Trend estimation and short-term forecasting of COVID-19 cases and deaths worldwide.

Since the beginning of the COVID-19 pandemic, many dashboards have emerged as useful tools to monitor its evolution, inform the public, and assist governments in decision-making. Here, we present a globally applicable method, integrated in a daily updated dashboard that provides an estimate of the trend in the evolution of the number of cases and deaths from reported data of more than 200 countries and territories, as well as 7-d forecasts. One of the significant difficulties in managing a quickly propagating epidemic is that the details of the dynamic needed to forecast its evolution are obscured by the delays in the identification of cases and deaths and by irregular reporting. Our forecasting methodology substantially relies on estimating the underlying trend in the observed time series using robust seasonal trend decomposition techniques. This allows us to obtain forecasts with simple yet effective extrapolation methods in linear or log scale. We present the results of an assessment of our forecasting methodology and discuss its application to the production of global and regional risk maps.

Multi-syndrome, multi-gene risk modeling for individuals with a family history of cancer with the novel R package PanelPRO.

Identifying individuals who are at high risk of cancer due to inherited germline mutations is critical for effective implementation of personalized prevention strategies. Most existing models focus on a few specific syndromes; however, recent evidence from multi-gene panel testing shows that many syndromes are overlapping, motivating the development of models that incorporate family history on several cancers and predict mutations for a comprehensive panel of genes.We present PanelPRO, a new, open-source R package providing a fast, flexible back-end for multi-gene, multi-cancer risk modeling with pedigree data. It includes a customizable database with default parameter values estimated from published studies and allows users to select any combinations of genes and cancers for their models, including well-established single syndrome BayesMendel models (BRCAPRO and MMRPRO). This leads to more accurate risk predictions and ultimately has a high impact on prevention strategies for cancer and clinical decision making. The package is available for download for research purposes at https://projects.iq.harvard.edu/bayesmendel/panelpro.

Genetic mutations that increase cancer risk can be passed down from parents to their children, which can affect families across many generations. In these families, multiple members may be affected by different types of cancer, and these cancers often develop at an early age. Unaffected family members are often referred to genetic counselling, where they can explore their own risk of cancer. Clinicians and genetic counselors can provide recommendations to minimize cancer risk and inform personal choices on how to manage that risk, such as opting for preventative surgeries or participating in regular screening. In genetic counselling sessions, highly trained clinicians and specialists use software that takes an individual's family history of cancer and uses it to estimate their individual risk of carrying certain genetic mutations. These estimates can in turn help to predict their future risk of cancer. Many existing software packages are limited to estimating risks based on mutations in well-known cancer-related genes, such as BRCA1 and BRCA2 in breast and ovarian cancer. However, emerging evidence suggests that many of the genes associated with cancer risk work as part of a complex and overlapping network. Since current risk-profiling software packages are only designed to consider such genes in isolation, they cannot generate the most robust, accurate or comprehensive cancer risk profiles. To address this challenge, Lee, Liang et al. have developed a new risk-profiling software that can integrate a large number of gene mutations and a wide range of potential cancer types to provide more accurate estimates of individual cancer risk. This software, called PanelPRO, uses evidence identified from extensive literature reviews to model the complex interplay between genes and cancer risk. The software not only calculates risks based on known genes, but also allows other developers to integrate new cancer-related genes that may be identified in the future. Importantly, the software is compatible with genetic counselling applications, since it returns answers within seconds when reasonable family and gene database sizes are used. PanelPRO is a new, modern, flexible and efficient software package that provides an important advance towards modelling the vast genetic and biological complexity that contributes to inherited cancer risk. This software is designed to provide a more accurate and comprehensive estimate of cancer risk for individuals with family histories of cancer. As an open-source software, it is freely available for research purposes, and can be licensed by software companies and healthcare organizations to integrate electronic patient records and rapidly identify at-risk individuals across larger patient groups. Ultimately, this software has the potential to improve cancer prevention strategies and optimize the personalized decision-making processes around cancer risk.

Removing a Retained Antibiotic Cement Nail from a Tibia: A Case Report.

CASE: We present a case of osteomyelitis after a grade 3A open tibial shaft fracture complicated by incomplete removal of an antibiotic intramedullary rod. The authors are unaware of any reports with this specific complication and provide a novel technique for cement mantle removal involving a distal tibial corticotomy and antegrade cement impaction. CONCLUSION: Antibiotic nails can successfully treat intramedullary osteomyelitis, but surgeons may encounter unexpected issues due to custom, intraoperative fabrication. This case describes one example of how to solve the intraoperative problem of a retained cement mantle during antibiotic rod extraction.

Musculoskeletal Ultrasound in Systemic Lupus Erythematosus: Systematic Literature Review by the Lupus Task Force of the OMERACT Ultrasound Working Group.

OBJECTIVE: To identify and synthesize the best available evidence on the application of musculoskeletal (MSK) ultrasound (US) in patients with systemic lupus erythematosus (SLE) and to present the measurement properties of US in different elementary lesions and pathologies. METHODS: A systematic literature search of PubMed, Embase, and the Cochrane Library was performed. Original articles were included that were published in English between August 1, 2014, and December 31, 2018, reporting US, Doppler, synovitis, joint effusion, bone erosion, tenosynovitis, and enthesitis in patients with SLE. Data extraction focused on the definition and quantification of US-detected synovitis, joint effusion, bone erosion, tenosynovitis, enthesitis, and the measurement properties of US according to the OMERACT Filter 2.1 instruments selection. RESULTS: Of the 143 identified articles, 15 were included. Most articles were cross-sectional studies (14/15, 93%). The majority of the studies used the OMERACT definitions for ultrasonographic pathology. Regarding the measurement properties of US in different elementary lesions and pathologies, all studies dealt with face validity, content validity, and feasibility. Most studies achieved construct validity. Concerning the reliability of image reading, 1 study (1/15, 7%) assessed both intraobserver and interobserver reliability. For image acquisition, 4 studies (4/15, 27%) evaluated interobserver reliability and none had evaluated intraobserver reliability. Criterion validity was assessed in 1 study (1/15, 7%). Responsiveness was not considered in any of the studies. CONCLUSION: This literature review demonstrates the need for further research and validation work to define the involvement of US as an outcome measurement instrument for the MSK manifestations in patients with SLE.

Comparison of patient and physician perspectives in the management of rheumatoid arthritis: results from global physician- and patient-based surveys.

BACKGROUND: In order to better understand the perspectives of patients and physicians regarding the treatment and management of rheumatoid arthritis (RA), we present and compare results from a patient-based and a physician-based survey developed by the RA NarRAtive advisory panel. METHODS: The RA NarRAtive initiative is directed by a global advisory panel of 39 healthcare providers and patient organization leaders from 17 countries. A survey of patients self-reporting a diagnosis of RA and a physician-based survey, designed by the advisory panel, were fielded online by Harris Poll from September 2014 to April 2016, and from August 2015 to October 2015, respectively. RESULTS: We present findings from 1805 patients whose RA was primarily managed by a rheumatologist, and 1736 physicians managing patients with RA. Results confirmed that RA carries a substantial disease burden; half of the patients surveyed reported stopping participation in certain activities as a result of their disease. While 90% of physicians were satisfied with their communications with their patients regarding RA treatment, 61% of patients felt uncomfortable raising concerns or fears with their physician. Of the patients providing responses, 52% felt that improved dialogue/discussion would optimize their RA management, and 68% of physicians wished that they and their patients talked more about their RA goals and treatment. Overall, 88% of physicians agreed that patients involved in making treatment decisions tend to be more satisfied with their treatment experience. CONCLUSION: The results of these surveys highlight the impact of RA on patients, and a discrepancy between patient and physician views on communication. Further research, focused on improving patient-physician dialogue, shared goal-setting, and treatment planning, is needed.

Long-term outcomes of end-stage kidney disease for patients with lupus nephritis.

Patient outcomes in end-stage kidney disease (ESKD) secondary to lupus nephritis have not been well described. To help define this we compared dialysis and transplant outcomes of patients with ESKD due to lupus nephritis to all other causes. All patients diagnosed with ESKD who commenced renal replacement therapy in Australia and New Zealand (1963-2012) were included. Clinical outcomes were evaluated in both a contemporary cohort (1998-2012) and the entire 50-year cohort. Of 64,160 included patients, 744 had lupus nephritis as the primary renal disease. For the contemporary cohort of 425 patients with lupus nephritis, the 5-year dialysis patient survival rate was 69%. Of 176 contemporary patients with lupus nephritis who received their first renal allograft, the 5-year patient, overall renal allograft, and death-censored renal allograft survival rates were 95%, 88%, and 93%, respectively. Patients with lupus nephritis had worse dialysis patient survival (adjusted hazard ratio 1.33, 95% confidence interval 1.12-1.58) and renal transplant patient survival (adjusted hazard ratio 1.87, 95% confidence interval 1.18-2.98), but comparable overall renal allograft survival (adjusted hazard ratio 1.19, 95% confidence interval 0.84-1.68) and death-censored renal allograft survival (adjusted hazard ratio 1.05, 95% confidence interval 0.68-1.62) compared with ESKD controls. Similar results were found in the entire cohort and when using competing-risks analysis. Thus, the ESKD of lupus nephritis was associated with worse dialysis and transplant patient survival but comparable renal allograft survival compared with other causes of ESKD.

The impact of fibroblast growth factor-23 on the cardiovascular system in chronic kidney disease.

Chronic kidney disease is associated with an accelerated risk of cardiovascular (CV) mortality. Seminal work over the last decade has identified abnormal bone metabolism as an important modulator of the increased CV burden in this cohort. In particular, FGF23, a phosphaturic hormone with serum levels found to be markedly elevated in chronic kidney disease, is independently associated with increased risks of all-cause mortality and CV events. This editorial will discuss the proposed mechanisms linking FGF23 to CV disease in chronic kidney disease, namely, direct cardiac myocyte toxicity, endothelial dysfunction and vascular calcification.

Management of rheumatoid arthritis: consensus recommendations from the Hong Kong Society of Rheumatology.

Given the recent availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), the Hong Kong Society of Rheumatology has developed consensus recommendations on the management of RA, which aim at providing guidance to local physicians on appropriate, literature-based management of this condition, specifically on the indications and monitoring of the biologic disease-modifying anti-rheumatic drugs (DMARDs). The recommendations were developed using the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis as a guide, along with local expert opinion. As significant joint damage occurs early in the course of RA, initiating therapy early is key to minimizing further damage and disability. Patients with serious disease or poor prognosis should receive early, aggressive therapy. Because of its good efficacy and safety profile, methotrexate is considered the standard first-line DMARD for most treatment-naïve RA patients. Patients with a suboptimal response to methotrexate monotherapy should receive step-up (combination) therapy with either the synthetic or biologic DMARDs. In recent years, combinations of methotrexate with tocilizumab, abatacept, or rituximab have emerged as effective therapies in patients who are unresponsive to traditional DMARDs or the anti-tumor necrosis factor (TNF)-α agents. As biologic agents can increase the risk of infections such as tuberculosis and reactivation of viral hepatitis, screening for the presence of latent tuberculosis and chronic viral hepatitis carrier state is recommended before initiating therapy.

The efficacy and tolerability of risedronate on bone mineral density and bone turnover markers in osteoporotic Chinese women: a randomized placebo-controlled study.

Osteoporosis has become an important health problem in postmenopausal Asian populations as the prevalence of hip and vertebral fractures in some Asian countries has risen to approach that of Caucasian populations. Risedronate, a pyridinyl-bisphosphonate agent, is a potent inhibitor of bone resorption. Risedronate increases bone mineral density (BMD), reduces markers of bone turnover, and reduces the risk of fractures in Caucasian postmenopausal women. To determine the efficacy and tolerability of risedronate in Chinese, a multicenter, randomized, double blind, placebo controlled study was performed in Hong Kong. Sixty-five (65) postmenopausal osteoporotic Southern Chinese women, aged 67+/-6 years, were randomly assigned to receive either risedronate 5 mg daily (n=31) or placebo (n=34) for 12 months. All women received calcium carbonate 500 mg daily and vitamin D 400 IU daily. Mean baseline BMD T-score at the spine and total hip was -3.4 and -2.6, respectively. A significant increase in spine BMD was already evident at month 3 of risedronate treatment (P<0.001). Risedronate significantly increased BMD and reduced bone turnover markers as compared with placebo. The risedronate group had significant increase in BMD at 12 months at both the spine and hip when compared with the placebo group (L1-4 6.6% vs. 0.4%, P<0.001; total hip 2.7% vs. 0.3, P<0.0001; femoral neck 1.8% vs. 1.1%, P<0.02; trochanter 4% vs. 1.1%, P<0.0001, respectively). Significant changes in urine N-telopeptide (NTx) and serum osteocalcin were evident as early as 1 and 3 months, respectively, with risedronate treatment. No significant changes were seen in both BMD and bone markers in the placebo group. Risedronate was well tolerated without major adverse effects. We conclude that risedronate is an effective and well-tolerated agent for the treatment of postmenopausal osteoporosis in Asian population.