RESUMO
Objective: To describe the pain intensity among hospitalized patients with calciphylaxis, elucidate the factors associated with pain improvement, and examine the link between pain improvement and clinical outcomes. Patients and Methods: Patients were identified from the Partners Research Patient Data Registry and the Partners Calciphylaxis Registry and Biorepository (Clinicaltrials.gov ID: NCT03032835). Those with calciphylaxis requiring hospitalization for at least 14 consecutive days during the study period from May 2016 through December 2021 were included. Pain intensity was assessed using patient-reported pain scores on numerical rating scales from 0 to 10. Associations between pain improvement and clinical outcomes, including lesion improvement, amputation, and mortality, were examined using univariate and multivariate regression models. Results: Our analysis included 111 patients (age, 58±14 years; men, 40%; on maintenance dialysis, 79%). No significant improvement of pain intensity was observed over the 14 days of hospitalization (mean difference, -0.71; P=.08). However, among 49 (44.1%) patients who showed at least 1-point improvement in the pain score, there was an association with surgical debridement during hospitalization (odds ratio, 3.37; 95% CI, 1.17-9.67; P=.02). Hyperbaric oxygen therapy was associated with pain improvement (odds ratio, 5.38; 95% CI, 1.14-25.50; P=.03) in patients on maintenance dialysis. Pain improvement was associated with lower rates of subsequent amputation at 6 months of follow up (6% vs 13%; P<.05) but did not predict lesion improvement or survival. Conclusion: Pain control remains a challenge among hospitalized patients with calciphylaxis. Surgical debridement and hyperbaric oxygen therapy may improve pain intensity. Pain improvement predicted a lower risk of future amputation.
RESUMO
Importance: Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label therapeutic in calciphylaxis, but there is a lack of clinical trials and studies that demonstrate its effect compared with those without STS treatment. Objective: To perform a meta-analysis of the cohort studies that provided data comparing outcomes among patients with calciphylaxis treated with and without intravenous STS. Data Sources: PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using relevant terms and synonyms including sodium thiosulphate and calci* without language restriction. Study Selection: The initial search was for cohort studies published before August 31, 2021, that included adult patients diagnosed with CKD experiencing calciphylaxis and could provide a comparison between patients treated with and without intravenous STS. Studies were excluded if they reported outcomes only from nonintravenous administration of STS or if the outcomes for CKD patients were not provided. Data Extraction and Synthesis: Random-effects models were performed. The Egger test was used to measure publication bias. Heterogeneity was assessed using the I2 test. Main Outcomes and Measures: Skin lesion improvement and survival, synthesized as ratio data by a random-effects empirical Bayes model. Results: Among the 5601 publications retrieved from the targeted databases, 19 retrospective cohort studies including 422 patients (mean age, 57 years; 37.3% male) met the eligibility criteria. No difference was observed in skin lesion improvement (12 studies with 110 patients; risk ratio, 1.23; 95% CI, 0.85-1.78) between the STS and the comparator groups. No difference was noted for the risk of death (15 studies with 158 patients; risk ratio, 0.88; 95% CI, 0.70-1.10) and overall survival using time-to-event data (3 studies with 269 participants; hazard ratio, 0.82; 95% CI, 0.57-1.18). In meta-regression, lesion improvement associated with STS negatively correlated with publication year, implying that recent studies are more likely to report a null association compared with past studies (coefficient = -0.14; P = .008). Conclusions and Relevance: Intravenous STS was not associated with skin lesion improvement or survival benefit in patients with CKD experiencing calciphylaxis. Future investigations are warranted to examine the efficacy and safety of therapies for patients with calciphylaxis.