Patient outcomes in longitudinal observational studies (POLOS) of rheumatoid arthritis: Determining the OMERACT core domain set.

OBJECTIVE: To define and select rheumatoid arthritis (RA)-specific core domain set for Longitudinal Observational Studies (LOS) within the Outcome Measures in Rheumatology (OMERACT) framework. METHODS: A three-round online Delphi exercise, including patient research partners (PRPs) and other community partners in healthcare, was conducted. Domains scored 7-9 (i.e., critically important to include) by ≥ 70 % of participants in both groups were included. Items were consolidated in a subsequent dedicated meeting. RESULTS: Nineteen domains scored ≥ 70 % consensus in both groups. The focus group refined these into a list of twelve domains. CONCLUSION: The achieved consensus will inform the next steps of developing the core domain set for LOS in RA.

Immunosuppression for the treatment of pulmonary hypertension in patients with systemic lupus erythematosus: A systematic review.

PURPOSE: To conduct a systematic review with meta-analysis to determine the effects of immunosuppression on Group 1 Pulmonary Arterial Hypertension in patients with systemic lupus erythematosus (SLE). METHODS: We searched Medline, Embase, Web of Science, Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) with a search strategy developed by a medical librarian. We included retrospective, cross-sectional, case-control, prospective studies, and randomized controlled trials (RCTs) in our analysis and only included studies that contained data for patients with SLE. We included any immunosuppressive agents (including but not limited to cyclophosphamide, glucocorticoids, mycophenolate mofetil, azathioprine, and rituximab) We assessed for risk of bias and certainty of evidence. Outcomes included hemodynamics (as measured by pulmonary arterial hypertension), functional status, 6 minute walk test (6MWT), quality of life, mortality, and serious adverse events. RESULTS: We included three studies. One RCT and two single-arm interventional observational studies. The RCT had a high risk of bias whereas the two single-arm interventional studies were graded as fair quality. Meta-analysis could not be conducted because of insufficient data. The RCT showed significant improvements in hemodynamics (as measured by pulmonary arterial pressures) and functional status. One observational study showed improvements in hemodynamics, functional status, and 6MWT. There were insufficient data for serious adverse events, mortality, and quality of life. CONCLUSIONS: Despite a high prevalence and with a poor prognosis, there is a paucity of data for the role of immunosuppression in the treatment of Group 1 Pulmonary Arterial Hypertension in SLE. More high-quality studies are needed, especially to investigate serious adverse events and quality of life.

Risks of mortality and severe coronavirus disease 19 (COVID-19) outcomes in patients with or without systemic lupus erythematosus.

OBJECTIVES: We compared the outcomes of patients with or without systemic lupus erythematosus (SLE) who were diagnosed with coronavirus disease 19 (COVID-19) and evaluated factors within patients with SLE associated with severe outcomes. METHODS: This retrospective cohort study used the deidentified Optum COVID-19 electronic health record dataset to identify patients with COVID-19 from 1/1/2020 to 31/12/2020. Cases with SLE were matched with general controls at a ratio of 1:10 by age, sex, race and ethnicity and COVID-19 diagnosis date. Outcomes included 30-day mortality, mechanical ventilation, hospitalisation and intensive care unit admission. We evaluated the relationship between COVID-19-related outcomes and SLE using multivariable logistic regression. In addition, within SLE cases, we examined factors associated with COVID-19 related outcomes, including disease activity and SLE therapy. RESULTS: We included 687 patients matched with 6870 controls. Unadjusted rates of outcomes for patients with SLE were significantly worse than for matched controls including mortality (3.6% vs 1.8%), mechanical ventilation (6% vs 2.5%) and hospitalisation (31% vs 17.7%) (all p<0.001). After multivariable adjustment, patients with SLE had increased risks of mechanical ventilation (OR 1.81, 95% CI 1.16 to 2.82) and hospitalisation (OR 1.32, 95% CI 1.05 to 1.65). Among patients with SLE, severe disease activity was associated with increased risks of mechanical ventilation (OR 5.83, 95% CI 2.60 to 13.07) and hospitalisation (OR 3.97, 95% CI 2.37 to 6.65). Use of glucocorticoids, mycophenolate and tacrolimus before COVID-19 was associated with worse outcomes. CONCLUSION: Patients with SLE had increased risk of severe COVID-19-related outcomes compared with matched controls. Patients with severe SLE disease activity or prior use of corticosteroids experienced worse outcomes.

Systemic Lupus Erythematosus and Mortality in Elderly Patients With Early Breast Cancer.

OBJECTIVE: Patients with cancer and systemic lupus erythematosus (SLE) may have worse outcomes than those without SLE, given their comorbidities. We examined survival in elderly women with breast cancer (BC) and SLE and hypothesized that survival would be decreased compared with women with BC but without SLE. METHODS: We identified patients with BC and SLE and patients with BC without SLE in the Texas Cancer Registry and Surveillance, Epidemiology, and End Results, linked to Medicare claims. Overall survival (OS) was estimated after matching (age and cancer stage) and in multivariable Cox proportional hazards models adjusting for other cancer characteristics, treatment, and comorbidities. Two additional cohorts of women without cancer with and without SLE were also studied. RESULTS: We identified 494 BC SLE cases and 145,517 BC non-SLE cases, of whom we matched 9,708. Women with SLE were less likely to receive radiation, breast conserving surgery, or endocrine therapy. The 8-year OS estimate for women with early BC (stages 0-II) with and without SLE was 52% (95% confidence interval [95% CI] 45%-59%) and 74% (95% CI 73%-75%), respectively. In the Cox multivariable model, BC and SLE had increased risk of death (hazard ratio [HR] 1.65, 95% CI 1.38-1.98). Women with BC and SLE also had increased risk of death compared with women with SLE but without cancer (HR 1.42, 95% CI 1.05-1.92) after adjusting for SLE severity. Women with SLE and BC received less glucocorticoids, antimalarials, and immunosuppressants after cancer diagnosis than those without cancer. CONCLUSION: Systemic lupus is a risk factor for increased mortality in women with early BC.

Expert Clinical Management of Severe Immune-Related Adverse Events: Results from a Multicenter Survey on Hot Topics for Management.

There are differences in recommendations for the management of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs). To assess the real-world management of irAEs, three surveys regarding ICI-induced hepatitis (IIH), renal irAEs, and myositis were developed and sent to experts in each area. Fifty-six surveys were completed (17 IIH, 20 renal irAEs, and 19 myositis). All experts agreed on performing imaging in every suspected case of severe IIH. Sixty-five percent agreed on performing a liver biopsy in patients not responding to corticosteroids. The most common indication for corticosteroid use (59%) was for severe IIH not improving after discontinuation of ICIs. Additionally, 60% of the experts agreed on performing a biopsy for stage 2/3 acute kidney injury (AKI), and 70% recommended imaging for any stage of AKI. Thirty-five percent favored corticosteroids in AKI patients with creatinine levels 2-3-fold above baseline. For myositis, 58% would recommend a muscle biopsy in a patient with weakness and creatine kinase levels of 5000 U/L; 47% would also opt for an endomyocardial biopsy when the troponin levels are increased. Fifty-eight percent recommended oral corticosteroids for myositis, and 37% recommended additional therapy, mainly immunoglobulins. These results show substantial differences in expert practice patterns for the management of severe liver, kidney, and muscular irAEs.

The effects of glucocorticoids and immunosuppressants on cancer outcomes in checkpoint inhibitor therapy.

The emergence of checkpoint inhibitors has created a paradigm shift for the treatment of various malignancies. However, although these therapies are associated with improved survival rates, they also carry the risk of immune-related adverse events (irAEs). Moderate to severe irAEs are typically treated with glucocorticoids, sometimes with the addition of immunosuppressants as steroid-sparing therapy. However, it is unclear how glucocorticoids and immunosuppressants may impact cancer survival and the efficacy of immune checkpoint therapy on cancer. In this narrative review, we discuss the effects of glucocorticoids and immunosuppressants including methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil, tumor-necrosis factor (TNF)-inhibitors, interleukin-6 inhibitors, interleukin-1 inhibitors, abatacept, rituximab, and Janus kinase inhibitors (JAKi) on cancer-specific outcomes in the setting of immune checkpoint inhibitor use.

Stem cell transplantation for systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment. OBJECTIVES: To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide). SEARCH METHODS: We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February 2022. SELECTION CRITERIA: We included RCTs that compared HSCT to immunomodulators in the treatment of SSc. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence using standard Cochrane methods. MAIN RESULTS: We included three RCTs evaluating: non-myeloablative non-selective HSCT (10 participants), non-myeloablative selective HSCT (79 participants), and myeloablative selective HSCT (36 participants). The comparator in all studies was cyclophosphamide (123 participants). The study examining non-myeloablative non-selective HSCT had a high risk of bias given the differences in baseline characteristics between the two arms. The other studies had a high risk of detection bias for participant-reported outcomes. The studies had follow-up periods of one to 4.5 years. Most participants had severe disease, mean age 40 years, and the duration of disease was less than three years. Efficacy No study demonstrated an overall mortality benefit of HSCT when compared to cyclophosphamide. However, non-myeloablative selective HSCT showed overall survival benefits using Kaplan-Meier curves at 10 years and myeloablative selective HSCT at six years. We graded our certainty of evidence as moderate for non-myeloablative selective HSCT and myeloablative selective HSCT. Certainty of evidence was low for non-myeloablative non-selective HSCT. Event-free survival was improved compared to cyclophosphamide with non-myeloablative selective HSCT at 48 months (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.16 to 0.74; moderate-certainty evidence). There was no improvement with myeloablative selective HSCT at 54 months (HR 0.54 95% CI 0.23 to 1.27; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not report event-free survival. There was improvement in functional ability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI, scale from 0 to 3 with 3 being very severe functional impairment) with non-myeloablative selective HSCT after two years with a mean difference (MD) of -0.39 (95% CI -0.72 to -0.06; absolute treatment benefit (ATB) -13%, 95% CI -24% to -2%; relative percent change (RPC) -27%, 95% CI -50% to -4%; low-certainty evidence). Myeloablative selective HSCT demonstrated a risk ratio (RR) for improvement of 3.4 at 54 months (95% CI 1.5 to 7.6; ATB -37%, 95% CI -18% to -57%; RPC -243%, 95% CI -54% to -662%; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; low-certainty evidence). The non-myeloablative non-selective HSCT trial did not report HAQ-DI results. All transplant modalities showed improvement of modified Rodnan skin score (mRSS) (scale from 0 to 51 with the higher number being more severe skin thickness) favoring HSCT over cyclophosphamide. At two years, non-myeloablative selective HSCT showed an MD in mRSS of -11.1 (95% CI -14.9 to -7.3; ATB -22%, 95% CI -29% to -14%; RPC -43%, 95% CI -58% to -28%; moderate-certainty evidence). At 54 months, myeloablative selective HSCT at showed a greater improvement in skin scores than the cyclophosphamide group (RR 1.51, 95% CI 1.06 to 2.13; ATB -27%, 95% CI -6% to -47%; RPC -51%, 95% CI -6% to -113%; moderate-certainty evidence). The NNTB was 4 (95% CI 3 to 18). At one year, for non-myeloablative non-selective HSCT the MD was -16.00 (95% CI -26.5 to -5.5; ATB -31%, 95% CI -52% to -11%; RPC -84%, 95% CI -139% to -29%; low-certainty evidence). No studies reported data on pulmonary arterial hypertension. Adverse events In the non-myeloablative selective HSCT study, there were 51/79 serious adverse events with HSCT and 30/77 with cyclophosphamide (RR 1.7, 95% CI 1.2 to 2.3), with an absolute risk increase of 26% (95% CI 10% to 41%), and a relative percent increase of 66% (95% CI 20% to 129%). The number needed to treat for an additional harmful outcome was 4 (95% CI 3 to 11) (moderate-certainty evidence). In the myeloablative selective HSCT study, there were similar rates of serious adverse events between groups (25/34 with HSCT and 19/37 with cyclophosphamide; RR 1.43, 95% CI 0.99 to 2.08; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not clearly report serious adverse events. AUTHORS' CONCLUSIONS: Non-myeloablative selective and myeloablative selective HSCT had moderate-certainty evidence for improvement in event-free survival, and skin thicknesscompared to cyclophosphamide. There is also low-certainty evidence that these modalities of HSCT improve physical function. However, non-myeloablative selective HSCT and myeloablative selective HSCT resulted in more serious adverse events than cyclophosphamide; highlighting the need for careful risk-benefit considerations for people considering these HSCTs. Evidence for the efficacy and adverse effects of non-myeloablative non-selective HSCT is limited at this time. Due to evidence provided from one study with high risk of bias, we have low-certainty evidence that non-myeloablative non-selective HSCT improves outcomes in skin scores, forced vital capacity, and safety. Two modalities of HSCT appeared to be a promising treatment option for SSc though there is a high risk of early treatment-related mortality and other adverse events. Additional research is needed to determine the effectiveness and adverse effects of non-myeloablative non-selective HSCT in the treatment of SSc. Also, more studies will be needed to determine how HSCT compares to other treatment options such as mycophenolate mofetil, as cyclophosphamide is no longer the first-line treatment for SSc. Finally, there is a need for a greater understanding of the role of HSCT for people with SSc with significant comorbidities or complications from SSc that were excluded from the trial criteria.

The utility of erythrocyte sedimentation rate, C-reactive protein, and procalcitonin in detecting infections in patients with systemic lupus erythematosus: A systematic review.

OBJECTIVES: We conducted a systematic review with metanalysis to investigate the utility of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) in diagnosing infections in hospitalized patients with SLE. METHODS: We searched Medline, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) with a search strategy developed by a medical librarian. We included retrospective, cross-sectional, case-control, and prospective studies in our analysis. We used the Quality Assessment of Diagnostic Studies (QUADAS-2) to assess for bias and applicability. We obtained mean differences, sensitivities, and specificities in our analysis. RESULTS: We included 26 studies in our analysis. Most studies had an unclear or high risk of bias and our results were widely heterogenous. For the diagnosis of infections, the CRP had a pooled sensitivity of 0.75 (95%CI 0.57-0.94) and specificity of 0.72 (0.59-0.85), PCT had a pooled sensitivity of 0.68 (95% CI 0.0.59-0.77) and specificity of 0.75 (0.59-0.90), and for ESR pooled estimates were not calculated but sensitivity ranged from 50 to 69.8 and specificity from 38.5 to 55.6. Modifying cut-offs improved sensitivities and specificities. The ESR, CRP, and PCT mean differences were all greater in infection groups versus non-infection (10.1, 95% CI 3.2-17.0; 46.8, 95% CI 36.5-57.0; 0.53, 95% CI 0.26-0.80; respectively). DISCUSSION: Poor sensitivities and specificities were observed for the evaluated biomarkers with substantial heterogeneity in the cut-offs used to determine infection. Although mean biomarker values were increased in the infection group compared with the non-infection, our findings do not support the widespread use of ESR, CRP, or PCT in diagnosing infection in hospitalized patients with SLE due to increased heterogeneity and risk of bias. Further investigation is needed.

Postoperative Major Adverse Cardiac Events in Patients With Systemic Lupus Erythematosus.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) have a high risk of cardiovascular disease that could potentially increase postoperative major adverse cardiac events (MACE). We determined the rate of MACE in patients with SLE undergoing noncardiac surgery using national claims-based data. METHODS: This was a retrospective cohort study using Optum Clinformatics Data Mart from 2007 to 2020. We identified a cohort of patients with SLE who had undergone noncardiac surgeries using Current Procedural Terminology codes. We also identified two control cohorts without SLE, one with diabetes mellitus (DM) and one without DM. After matching cases and controls by age and sex, the odds of MACE were estimated using multivariable logistic regression models also including race and the Revised Cardiac Risk Index (RCRI) scores. We also examined use of preoperative cardiac testing. RESULTS: We identified 4750 patients with SLE, 496,381 DM controls, and 1,484,986 non-DM controls. After matching, the odds ratio (OR) for MACE in patients with SLE versus non-DM controls was 1.51 (95% confidence interval 1.09-2.08), which decreased after adjustment for RCRI score (OR: 0.97, 95% confidence interval 0.7-1.36). No significant differences were observed in the incidence of MACE between patients with SLE and DM controls (0.82 vs 1.04, P = 0.16). High-risk patients with SLE (RCRI score of ≥3) were less likely to receive preoperative cardiac testing than non-DM controls (42.7% vs 35.1%, P < 0.05). CONCLUSION: Patients with SLE have an increased risk of postoperative MACE, which is driven by increased RCRI scores. Concerningly, high-risk patients received less cardiac testing 2 months before surgery than non-DM controls.

Targeting type I interferons in systemic lupus erythematous.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with systemic clinical manifestations including, but not limited to, rash, inflammatory arthritis, serositis, glomerulonephritis, and cerebritis. Treatment options for SLE are expanding and the increase in our understanding of the immune pathogenesis is leading to the development of new therapeutics. Autoantibody formation and immune complex formation are important mediators in lupus pathogenesis, but an important role of the type I interferon (IFN) pathway has been identified in SLE patients and mouse models of lupus. These studies have led to the development of therapeutics targeting type I IFN and related pathways for the treatment of certain manifestations of SLE. In the current narrative review, we will discuss the role of type I IFN in SLE pathogenesis and the potential translation of these data into strategies using type I IFN as a biomarker and therapeutic target for patients with SLE.

Displasia ósea esclerosante en paciente adulto sin diagnóstico previo: presentación de un caso / Bone sclerosing dysplasia in an adult patient without previous diagnosis: a case report

La displasia ósea esclerosante es una afectación en el desarrollo intrínseco del esqueleto, por alteración en la formación y modelado del hueso, que lleva a una excesiva acumulación ósea con un aumento de la densidad (esclero-sis). Existen varios tipos y todos ellos son de origen genético. Presentamos el caso de una paciente de 37 años que llega a la consulta sin diagnóstico previo, por dolor en miembros inferiores de larga evolución con reagudizaciones, asociado a deformidad e impotencia funcional, que cedía parcialmente con analgésicos comunes. (AU)

Bone sclerosing dysplasia is an affectation of the intrinsic development of the skeleton by an alteration in bone formation and modeling. It causes excessive bone accumulation with an increase in density (sclerosis). There are several types of bone sclerosing dysplasia. They are of genetic origin. We report here a 37 year-old patient without a previous diagnosis of sclerosing bone dysplasia who was seen in the clinic for pain in the lower limbs associated with bone deformity with only partial response to analgesics. (AU)

Development of a patient-centered core domain set for prospective observational longitudinal outcome studies in rheumatoid arthritis: an OMERACT initiative.

OBJECTIVES: To identify patient-centered core domains for prospective longitudinal observational studies (LOS) in rheumatoid arthritis. METHODS: Our working group held a virtual meeting in November 2020 to review data from a literature review and patient qualitative interviews, and to discuss strategies to move forward on domain identification and selection using the OMERACT 2.1 domain selection process. RESULTS: Important candidate domains and subdomains were identified including in the areas of life impact. Consensus was reached on moving forward with a Delphi process. CONCLUSIONS: The meeting provided future directions to identify and select a core set of domains for use in LOS.

Cervical Cancer Screening in Women With Systemic Lupus Erythematosus.

OBJECTIVE: To determine rates of cervical cancer screening and associated abnormal results in women with systemic lupus erythematosus (SLE). METHODS: We identified women with an initial diagnosis of SLE in the MarketScan Commercial Claims and Encounters Database from 2001 to 2014. Cervical cancer screening rates and associated diagnostic claims within 3 years of the initial claim were determined. Multivariable logistic regression was performed to evaluate the association of screening with lupus treatment. A matched logistic regression analysis was conducted to compare screening rates to those in age-matched women without connective tissue disease. RESULTS: We included 4,316 women with SLE. Screening rates were higher in women with SLE than in general controls (73.4% versus 58.5%; P < 0.001). Factors associated with decreased screening included recent time (odds ratio [OR] 0.70 [95% confidence interval (95% CI)] 0.55-0.89) (2012-2014 compared to 2001-2005), age ≥61 years (OR 0.27 [95% CI 0.18-0.39]), comorbidity score ≥2 (OR 0.71 [95% CI 0.6-0.83]), corticosteroid use (OR 0.77 [95% CI 0.61-0.97]), and use of immunosuppressants (OR 0.80 [95% CI 0.69-0.94]). Abnormal pathology result claims were more common in women with SLE than in general controls (12.3% versus 9.8%; P < 0.001). CONCLUSION: Though with higher rates than the general cohort, over 25% of the patients with SLE were not screened, and screening rates seem to be decreasing over time. Patients with SLE are at higher risk of abnormal cervical screening test results than controls, supporting the need for regular screening.

Lone Hepatocellular Carcinoma: An Isolated Chest Wall Malignancy.

Herein we describe the case of an elderly diabetic gentleman presenting with a two-week history of dyspnea and nonproductive cough, found to have a large left anterolateral chest wall mass. Further characterization through computed tomography (CT) of the chest revealed a soft tissue mass in the left anterior lower hemithorax found to be hepatocellular carcinoma (HCC). The liver, spleen, and pancreas were unremarkable. Diagnostic labs were unremarkable. The patient had no history of hepatitis, alcohol abuse, or illicit substance use. Pathological examination and immunohistochemical staining of the chest mass biopsy were consistent with metastatic hepatocellular carcinoma (HCC). The patient opted to pursue no further medical intervention and expired two weeks later. To the authors' knowledge, this is one of very few descriptions of isolated hepatocellular carcinoma found in the absence of a primary liver lesion and classical risk factors for hepatocarcinogenesis. This case highlights that HCC may present independently of liver lesions seen on imaging in a patient without clear signs or symptoms of liver. HCC should be considered in cases of isolated tumors with unclear primaries as ectopic carcinogenesis and occult primary malignancy are possibilities.

Off-Label Medication Use in the Inpatient Palliative Care Unit.

CONTEXT: Although off-label medications are frequently prescribed in palliative care, there are no published studies examining their use in the U.S. OBJECTIVES: We examined the frequency of off-label medication use in cancer patients admitted to an acute palliative care unit (APCU). METHODS: This prospective observational study enrolled consecutive patients with advanced cancer admitted to the APCU of a tertiary care cancer center. We collected data on all prescription events, including indications for use, from admission to discharge. Off-label use was checked against the U.S. Food and Drug Administration-approved indications. RESULTS: Among the 201 patients, median survival was 10 days (95% CI 7-13), and 85 (42%) patients died in the APCU. We documented 6276 prescription events, and 2199 (35%) were off-label. Among off-label prescriptions, central nervous system agents (n = 1606, 73%), hormones and synthetic substitutes (n = 302, 14%), and autonomic drugs (n = 183, 8%) were most commonly prescribed. Haloperidol (n = 720, 33%), chlorpromazine (n = 292, 13%), dexamethasone (n = 280, 13%), glycopyrrolate (n = 175, 8%), hydromorphone (n = 161, 7%), and morphine (n = 156, 7%) were most frequently prescribed off-label. The most common indications for off-label prescribing were delirium (n = 783, 36%) and dyspnea (n = 449, 20%). Seventy percent of all off-label prescription events had strong evidence supporting use, and 19% of prescription events had moderate or weak evidence for use. CONCLUSION: One-third of prescription events in the APCU were off-label, with majority of off-label use having a strong level of supporting evidence. Our findings highlight the need for more research in key areas such as delirium and dyspnea management.

Use of medication reminders in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) often have difficulties adhering to their medical treatment plans. We determined the characteristics of patients with RA who used reminders and the association between reminders and adherence. A total of 201 patients with RA were asked the frequency of reminders use such as pill containers, calendars, or diaries. Patients completed self-reported adherence questionnaires, and their disease activity and functional ability were measured. Sixty-eight patients (34 %) reported using a reminder. Factors associated with reminder use were older age (yes-mean age 54 vs no-mean age 49, p = 0.004), race (Whites-54 % vs Blacks-30 % vs Hispanics-26 %, p = 0.003), and sex (males-50 % vs females 28 %, p = 0.005). Working patients were less likely to use reminders (employed-21 % vs unemployed-43 %, p = 0.006). Use of calendars was associated with adherence while away from home (ρ = 0.16, p = 0.03), when busy (ρ = 0.16, p = 0.03), and use of any reminder was associated with adherence when running out of pills (ρ = 0.15, p = 0.04). The use of calendar reminders was associated with fewer tender joints (ρ = -0.17, p = 0.02). Few patients with RA used reminders, and whites, males and patients of increasing age were most likely to use reminders. Our findings show that reminders can assist patients with RA in taking medications, particularly when they are most prone to forgetting, such as when they are away from home or busy. Providers should encourage using reminders as a low-cost aid to enhance adherence.

Referral Criteria for Outpatient Palliative Cancer Care: A Systematic Review.

BACKGROUND: Outpatient palliative care clinics facilitate early referral and are associated with improved outcomes in cancer patients. However, appropriate candidates for outpatient palliative care referral and optimal timing remain unclear. We conducted a systematic review of the literature to identify criteria that are considered when an outpatient palliative cancer care referral is initiated. METHODS: We searched Ovid MEDLINE (1948-2013 citations) and Ovid Embase (1947-2015 citations) for articles related to outpatient palliative cancer care. Two researchers independently reviewed each citation for inclusion and extracted the referral criteria. The interrater agreement was high (κ = 0.96). RESULTS: Of the 186 publications in our initial search, 21 were included in the final sample. We identified 20 unique referral criteria. Among these, 6 were recurrent themes, which included physical symptoms (n = 13 [62%]), cancer trajectory (n = 13 [62%]), prognosis (n = 7 [33%]), performance status (n = 7 [33%]), psychosocial distress (n = 6 [29%]), and end-of-life care planning (n = 5 [24%]). We found significant variations among the articles regarding the definition of advanced cancer and the assessment tools for symptom/distress screening. The Edmonton Symptom Assessment Scale (n = 7 [33%]) and the distress thermometer (n = 2 [10%]) were used most often. Furthermore, there was a lack of consensus in the cutoffs in symptom assessment tools and timing for outpatient palliative care referral. CONCLUSION: This systematic review identified 20 criteria including 6 recurrent themes for outpatient cancer palliative care referral. It highlights the significant heterogeneity regarding the timing and process for referral and the need for further research to develop standardized referral criteria. IMPLICATIONS FOR PRACTICE: Outpatient palliative care clinics improve patient outcomes; however, it remains unclear who is appropriate for referral and what is the optimal timing. A better understanding of the referral criteria would help (a) referring clinicians to identify appropriate patients for palliative care interventions, (b) administrators to assess their programs with set benchmarks for quality improvement, (c) researchers to standardize inclusion criteria, and (d) policymakers to develop clinical care pathways and allocate appropriate resources. This systematic review identified 20 criteria including 6 recurrent themes for outpatient palliative cancer care referral. It represents the first step toward developing standardized referral criteria.

Use of Palliative Care Services in a Tertiary Cancer Center.

BACKGROUND: Despite increasing prevalence of palliative care (PC) services in cancer centers, most referrals to the service occur exceedingly late in the illness trajectory. Over the years, we have made several attempts to promote earlier patient access to our PC program, such as changing the name of our service from PC to supportive care (SC). This study was conducted to determine the use of PC/SC service over the past 8 years. METHODS: We reviewed billing data for all PC/SC encounters. We examined five metrics for use: inpatient consultations as a percentage of hospital admissions, ratio of inpatient consultations to average number of operational beds, time from hospital registration to outpatient consultation, time from advanced cancer diagnosis to consultation, and time from first outpatient consultation to death/last follow-up. RESULTS: Over the years, we found a consistent increase in patient referrals to the PC/SC program. In the inpatient setting, we found approximate doubling of the inpatient consultations as a percentage of hospital admissions and the ratio of inpatient consultations to hospital beds (from 10% to 19% and from 2.4 to 4.9, respectively; p < .001). In the outpatient setting, we observed variations in referral pattern between oncology services, but, overall, the time from consultation to death/last follow-up increased from 4.8 months to 7.9 months (p = .001), which was accompanied by a significant decrease in the interval to consultation from hospital registration and advanced cancer diagnosis (p < .001). CONCLUSION: We have observed a consistent annual increase in new patient referrals as well as earlier access for outpatient referrals to our SC service, supporting increased use of palliative care at our cancer center. IMPLICATIONS FOR PRACTICE: In response to accumulating evidence on the benefits of palliative care (PC) referral to oncology patients, efforts are being made to increase PC use. This study, conducted at MD Anderson Cancer Center, demonstrates consistent annual growth in PC referrals, which was accompanied by a significant increase in the outpatient referral of patients with nonadvanced cancer and earlier referral of those with advanced cancer. However, significant variations in the referral patterns between oncology services were observed. These results have implications for other cancer centers looking to enhance use of PC services by having a business model that allows for appropriate space and staff expansion.

Síndrome TAR en paciente adulto sin diagnóstico previo: presentación de un caso / TAR syndrome in an adult patient without previous diagnosis, a case report

El síndrome TAR (Thrombocytopenia with Absent Radius) es una patología congénita autosómica recesiva infrecuente, caracterizada por trombocitopenia con aplasia de radio bilateral. Incluye malformaciones esqueléticas, renales, hematológicas y cardíacas. Su base genética todavía no está clara. Presentamos el caso de una paciente sin diagnóstico previo de síndrome TAR que llega a la consulta, tras haber sido evaluada por varios profesionales médicos, para el diagnóstico y el tratamiento de trastornos hematológicos, que finalmente estuvieron asociados a su síndrome congénito. (AU)

Thrombocytopenia with Absent Radius (TAR) is a rare autosomic recessive disease characterized by thrombocytopenia and bilateral radial aplasia, which includes skeletal, hematologic, renal and cardiac abnormalities. The genetics bases of this syndrome remain unclear. We report here a patient without a previous diagnosis of TAR syndrome who was seen in the clinic, after being evaluated by several medical professionals for diagnosis and treatment of blood disorders, which eventually were associated with the congenital syndrome. (AU)