Challenges in Fabry disease: the combination of two individually amenable GLA variants may be nonamenable to migalastat.

Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, resulting in reduced or absent α-Gal A activity. Migalastat is an oral chaperone therapy for Fabry patients with amenable GLA variants. We previously reported a case of a 60-year-old male patient with a classic phenotype of Fabry disease, presenting with two GLA variants: p.R356Q and p.G360R. Herein, we report that, although these two missense variants are individually classified as amenable to migalastat in the validated in vitro human embryonic kidney-293 cell-based assay, their combination precludes the patient to be treated with this oral chaperone. This case illustrates how therapeutic decisions may be challenging and how a good genotypic characterization of Fabry patients is critical for the selection of the correct therapeutic strategy.

Fabry disease is a rare genetic disease that is part of a group of conditions called lysosomal storage diseases. It is characterized by an abnormal accumulation of glycosphingolipids, a subclass of glycolipids which are important components of the body's cell membranes. This accumulation is caused by a reduction in, or absence of, enzyme α-Gal A activity, which normally breaks glycosphingolipids down into smaller units, avoiding their accumulation. The absence or reduction in the α-Gal A enzyme activity is caused by mutations (changes in the normal DNA sequence) in the GLA gene. Migalastat is an oral treatment for Fabry patients with GLA mutations that respond to this treatment. We report a case of a 60-year-old male patient with Fabry disease, presenting with two GLA mutations (p.R356Q and p.G360R). Although these mutations are individually amenable to migalastat, their combination and interaction in the same chromosome precludes response to this treatment. This case illustrates how therapeutic decisions for treating Fabry disease can be challenging depending on the mutations causing the disease and how genetic material is decisive for therapy selection.

Standardized assessment of medication reconciliation in post-acute care.

BACKGROUND: Medication reconciliation (MR) facilitates safety during transitions of care, which occur frequently across post-acute care (PAC) settings. Under the intent of the IMPACT Act of 2014, the Centers for Medicare & Medicaid Services contracted with the RAND Corporation to develop and test standardized assessment data elements (SADEs) that assess the MR process. METHODS: We employed an iterative process that incorporated stakeholder input and three rounds of testing to identify, refine, and evaluate MR SADEs. Testing took place in 186 PAC sites (57 home health agencies, 28 inpatient rehabilitation facilities, 28 long-term care hospitals, and 73 skilled nursing facilities). There were 2951 patients in the final test. Novel MR SADEs, based on the Joint Commission's framework, were refined. The final SADEs assessed whether: patient was taking high-risk medications; an indication was noted for each medication class; discrepancies were identified; patient or family/caregiver was involved in addressing discrepancies; discrepancies were communicated to physician (or designee) within 24 h; recommended physician actions regarding discrepancies were implemented within 24 h after physician response; and the reconciled list was communicated to patient, prescriber, and/or pharmacy. Two assessors per facility collected data for each patient. Analyses described completion time, data missingness, and interrater reliability, as well as feedback on assessor burden. RESULTS: Time to complete the MR SADEs was 3.2 min. Missing data were <5%. Interrater reliability was moderate to high (κ: 0.42 [whether a reconciled list was communicated to prescribers] to 0.89 [identifying patients taking hypoglycemics]). For identifying high-risk medication classes, interrater reliability was high (κ: 0.72-0.89). There were minimal differences by setting. CONCLUSIONS: This is the first set of MR SADEs that have been assessed across the PAC settings. Results demonstrate feasibility, based on missing data and completion time, and moderate to strong reliability, based on interrater comparisons, of assessing MR.

Who receives post-acute care? Characteristics of national population and field test sample.

BACKGROUND: Each year millions of Medicare beneficiaries in the United States receive post-acute care (PAC) in skilled nursing facilities (SNFs), inpatient rehabilitation facilities (IRFs), long-term care hospitals (LTCHs), and home health agencies (HHA). We describe, overall and by PAC setting, the national population of facilities and patients, evaluate the representativeness of a national field test sample, and describe patient characteristics in the national field test sample. METHODS: We analyzed the 2016 Provider of Service file, 2016 patient assessment data reported by PAC providers to Centers for Medicare & Medicaid, and data collected from PAC providers participating in a national field test. National data included 27,234 PAC settings and 5,033,820 beneficiaries receiving PAC. The national field test sample consisted of 143 facilities across 14 markets with 25-30 patients sampled from each facility (n = 3669). We describe PAC facility and patient characteristics for both the national and field test sample. RESULTS: Nationally, PAC facilities were more likely for-profit versus not for-profit, have an average nurse-to-bed ratio between 1:10 to 1:1 (lowest in SNFs) and be in metropolitan versus other areas. PAC patients were more likely to be white, female, and 75-89 years of age; heart failure as a primary medical condition tended to be more common than stroke or sepsis. There was limited variability across setting types. In the national field test, patients in LTCHs demonstrated a greater likelihood of cognitive impairment, positive depression screening, bowel and bladder appliance use, higher rates of medication drug classes taken, and use of therapeutic diets and IV medications. CONCLUSION: The national field test facility and patient samples were fairly representative of the national population overall and across settings with a few exceptions. Moreover, differences according to PAC setting on patient characteristics in the national field test aligned with general differences in patient populations.

Development and testing of a standardized pain interview assessment for use in post-acute care.

OBJECTIVES: Pain is highly prevalent among patients in post-acute care (PAC) settings and can affect quality of life, treatment outcomes, and transitions in care. Routine, accurate assessment of pain across settings is important for pain management and care planning; however, existing PAC assessment instruments do not assess patient pain in a standardized manner. METHODS: We developed and tested a set of pain interview data elements for use across PAC settings (skilled nursing facilities, inpatient rehabilitation facilities, long term care hospitals, home health agencies) as part of a larger effort undertaken by the Centers for Medicare & Medicaid Services to develop standardized assessment data elements to meet the requirements of the IMPACT Act of 2014. The interview assessed six pain constructs: presence; frequency; interference with sleep; interference with rehabilitation therapies [if applicable]; interference with daily activities; worst pain; and pain relief from treatments/medications). A total of 3031 PAC patients at 143 PAC settings (across 14 U.S. geographic/metropolitan areas in 10 states) participated in a national field test of standardized data elements from November 2017 to August 2018. We assessed item response distributions, time to complete interviews, inter-assessor agreement, and, for a subset of patients, change in responses between admission and discharge assessments. We also conducted focus groups with nurse assessors about their experiences administering the items. RESULTS: For patients reporting any pain, average time to complete the pain interview was 3.1 min (SD = 1.3), and interrater reliability was excellent for all data elements (kappa range: 0.95-0.99). Findings were similar across types of PAC settings. Qualitative data from nurses emphasized ease of administration and high perceived clinical utility. CONCLUSION: Findings provide support for feasibility of implementing a standardized pain interview assessment in PAC settings. This tool can support tracking of patient needs across settings and interoperability of data in electronic medical records.

Standardized assessment of cognitive function of post-acute care patients.

BACKGROUND: The assessment of cognitive function in post-acute care (PAC) settings is important for understanding an individual's condition and care needs, developing better person-directed care plans, predicting resource needs and understanding case mix. Therefore, we tested the feasibility and reliability of cognitive function assessments, including the Brief Interview for Mental Status (BIMS), Confusion Assessment Method (CAM©), Expression and Understanding, and Behavioral Signs and Symptoms for patients in PAC under the intent of the IMPACT Act of 2014. METHODS: We conducted a national test of assessments of four standardized cognitive function data elements among patients in PAC. One hundred and forty-three PAC settings (57 home health agencies, 28 inpatient rehabilitation facilities, 28 long-term care hospitals, and 73 Skilled Nursing Facilities) across 14 U.S. markets from November 2017 to August 2018. At least one of four cognitive function data elements were assessed in 3026 patients. We assessed descriptive statistics, percent of missing data, time to complete, and interrater reliability between paired research nurse and facility staff assessors, and assessor feedback. RESULTS: The BIMS, CAM©, Expression and Understanding, and Behavioral Signs and Symptoms demonstrated low rates of missing data (less than 2%), high percent agreement, and substantial support from assessors. The prevalence of Behavioral Signs and Symptoms was low in our sample of PAC settings. CONCLUSION: Findings provide support for feasibility of implementing standardized assessment of all our cognitive function data elements for patients in PAC settings. The BIMS and CAM© were adopted into federal Quality Reporting Programs in the fiscal year/calendar year 2020 final rules. Future work could consider implementing additional cognitive items that assess areas not covered by the BIMS and CAM©.

Standardized assessment of cognitive function, mood, and pain among patients who are unable to communicate.

BACKGROUND: Assessments of patients have sought to increase the patient voice through direct patient interviews and performance-based testing. However, some patients in post-acute care (PAC) are unable to communicate and cannot participate in interviews or structured cognitive tests. Therefore, we tested the feasibility and reliability of observational assessments of cognitive function, mood, and pain for patients who are unable to communicate in PAC settings. METHODS: We conducted a national test of observational assessments of cognitive function, mood, and pain in 143 PAC facilities (57 home health agencies, 28 Inpatient Rehabilitation Facilities, 28 Long-Term Care Hospitals, and 73 Skilled Nursing Facilities) across 14 U.S. markets from November 2017 to August 2018. For the 548 patients identified as unable to make themselves understood, we assessed descriptive statistics, percent of missing data, time to complete, and inter-rater reliability (IRR) between paired research nurse and facility staff assessors. RESULTS: Most sampled non-communicative patients were administered all three observational assessments. Among assessed patients, overall missing data was high for some items within the Staff Assessment for Mental Status (2.9% to 33.5%) and Staff Assessment of Patient Mood (12.4% to 44.3%), but not the Observational Assessment of Pain or Distress (0.0% to 4.4%). Average time to complete the data elements ranged from 2.4 to 3.5 min and IRR was good to excellent for all items (kappa range: 0.74-0.98). CONCLUSION: The three observational data elements had acceptable reliability. Although results revealed varying feasibility, there was support for feasibility overall in terms of implementing a standardized observational assessment of pain for patients in PAC settings. Additional work is needed for the Staff Assessment for Mental Status and the Staff Assessment of Patient Mood to improve the observable nature of these data elements and enhance instructions and training for standardizing the assessments.

Developing standardized patient assessment data elements for Medicare post-acute care assessments.

BACKGROUND: To support interoperability and care planning across provider types, the Improving Medicare Post-Acute Care Transformation Act of 2014 (IMPACT Act) requires the submission of standardized patient assessment data using the assessment instruments provided by the Centers for Medicare & Medicaid Services (CMS). CMS was tasked with developing standardized assessment data elements (SADEs) within clinical categories named in the IMPACT Act. METHOD: We used environmental scans, subject matter expert, and stakeholder input to identify candidate SADEs; tested candidate data elements in alpha testing; revised SADEs and training protocols based on alpha analyses and stakeholder feedback; tested SADEs across post-acute care (PAC) settings in a national field test that included 3121 patients across 143 home health agencies, inpatient rehabilitation facilities, long-term care hospitals, and skilled nursing facilities in 14 markets across the United States; and analyzed data and stakeholder input from national testing. Field testing measured the time required for assessment, percent completion, and inter-rater reliability. We analyzed qualitative feedback from stakeholder focus groups and technical expert panels. We also obtained survey and focus group feedback from data collectors. RESULTS: We developed a mixed-method, multi-stakeholder procedure to identify and gather input on SADE for cross-setting use. This process yielded feasible and reliable SADEs for PAC settings that assess pain, cognitive status, mood, and medication reconciliation. The success of this work depended on working iteratively with diverse stakeholders and providing qualitative as well as quantitative evidence. CONCLUSIONS: The procedures applied in this project for developing and adopting SADEs for PAC, as well as the challenges and strategies to overcome challenges, should be considered in future item and quality measure development.

Standardized assessment of depression symptoms in post-acute care: A screening threshold approach.

BACKGROUND: Depression symptoms have impacts on quality of life, rehabilitation and treatment adherence, and resource utilization among patients in post-acute care (PAC) settings. The PHQ-2 and PHQ-9 are instruments for the assessment of depression, previously used in PAC settings, that have tradeoffs in terms of measurement depth versus respondent/assessor burden. Therefore, the present study tested a gateway version of the protocol (PHQ-2 to 9). METHODS: In 143 PAC settings in 14 U.S. markets across 10 states from November 2017 to August 2018, facility and research nurses administered the PHQ-2 to communicative patients (n = 3010). Nurses administered the full PHQ-9 if the patient screened positive for either of the two cardinal symptoms assessed by the PHQ-2 (depressed mood and anhedonia). We assessed the prevalence and frequency of depression symptoms using the PHQ-2 to 9, associations between depression screening results and patient characteristics and clinical conditions, and feasibility indicators. RESULTS: More than 1 in 4 patients (28%) screened positive on the PHQ-2. Only 6% of those completing the full PHQ-9 had a score indicating "minimal" severity. The average score (M = 11.9) met the threshold for moderate depression. Positive PHQ-2 screening was associated with age, female gender, disposition at discharge, septicemia/severe sepsis, and dependence for ADLs of toileting and lying to sitting mobility. Age was also associated with full PHQ-9 scores; patients ages 45-64 had the highest mean score. Length of stay was not associated with PHQ-2 screening results or full PHQ-2 to 9 scores. Missing data were minimal (<2.4%). The average time to complete was 2.3 min. Interrater reliability and percent agreement were excellent. CONCLUSIONS: These findings suggest the feasibility of a gateway scoring approach to standardized assessment of depression symptoms among PAC patients, and that depression symptoms are relatively common among this inpatient population.

Premature acute coronary syndrome: understanding the early onset.

INTRODUCTION: Acute coronary syndrome (ACS) is less frequent in young adults, but it has become a significant health problem, associated with the increasing prevalence of modifiable risk factors. OBJECTIVES: To characterize patients admitted with premature ACS, comparing with those with nonpremature ACS. METHODS: We performed a retrospective study encompassing patients of the Portuguese Registry (ProACS), comparing two groups: one composed of men less than 55 and women less than 65 years old; and other with men ≥55 and women ≥65 years old at the ACS admission. The primary endpoint was the composite of in-hospital mortality, stroke and myocardial reinfarction (re-MI). RESULTS: A total of 29 870 patients were enrolled and 25% had premature ACS, with a mean age of 50 ± 7 years old. They had a larger prevalence of smoking habits, obesity and dyslipidemia. ST-segment elevation MI (STEMI) was the main admission diagnosis in young patients and coronary angiogram mainly revealed one vessel disease in this subgroup. They had a lower Killip-Kimball (KK) class and mostly preserved left ventricular ejection fraction (LVEF). Composite endpoint was more frequent in nonpremature ACS patients. Nonpremature age, presentation with syncope or cardiac arrest, KK class >1, multivessel disease and LVEF <40% were independent predictors of the primary endpoint ( P < 0.001). Younger patients had lower rates of in-hospital all-cause mortality, re-MI and stroke. One-year all-cause mortality and 1-year cardiovascular and non-cardiovascular readmissions were also lower. CONCLUSIONS: Premature ACS affects 25% of the ACS population, mostly presenting with STEMI, but generally associated with better clinical evolution. Nevertheless, prevention measures are essential to correct modifiable cardiovascular risk factors and reduce coronary events.

Giant Left Ventricular (Pseudo?) Aneurysm Complicating Anterior Myocardial Infarction.

The differential diagnosis of true aneurysms and pseudoaneurysms is challenging, and multimodality cardiac imaging is often necessary. We report a case in which the limitations of these techniques are exposed, showing that post-operative evaluation of tissue layers remains the gold standard in establishing this diagnosis. (Level of Difficulty: Beginner.).

P2Y12 inhibitor loading dose before catheterization in ST-segment elevation myocardial infarction: Is this the best strategy? / Dose de carga do inibidor P2Y12 antes do laboratório de hemodinâmica no enfarte agudo do miocárdio com supradesnivelamento do segmento ST ­ Será mesmo a melhor estratégia?

INTRODUCTION AND OBJECTIVES: In ST-segment elevation myocardial infarction (STEMI) the benefit of dual antiplatelet therapy is unequivocal, but the optimal time to administer the loading dose (LD) of a P2Y12 inhibitor is the subject of debate and disagreement. The main aim of this study was characterize current practice in Portugal and to assess the prognostic impact of P2Y12 inhibitor LD administration strategy, before versus during or after primary percutaneous coronary intervention (PCI). METHODS: This multicenter retrospective study based on the Portuguese National Registry on Acute Coronary Syndromes included patients with STEMI and PCI performed between October 1, 2010 and September 19, 2017. Two groups were established: LD before PCI (LD-PRE) and LD during or after PCI (LD-CATH). RESULTS: A total of 4123 patients were included, 66.3% in the LD-PRE group and 32.4% in the LD-CATH group. Prehospital use of a P2Y12 inhibitor was a predictor of the composite bleeding endpoint (major bleeding, need for transfusion or hemoglobin [Hb] drop >2g/dl), Hb drop >2g/dl and reinfarction. There were no differences between groups in major adverse events (MAE) (in-hospital mortality, reinfarction and stroke) or in-hospital mortality. CONCLUSIONS: Prehospital use of a P2Y12 inhibitor was associated with an increased risk of bleeding, predicting the composite bleeding outcome and Hb drop >2g/dl, with no differences in mortality or MAE, calling into question the benefit of this strategy.

EGSYS score for the prediction of cardiac etiology in syncope: Is it useful in an outpatient setting? / Score EGSYS para predição de etiologia cardíaca na síncope: tem utilidade no contexto de consulta?

INTRODUCTION: The EGSYS score uses clinical variables to predict which patients may have cardiac (CS) or non-cardiac syncope (NCS) and has been validated in the emergency department setting. This study aims to determine whether the score has the same applicability in an outpatient setting. METHODS: In this retrospective study of all patients observed in the outpatient setting of a hospital with a syncope unit between January 2015 and December 2016, the EGSYS score was calculated for each patient, and its sensitivity and specificity were determined for the prediction of CS in patients with score ≥3. RESULTS: A total of 224 patients, mean age 64.3±21.7 years, 116 (51.8%) male, were analyzed. In the 163 (72.7%) patients with confirmed syncope, CS was diagnosed in 27 (16.6%) and NCS in 136 (83.4%). The EGSYS score was ≥3 in 40 (20.0%) patients with NCS and in 13 (48.1%) with CS. A positive score had a sensitivity of 48.2% (95% CI: 28.7-68.1), a specificity of 77.9% (95% CI: 70.0-84.6), and a positive and negative predictive value of 30.2% (95% CI: 20.8-41.8) and 88.3% (95% CI: 83.9-91.7), respectively. CONCLUSION: The EGSYS score has limited usefulness in an outpatient setting, where observed patients have already been been medically assessed. Given its high specificity and negative predictive value, it may be useful to reassure low-risk patients and family members.

p.G360R Is a Pathogenic GLA Gene Mutation Responsible for a Classic Phenotype of Fabry Disease.

The authors report the case of a classic phenotype of Fabry disease in a 60-year-old male patient presenting with left ventricular hypertrophy and stroke. Genetic analysis revealed 2 GLA-gene variants, i.e., p.R356Q and p.G360R. This clinical case highlights that the finding of 2 or more GLA gene variants in a Fabry patient should lead to a careful evaluation in order to determine their exact role in the condition. This case also provides the first clinical evidence that the p.G360R mutation is pathogenic and responsible for a classic phenotype of Fabry disease. The clinical improvement following the initiation of enzyme replacement therapy reinforces the importance of Fabry disease awareness and diagnosis in patients exhibiting red flags, such as left ventricular hypertrophy and stroke.

Hyponatremia in a Teenager: A Rare Diagnosis.

INTRODUCTION: Hyponatremia is a common electrolyte alteration which has the potential for significant morbidity and mortality. Endocrine disorders, such as primary hypothyroidism and adrenal insufficiency are uncommon causes of hyponatremia. We present the case of a teenager with symptomatic hyponatremia caused by a rare disorder. CASE: A 17-year-old boy was admitted to the emergency department with abdominal pain, nausea and vomiting, asthenia, and weight loss. He was in poor general condition, hypotensive, and he had dry mucous membranes and skin as well as mucosa hyperpigmentation. The laboratory findings showed severe hyponatremia, hyperkalemia, and renal dysfunction. The patient started inotropic support and antibiotics. Plasma cortisol and corticotropin levels allowed the diagnosis of primary adrenal insufficiency. He began replacement therapy with hydrocortisone and fludrocortisone, with gradual symptom resolution. An abdominal computed tomography scan showed adrenal hypoplasia. Findings for antiadrenal and antithyroid antibodies were positive, allowing the diagnosis of autoimmune polyglandular syndrome type II. DISCUSSION: Adrenal insufficiency is a rare disease, especially in children, and its clinical manifestations are due to glucocorticoid and mineralocorticoid deficiency. In most of the cases, symptoms are nonspecific, requiring a high index of clinical suspicion. If the diagnosis and treatment are delayed, acute adrenal insufficiency carries a high morbidity and mortality.

The Nuts and Bolts of Long-term Care In Rhode Island: Demographics, Services and Costs.

Nearly 8,000 people reside in Rhode Island's (RI's) 84 nursing homes at any single point in time. Many of these people are highly vulnerable because of illness or frailty. In this article, we describe the reasons that RI residents seek care from nursing homes, the associated costs (with a focus on Medicare and Medicaid payment), and different ways to assess nursing home quality. We also describe the home- and community-based services that can help people remain in the community. A resource list provides additional information for those seeking to better understand RI nursing homes and long-term care supports and services.

Performance of PRISM III and PELOD-2 scores in a pediatric intensive care unit.

UNLABELLED: The study aims were to compare two models (The Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD-2)) for prediction of mortality in a pediatric intensive care unit (PICU) and recalibrate PELOD-2 in a Portuguese population. To achieve the previous goal, a prospective cohort study to evaluate score performance (standardized mortality ratio, discrimination, and calibration) for both models was performed. A total of 556 patients consecutively admitted to our PICU between January 2011 and December 2012 were included in the analysis. The median age was 65 months, with an interquartile range of 1 month to 17 years. The male-to-female ratio was 1.5. The median length of PICU stay was 3 days. The overall predicted number of deaths using PRISM III score was 30.8 patients whereas that by PELOD-2 was 22.1 patients. The observed mortality was 29 patients. The area under the receiver operating characteristics curve for the two models was 0.92 and 0.94, respectively. The Hosmer and Lemeshow goodness-of-fit test showed a good calibration only for PRISM III (PRISM III: χ (2) = 3.820, p = 0.282; PELOD-2: χ (2) = 9.576, p = 0.022). CONCLUSIONS: Both scores had good discrimination. PELOD-2 needs recalibration to be a better reliable prediction tool. WHAT IS KNOWN: • PRISM III (Pediatric Risk of Mortality III) and PELOD (Pediatric Logistic Organ Dysfunction) scores are frequently used to assess the performance of intensive care units and also for mortality prediction in the pediatric population. • Pediatric Logistic Organ Dysfunction 2 is the newer version of PELOD and has recently been validated with good discrimination and calibration. What is New: • In our population, both scores had good discrimination. • PELOD-2 needs recalibration to be a better reliable prediction tool.

Folie à deux: a case report.

Folie à deux is a relatively rare mental disorder first described in France in 1877 by Lasègue and Falret. However, folie à deux is still a matter of study and debate today as it remains a challenge for psychiatrists. The aim of our work is to report a clinical case of folie à deux, subtype A of Gralnick, between an inducer daughter and an induced mother who lived quite socially isolated and had a strong and close relationship. In the clinical case presented, folie à deux was easily diagnosed but its treatment proved to be a higher challenge. The main diagnosis of the inducer patient was also quite interesting. Many years after it was first described, folie à deux is still an interesting and challenging disorder to psychiatrists, especially concerning its pathophysiology and treatment.