A framework for conducting policy-relevant primary care research: a COVID-19 case study in Australia.

The onset of the coronavirus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, and the ensuing implementation of response measures directly impacted the delivery of Australian primary care services. Understanding how these measures affected practice activity is important for gauging both their effectiveness and implications for future service planning. During the first 2years of the COVID-19 pandemic, a research project was undertaken to determine the impact of the pandemic on Australian general practice activity as a collaborative undertaking between researchers, general practitioners, data custodians, and five primary health networks from New South Wales and Victoria, Australia. The project methodology was based on an established research approach called action research, which involves participatory involvement from key stakeholders throughout the research process. The strength and success of the project's methodological approach stemmed from the synergistic interrelationship between the four key elements of: collaboration, repeated action research cycles (utilising electronic general practice data), engaged governance, and the production and dissemination of apposite knowledge outcomes. The project approach, knowledge outputs and lessons learned can be adapted to future research undertakings across any primary care setting and highlight the utility of action research and interdisciplinary research collaboration to produce knowledge directly relevant to clinical practice.

Phase II/III trial of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy in severe COVID-19 patients: study protocol for a randomized controlled trial.

BACKGROUND: COVID-19 poses a global health challenge with more than 325 million cumulative cases and above 5 million cumulative deaths reported till January 17, 2022, by the World Health Organization. Several potential treatments to treat COVID-19 are under clinical trials including antivirals, steroids, immunomodulators, non-specific IVIG, monoclonal antibodies, and passive immunization through convalescent plasma. The need to produce anti-COVID-19 IVIG therapy must be continued, alongside the current treatment modalities, considering the virus is still mutating into variants of concern. In this context, as the present study will exploit pooled diversified convalescent plasma collected from recovered COVID-19 patients, the proposed hyperimmune Anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy would be able to counter new infectious COVID-19 variants by neutralizing the virus particles. After the successful outcome of the phase I/II clinical trial of C-IVIG, the current study aims to further evaluate the safety and efficacy of single low dose C-IVIG in severe COVID-19 patients for its phase II/III clinical trial. METHODS: This is a phase II/III, adaptive, multi-center, single-blinded, randomized controlled superiority trial of SARS-CoV-2 specific polyclonal IVIG (C-IVIG). Patients fulfilling the eligibility criteria will be block-randomized using a sealed envelope system to receive either 0.15 g/Kg C-IVIG with standard of care (SOC) or standard of care alone in 2:1 ratio. The patients will be followed-up for 28 days to assess the primary and secondary outcomes. DISCUSSION: This is a phase II/III clinical trial evaluating safety and efficacy of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) in severe COVID-19 patients. This study will provide clinical evidence to use C-IVIG as one of the first-line therapeutic options for severe COVID-19 patients. TRIAL REGISTRATION: Registered at clinicaltrial.gov with NCT number NCT04891172 on May 18, 2021.

Beyond transmission: Dire need for integration of nutrition interventions in COVID-19 pandemic-response strategies in Developing Countries like Pakistan.

Synergistic associations between infection and nutrition are well known. Impact of nutrition interventions on the outcomes have been scientifically assessed and reported. The role of nutrition in limiting the infection related morbidity and mortality does not appear to be a debatable question but nutrition interventions do not appear to be an essential part of current COVID-19 management strategies. Given the nature of pandemic and lack of organism-specific evidence, variability in nutrition interventions and lack of nutrition interventions is not unexpected. However, delay in realization of the crucial need of nutrition interventions to limit the immediate and long term outcomes at personal and community level may aggravate health related issues that can have long term impact on quality of life and economy. Due to existing undernutrition and lack of nutrition related awareness and competence, need for timely and appropriate interventions is much more critical for developing countries. This manuscript highlights the need and feasibility of various nutrition interventions to assure optimum quality of life during and after COVID-19 pandemic. Available evidence provides enough guidance for nutrition interventions that are safe and promise to accrue various degrees of benefits with almost no likelihood of harm. Nutrition interventions suggested by author are: 1) population level efforts for promoting better use of existing resources; 2) quicker augmentation of nutrition status of high risk people and non-hospitalized cases by use of supplement and individualized guidance and 3) nutritional support of sever case by timely and adequate enteral and parenteral feeding.

Telehealth-based diagnostic testing in general practice during the COVID-19 pandemic: an observational study.

BACKGROUND: Since the World Health Organization declared COVID-19 a pandemic on 11 March 2020, health technologies have been rapidly scaled up to ensure access to care. A significant innovation has been telehealth in general practice. Now widespread, it remains unknown how this shift to virtual care has impacted on quality-of-care indicators such as pathology testing and diagnosis. AIM: To undertake a comparison of telehealth and face-to-face general practice consultations to: identify if there were differences in the proportion of pathology test referrals from 2019-2020; and quantify any change in pathology test collection and follow-up patterns. DESIGN & SETTING: Retrospective observational study of routinely collected electronic patient data from 807 general practices across New South Wales (NSW) and Victoria, Australia. METHOD: Multivariate generalised estimating equation models were used to estimate the proportion of pathology test referrals for overall, face-to-face, and telehealth consultations. Pathology test follow-up was described through median (and interquartile range [IQR]) time. RESULTS: Pathology test referrals declined during periods of high COVID-19 cases, falling from 10.8% in February 2020 to a low of 4.5% during the first peak in April. Overall, pathology test referrals were lower for telehealth than face-to-face consultations. Median time between referral and test collection was 3 days (IQR 1-14) for telehealth and 1 day (IQR 0-7) for face to face. CONCLUSION: For telehealth to become part of routine care, it is crucial that gaps in functionality, including difficulty in test referral processes, be addressed. Quality improvements supporting care practices will ensure clinicians' workflows are supported and patients receive diagnostic testing.

Medication prescribing in face-to-face versus telehealth consultations during the COVID-19 pandemic in Australian general practice: a retrospective observational study.

BACKGROUND: There has been a precipitous rise in telehealth use in general practice during the COVID-19 pandemic. Understanding differences between face-to-face and telehealth consulting is an important component for planning the future use of telehealth services beyond the pandemic. However, there is limited evidence on whether telehealth consulting impacts medication prescribing under pandemic circumstances. AIM: To compare medication prescribing in face-to-face consultations with telehealth during the COVID-19 pandemic in Australian general practice. DESIGN & SETTING: A multisite, retrospective observational study. De-identified routinely collected electronic health data were used, which were extracted from 806 general practices in Victoria and New South Wales (NSW), Australia, between April and December 2020. METHOD: The primary outcome measure was whether at least one medication was prescribed following a telehealth or face-to-face consultation. Data were reported by medication and for each of the Anatomical Therapeutic Chemical (ATC) classification system level 1 groups. The secondary outcome measure was first-time prescribing. Telehealth included both telephone and video consultations. RESULTS: A total of 13 608 216 consultations satisfied the inclusion criteria (61.0% face to face and 39.0% telehealth). Most telehealth consultations were conducted via telephone (97.8%). Overall, 39.3% of face-to-face and 33.0% of telehealth consultations prescribed at least one medication, which is a statistically significant difference (adjusted odds ratio [OR] 1.38, 95% confidence interval [CI] = 1.379 to 1.381). The prescribing rate was greater for face-to-face versus telehealth consultations for all drug groups except ATC level 1N (nervous system). CONCLUSION: Under COVID-19 restrictions in the states of Victoria and NSW, Australia, medication prescribing was higher in face-to-face consultations when compared with telehealth consultations in the study population.

Risk factors for mortality and progression to severe COVID-19 disease in the Southeast region in the United States: A report from the SEUS Study Group.

OBJECTIVE: Identify risk factors that could increase progression to severe disease and mortality in hospitalized SARS-CoV-2 patients in the Southeast region of the United States. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, retrospective cohort including 502 adults hospitalized with laboratory-confirmed COVID-19 between March 1, 2020, and May 8, 2020 within 1 of 15 participating hospitals in 5 health systems across 5 states in the Southeast United States. METHODS: The study objectives were to identify risk factors that could increase progression to hospital mortality and severe disease (defined as a composite of intensive care unit admission or requirement of mechanical ventilation) in hospitalized SARS-CoV-2 patients in the Southeast United States. RESULTS: In total, 502 patients were included, and 476 of 502 (95%) had clinically evaluable outcomes. The hospital mortality rate was 16% (76 of 476); 35% (177 of 502) required ICU admission and 18% (91 of 502) required mechanical ventilation. By both univariate and adjusted multivariate analyses, hospital mortality was independently associated with age (adjusted odds ratio [aOR], 2.03 for each decade increase; 95% confidence interval [CI], 1.56--2.69), male sex (aOR, 2.44; 95% CI, 1.34-4.59), and cardiovascular disease (aOR, 2.16; 95% CI, 1.15-4.09). As with mortality, risk of severe disease was independently associated with age (aOR, 1.17 for each decade increase; 95% CI, 1.00-1.37), male sex (aOR, 2.34; 95% CI, 1.54-3.60), and cardiovascular disease (aOR, 1.77; 95% CI, 1.09-2.85). CONCLUSIONS: In an adjusted multivariate analysis, advanced age, male sex, and cardiovascular disease increased risk of severe disease and mortality in patients with COVID-19 in the Southeast United States. In-hospital mortality risk doubled with each subsequent decade of life.

COVID-19: protocol for observational studies utilizing near real-time electronic Australian general practice data to promote effective care and best-practice policy-a design thinking approach.

BACKGROUND: Health systems around the world have been forced to make choices about how to prioritize care, manage infection control and maintain reserve capacity for future disease outbreaks. Primary healthcare has moved into the front line as COVID-19 testing transitions from hospitals to multiple providers, where tracking testing behaviours can be fragmented and delayed. Pooled general practice data are a valuable resource which can be used to inform population and individual care decision-making. This project aims to examine the feasibility of using near real-time electronic general practice data to promote effective care and best-practice policy. METHODS: The project will utilize a design thinking approach involving all collaborators (primary health networks [PHNs], general practices, consumer groups, researchers, and digital health developers, pathology professionals) to enhance the development of meaningful and translational project outcomes. The project will be based on a series of observational studies utilizing near real-time electronic general practice data from a secure and comprehensive digital health platform [POpulation Level Analysis and Reporting (POLAR) general practice data warehouse]. The study will be carried out over 1.5 years (July 2020-December 2021) using data from over 450 general practices within three Victorian PHNs and Gippsland PHN, Eastern Melbourne PHN and South Eastern Melbourne PHN, supplemented by data from consenting general practices from two PHNs in New South Wales, Central and Eastern Sydney PHN and South Western Sydney PHN. DISCUSSION: The project will be developed using a design thinking approach, leading to the building of a meaningful near real-time COVID-19 geospatial reporting framework and dashboard for decision-makers at community, state and nationwide levels, to identify and monitor emerging trends and the impact of interventions/policy decisions. This will integrate timely evidence about the impact of the COVID-19 pandemic related to its diagnosis and treatment, and its impact across clinical, population and general practice levels.

Acute Pancreatitis in a Patient With COVID-19 After the Resolution of Respiratory Symptoms.

The gastrointestinal (GI) involvement, including acute pancreatitis (AP) from the novel coronavirus disease-2019 (COVID-19), is increasingly being reported. Recent evidence suggests that the pathogenesis of COVID-19 is mediated by the angiotensin-converting enzyme 2 (ACE-2) receptors and transmembrane protease serine 2 (TMPRSS2) for "priming," which is highly expressed in the pancreas. To our knowledge, there is no other reported case of AP associated with COVID-19 after the respiratory symptoms are resolved. In this article, we present a patient with COVID-19, who came with intractable epigastric pain and resolved respiratory symptoms. A diagnosis of AP complicated with COVID-19 was made after laboratory and imaging workup, which was successfully managed conservatively.

Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial.

BACKGROUND: Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis. METHODS: A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intention-to-treat population). The trial was registered at clinicaltrials.gov (NCT04521309). FINDINGS: Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54±13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087-1.272), arm II (RR, 0.5; 95% CI, 0.171-1.463), arm III (RR, 0.167; 95% CI, 0.024-1.145), and arm IV (RR, 0.667; 95% CI, 0.268-1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127-400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study. INTERPRETATION: Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression. FUNDING: Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).

Impacts of Autonomous Vehicles on Greenhouse Gas Emissions-Positive or Negative?

The potential effects of autonomous vehicles (AVs) on greenhouse gas (GHG) emissions are uncertain, although numerous studies have been conducted to evaluate the impact. This paper aims to synthesize and review all the literature regarding the topic in a systematic manner to eliminate the bias and provide an overall insight, while incorporating some statistical analysis to provide an interval estimate of these studies. This paper addressed the effect of the positive and negative impacts reported in the literature in two categories of AVs: partial automation and full automation. The positive impacts represented in AVs' possibility to reduce GHG emission can be attributed to some factors, including eco-driving, eco traffic signal, platooning, and less hunting for parking. The increase in vehicle mile travel (VMT) due to (i) modal shift to AVs by captive passengers, including elderly and disabled people and (ii) easier travel compared to other modes will contribute to raising the GHG emissions. The result shows that eco-driving and platooning have the most significant contribution to reducing GHG emissions by 35%. On the other side, easier travel and faster travel significantly contribute to the increase of GHG emissions by 41.24%. Study findings reveal that the positive emission changes may not be realized at a lower AV penetration rate, where the maximum emission reduction might take place within 60-80% of AV penetration into the network.

Management of COVID-19: current status and future prospects.

COVID-19, a highly transmissible pandemic disease, is affecting millions of lives around the world. Severely infected patients show acute respiratory distress symptoms. Sustainable management strategies are required to save lives of the infected people and further preventing spread of the virus. Diagnosis, treatment, and vaccination development initiatives are already exhibited from the scientific community to fight against this virus. In this review, we primarily discuss the management strategies including prevention of spread, prophylaxis, vaccinations, and treatment for COVID-19. Further, analysis of vaccine development status and performance are also briefly discussed. Global socioeconomic impact of COVID-19 is also analyzed as part of this review.

Diagnosis for COVID-19: current status and future prospects.

Introduction: Coronavirus disease 2019 (COVID-19), a respiratory illness caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had its first detection in December 2019 in Wuhan (China) and spread across the world. In March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic disease. The utilization of prompt and accurate molecular diagnosis of SARS-CoV-2 virus, isolating the infected patients, and treating them are the keys to managing this unprecedented pandemic. International travel acted as a catalyst for the widespread transmission of the virus.Areas covered: This review discusses phenotype, structural, and molecular evolution of recognition elements and primers, its detection in the laboratory, and at point of care. Further, market analysis of commercial products and their performance are also evaluated, providing new ways to confront the ongoing global public health emergency.Expert commentary: The outbreak for COVID-19 created mammoth chaos in the healthcare sector, and still, day by day, new epicenters for the outbreak are being reported. Emphasis should be placed on developing more effective, rapid, and early diagnostic devices. The testing laboratories should invest more in clinically relevant multiplexed and scalable detection tools to fight against a pandemic like this where massive demand for testing exists.

Social stigmatisation among COVID-19 patients: addressing a potential source of COVID-19 transmission to healthcare staff in cardiac emergency and cardiac care units

During our routine work, we noticed an increased incidence of COVID-19 diagnoses among patients in the cardiac unit, which led to an exponential increase in COVID-19 cases among hospital staff. We found that patients hid their symptoms from the emergency doctors and attributed those symptoms to cardiac or other causes. Social stigmatisation appeared to be the root cause for hiding their symptoms. Hence, we recommended a strategy to introduce psychological counselling of patients who were suspected to be infected with COVID-19, with a normal cardiac workup to overcome social stigmatisation and save our general wards from COVID-19.

Hyperimmune anti-COVID-19 IVIG (C-IVIG) Therapy for Passive Immunization of Severe and Critically Ill COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on severe and critically ill patients with COVID-19. TRIAL DESIGN: This is a phase I/II single centre, randomised controlled, single-blinded, superiority trial, through parallel-group design with sequential assignment. Participants will be randomised either to receive both C-IVIG and standard care or only standard care (4:1). PARTICIPANTS: The study is mono-centric with the participants including COVID19 infected individuals (positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs) admitted in institute affiliated with Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan. Consenting patients above 18 years that are classified by the treating physician as severely ill i.e. showing symptoms of COVID-19 pneumonia; dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93%, PaO2/FiO2 <300, and lung infiltrates >50% on CXR; or critically ill i.e. respiratory failure, septic shock, and multiple organ dysfunction or failure. Patients with reported IgA deficiency, autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents to maintain blood pressure and patients with acute or chronic kidney injury/failure, were also excluded from the study. INTERVENTION AND COMPARATOR: The study consists of four interventions and one comparator arm. All participants receive standard hospital care which includes airway support, anti-viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti-pyretics. Randomised test patients will receive single dose of C-IVIG in following four dosage groups: Group 1: 0.15g/Kg with standard hospital care Group 2: 0.2g/Kg with standard hospital care Group 3: 0.25g/Kg with standard hospital care Group 4: 0.3g/Kg with standard hospital care Group 5 (comparator) will receive standard hospital care only MAIN OUTCOMES: The primary outcomes are assessment and follow-up of participants to observe 28-day mortality and, • the level and duration of assisted ventilation during hospital stay, • number of days to step down (shifting from ICU to isolation ward), • number of days to hospital discharge, • adverse events (Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)) during hospital stay, • change in C-Reactive Protein (CRP) levels, • change in neutrophil lymphocyte ratio to monitor inflammation. RANDOMISATION: Consenting participants who fulfill the criteria are allocated to either intervention or comparator arm with a ratio of 4:1, using sequentially numbered opaque sealed envelope simple randomization method. The participant allocated for intervention will be sequentially assigned dosage group 1-4 in ascending order. Participants will not be recruited in the next dosage group before a set number of participants in one group (10) are achieved. BLINDING (MASKING): Single blinded study, with participants blinded to allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Total 50 patients are randomised. The intervention arms consist of 40 participants divided in four groups of 10 participants while the comparator group consists of 10 patients. TRIAL STATUS: Current version of the protocol is "Version 2" dated 29th September, 2020. Participants are being recruited. Recruitment started on June, 2020 and is estimated to primarily end on January, 2021. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov, NCT04521309 on 20 August 2020 and is retrospectively registered. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).

Chest computed tomography findings in hospitalized COVID-19 patients: a systematic review and meta-analysis.

Most studies evaluating chest computed tomography (CT) features in coronavirus disease 2019 (COVID-19) have been small-sized and have presented varied findings. We aim to systematically review these studies and to conduct a meta-analysis of their results to provide a well-powered assessment of chest CT findings in patients with COVID-19. PubMed and EMBASE databases were systematically searched to identify published studies that evaluated chest CT findings in COVID-19 patients. Data regarding study characteristics and CT findings, including distribution of lesions, the lobe of lung involved, lesion densities, and radiological patterns, were extracted. Arcsine transformed proportions from individual studies were pooled using a random-effects model to derive pooled proportions (PPs) and 95% confidence intervals (CIs). A total of fifty-four studies (n=2693 confirmed COVID-19 patients) were included in the final review. Prevalence of different CT findings varied across studies; however, the most common findings were bilateral pulmonary involvement (PP: 74.1% [68.4%, 79.5%]; I2 = 85.76%), ground glass opacification (PP: 64.6% [57.6%, 71.4%]; I2 = 91.52%), involvement of the left lower lobe (PP: 71.2% [58.9%, 82.1%]; I2 = 90.91%), and subpleural distribution of lesions (PP: 57.2% [39.0%, 74.3%]; I2 = 93.08%). Multivariate meta-regression revealed a positive association between prevalence of air bronchograms and average age of the population (p=0.013). Bilateral ground glass opacification, a subpleural distribution of lesions, and involvement of the left lower lobe were the most notable chest CT findings in COVID-19 patients.

COVID-19 Pneumonia: An Emerging Cause of Syndrome of Inappropriate Antidiuretic Hormone.

Syndrome of inappropriate antidiuretic hormone (SIADH) is the leading cause of hyponatremia. We, herein, report a case of a patient with coronavirus disease-2019 (COVID-19) who developed sudden exertional dyspnea and hypoxia and was found to be hyponatremic. A diagnosis of SIADH was made due to COVID-19 pneumonia. The patient was managed conservatively with a significant improvement during the course of hospitalization and on follow-up.