, Scopus, CINAHL, CENTRAL and PsycInfo. Randomised controlled trials (RCTs) which evaluated the use of MBM among adult CKD patients were included. The grading of recommendations, assessment, development, and evaluation (GRADE) approach was used to determine the risk of bias and certainty of evidence. The efficacy of each MBM was determined by reduction in symptom severity scores. All adverse reactions were documented.Of 8529 articles screened, 55 RCTs were included. Acupressure (n = 23), massage therapy (n = 17), reflexology (n = 6) and acupuncture (n = 5) were the most studied MBMs. Acupressure and reflexology were shown to reduce sleep disturbance and fatigue by 6.2-50.0% and 9.1-37.7% respectively. For uremic pruritus, acupressure and acupuncture reduced symptoms by 34.5-77.7% and 56.5-60.2% respectively. Common adverse reactions associated with acupressure included intradialytic hypotension (20.4%) and dizziness (11.1%) while that of acupuncture included elbow soreness (7.5%) and bleeding (7.5%). No adverse effects were reported for massage therapy, moxibustion, reflexology and yoga therapy.Acupressure, reflexology and massage therapies were the most well-studied MBMs which have demonstrated efficacy in alleviating sleep disturbance, fatigue and uremic pruritus symptoms in CKD patients.

AimThe objective of this study was to assess determinants of poor sleep quality which is an under-diagnosed and under-treated problem in elderly patients with diabetes mellitus, hyperlipidemia and hypertension.BackgroundPoor sleep quality is linked to decreased quality of life, increased morbidity and mortality. Poor sleep quality is common in the elderly population with associated cardiometabolic risk factors such as diabetes, hyperlipidemia and hypertension.MethodsThis is a cross-sectional study undertaken in the primary healthcare setting (Singhealth Polyclinics-Outram) in Singapore. Singaporeans aged 65 years and above who had at least one of the three cardiometabolic risk factors (diabetes, hypertension and hyperlipidemia) were identified. Responders’ sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire and were divided into those with good quality sleep and those with poor quality sleep, based on the PSQI score. Information on demographics, co-morbidities and lifestyle practices were collected. Descriptive and multivariate analyses of determinants of poor sleep were determined.FindingsThere were 199 responders (response rate 88.1%). Nocturia (adjusted prevalence rate ratio 1.54, 95% confidence interval 1.06–2.26) was found to be associated with an increased risk of poor sleep quality in elderly patients with diabetes mellitus, hypertension and hyperlipidaemia. Nocturia, a prevalent problem in the Asian elderly population, has been found to be associated with poor sleep quality in our study. Hence, it is imperative to identify and treat patients with nocturia to improve sleep quality among them.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is increasingly widespread with an overall global estimated prevalence of 25%. Type 2 diabetes Mellitus (T2DM) is a key contributor to NAFLD progression and predicts moderate-severe liver fibrosis and mortality. However, there is currently no uniform consensus on routine NAFLD screening among T2DM patients, and the risk factors of NAFLD and advanced fibrosis among T2DM patients remain to be clarified fully.AimWe explored the prevalence, clinical spectrum, and risk factors of NAFLD and liver fibrosis among T2DM patients.MethodsThis is a cross-sectional study that enrolled subjects from a primary care clinic and a diabetes centre in Singapore. Subjects aged 21 to 70 years of all ethnic groups with an established T2DM diagnosis were included. Subjects with chronic liver diseases of other aetiologies were excluded. All subjects underwent transient elastography for hepatic steatosis and fibrosis assessment. Their demographics, anthropometric measurements and clinical parameters were collected. Statistical analysis was performed using STATA/SE16.0 software.ResultsAmong 449 enrolled T2DM subjects, 436 with complete data and valid transient elastography results were analysed. Overall, 78.72% (344/436) of the T2DM subjects had NAFLD, of which 13.08% (45/344) had increased liver stiffness. Higher ALT level (OR = 1.08; 95% CI: 1.03-1.14; p = 0.004), obesity (BMI ≥ 27.5 kg/m2, OR = 2.64; 95% CI: 1.28-5.44; p = 0.008) and metabolic syndrome (OR = 4.36; 95% CI 1.40-13.58; p = 0.011) were independent factors associated with increased CAP (NAFLD). Higher AST level (OR = 1.06; 95% CI: 1.02-1.11; p = 0.008), CAP value (OR = 1.02; 95% CI: 1.00-1.03; p = 0.003), lower platelet count (OR = 0.99; 95% CI: 0.98-1.00; p = 0.009) and concomitant hypertension (OR = 4.56; 95% CI: 1.18-17.62; p = 0.028) were independent factors associated with increased liver stiffness.ConclusionsOur study demonstrated a considerably high prevalence of NAFLD among T2DM patients, with the proportion of advanced liver fibrosis among T2DM NAFLD patients much higher than the general population. Given that NAFLD is largely asymptomatic, increased awareness and vigilance for identifying NAFLD and increased liver stiffness among T2DM patients should be advocated.

Background The prevalence of dementia, which presents as cognitive decline in one or more cognitive domains affecting function, is increasing worldwide. Traditional cognitive screening tools for dementia have their limitations, with emphasis on memory and, to a lesser extent, on the cognitive domain of executive function. The use of virtual reality (VR) in screening for cognitive function in older persons is promising, but evidence for its use is sparse. Objective The primary aim was to examine the feasibility and acceptability of using VR to screen for cognitive impairment in older persons in a primary care setting. The secondary aim was to assess the module’s ability to discriminate between cognitively intact and cognitively impaired participants. Methods A comparative study was conducted at a public primary care clinic in Singapore, where persons aged 65-85 years were recruited based on a cut-off score of 26 on the Montreal Cognitive Assessment (MoCA) scale. They participated in a VR module for assessment of their learning and memory, perceptual-motor function, and executive function. Each participant was evaluated by the total performance score (range: 0-700) upon completion of the study. A questionnaire was also administered to assess their perception of and attitude toward VR. Results A total of 37 participants in Group 1 (cognitively intact; MoCA score≥26) and 23 participants in Group 2 (cognitively impaired; MoCA score Conclusions We demonstrated the feasibility of using a VR-based screening tool for cognitive function in older persons in primary care, who were largely in favor of this tool.

BACKGROUND Dementia, which presents as cognitive decline in one or more cognitive domains affecting function, is becoming more prevalent. Traditional cognitive screening tools for dementia have their limitations, with emphasis on memory and to a lesser extent on the cognitive domain of executive function. The use of virtual reality (VR) in screening for cognitive function in older person is promising but evidence for its use is sparse. OBJECTIVE The primary aim is to examine the feasibility and acceptability of using VR to screen for cognitive impairment in older person in a primary care setting, through a VR module. The secondary aim is to assess the module’s ability to discriminate between cognitively normal and cognitively impaired participants. METHODS A comparative study was conducted at a public primary care clinic in Singapore, where 60 older persons were recruited based on a cut-off score of 26 using the Montreal Cognitive Assessment (MoCA) scale. They participated in the VR module to assess their learning and memory, perceptual-motor function and executive function. Each participant was evaluated by a total performance score (range: 0 – 700) upon completion. An assisted questionnaire was also administered to assess their perception of and attitude towards VR. RESULTS 37 participants in Group 1 (cognitively normal; MoCA >= 26) and 23 participants in Group 2 (cognitively impaired; MoCA < 26) were assessed. All participants completed the study with a mean total time of 19.1±3.6 minutes in Group 1 and 20.4±3.4 minutes in Group 2. Mean feedback scores ranged from 3.80 to 4.48 (max=5) in favour of VR. The total performance score in Group 1 (552.0±57.2) was higher than in Group 2 (476.1±61.9) (P < .001), and exhibited moderate positive correlation with scores from other cognitive screening tools: Abbreviated Mental Test (AMT) (0.312), Mini-Mental State Examination (MMSE) (0.373) and MoCA (0.427). A ROC curve analysis, relating total performance score to the presence of cognitive impairment, showed an area under curve of 0.821 (95% confidence interval: 0.714 to 0.928). CONCLUSIONS We demonstrated the feasibility of using an VR-based screening tool for cognitive function in older persons in primary care, who were largely in favour of this tool.

Purpose To determine the association of iris surface features with iris volume change after physiologic pupil dilation in adults. Design Cross-sectional observational study. Participants Chinese adults aged ≥ 50 years without ocular diseases. Methods Digital iris photographs were taken from eyes of each participant and graded for crypts (by number and size) and furrows (by number and circumferential extent) following a standardized grading scheme. Iris color was measured objectively, using the Commission Internationale de l'Eclairage (CIE) L* color parameter (higher value denoting lighter iris). The anterior segment was imaged by swept-source optical coherence tomography (SS-OCT) (Casia; Tomey, Nagoya, Japan) under bright light and dark room conditions. Iris volumes in light and dark conditions were measured with custom semiautomated software, and the change in iris volume was quantified. Associations of the change in iris volume after pupil dilation with underlying iris surface features in right eyes were assessed using linear regression analysis. Main Outcome Measures Iris volume change after physiologic pupil dilation from light to dark condition. Results A total of 65 Chinese participants (mean age, 59.8±5.7 years) had gradable data for iris surface features. In light condition, higher iris crypt grade was associated independently with smaller iris volume (β [change in iris volume in millimeters per crypt grade increment] = −1.43, 95% confidence interval [CI], −2.26 to −0.59; P = 0.001) and greater reduction of iris volume on pupil dilation (β [change in iris volume in millimeters per crypt grade increment] = 0.23, 95% CI, 0.06–0.40; P = 0.010), adjusting for age, gender, presence of corneal arcus, and change in pupil size. Iris furrows and iris color were not associated with iris volume in light condition or change in iris volume (all P > 0.05). Conclusions Although few Chinese persons have multiple crypts on their irides, irides with more crypts were significantly thinner and lost more volume on pupil dilation. In view that the latter feature is known to be protective for acute angle-closure attack, it is likely that the macroscopic and microscopic composition of the iris is a contributing feature to angle-closure disease.

Aim Older adults are susceptible to two or more chronic ailments or multimorbidity. The present study aimed to establish the relationship between multimorbidity and health-related quality of life (HRQoL) amongst Asian elderly patients in primary care in a developed nation. It also assessed how functional disability and chronic musculoskeletal pain are associated with HRQoL. Methods A cross-sectional study was carried out in a Singapore public primary care clinic. An interviewer-administered questionnaire was used to collect data on chronic disease profile, HRQoL (using the European Quality of Life 5 Dimension), basic activities of daily living, instrumental activities of daily living, musculoskeletal pain and sociodemographic characteristics. The association of multimorbidity, functional disability and chronic musculoskeletal pain with HRQoL was assessed using multivariate linear regression analysis. Results A total of 498 outpatients aged 65 years and older with multimorbidity were enrolled. Their mean age was 73.9 years, and approximately 75% had between two and four chronic conditions. The most commonly reported chronic conditions were hypertension (86.1%), hyperlipidemia (80.7%), diabetes (40.2%) and arthritis (33.3%). The European Quality of Life 5 Dimension index score decreased significantly when the number of comorbidities was more than five. Chronic hip and knee pain, one or more “dependent” activities of daily living dimensions and two or more “dependent” IADL dimensions were independently associated with worse HRQoL. Conclusions Multimorbidity is associated with poorer HRQoL amongst older adults in Singapore. Review of chronic musculoskeletal pain and functional disabilities should be integrated into the comprehensive assessment of older adults in an enhanced model of primary care to improve the HRQoL of these older patients. Geriatr Gerontol Int 2016; ••: ••–••.

To characterise the association of iris surface features (crypts, furrows and colour) with iris volume and curvature assessed by swept-source optical coherence tomography (SSOCT) in Asian eyes.Iris crypts (by number and size) and furrows (by number and circumferential extent) were graded from iris photographs. Iris colour was measured by a customised algorithm written on MATLAB (MathWorks, Natick, Massachusetts, USA). The iris was imaged by SSOCT (SS-1000, CASIA, Tomey, Nagoya, Japan). The associations of surface features with iris parameters were analysed using a generalised estimating equation.A total of 1704 subjects (3297 eyes) were included in the analysis. The majority was Chinese (86.4%), and 63.2% were females, and their mean age (±SD) was 61.4±6.6 years. After adjusting for age, sex, ethnicity, pupil size and corneal arcus, higher iris crypt grade was independently associated with smaller iris volume (β=-0.54, p0.001), whereas darker irides and higher iris furrow grade were associated with larger iris volume (β=-0.041, p0.001) and (β=0.233, p0.001), respectively. Lighter coloured irides with more crypts and/or more furrows were also associated with less convexity (crypts: β=-0.003, p=0.03; furrows: β=-0.004, p=0.007; and colour: β=-0.001, p=0.005).Iris surface features were highly correlated with iris volume and curvature. Irides with more crypts have a smaller volume; and darker irides with more furrows have a larger volume. Lighter irides with more crypts and/or furrows have less convexity.

Purpose To evaluate the diagnostic performance of swept-source optical coherence tomography (SS-OCT, CASIA SS-1000; Tomey Corporation, Nagoya, Japan) for angle closure detection, in comparison with gonioscopy, in a community setting. Design Reliability analysis. Methods A total of 2027 phakic subjects aged ≥50 years, with no previous history of glaucoma, laser (including peripheral iridotomy), intraocular surgery, or ocular trauma, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy was performed by a single trained ophthalmologist. SS-OCT angle scans, which obtain radial scans for the entire circumference of the angle, were analyzed by a single examiner, masked to the subject's clinical details. On SS-OCT images, angle closure was defined as contact between the iris and any part of the angle wall anterior to the scleral spur. Different cutoff values of the degree of circumferential angle closure (≥35%, ≥50%, and ≥75%) were taken for analysis to assess SS-OCT performance in detecting angle closure. Results A total of 1857 subjects (91.6%) were included in the final analysis after excluding poor-quality SS-OCT scans. Almost 90% of the subjects were Chinese, with a mean age of 61.8 ± 6.7 years, and more than half were women (63.5%). The overall AUC of SS-OCT manual grading against gonioscopy was 0.84 (95% confidence interval, 0.81-0.88). The prevalence of angle closure on SS-OCT was 26.1% for the ≥35% definition, with an area under the curve of 0.80 (0.77-0.84), sensitivity of 82.5% (75.3%-88.4%), and specificity of 78.5% (76.5%-80.4%). The first-order agreement coefficient statistics for the 2-quadrant gonioscopic definition of angle-closure with corresponding ≥35%, ≥50%, and ≥75% angle closure definitions for SS-OCT were good at 0.89 (0.83-0.93), 0.88 (0.842-0.93), and 0.88 (0.831-0.99), respectively. Conclusions In this large community-based study, SS-OCT exhibited moderate performance for angle closure detection compared to gonioscopy as the reference standard.

We introduced a new method for detecting iris surface furrows and identify its associations with dynamic changes in iris volume in healthy eyes. Swept-source optical coherence tomography was performed on 65 subjects with open angle under light and dark conditions. Iris boundaries were identified and a reconstruction of the anterior iris surface was obtained. Furrows were detected by identifying locally deep (minima) points on the iris surface and reported as furrow length in millimetres. Iris volume was quantified. Associations between furrow length and dynamic changes in iris volume were assessed using linear regression model. With pupil dilation, furrow length increased (15.84 mm) whereas iris volume decreased (−1.19 ± 0.66 mm3). Longer furrow length was associated with larger static iris volume, as well as smaller loss of iris volume with pupil dilation (β = −0.10, representing 0.1 mm3 less loss in iris volume per 10 mm increase in iris furrow length; P = 0.002, adjusted for age, gender and changes in pupil size). Our iris furrow length measurements are robust and intuitive. Eyes with longer furrows have larger iris volume and lose less volume during physiological pupil dilation. These findings highlight the potential for iris surface features as indicators of iris morphological behavior.

Purpose The primary healthcare setting is well placed for health screening. Tear fluid composition gives valuable information about the eye and systemic health, and there is now significant interest in the potential application of tears as a tool for health screening; however, the acceptability of tear collection in the primary healthcare setting as compared with other methods of human sample collection has not been previously addressed. The objective of this study was to evaluate the patient acceptability of tear collection in a primary healthcare setting. Methods This was a cross-sectional study on 383 adult patients seeking primary healthcare, who were not diabetic and were not attending for an eye-related complaint. Tear collection was done using Schirmer strips, and an interviewer-administered questionnaire was conducted to collate information on the pain score (0–10) of the Schirmer tear collection, as well as to score the pain associated with their previous experience of antecubital venous puncture and finger prick test. Results The pain score for Schirmer tear collection was significantly lower (p < 0.001) than antecubital venous puncture but higher (p < 0.001) than finger prick. The pain scores for all three procedures were significantly higher in participants of younger age, female gender, and higher education level. Among the participants, 70% did not mind their tears being collected to screen for eye problems, whereas only 38% did not mind this procedure being performed for general health screening. Nevertheless, 69% of the participants preferred tear to urine collection, and 74% of participants preferred tear to blood collection. Conclusions Tear collection using Schirmer strips is a highly acceptable form of investigation that has the potential for use in health screening in the primary healthcare setting. This study has implications on using tear collection as a method of ocular and systemic health screening in the primary healthcare setting.

The Academy of Medicine (AMS) and Ministry of Health (MOH) have developed the clinical practice guidelines on Assessment and Management of Infertility at Primary Healthcare Level to provide doctors and patients in Singapore with evidence-based treatment for infertility. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the AMS-MOH clinical practice guidelines on Assessment and Management of Infertility at Primary Healthcare Level, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_ medical/2013/cpgmed_infertility.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Hand dermatitis is commonly seen in primary care, although it is often underdiagnosed. Exogenous causes should always be considered and a detailed environmental and occupational history taken, especially in patients presenting in adulthood. Although not life-threatening, the condition may have significant impact on the patient's quality of life and employment. Refractory cases or those suspected to be due to exogenous workplace agents may need to be referred for further investigation. Hand dermatitis can be treated effectively using pharmacotherapy and prevented by minimising subsequent exposure to irritants and allergens. Occupational skin disorders, once diagnosed, should be notified to the relevant authorities, i.e. the Ministry of Manpower in Singapore.

To report three patients who developed unilateral choroidal neovascularization (CNV) following laser in situ keratomileusis (LASIK) for high myopia. Retrospective chart reviews of three highly myopic patients who developed CNV following LASIK and who attended a tertiary care private practice were conducted. The clinical presentation of the patients was analyzed. All patients were treated with a combination of intravitreal ranibizumab and photodynamic therapy with verteporfin. Main outcome measures were clinical fundus appearance and best-corrected visual acuity (BCVA) after treatment. Two females and one male with a mean age of 34 ± 2.8 years underwent LASIK for high myopia in both eyes. The mean spherical equivalent was -11.42 diopters (D) (range -6.75 to -20.00). The mean time interval between LASIK and the appearance of symptoms was 9.3 ± 8.5 weeks. One patient developed an extrafoveal CNV at the edge of a laser photocoagulation scar, one developed a subfoveal CNV and the third patient developed a juxtafoveal CNV. The mean BCVA at the time of CNV presentation was 0.44 logMAR (range 0.10-0.70 logMAR). Following treatment, the mean BCVA improved to 0.17 logMAR with complete resolution of CNV in two patients. CNV is a rare but potentially blinding complication following LASIK. Short-term good visual outcome can be achieved with timely intervention with current treatment modalities.

Traumatic diaphragmatic rupture (TDR) following blunt trauma such as a road traffic accident is well reported. We present a case of delayed presentation of TDR that occurred after a party game of “musical chairs”. Clinical presentation, signs and the initial chest radiograph were suggestive of a large pneumothorax. Timely consideration of gastrothorax as a possible differential diagnosis; we inserted a nasogastric tube which clinched our diagnosis and decompressed the gastric contents. We discuss briefly the diagnostic tools usually recruited in such clinical scenarios and possible complications arising from clinical management. Conflict of interest and funding Nil.

Coxsackievirus A21 (CAVATAK™) is a bio-selected oncolytic immunotherapy virus. Following intratumoral (i.t) injection, CAVATAK selectively infects ICAM-1-expressing tumor cells, resulting in tumor cell lysis and a systemic immune-mediated anti-tumor response. A Phase II trial of i.t delivered CAVATAK (NCT01227551) in advanced melanoma patients has highlighted antitumor activity in both injected and distant non-injected lesions. Such responses have occurred at times when no circulating infectious CAVATAK was detected in patient serum and in an environment of high levels of anti-CAVATAK neutralizing antibodies. In further support of the generation of CAVATAK-mediated immune anti-tumor activity is the identification of a possible novel serum cytokine signature of elevated levels of IL-8 and IFN-γ in treated patients associated with tumor inflammation and systemic tumor response. Blockade of programmed death-1 (PD-1) in patients with metastatic melanoma has resulted in substantial tumor responses via a mechanism involving reversal of tumor-induced T cell suppression. We hypothesized that a combination of CAVATAK and PD-1 blockade may enhance anti-tumor responses, potentially leading to improved clinical activity. Preclinical studies in C57BL mice were conducted to assess the anti-tumor activity of CAVATAK and anti-mouse PD-1 (mPD-1) mAb in a B16-ICAM-1 melanoma immune competent mouse model. B16-ICAM-1 cells are murine melanoma B16 cells stably transfected to express human ICAM-1 allowing CAVATAK binding and cell infection. CAVATAK was administered i.t, while anti mPD-1 mAb was delivered intraperitoneally. Following treatment of the primary cutaneous B16-ICAM-1 tumor with 8 cycles of CAVATAK injections and 4 cycles of anti-PD-1mAb, mice were challenged with additional subcutaneous administration of B16 cells. Significant single agent anti-tumor activities against the primary B16-ICAM-1 tumor were observed in mice treated with either CAVATAK or anti-PD-1 mAb relative to saline controls. Combination of CAVATAK and anti-PD-1 mAb mediated significantly greater anti-tumor activity and offered greater survival benefit when compared to use of either agent alone. Of particular interest was the finding that a combination of CAVATAK and anti-PD-1 mAb was able to noticeably delay the onset of palpable tumor development following B16 cell challenge when compared to all other single agent treatment regimes. The significant anti-tumor activity mediated by the combination of CAVATAK and the checkpoint inhibitor antibody (anti-PD-1) observed in the presented murine melanoma model supports clinical evaluation of such an immunotherapeutic combination treatment regimen in patients with advanced melanoma.