An evidence based clinical guideline for the diagnosis and management of Paget’s disease of Bone (PDB) was developed using GRADE methodology, by a Guideline Development Group (GDG) led by the Paget’s Association (UK). A systematic review of diagnostic tests, pharmacological and non-pharmacological treatment options was conducted which sought to address several key questions of clinical relevance. Twelve recommendations and five conditional recommendations were made but there was insufficient evidence to address eight of the questions posed. The following recommendations were identified as the most important. Radionuclide bone scans, in addition to targeted radiographs, are recommended as a means of fully and accurately defining the extent of the metabolically active disease in patients with PDB.Serum total alkaline phosphatase (ALP) is recommended as a first line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB.Bisphosphonates are recommended for the treatment of bone pain associated with Paget’s disease. Zoledronic acid is recommended as the bisphosphonate most likely to give a favourable pain response.Treatment aimed at improving symptoms is recommended over a treat-to-target strategy aimed at normalising total ALP in PDB.Total hip or knee replacements are recommended for patients with PDB who develop osteoarthritis in whom medical treatment is inadequate. There is insufficient information to recommend one type of surgical approach over another. The guideline was endorsed by the European Calcified Tissues Society, the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the Bone research Society (UK) and the British Geriatric Society. The GDG noted that there had been a lack of research on patient-focused clinical outcomes in PDB and identified several areas where further research was needed.

Summary Purpose To determine whether a 6-day course of methylprednisolone (MP) improves outcome in patients with severe SARS-CoV‑2 (Corona Virus Disease 2019 [COVID-19]). Methods The study was a multicentric open-label trial of COVID-19 patients who were aged ≥ 18 years, receiving oxygen without mechanical ventilation, and with evidence of systemic inflammatory response who were assigned to standard of care (SOC) or SOC plus intravenous MP (40 mg bid for 3 days followed by 20 mg bid for 3 days). The primary outcome was a composite of death, admission to the intensive care unit, or requirement for noninvasive ventilation. Both intention-to-treat (ITT) and per protocol (PP) analyses were performed. Results A total of 91 patients were screened, and 64 were randomized (mean age70 ± 12 years). In the ITT analysis, 14 of 29 patients (48%) in the SOC group and 14 of 35 (40%) in the MP group suffered the composite endpoint (40% versus 20% in patients under 72 years and 67% versus 48% in those over 72 years; p = 0.25). In the PP analysis, patients on MP had a significantly lower risk of experiencing the composite endpoint (age-adjusted risk ratio 0.42; 95% confidence interval, CI 0.20–0.89; p = 0.043). Conclusion The planned sample size was not achieved, and our results should therefore be interpreted with caution. The use of MP had no significant effect on the primary endpoint in ITT analysis; however, the PP analysis showed a beneficial effect due to MP, which consistent with other published trials support the use of glucocorticoids in severe cases of COVID-19. Supplementary Information The online version of this article (10.1007/s00508-020-01805-8) contains supplementary material, which is available to authorized users.

Background. We aimed to determine whether a 6-day course of intravenous methylprednisolone (MP) improves outcome in patients with SARS CoV-2 infection at risk of developing Acute Respiratory Distress Syndrome (ARDS). Methods. Multicentric, partially randomized, preference, open-label trial, including adults with COVID-19 pneumonia, impaired gas exchange and biochemical evidence of hyper-inflammation. Patients were assigned to standard of care (SOC), or SOC plus intravenous MP [40mg/12h 3 days, then 20mg/12h 3 days]. The primary endpoint was a composite of death, admission to the intensive care unit (ICU) or requirement of non-invasive ventilation (NIV). Results. We analyzed 85 patients (34, randomized to MP; 22, assigned to MP by clinician preference; 29, control group). Patient age (mean 68±yr) was related to outcome. The use of MP was associated with a reduced risk of the composite endpoint in the intention-to-treat, age-stratified analysis (combined risk ratio -RR- 0.55 [95% CI 0.33-0.91]; p=0.024). In the per-protocol analysis, RR was 0.11 (0.01-0.83) in patients aged 72 yr or less, 0.61 (0.32-1.17) in those over 72 yr, and 0.37 (0.19-0.74, p=0.0037) in the whole group after age-adjustment by stratification. The decrease in C-reactive protein levels was more pronounced in the MP group (p=0.0003). Hyperglycemia was more frequent in the MP group. Conclusions A short course of MP had a beneficial effect on the clinical outcome of severe COVID-19 pneumonia, decreasing the risk of the composite end point of admission to ICU, NIV or death.