Genomic and comparative clinico-pathological assessment of two Pakistani pigeon-derived newcastle disease virus sub-genotypes XXI.1.1 and XXI.1.2 isolated in 2017.

Pigeon paramyxovirus type-1 (PPMV-1) is an antigenic-variant of Newcastle disease virus (NDV) which is associated with infection in Columbidae family. In this study, we isolated two pigeon-derived strains pi/Pak/Lhr/SA_1/17 (designed as SA_1) and pi/Pak/Lhr/SA_2/17 (designed as SA_2) from diseased pigeons collected in Punjab province in 2017. We performed the whole genome, phylogenetic analysis and comparative clinico-pathological evaluation of two viruses in pigeons. Phylogenetic analysis based on fusion (F) gene and complete genome sequences showed that SA_1 belonged to sub-genotype XXI.1.1 and SA_2 clustered in sub-genotype XXI.1.2. SA_1 and SA_2 viruses contributed to morbidity and mortality in pigeons. Remarkably, although the two viruses resulted in comparatively similar pattern of pathogenesis and replication ability in various tissues of infected pigeons, SA_2 could cause more severe histopathological lesions and had comparatively high replication ability in pigeons than SA_1. Moreover, pigeons infected with SA_2 had higher shedding efficiency than that of pigeons infected with SA_1. Moreover, several aa substitutions in the major functional domains of the F and HN proteins might be contributed to the pathogenic differences between the two isolates in pigeons. Overall, these findings provide us with important insight into the epidemiology and evolution of PPMV-1 in Pakistan and laid the foundation for the further elucidation of the mechanism underlying the pathogenic difference of PPMV-1 in pigeons.

Adverse Childhood Experiences and Obesity: A One-to-One Correlation?

INTRODUCTION: Adverse childhood experiences (ACEs) have been associated with physical and emotional problems such as obesity and depression in adulthood. This study evaluated the relationship between ACE scores and the severity of obesity. METHODS: We conducted a cross-sectional study of 119 adult patients at the GW Weight Management Clinic. They filled out an ACE survey examining trauma and household dysfunction. The main outcome was the severity of obesity measured by Body Mass Index (BMI). We estimated the adjusted mean difference between high and low ACE risk groups using - linear regression. RESULTS: The data suggest a positive relationship between ACE score and BMI. Patients with severe obesity are more likely to be a high ACE risk (50%) compared to others (24-25%). The average BMI in the high ACE risk group is 3.64 (95% CI: 0.25-7.03) higher than those in the low ACE risk group. The linear regression also showed that as the ACE score increased by 1, BMI increased by 1 unit (95% CI: 0.15-1.77). CONCLUSIONS: Our findings suggest ACE is not just related with the prevalence of obesity, but also the severity of obesity in the overweight and obese population. The linear regression also showed that as the ACE score increased by 1, the BMI increased by 1 unit as well.

The iHealth-T2D study: a cluster randomised trial for the prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes-a statistical analysis plan.

BACKGROUND: South Asians are at high risk of type 2 diabetes (T2D). Lifestyle modification is effective at preventing T2D amongst South Asians, but the approaches to screening and intervention are limited by high costs, poor scalability and thus low impact on T2D burden. An intensive family-based lifestyle modification programme for the prevention of T2D was developed. The aim of the iHealth-T2D trial is to compare the effectiveness of this programme with usual care. METHODS: The iHealth-T2D trial is designed as a cluster randomised controlled trial (RCT) conducted at 120 sites across India, Pakistan, Sri Lanka and the UK. A total of 3682 South Asian men and women with age between 40 and 70 years without T2D but at elevated risk for T2D [defined by central obesity (waist circumference ≥ 95 cm in Sri Lanka or ≥ 100 cm in India, Pakistan and the UK) and/or prediabetes (HbA1c ≥ 6.0%)] were included in the trial. Here, we describe in detail the statistical analysis plan (SAP), which was finalised before outcomes were available to the investigators. The primary outcome will be evaluated after 3 years of follow-up after enrolment to the study and is defined as T2D incidence in the intervention arm compared to usual care. Secondary outcomes are evaluated both after 1 and 3 years of follow-up and include biochemical measurements, anthropometric measurements, behavioural components and treatment compliance. DISCUSSION: The iHealth-T2D trial will provide evidence of whether an intensive family-based lifestyle modification programme for South Asians who are at high risk for T2D is effective in the prevention of T2D. The data from the trial will be analysed according to this pre-specified SAP. ETHICS AND DISSEMINATION: The trial was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and in conference presentations. TRIAL REGISTRATION: EudraCT 2016-001,350-18 . Registered on 14 April 2016. CLINICALTRIALS: gov NCT02949739 . Registered on 31 October 2016.

Reference equations for evaluation of spirometry function tests in South Asia, and among South Asians living in other countries.

BACKGROUND: There are few data to support accurate interpretation of spirometry data in South Asia, a major global region with a high reported burden of chronic respiratory disease. METHOD: We measured lung function in 7453 healthy men and women aged ≥18 years, from Bangladesh, North India, South India, Pakistan and Sri Lanka, as part of the South Asia Biobank study. First, we assessed the accuracy of existing equations for predicting normal forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio. Then, we used our data to derive (n=5589) and internally validate (n=1864) new prediction equations among South Asians, with further external validation among 339 healthy South Asians living in Singapore. RESULTS: The Global Lung Initiative (GLI) and National Health and Nutrition Examination Survey consistently overestimated expiratory volumes (best fit GLI-African American, mean±sd z-score: FEV1 -0.94±1.05, FVC -0.91±1.10; n=7453). Age, height and weight were strong predictors of lung function in our participants (p<0.001), and sex-specific reference equations using these three variables were highly accurate in both internal validation (z-scores: FEV1 0.03±0.99, FVC 0.04±0.97, FEV1/FVC -0.03±0.99) and external validation (z-scores: FEV1 0.31±0.99, FVC 0.24±0.97, FEV1/FVC 0.16±0.91). Further adjustment for study regions improves the model fit, with highest accuracy for estimation of region-specific lung function in South Asia. CONCLUSION: We present improved equations for predicting lung function in South Asians. These offer the opportunity to enhance diagnosis and management of acute and chronic lung diseases in this major global population.

Incidence of synchronous contralateral tonsillar malignancy in a known case of unilateral tonsillar carcinoma.

OBJECTIVE: The literature is divided with regards to contralateral tonsillectomy in a known/suspected case of ipsilateral tonsillar malignancy. In this study, we evaluate the incidence of indolent synchronous contralateral tonsillar malignancy (SCTC) in patients with known ipsilateral tonsillar malignancy. METHODS: All patients diagnosed with ipsilateral tonsillar carcinoma (TC) at a tertiary teaching center between January 2016 and December 2019 were screened. None of the patients were suspected to have bilateral TC. All patients underwent appropriate imaging in the form of Magnetic resonance imaging and computed tomography of head and neck region and then underwent bilateral tonsillectomy. The prevalence of bilateral tonsillar malignancy and the factors predicting them were analyzed. RESULTS: In all 59 patients were included in the study. The mean and median age of the patient population was 60.8 and 59 years, respectively, with a male to female ratio of 3.2:1. The incidence of bilateral tonsillar malignancy in carcinoma of unknown primary (CUP) was 3/10 (33.3%). Among the remaining 49 patients, incidence of synchronous contralateral tonsillar carcinoma (SCTC) was 2/49 (4.08%). Overall, 5/59 (8.5%) patients had synchronous bilateral tonsillar malignancy. Furthermore, dysplasia was found in the contralateral tonsil in 4/10 (40%) CUP patients. Among the remaining 49 patients, dysplasia was seen in the contralateral tonsil in 20/49 (40.8%) patients. The absence of p16 expression predicted higher probability of SCTC. Factors like gender, T stage, nodal status or smoking did not predict SCTC. CONCLUSION: We recommend bilateral tonsillectomy in all patients with suspected or proven TC (unilateral or bilateral) and CUP as it helps identify indolent SCTC and it does not add any significant morbidity to the patients. LEVEL OF EVIDENCE: III.

Diagnostic efficacy of combined CT and MRI in detecting nodal metastasis in patients with oral cancer.

OBJECTIVE: The objective of this study was to assess the diagnostic efficacy of combined computed tomography (CT) and magnetic resonance imaging (MRI) in detecting metastases of oral cancers to lymph nodes in the neck. STUDY DESIGN: In total, 105 patients with previously untreated oral squamous cell carcinoma underwent both CT and MRI within 6 weeks before tumor excision and selective neck dissection. The diagnostic efficacy of combined CT and MRI was compared with published data on the efficacy of CT and MRI alone. RESULTS: The sensitivity, specificity, positive and negative predictive values, and accuracy of diagnosis based on CT and MRI were 80%, 90%, 80%, 90%, and 87%, respectively. These values were similar to or higher than those reported in a meta-analysis for CT or MRI alone. The highest and lowest sensitivities were found for metastatic nodes at levels I (75%) and III (33%). The highest and lowest specificities were discovered for nodes at levels IV (99%) and I (88%). CONCLUSIONS: Combined CT and MRI may be superior to a single modality alone in detecting metastatic neck nodes. This may have an advantage in both preoperative planning and neck surveillance in superficial oral cancers.

The iHealth-T2D study, prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes: study protocol for a randomised controlled trial.

BACKGROUND: People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings. HYPOTHESIS: Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers. DESIGN: Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years. ENTRY CRITERIA: South Asian, men or women, age 40-70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0-6.4% inclusive). EXCLUSION CRITERIA: known type 1 or 2 diabetes, normal or underweight (body mass index < 22 kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness. ENDPOINTS: The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance. INTERVENTION: Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker. RESULTS: We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). CONCLUSION: The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB APPROVAL: 16/WM/0171 TRIAL REGISTRATION: EudraCT 2016-001350-18 . Registered on 14 April 2016. ClinicalTrials.gov NCT02949739 . Registered on 31 October 2016, First posted on 31/10/2016.

Effects of a lifestyle intervention programme after 1 year of follow-up among South Asians at high risk of type 2 diabetes: a cluster randomised controlled trial.

INTRODUCTION: South Asians are at high risk of type 2 diabetes (T2D). We assessed whether intensive family-based lifestyle intervention leads to significant weight loss, improved glycaemia and blood pressure in adults at elevated risk for T2D. METHODS: This cluster randomised controlled trial (iHealth-T2D) was conducted at 120 locations across India, Pakistan, Sri Lanka and the UK. We included 3684 South Asian men and women, aged 40-70 years, without T2D but with raised haemoglobin A1c (HbA1c) and/or waist circumference. Participants were randomly allocated either to the family-based lifestyle intervention or control group by location clusters. Participants in the intervention received 9 visits and 13 telephone contacts by community health workers over 1-year period, and the control group received usual care. Reductions in weight (aim >7% reduction), waist circumference (aim ≥5 cm reduction), blood pressure and HbA1C at 12 months of follow-up were assessed. Our linear mixed-effects regression analysis was based on intention-to-treat principle and adjusted for age, sex and baseline values. RESULTS: There were 1846 participants in the control and 1838 in the intervention group. Between baseline and 12 months, mean weight of participants in the intervention group reduced by 1.8 kg compared with 0.4 kg in the control group (adjusted mean difference -1.10 kg (95% CI -1.70 to -1.06), p<0.001). The adjusted mean difference for waist circumference was -1.9 cm (95% CI -2.5; to 1.3), p<0.001). No overall difference was observed for blood pressure or HbA1c. People who attended multiple intervention sessions had a dose-dependent effect on waist circumference, blood pressure and HbA1c, but not on weight. CONCLUSION: An intensive family-based lifestyle intervention adopting low-resource strategies led to effective reduction in weight and waist circumference at 12 months, which has potential long-term benefits for preventing T2D. A higher number of attended sessions increased the effect on waist circumference, blood pressure and HbA1c. TRIAL REGISTRATION NUMBER: EudraCT: 2016-001350-18; ClinicalTrials.gov: NCT02949739.

Pemphigus Vulgaris and Bullous Pemphigoid of the Upper Aerodigestive Tract: A Review Article and Novel Approaches to Management.

BACKGROUND: Autoimmune bullous diseases are rare conditions characterized by blistering of the skin and mucous membranes. The 2 commonest forms are pemphigus vulgaris and bullous pemphigoid. The oral cavity or oropharynx may be the initial site of presentation or often the only site involved. SUMMARY: These conditions are often misdiagnosed or overlooked leading to poorer patient outcomes. Due to the chronic nature of these conditions and the systemic effects of treatment, there is a significant associated morbidity and mortality. As such, an understanding of the fundamentals of autoimmune bullous diseases is vital to those working in otolaryngology. The mainstay of management in both conditions is topical and systemic corticosteroids. There is also a role for immunomodulating and non-steroidal anti-inflammatory drugs as adjunct or alternative therapies. Surgical intervention may be required to protect the airway. Often multimodality treatment is required involving multidisciplinary input from otolaryngologists, oral surgeons, dermatologists, and rheumatologists. This review article will highlight the aetiology, pathology, clinical features, investigations, and management of both pemphigus vulgaris and bullous pemphigoid including recent advances in management.

Low uptake of COVID-19 prevention behaviours and high socioeconomic impact of lockdown measures in South Asia: Evidence from a large-scale multi-country surveillance programme.

BACKGROUND: South Asia has become a major epicentre of the COVID-19 pandemic. Understanding South Asians' awareness, attitudes and experiences of early measures for the prevention of COVID-19 is key to improving the effectiveness and mitigating the social and economic impacts of pandemic responses at a critical time for the Region. METHODS: We assessed the knowledge, behaviours, health and socio-economic circumstances of 29,809 adult men and women, at 93 locations across four South Asian countries. Data were collected during the national lockdowns implemented from March to July 2020, and compared with data collected prior to the pandemic as part of an ongoing prospective surveillance initiative. RESULTS: Participants were 61% female, mean age 45.1 years. Almost half had one or more chronic disease, including diabetes (16%), hypertension (23%) or obesity (16%). Knowledge of the primary COVID-19 symptoms and transmission routes was high, but access to hygiene and personal protection resources was low (running water 63%, hand sanitisers 53%, paper tissues 48%). Key preventive measures were not widely adopted. Knowledge, access to, and uptake of COVID-19 prevention measures were low amongst people from disadvantaged socio-economic groups. Fifteen percent of people receiving treatment for chronic diseases reported loss of access to long-term medications; 40% reported symptoms suggestive of anxiety or depression. The prevalence of unemployment rose from 9.3% to 39.4% (P < 0.001), and household income fell by 52% (P < 0.001) during the lockdown. Younger people and those from less affluent socio-economic groups were most severely impacted. Sedentary time increased by 32% and inadequate fruit and vegetable intake increased by 10% (P < 0.001 for both), while tobacco and alcohol consumption dropped by 41% and 80%, respectively (P < 0.001), during the lockdown. CONCLUSIONS: Our results identified important knowledge, access and uptake barriers to the prevention of COVID-19 in South Asia, and demonstrated major adverse impacts of the pandemic on chronic disease treatment, mental health, health-related behaviours, employment and household finances. We found important sociodemographic differences for impact, suggesting a widening of existing inequalities. Our findings underscore the need for immediate large-scale action to close gaps in knowledge and access to essential resources for prevention, along with measures to safeguard economic production and mitigate socio-economic impacts on the young and the poor.

Complicated sinusitis with sphenopalatine artery thrombosis in a COVID-19 patient: a case report.

COVID-19 has been a mystery against healthcare professionals. We herein report a rare presentation of complicated sinusitis with pre-septal cellulitis and hard palatal necrosis in a COVID-19 patient. A 52-year-old male was admitted to the hospital with typical COVID manifestations where he had two successive COVID-19 positive swabs. During his admission, he developed symptoms of right orbital complications of sinusitis along with both clinical and radiological evidence of ipsilateral hard palatal necrosis. Imaging confirmed a diagnosis of right pan-sinusitis complicated with right pre-septal infection and hard palatal bony defect on the same side. Our case focuses on the possible association between these manifestations and the known thromboembolic complications of COVID-19. Ongoing management of such complicated rare cases should be through multidisciplinary team.

Delays in surgery for cholesteatoma due to COVID-19: is there an impact on rates of recidivism and major complications?

PURPOSE: To evaluate the relationship between the waiting time for surgery, and cholesteatoma recidivism rates and major complications. The secondary aims were to identify any other prognostic factors for cholesteatoma recidivism. METHODS: A retrospective single-centre study of 312 patients who underwent cholesteatoma surgery under the care of a single-surgeon, between 2004 and 2018, was performed. Waiting times for surgery were categorised into ≤ 90 days, 91-180 days, 181-270 days and > 271 days. The outcome measures were cholesteatoma recidivism and major complications (facial nerve palsy or intracranial complications). RESULTS: The mean age was 36.1 years ± 21.5 with 242 adults (77.6%) and 70 children (22.4%). The mean waiting time for surgery was 126.2 days (4.1 months) ± 96.0 days and the overall rate of recidivism was 11.2% (35/312 patients). No instances of facial nerve palsy or intracranial complications were identified. Rates of recidivism by waiting time for surgery were: 15.3% for 118 patients who waited ≤ 90 days, 9.7% for 134 patients who waited 91-180 days, 6.7% for 30 patients who waited 181-270 days and 4.3% for 23 patients who waited > 271 days. There was no significant difference amongst the different waiting time groups for rates of recidivism (p = 0.266). CONCLUSION: Increased waiting times for cholesteatoma surgery do not appear to be associated with increased rates of recidivism or major complications. Clinical judgement will always be required for complicated disease or patients with additional risk factors. The other prognostic factors for recidivism identified in this study were age (< 15 years) and congenital cholesteatoma.

Tracheal swab from front of neck airway for SARS-CoV-2; a bronchial foreign body.

We report the case of a bronchial foreign body, following a tracheostomy site swab for SARS-CoV-2, aiming to raise awareness and vigilance. A qualified nurse was performing a routine SARS-CoV-2 swab on a 51-year-old woman, fitted with a tracheostomy in the recent past following a craniotomy. This was part of the discharging protocol to a nursing home. During the sampling, part of the swab stylet snapped and was inadvertently dropped through the tracheostomy site. Initial CT imaging was reported as showing no signs of a foreign body but some inflammatory changes. Bedside flexible endoscopy through the tracheostomy site revealed the swab in a right lobar bronchus. This was subsequently removed by flexible bronchoscopy. This case highlights the need for clear guidance on how samples for SARS-CoV-2 are taken from patients with front of neck airways (laryngectomy/tracheοstomy) and the potential pitfalls involved.

Traumatic pseudoaneurysm of the cavernous carotid: a lethal complication of craniofacial trauma.

Pseudoaneurysm of the cavernous carotid artery is a rare, yet life-threatening complication of craniofacial trauma. It may well present itself with delayed massive epistaxis up to several months after the initial insult. Early recognition and prompt treatment are the key in management and a high index of clinical suspicion is always required. In this article, we report a patient with a penetrating head injury who developed delayed epistaxis along with unilateral abducent and partial oculomotor palsy. Urgent diagnostic carotid angiography was undertaken, followed by endovascular coiling that resulted in no recurrence for a year of follow-up.