Background:

Patients with multimorbidity often require services across different health care settings, yet team processes among settings are rarely implemented. We explored perceptions of specialists and family physicians collaborating in a telemedicine interprofessional consultation for patients with multimorbidity to better understand the value of bringing physicians together across the boundaries of health care settings.

Methods:

This was a descriptive qualitative, interview-based study. Physicians who had previously participated in the Telemedicine Interprofessional Model of Practice for Aging and Complex Treatments (Telemedicine IMPACT Plus [TIP] Program) were invited to participate and asked to describe their experience of being a member of the program. Interviews were conducted from March to May 2016. We conducted an iterative and interpretive process using both individual and team analysis to identify themes.

Results:

There were 15 participants, 9 specialists and 6 family physicians. Three themes emerged in the analysis: creating new perspectives on care for patients with multimorbidity by sharing knowledge, skills and attitudes; the shift from a consultant model to an interprofessional team model (allowing a window into the community, extending discussions beyond the medical model and focusing on the patient’s health in context); and opportunities for learners, including learning about interprofessional collaboration and gaining exposure to a real-world model for caring for people with multimorbidity in outpatient settings.

Interpretation:

Family physicians and specialists participating in a TIP Program believed the program improved their knowledge and skills, while also serving as an effective care delivery strategy. The findings also support that learners require more exposure to nontraditional consultant models in order to care for patients with multimorbidity effectively.

Background:

Female physicians have been shown to receive fewer awards from medical societies than their male colleagues. We examined the sex distribution of recipients of Canadian residency association awards.

Methods:

We conducted a retrospective observational study of the sex of staff and resident physician recipients of resident-selected awards from provincial and national residency associations using data from 2000–2018. We classified awards into professionalism, advocacy and wellness awards, and education and teaching awards based on award names and descriptions, and compared the proportion of male and female recipients in these categories.

Results:

We identified 314 recipients of staff physician awards and 129 recipients of resident physician awards. Male staff and resident physicians had higher odds of receiving awards than their female counterparts (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.13–1.89 and OR 1.70, 95% CI 1.18–2.46, respectively). There was a reduction in the odds of male residents’ receiving an award over the study period (OR 0.94, 95% CI 0.90–0.98). Male physicians had higher odds of receiving education and teaching awards than female physicians as staff but not as residents (OR 3.21, 95% CI 1.72–5.95 and OR 1.96, 95% CI 0.84–4.60, respectively).

Interpretation:

Male staff and resident physicians in Canada had higher odds of receiving awards from provincial and national residency associations between 2000 and 2018 than their female counterparts. Given this disparity, it would be prudent for organizations that distribute awards to physicians, residents and medical students to examine their nomination criteria and processes for potential bias.

At the end of 2019 and early 2020, an outbreak of pneumonia of unknown etiology emerged in the city of Wuhan in China. The cases were found to be caused by a novel beta coronavirus, which was subsequently named SARS-CoV-2 by the World Health Organization (WHO). The virus has since spread further in China and to other regions of the world, having infected more than 88 K people, and causing close to 3000 deaths as of March 1, 2020. More than 50 million people remain in quarantine at this time. Scientists and clinicians globally are working swiftly to combat COVID-19, the respiratory disease caused by the virus. Notably, diagnostic assays have been developed rapidly in many countries, and have played significant roles in diagnosis, monitoring, surveillance, and infection control. Starting February 29, 2020, the development and performance of molecular testing for SARS-CoV-2 in high complexity Clinical Laboratory Improvement Amendments (CLIA) laboratories prior to emergency use authorization was allowed by the US FDA. Although the epidemic is evolving rapidly, many valuable lessons have been learned and many questions remain to be answered. Here we invited multiple experts across the globe from clinical laboratories, public health laboratories, infection control, and diagnostic industry to share their views on the diagnosis, infection control, and public perception of SARS-CoV-2.

Whether low plasma 25-hydroxyvitamin D concentrations cause osteoporotic fractures is unclear. We tested the hypothesis that low plasma 25-hydroxyvitamin D concentrations are associated with increased risk of osteoporotic fractures using a Mendelian randomization analysis.We genotyped 116 335 randomly chosen white Danish persons aged 20–100 years in 2 population-based cohort studies for plasma 25-hydroxyvitamin D decreasing genotypes in CYP2R1 (rs117913124 and rs12794714), DHCR7 (rs7944926 and rs11234027), GEMIN2 (rs2277458), and HAL (rs3819817); 35 833 had information on plasma 25-hydroxyvitamin D. We assessed risk of total, osteoporotic, and anatomically localized fractures from 1981 through 2017. Information on fractures and vital status was obtained from nationwide registries.During up to 36 years of follow-up, we observed 17 820 total fractures, 10 861 osteoporotic fractures, and 3472 fractures of hip or femur. Compared with individuals with 25-hydroxyvitamin D ≥ 50nmol/L, multivariable adjusted hazard ratios (95% CIs) for total fractures were 1.03 (0.97–1.09) for individuals with 25–49.9 nmol/L, 1.19 (1.10–1.28) for individuals with 12.5–24.9 nmol/L, and 1.39 (1.21–1.60) for individuals with 25-hydroxyvitamin D < 12.5 nmol/L. Corresponding hazard ratios were 1.07 (1.00–1.15), 1.25 (1.13–1.37), and 1.49 (1.25–1.77) for osteoporotic fractures and 1.09 (0.98–1.22), 1.37 (1.18–1.57), and 1.41 (1.09–1.81) for fractures of hip or femur, respectively. Hazard ratios per 1 increase in vitamin D allele score, corresponding to 3.0% (approximately 1.6 nmol/L) lower 25-hydroxyvitamin D concentrations, were 0.99 (0.98–1.00) for total fractures, 0.99 (0.97–1.00) for osteoporotic fractures, and 0.98 (0.95–1.00) for fractures of hip or femur.Low plasma 25-hydroxyvitamin D concentrations were associated with osteoporotic fractures; however, Mendelian randomization analysis provided no evidence supporting a causal role for vitamin D in the risk for osteoporotic fractures.

S100A8/A9 is implicated in inflammation mechanisms related to atherosclerosis and plaque vulnerability, but it remains unclear whether S100A8/A9 is associated with the prognosis of ischemic stroke. The aim of this study was to investigate these associations in 2 independent multicenter cohorts.Plasma S100A8/A9 concentrations at baseline were measured among 4785 patients with ischemic stroke from 2 independent cohorts: Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke (IIPAIS) and China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite outcome of death or major disability at 3 months after ischemic stroke. Secondary outcomes were major disability, death, and a composite outcome of death or vascular events.Among the combined participants of IIPAIS and CATIS, the adjusted odds ratios associated with the highest quartile of plasma S100A8/A9 were 2.11 (95% CI, 1.66–2.68) for the primary outcome and 1.62 (95% CI, 1.27–2.07) for the secondary outcome of major disability; adjusted hazard ratios were 4.14 (95% CI, 2.10–8.15) for the secondary outcome of death and 2.08 (95% CI, 1.38–3.13) for the composite outcome of death or vascular events. Each SD increase of log-transformed S100A8/A9 was associated with 28% (95% CI, 18%–39%; P < 0.001) increased risk of the primary outcome. Multivariable-adjusted spline regression analyses showed a linear association between plasma S100A8/A9 concentrations and primary outcome (P < 0.001 for linearity). Subgroup analyses further confirmed these associations.High plasma S100A8/A9 concentrations at baseline were independently associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that S100A8/A9 might have a role as a prognostic marker of ischemic stroke.

Cushing syndrome results from chronic excessive exposure to glucocorticoids, impacting virtually every organ system with the most dominant effects on fat metabolism, immune function, and musculoskeletal systems. Endogenous Cushing syndrome is rare, most usually due to excess ACTH secretion from pituitary, and less frequently from ectopic tumors. Other cases result from ACTH-independent adrenal overproduction of cortisol.

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Lai et al. report the case of an elderly gentleman who presented with resolving neurologic findings from a transient ischemic attack and who was found to have hyponatremia with a serum sodium concentration of 123 mmol/L. Hypoosmolality was confirmed, and a diluting defect identified with a urine osmolality that ranged between 167 and 285 mOsm/kg. As the urine osmolality rose to > 400 mOsm/kg with water deprivation, a diagnosis of syndrome of inappropriate antidiuresis (SIAD) from reset osmostat was entertained.

This interesting case report from South Africa focuses on a difficult diagnostic challenge: apparent Cushing syndrome with inconsistent laboratory findings.

The measurement of neuron-specific enolase (NSE) in serum is frequently requested for diagnosis, risk stratification, and treatment monitoring of neuroblastoma (NB) in the pediatric population. However, authoritative clinical practice guidelines advise about the poor diagnostic performance of NSE.We critically appraised the available literature evaluating the diagnostic and prognostic value of NSE in the management of NB, paying special attention to the definition of appropriate threshold levels. In addition, we discuss the interfering conditions causing artifactual increases of NSE concentrations in serum and potentially influencing the clinical evaluation of patients with suspected NB.No definitive evidence supports the use of serum NSE for diagnosis and monitoring of NB. The risk of obtaining false-positive NSE results associated with confounders (e.g., sample hemolysis) and other pathophysiologic conditions (e.g., inflammation) is remarkable and hampers the diagnostic value of this test. NSE may be helpful to define the risk of death of patients with NB, mainly in the advanced stages of disease. However, further studies validating currently marketed immunoassays and defining threshold values useful for this scope are warranted.

Hyponatremia, the most common electrolyte disorder, is present in 2%–4% of ambulatory patients and up to 22% of geriatric inpatients (1). Clinicians classify hyponatremia into three main categories: hypovolemic (decreased intravascular volume from salt and water loss with inadequate replacement), euvolemic (normal intravascular volume, but increased water dilutes sodium), and hypervolemic (total body water is increased, usually causing edema, while intravascular volume is often decreased). Less frequent causes are pseudohyponatremia (due to decreased water in a fixed volume of plasma, usually due to increased lipids or protein) and water shifting due to increased osmolality (most commonly due to glucose). While the most extreme examples of hypovolemic and hypervolemic states can be determined by physical examination, in many cases the patient is euvolemic clinically.

Cancer continues to be one of the leading causes of morbidity and mortality in the US. Although the treatment of cancer has evolved over the past decades with the use of targeted therapies and immunotherapy, many of these new treatments are expensive and are not readily available to everyone. Moreover, the recent success with treatment advances are not generalized to all cancer types, as some cancers continue to be devastating without significant progress in treatment options. Hence, early detection through population screening remains a critical armament against cancer.

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Dramatically rising costs in drug development are in large part because of the high failure rates in clinical phase trials. The poor correlation of animal studies to human toxicity and efficacy have led many developers to question the value of requiring animal studies in determining which drugs should enter in-human trials. Part 1 of this 2-part series examined some of the data regarding the lack of concordance between animal toxicity studies and human trials, as well as some of the potential reasons behind it. This second part of the series focuses on some alternatives to animal trials (hereafter referred to as animal research) as well as current regulatory discussions and developments regarding such alternatives.

Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development.

This study showed that treatment with a therapeutic monoclonal immunoglobulin-G1 antibody against phosphorylcholine on oxidized phospholipids preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of ¹⁸F-fluorodeoxyglucose in atherosclerotic mice. The noninvasive imaging techniques represent translational tools to assess the efficacy of phosphorylcholine-targeted therapy on coronary artery function and atherosclerosis in clinical studies.

This work established a new murine venous thromboembolism (VTE) model. This model has multiple novel features representing clinical VTE that include the following: 1) deep venous thrombosis (DVT) was formed and extended in the long axis of femoral/saphenous vein; 2) thrombus was formed in a venous valve pocket; 3) deligation of suture-induced spontaneous pulmonary emboli of fibrin-rich DVT; and 4) cardiac motion-free femoral/saphenous vein allowed high-resolution intravital microscopic imaging of fibrin-rich DVT. This new model requires only commercially available epifluorescence microscopy. Therefore, this model has significant potential for better understanding of VTE pathophysiology.

Combined pre-and post-capillary hypertension (CpcPH) is a relatively common complication of heart failure (HF) associated with a poor prognosis. Currently, there is no specific therapy approved for this entity. Recently, treatment with beta-3 adrenergic receptor (β3AR) agonists was able to improve pulmonary hemodynamics and right ventricular (RV) performance in a translational, large animal model of chronic PH. The authors present the design of a phase II randomized clinical trial that tests the benefits of mirabegron (a clinically available β3AR agonist) in patients with CpcPH due to HF. The effect of β3AR treatment will be evaluated on pulmonary hemodynamics, as well as clinical, biochemical, and advanced cardiac imaging parameters. (Beta3 Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure [SPHERE-HF]; NCT02775539)

We are already a couple of months into 2020 and I hope you had a good start to the new year. I wish you, our readers, reviewers, authors and editors, happiness, success and health in this new decade.

In low-dose computed tomography (LDCT) screening for lung cancer, all three main conditions for overdiagnosis in cancer screening are present: 1) a reservoir of slowly or nongrowing lung cancer exists; 2) LDCT is a high-resolution imaging technology with the potential to identify this reservoir; and 3) eligible screening participants have a high risk of dying from causes other than lung cancer. The degree of overdiagnosis in cancer screening is most validly estimated in high-quality randomised controlled trials (RCTs), with enough follow-up time after the end of screening to avoid lead-time bias and without contamination of the control group.

Nine RCTs investigating LDCT screening were identified. Two RCTs were excluded because lung cancer incidence after the end of screening was not published. Two other RCTs using active comparators were also excluded. Therefore, five RCTs were included: two trials were at low risk of bias, two of some concern and one at high risk of bias. In a meta-analysis of the two low risk of bias RCTs including 8156 healthy current or former smokers, 49% of the screen-detected cancers were overdiagnosed. There is uncertainty about this substantial degree of overdiagnosis due to unexplained heterogeneity and low precision of the summed estimate across the two trials.

Key points

Nine randomised controlled trials (RCTs) on low-dose computed tomography screening were identified; five were included for meta-analysis but only two of those were at low risk of bias.

In a meta-analysis of recent low risk of bias RCTs including 8156 healthy current or former smokers from developed countries, we found that 49% of the screen-detected cancers may be overdiagnosed.

There is uncertainty about the degree of overdiagnosis in lung cancer screening due to unexplained heterogeneity and low precision of the point estimate.

If only high-quality RCTs are included in the meta-analysis, the degree of overdiagnosis is substantial.

Educational aims

To appreciate that low-dose computed tomography screening for lung cancer meets all three main conditions for overdiagnosis in cancer screening: a reservoir of indolent cancers exists in the population; the screening test is able to "tap" this reservoir by detecting biologically indolent cancers as well as biologically important cancers; and the population being screened is characterised by a relatively high competing risk of death from other causes

To learn about biases that might affect the estimates of overdiagnosis in randomised controlled trials in cancer screening

Chronic obstructive pulmonary disease (COPD) is characterised by persistent respiratory symptoms and airflow limitation, which is caused by small airway disease (bronchiolitis) and alveolar destruction (emphysema) [1]. Patients primarily suffering from severe emphysema are often limited in exercise capacity due to the consequences of hyperinflation [2].

Some years ago, I entered a completely unfamiliar world. This was a landscape that clinicians deal with every day but for the individual suspected of having lung cancer, it can appear hostile and scary, often misrepresented by outdated imagery, information and television portrayal. Lung cancer is not awash with celebrities admitting to having it or grand fundraising campaigns like other conditions. Despite many changes in the treatment landscape, it's still generally much more stigmatised than other cancers.

Sleep and breathing disorders are highly prevalent, representing a growing subspecialty of respiratory medicine. The term sleep disordered breathing (SDB) encompasses a range of conditions characterised by abnormal breathing during sleep, from chronic or habitual snoring, to frank obstructive sleep apnoea (OSA) or, in some cases, central sleep apnoea (CSA) and hypoventilation syndromes. OSA is the commonest form of SDB, leading to many potential consequences and adverse clinical outcomes, including excessive daytime sleepiness, impaired daytime function, metabolic dysfunction, and an increased risk of cardiovascular disease and mortality [1]. The estimated reported prevalence of moderate-to-severe SDB (≥15 events·h^–1) was 23.4% in women and 49.7% in men, and the prevalence of symptomatic OSA was 9% and 13%, respectively [2]. However, in some populations, the prevalence of OSA is substantially higher, such as in patients been evaluated for bariatric surgery (estimated range 70–80%), in patients who have had a transient ischaemic attack or stroke (estimated range 60–70%) and in patients with cardiometabolic disease [3–6]. Limited data have been reported on CSA and non-obstructive sleep-related hypoventilation, which have received considerable interest in the sleep field within the past 10 years. Even if their prevalence was noted to be quite low relative to the prevalence of OSA [7], they are quite common in specific subpopulations [8–10].

Since lung cancer (LC) is still the leading cause of cancer deaths worldwide [1], early detection through screening represents an important opportunity to improve LC survival and is a priority area for cancer care. The National Lung Screening Trial (NLST) aimed to compare low-dose helical computed tomography (LDCT) with chest radiography in LC screening of current or former heavy smokers. The trial found a relative reduction in mortality from LC of 20% in those who had undergone LDCT screening. LC screening has regained prominence in the thoracic oncology literature with the completion of NELSON and other European trials, which support the role of LC screening in achieving early diagnosis and reducing mortality. A growing number of implementation pilots are providing an impetus towards organised, national programmes for LC screening, which are in need of long-term follow-up data such as those presented in this study.

The diagnostic process of idiopathic interstitial pneumonias (IIPs) is complex and the underlying mechanisms that participate in these diseases still need to be fully understood. In 2015, the European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-Associated Interstitial Lung Disease introduced the term "interstitial pneumonia with autoimmune features" (IPAF) to identify subjects with IIP and features suggesting background autoimmunity but not characterisable connective tissue disease (CTD) [1]. The need for a proper clinical, serological and morphological assessment of IIP was highlighted to identify potential subjects with IPAF and CTD-ILD. However, the measurement of anti-neutrophil cytoplasmic antibodies (ANCAs) is not included in the definition of IPAF and ANCA serological testing is only recommended in idiopathic pulmonary fibrosis (IPF) when a clinical suspicion of vasculitis exists [2]. As current research evaluates the prognostic relevance of autoimmune features in IIP, the clinical importance of ANCA positivity still needs to be determined.

A 25-year-old male is admitted with complaints of dry cough for the past 5 years, and increased thirst, urinary frequency and output for the past 18 months. He also complains of shortness of breath on climbing a flight of stairs, and itchy lesions on the scalp and back for the past 2–3 months. There is no history of bone pain or abdominal pain. He has history of bilateral recurrent pneumothoraxes, twice on the right and once on the left side, in the past month. Pleurodesis with povidone iodine is performed on left side and the patient is transferred to your hospital with persistent right pneumothorax with air leak, with an intercostal drainage tube in situ. The patient is a never-smoker with no family history of pneumothorax. On general examination, he has small papules, 1–2 mm in diameter, with scaling over scalp and back. Onycholysis, onychoschisis and subungual splinter haemorrhages are present (figure 1).

Venous thromboembolism (VTE), as a term that encompasses pulmonary embolism (PE) and deep vein thrombosis (DVT), is one of the leading causes of maternal morbidity and mortality [1], especially in developed countries, where PE takes second place after complications of hypertensive disorders [2]. When compared to non-pregnant women of similar age, pregnant women have an approximately four to five times higher risk of VTE [3], with an incidence of 1 in 1000 pregnancies [4]. Approximately 20–25% of VTE cases are caused by PE and 75–80% of cases are caused by DVT [5]. About 60% of DVT occurs antepartum, with the highest risk of antepartum pregnancy-associated VTE being in the third trimester.However, about 60% of PE occurs postpartum [3].

A 78-year-old male presented at the emergency room complaining of dry cough, fever up to 38.5 °C and malaise for 1 month. He had visited a general practitioner and received amoxicillin 500 mg three times a day for 7 days for a presumed chest infection, without improvement. He had a history of diabetes and arterial blood hypertension, for which he was receiving metformin 1000 mg twice a day and amlodipine 10 mg a day for 7 years. He reported no alcohol abuse and was an ex-smoker of 20 pack-years (quit 30 years ago). He had no recent hospitalisations or any medical interventions.

Professional drivers show a higher prevalence of obstructive sleep apnoea (OSA) compared with the general population. Furthermore, there is concern about the association between OSA and car crash risk given that drivers with OSA show an increased risk for car accidents. Despite this risk, OSA is often underdiagnosed and undertreated in this population, mainly due to lack of appropriate screening and sleep study referrals. Polysomnography (PSG), the gold standard test, is inappropriate for systematic screening because of its high expense, complexity and relative inaccessibility in this population. Therefore, there is a strong demand for good screening tools, including both subjective and objective data that may assist in early identification of possible OSA among professional drivers and, thus, aid in PSG examination referral and OSA management in an accredited sleep centre. However, there is considerable disagreement over screening methods and criteria for triggering a sleep study referral in different countries. There is also a strong need for further research in the area of OSA screening of commercial drivers in order to improve the diagnostic accuracy of screening tools and ensure that patients with OSA are accurately identified.

Key points

Obstructive sleep apnoea (OSA) is often undiagnosed and undertreated in professional drivers.

Professional drivers often under-report and are reluctant to report OSA symptoms.

Barriers to OSA diagnosis include appropriate screening and sleep study referrals.

Screening tools including both subjective and objective data may assist in early identification of possible OSA among professional drivers.

Educational aims

To evaluate screening instruments currently used to identify OSA risk in professional drivers.

To provide guidance for developing an assessment strategy for OSA by professional driver medical examiners.