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Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry.

ABSTRACT: BACKGROUND:Hypophosphatasia (HPP) is a rare, systemic disease caused by mutation(s) within the ALPL gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP has a heterogeneous presentation, which coupled with its rarity, often leads to missed/delayed diagnosis and an incomplete understanding of its natural history. To better understand the epidemiology and clinical course of HPP, including timing of diagnosis after first reported manifestation, we present baseline data for patients enrolled in the Global HPP Registry. METHODS:Data were analyzed from patients with an HPP diagnosis confirmed by low serum ALP activity and/or an ALPL pathogenic variant, regardless of prior or current treatment, according to age at enrollment (children: ?12?months before diagnosis at age 20.4?months (-?0.2 mo, 16.0 y). In adults, the earliest reported manifestation occurred at a median (min, max) age of 37.6?years (0.2 y, 75.2 y), which preceded age at diagnosis (47.5?years [0.2 y, 75.2 y]) by ~?10?years. Premature loss of deciduous teeth (48.2%, age???6 mo), bone deformity (32.5%), and failure to thrive (26.7%) were most commonly reported in the HPP-related disease history of children. Pain (74.5%), orthopedic procedures and therapies (44.6%), and recurrent and poorly healing fractures (36.5%) were most commonly reported in the HPP-related disease history of adults. CONCLUSIONS:The Global HPP Registry represents the largest observational study of patients with HPP, capturing real world data. This analysis shows that diagnostic delay is common, reflecting limited awareness of HPP, and that HPP is associated with systemic manifestations across all ages. Many patients diagnosed in adulthood had HPP manifestations in childhood, highlighting the importance of taking thorough medical histories to ensure timely diagnosis. TRIAL REGISTRATION:Clinicaltrials.gov : NCT02306720 , December 2014; ENCePP.eu: EUPAS13526 , May 2016 (retrospectively registered).

SUBMITTER: Hogler W

PROVIDER: S-EPMC6376686 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry.

Högler Wolfgang W Langman Craig C Gomes da Silva Hugo H Fang Shona S Linglart Agnès A Ozono Keiichi K Petryk Anna A Rockman-Greenberg Cheryl C Seefried Lothar L Kishnani Priya S PS

BMC musculoskeletal disorders 20190214 1

<h4>Background</h4>Hypophosphatasia (HPP) is a rare, systemic disease caused by mutation(s) within the ALPL gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP has a heterogeneous presentation, which coupled with its rarity, often leads to missed/delayed diagnosis and an incomplete understanding of its natural history. To better understand the epidemiology and clinical course of HPP, including timing of diagnosis after first reported manifestation, we present baseline data for patie ...[more]

PMID: 30764793

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Project description:BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI).ObjectivesThe goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI.MethodsA prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization.ResultsAs of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p < 0.001 relative to PUIs). COVID+ patients were more likely to present with cardiogenic shock (18%) but were less likely to receive invasive angiography (78%) (all p < 0.001 relative to control patients). Among COVID+ patients who received angiography, 71% received PPCI and 20% received medical therapy (both p < 0.001 relative to control patients). The primary outcome occurred in 36% of COVID+ patients, 13% of PUIs, and 5% of control patients (p < 0.001 relative to control patients).ConclusionsCOVID+ patients with STEMI represent a high-risk group of patients with unique demographic and clinical characteristics. PPCI is feasible and remains the predominant reperfusion strategy, supporting current recommendations.

Project description:Hypophosphatasia (HPP) is a rare, commonly unrecognized hereditary mineralization defect with a dramatically poor prognosis in severe cases. This study is the first to examine the detailed clinical and laboratory characteristics of patients with HPP and healthy carriers in Turkey.The study data were obtained retrospectively from the files of 10 healthy carriers and of 16 cases with HPP (12 children and 4 adults) who were followed in our center from 2012 to 2016.The annual incidence of perinatal lethal hypophosphatasia (PLH) was estimated to be approximately 1 case per 435,517 live births,, which is the first report from Turkey. The clinical courses of the cases differed depending on the type of HPP. All of the seven cases (58.3% of all cases) with perinatal lethal form of HPP died. A need for respiratory support (p=0.001), a history of pyridoxine-dependent seizures (p=0.001), a low chest circumference measurement (p=0.017), younger age at diagnosis (p=0.029), a small head circumference at the time of presentation (p=0.042), a low arm span to height ratio (p=0.048), and a low serum alkaline phosphatase (ALP) level (p=0.042) seemed to be predicting factors for mortality. The mean height standard deviation score of the patients and those of the healthy carriers did not differ significantly (p=0.173). Different mutations were detected in nine of 14 cases (64.2%) in whom an ALPL gene mutation analysis could be performed, and five of these cases (35.7%) had novel mutations. The most common mutations were c746G>T (five alleles), c346G>A (three alleles), and c.140C>T (three alleles). In addition, the most frequently observed genotype in Turkish HPP cases was autosomal-dominant c.346G>A (p.A116T) mutations which were detected in three cases in two different families.Because of the respiratory problems, especially the lung hypoplasia, the clinical course is poor in cases with the perinatal lethal form of HPP. Some minor abnormalities such as mild short stature and osteopenia could be observed in asymptomatic heterozygote carriers. Laboratory findings were normal in these cases.

Project description:IntroductionTrauma is a leading cause of morbidity and mortality worldwide. Data characterizing the burden of trauma in Cameroon is limited. Regular, prospective injury surveillance can address the shortcomings of existing hospital administrative logs and medical records. This study aims to characterize trauma as seen at the emergency department (ED) of Limbe Regional Hospital (LRH) and assess the completeness of data obtained by a trauma registry.Methods and findingsFrom January 2008 to October 2013, we prospectively captured data on injured patients using a strategically designed, context-relevant trauma registry instrument. Indicators around patient demographics, injury characteristics, delays in accessing care, and treatment outcomes were recorded. Descriptive, bivariate, and multivariate statistical analyses were conducted. About 5,617 patients, aged from 0.5-95years (median age of 26 years), visited the LRH ED with an injury; 67% were male. Students (27%) were the most affected occupation category. Road traffic injuries (RTIs) (56%), assault (22%), and domestic injuries (13%) were the leading causes of injury. Two-thirds of RTIs were motorcycle-related. Working in transportation (AOR 4.42, p<0.001) and law enforcement (AOR 1.73, p = 0.004) were significant predictors of having a RTI. The trauma registry showed a significant improvement in completeness of all data (p<0.001) and it improved over time compared with previous administrative records. However, proportions of missing data still ranged from 0.5% to 8.2% and involved respiratory rate or Glasgow Coma scale.ConclusionsImplementation of a context-appropriate trauma registry in resource-constrained settings is feasible. Providing valuable, high-quality data, the trauma registry can inform trauma care quality improvement efforts and policy development. Study findings indicate the need for injury prevention interventions and policies that will prioritize high-risks groups, such as those aged 20-29 years, and those in occupations requiring frequent road travel. The high incidence of motorcycle-related injuries is concerning and calls for a proactive solution.

Project description:BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is a rare sequela of acute pulmonary embolism that is treatable when recognized. Awareness of this disease has increased with recent advancements in therapeutic options, but delays in diagnosis remain common, and diagnostic and treatment guidelines are often not followed. Data gathered from international registries have improved our understanding of CTEPH, but these data may not be applicable to the US population owing to differences in demographics and medical practice patterns.ObjectiveThe US CTEPH Registry (US-CTEPH-R) was developed to provide essential information to better understand the demographics, risk factors, evaluation, and treatment of CTEPH in the United States, as well as the short- and long-term outcomes of surgical and nonsurgical therapies in the modern treatment era.MethodsThirty sites throughout the United States enrolled 750 subjects in this prospective, longitudinal, observational registry of patients newly diagnosed with CTEPH. Enrollment criteria included a mean pulmonary artery pressure ≥25 mmHg by right heart catheterization and radiologic confirmation of CTEPH by a multidisciplinary adjudication committee. Following enrollment, subjects were followed biannually until the conclusion of the study. Quality of life surveys were administered at enrollment and biannually, and all other testing was at the discretion of the treating clinician. Details regarding surgical therapy, balloon pulmonary angioplasty, and medical therapy were collected at enrollment and at follow-up, as well as information related to health care utilization and survival.ResultsData from this registry will improve understanding of the demographics, risk factors, and treatment patterns of patients with CTEPH, and the longitudinal impact of therapies on quality of life, health care utilization, and survival.ConclusionsThis manuscript details the methodology and design of the first large, prospective, longitudinal registry of patients with CTEPH in the United States.Trial registrationClinicalTrials.gov NCT02429284; https://www.clinicaltrials.gov/ct2/show/NCT02429284.International registered report identifier (irrid)DERR1-10.2196/25397.

Project description:Background: Determinants of changes in cognitive function during aging are not well-understood. We aimed to estimate the effects of depression-, anxiety- and anger symptoms on cognition and on cognition changes, especially on changes in episodic memory (EM) and executive functioning (EF). Methods: We analyze data from the Mid-Life in the Midlife in the United States Biomarker study at two time points including n = 710 women, and n = 542 men (1996/1997) at the first assessment and n = 669 women, and n = 514 men at the second assessment (2013/2014). To assess cognition we used the Brief Test of Adult Cognition (BTACT). To measure depression-, anxiety- and anger symptoms we used the Mood and Anxiety Symptom Questionnaire (MASQ), the Center for Epidemiologic Studies Depression Scale (CES-D) and the State-Trait Anger Expression Inventory (STAXI). We used repeated models analyses to explore changes in cognition, and repeated measures linear mixed-effects models to investigate depression, anxiety and anger effects on cognition. All analyses were adjusted for potential confounders (cognition at baseline, age, education, income). Results: At the first assessment, women had significantly better episodic memory functioning than men; men in the oldest age group had significant better executive functioning. At the second assessment, more education, and white ethnicity were associated with less negative changes on episodic memory and executive functioning. Depression- and anger symptoms were associated with declines in episodic memory among women; anxiety symptoms were associated with declines in episodic memory and executive functioning in both gender in men (EF: β: -0.02, (95% CI: -0.03, -0.01; EM: β -0.02 (-0.02, 95% CI: -0.03, -0.01) and in women (EF: β -0.01, 95% CI: -0.02, -0.0004; EM: β -0.013, 95% CI: -0.03, -0.001). Conclusions: Depression-, anxiety- and anger symptoms were associated with changes in episodic memory and executive functioning. Further longitudinal studies are critical in populations in more countries to better understand the impact of depression, anxiety and anger symptoms on cognition changes.

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Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry.

Publications

Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry.

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