Impact and applicability of pharmacogenomics in rheumatology: an integrated analysis.

OBJECTIVES: Rheumatology medications are often associated with adverse drug reactions (ADRs) or inadequate response (IR). Pharmacogenomics may be a solution, but there is limited knowledge of its potential utility within rheumatology. METHODS: We analysed medication changes and pharmacogenomically actionable prescriptions for all adult rheumatology outpatient encounters at our medical centre between 10/2012-12/2018. Three sources defined pharmacogenomic actionability: FDA labels, Clinical Pharmacogenetics Implementation Consortium guidelines, and our institutionally-deliverable pharmacogenomic clinical decision support (CDS) summaries. A subset of patients (validation cohort) had previously undergone broad, preemptive pharmacogenomic testing within other clinics but results were unavailable within rheumatology. We assessed the occurrence of specific pharmacogenomic ADRs/IRs in this group. RESULTS: From 174,834 prescribing events, 6300/7761 patients (81%) had clinically actionable pharmacogenomic drug prescriptions (i.e. institutional CDS summaries would have been deployable if testing had been done). Using more conservative standards (pharmacogenomically actionable by ≥2 guidance bodies), 4158/7761 (54%) patient prescriptions could have been impacted. The greatest proportions of potentially impacted rheumatologic prescriptions were for tramadol (47%), allopurinol (21%), azathioprine (17%) and celecoxib (8%). Among our validation cohort (94 previously-genotyped patients), 29 (31%) patients had a pharmacogenomic genotype that would have cautioned possible ADRs/IRs for ≥1 medication. Four patients actually suffered ADRs/IRs that would have been predicted by preemptive genotyping. CONCLUSIONS: Pharmacogenomic genotyping could inform prescribing for the majority of rheumatology patients and may prevent a subset of ADRs/IRs. These findings justify prospective evaluation of pharmacogenomic testing including assessment of cost-effectiveness in selected rheumatology populations to further understand impact on therapy-related toxicities and treatment outcomes.

Pulmonary manifestations of systemic lupus erythematosus and Sjögren's syndrome.

PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) and Sjögren syndrome are chronic autoimmune inflammatory disorders that can present with multiorgan involvement including the lungs. This review will focus on recent literature pertaining to the epidemiology, pathogenesis, clinical presentation and diagnosis and management of SLE and Sjögren syndrome-associated pulmonary conditions. RECENT FINDINGS: Pulmonary manifestations of both disease entities have been well characterized and lung involvement can be observed during the course of the disease in most cases. Pulmonary manifestations of SLE and Sjögren syndrome can be classified based on anatomical site of involvement; and the large and small airways, lung parenchyma, lung vasculature, pleura and respiratory muscles can be involved. The pleura is most commonly involved in SLE, whereas the airways are most commonly involved in primary Sjögren's syndrome (pSS). Sleep disturbances have also been described in both entities. SUMMARY: Although further research into treatment strategies for the pulmonary complications seen in SLE and pSS is needed, the clinician should be aware of the risk factors and clinical presentation of the various pulmonary complications in SLE and pSS in order to identify patients who should be screened and/or have modifications in treatment strategies to mitigate the morbidity and mortality associated with these complications.

Hospital-acquired infections at an oncological intensive care cancer unit: differences between solid and hematological cancer patients.

BACKGROUND: Cancer patients have a higher risk of severe sepsis in comparison with non-cancer patients, with an increased risk for hospital-acquired infections (HAI), particularly with multidrug resistant bacteria (MDRB). The aim of the study is to describe the frequency and characteristics of HAI and MDRB in critically ill cancer patients. METHODS: We conducted an 18-month prospective study in patients admitted ≥48 h to an ICU at a cancer referral center in Mexico. Patients with hematological malignancies (HM) were compared with solid tumors. Demographic and clinical data were recorded. Mortality was evaluated at 30-days. RESULTS: There were 351 admissions during the study period, among whom 157 (66 %) met the inclusion criteria of the study as follows: 104 patients with solid tumors and 53 with HM. Sixty-four patients (40.7 %) developed 95 episodes of HAI. HAI rate was 4.6/100 patients-days. MDRB were isolated in 38 patients (24 %), with no differences between both groups. Escherichia coli was the main bacteria isolated (n = 24), 78 % were extended spectrum beta-lactamases producers. The only risk factor associated with HAI was the presence of mechanical ventilation for more than 5 days (OR 3.12, 95 % CI 1.6 - 6.2, p = 0.001). At 30-day follow-up, 61 patients (39 %) have died (38 % with solid tumors and 60 % with HM, p < 0.001). No differences were found in mortality at 30-day between patients with HAI (n = 25, 39 %) vs. non-HAI (n = 36, 38.7 %, p = 0.964); neither in those who developed a HAI with MDRB (n = 12, 35.3 %) vs. HAI with non-MDRB (n = 13, 43.3 %, p = 0.51). CONCLUSIONS: Patients with cancer who are admitted to an ICU, have a high risk of HAI, but there were no differences patients with solid or hematologic malignancies.