Gaucher disease epidemiology and natural history: a comprehensive review of the literature.

OBJECTIVES: The objectives of this research were: (1) to heighten awareness of Gaucher disease (GD), a rare lysosomal storage disorder with highly heterogeneous patterns of organ involvement and disease severity, to clinicians most likely to encounter these patients, and; (2) to summarize the published evidence on GD epidemiology which is essential to accurately depict the total societal burden of this rare worldwide disorder. METHODS: A comprehensive literature review was undertaken to summarize the published evidence on the epidemiology of GD. MEDLINE, EMBASE, CENTRAL, and 'grey' literature sources published in English between January 1990 and March 2015 were searched to identify relevant publications. RESULTS: In total, 188 full-text articles were reviewed and findings from 49 studies are summarized herein. The standardized birth incidence of GD in the general population varied from 0.39 to 5.80 per 100 000, and prevalence ranged from 0.70 to 1.75 per 100 000, respectively. Time from onset of GD symptoms to clinical diagnosis was highly variable, with median delays of up to 7 years reported. DISCUSSION: The incidence and prevalence of GD is substantially higher among the Ashkenazi Jewish population than the general population. Limited epidemiologic information was available from Latin America, Africa, Asia, and developed nations such as the United States, Germany, and the United Kingdom. CONCLUSIONS: Signs and symptoms of GD frequently mimic more common hematologic conditions resulting in missed or delayed diagnosis. Early diagnosis and prompt initiation of treatment when indicated is crucial to prevent or minimize life-altering or life-threatening liver and skeletal complications.

An evaluation of variation in published estimates of schizophrenia prevalence from 1990─2013: a systematic literature review.

BACKGROUND: There is a lack of consistency in findings across studies on the prevalence of schizophrenia, and no recent systematic review of the literature exists. The purpose of this study is to provide an updated systematic review of population-based prevalence estimates and to understand the factors that could account for this variation in prevalence estimates. METHODS: MEDLINE, Embase, and PsycInfo databases were searched for observational studies describing schizophrenia prevalence in general populations from 2003-2013 and supplemented by studies from a prior review covering 1990-2002. Studies reporting prevalence estimates from specialized populations such as institutionalized, homeless, or incarcerated persons were excluded. Prevalence estimates were compared both across and within studies by factors that might contribute to variability using descriptive statistics. RESULTS: Sixty-five primary studies were included; thirty-one (48 %) were from Europe and 35 (54 %) were conducted in samples of ≥50,000 persons. Among 21 studies reporting 12-month prevalence, the median estimate was 0.33 % with an interquartile range (IQR) of 0.26 %-0.51 %. The median estimate of lifetime prevalence among 29 studies was 0.48 % (IQR: 0.34 %-0.85 %). Prevalence across studies appeared to vary by study design, geographic region, time of assessment, and study quality scores; associations between study sample size and prevalence were not observed. Within studies, age-adjusted estimates were higher than crude estimates by 17 %-138 %, the use of a broader definition of schizophrenia spectrum disorders compared to schizophrenia increased case identification by 18 %-90 %, identification of cases from inpatient-only settings versus any setting decreased prevalence by 60 %, and no consistent trends were noted by differing diagnostic criteria. CONCLUSIONS: This review provides updated information on the epidemiology of schizophrenia in general populations, which is vital information for many stakeholders. Study characteristics appear to play an important role in the variation between estimates. Overall, the evidence is still sparse; for many countries no new studies were identified.

Clinical characteristics and healthcare utilization of patients with multicentric Castleman disease.

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disease. Little is known about how patient clinical features and healthcare utilization varies by human immunodeficiency virus (HIV) status and disease subtype. Data of MCD patients identified between 2000 and 2009 were collected from medical records at two United States treatment centres. Clinical, demographic, and biochemical characteristics, drug therapies and medical utilization were descriptively reported by HIV status and cell histology, and statistically compared with the Fisher's Exact and Kruskal-Wallis tests. Patients (n = 59) had a pathologically and clinically confirmed MCD diagnosis: plasmacytic (42%), hyaline vascular (29%) and mixed (15%); 10% had HIV infection. In the first year after diagnosis, MCD patients on average saw a healthcare provider more than six times, were hospitalized at least once and underwent frequent radiological and laboratory testing. Rituximab was the most commonly used drug therapy, followed by corticosteroids and conventional chemotherapy. One- and 2-year survival was excellent in HIV-negative patients (100% and 97%, respectively) but inferior for HIV-positive cases (67% and 67%, respectively). Heterogeneous treatment decisions were observed in this MCD study; HIV status was the only distinguishing clinical criteria associated with pharmacotherapies. Additional research is necessary to guide treatment of this rare lymphoproliferative disorder.

Lung transplantation in idiopathic pulmonary fibrosis: a systematic review of the literature.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a distinct form of interstitial pneumonia with unknown origin and poor prognosis. Current pharmacologic treatments are limited and lung transplantation is a viable option for appropriate patients. The aim of this review was to summarize lung transplantation survival in IPF patients overall, between single (SLT) vs. bilateral lung transplantation (BLT), pre- and post Lung Allocation Score (LAS), and summarize wait-list survival. METHODS: A systematic review of English-language studies published in Medline or Embase between 1990 and 2013 was performed. Eligible studies were those of observational design reporting survival post-lung transplantation or while on the wait list among IPF patients. RESULTS: Median survival post-transplantation among IPF patients is estimated at 4.5 years. From ISHLT and OPTN data, one year survival ranged from 75% - 81%; 3-year: 59% - 64%; and 5-year: 47% - 53%. Post-transplant survival is lower for IPF vs. other underlying pre-transplant diagnoses. The proportion of IPF patients receiving BLT has steadily increased over the last decade and a half. Unadjusted analyses suggest improved long-term survival for BLT vs. SLT; after adjustment for patient characteristics, the differences tend to disappear. IPF patients account for the largest proportion of patients on the wait list and while wait list time has decreased, the number of transplants for IPF patients has increased over time. OPTN data show that wait list mortality is higher for IPF patients vs. other diagnoses. The proportion of IPF patients who died while awaiting transplantation ranged from 14% to 67%. While later transplant year was associated with increased survival, no significant differences were noted pre vs. post LAS implementation; however a high LAS vs low LAS was associated with decreased one-year survival. CONCLUSIONS: IPF accounts for the largest proportion of patients awaiting lung transplants, and IPF is associated with higher wait-list and post-transplant mortality vs. other diagnoses. Improved BLT vs. SLT survival may be the result of selection bias. Survival pre- vs. post LAS appears to be similar except for IPF patients with high LAS, who have lower survival compared to pre-LAS. Data on post-transplant morbidity outcomes are sparse.

Clinical epidemiology and treatment patterns of patients with multicentric Castleman disease: results from two US treatment centres.

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disease with little known about its epidemiology or treatment modalities. Clinical and demographic data of MCD patients identified between 2000 and 2009 were collected from medical records at two United States (US) MCD referral centres. ZIP codes identified patient residences; prevalence and incidence were estimated based on catchment areas. Patient clinical, demographic, and biochemical characteristics, drug therapies and medical utilization were descriptively reported. MCD patients (n = 59) were 61% male, mean age of 53 years (median = 55 years) and 68% Caucasian. Of those with known human immunodeficiency virus (HIV) status (n = 41), 85% (n = 35) were negative, 15% (n = 6) were positive. Most frequent physician-reported symptoms (n = 33) were fatigue (49%, n = 16), fever (39%, n = 13), and night sweats (30%, n = 10). The estimated US 10-year prevalence was 2·4 per million. During first year of follow-up after study entry, the top two systemic therapies (n = 27) were monotherapies: prednisone (33%, n = 9) and rituximab (19%, n = 5). After a follow-up of 2 years, 92% of patients were alive. This study provides new information on MCD population demographics, treatment patterns, and medical utilization; a minimal US period prevalence rate is proposed. Study replication is needed to improve external validity.

OnabotulinumtoxinA muscle injection patterns in adult spasticity: a systematic literature review.

BACKGROUND: OnabotulinumtoxinA has demonstrated significant benefit in adult focal spasticity. This study reviews the injection patterns (i.e., muscle distribution, dosing) of onabotulinumtoxinA for treatment of adult spasticity, as reported in published studies. METHODS: A systematic review of clinical trials and observational studies published between 1990 and 2011 reporting data on muscles injected with onabotulinumtoxinA in adult patients treated for any cause of spasticity. RESULTS: 28 randomized, 5 nonrandomized, and 37 single-arm studies evaluating 2,163 adult patients were included. The most frequently injected upper-limb muscles were flexor carpi radialis (64.0% of patients), flexor carpi ulnaris (59.1%), flexor digitorum superficialis (57.2%), flexor digitorum profundus (52.5%), and biceps brachii (38.8%). The most frequently injected lower-limb muscles were the gastrocnemius (66.1% of patients), soleus (54.7%), and tibialis posterior (50.5%). The overall dose range reported was 5-200 U for upper-limb muscles and 10-400 U for lower-limb muscles. CONCLUSIONS: The reviewed evidence indicates that the muscles most frequently injected with onabotulinumtoxinA in adults with spasticity were the wrist, elbow, and finger flexors and the ankle plantar flexors. OnabotulinumtoxinA was injected over a broad range of doses per muscle among the studies included in this review, but individual practitioners should be mindful of local regulatory approvals and regulations.

Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown aetiology. It is a rare disease, and its incidence and prevalence are not clear. Therefore, we sought to review the published evidence on the global epidemiology of IPF. A comprehensive review of English language literature was performed by searching Medline and EMBASE for studies on IPF epidemiology published between January 1990 and August 2011. Studies providing quantitative data on IPF incidence and/or prevalence were identified and key data collected. 15 studies reporting on the incidence and/or prevalence of IPF were identified and summarised. IPF prevalence estimates in the USA varied between 14 and 27.9 cases per 100,000 population using narrow case definitions, and 42.7 and 63 per 100,000 population using broad case definitions. In Europe, IPF prevalence ranged from 1.25 to 23.4 cases per 100,000 population. The annual incidence of IPF in the USA was estimated at 6.8-8.8 per 100,000 population using narrow case definitions and 16.3-17.4 per 100,000 population using broad case definitions. In Europe, the annual incidence ranged between 0.22 and 7.4 per 100,000 population. IPF prevalence and incidence increase with age, are higher among males and appear to be on the increase in recent years. IPF is an orphan disease that affects a potentially increasing number of people in Europe and the USA. The observed variability in IPF incidence and prevalence may be explained by the differences in diagnostic criteria used, case definition, study population and study design.

A systematic review of validated methods for identifying erythema multiforme major/minor/not otherwise specified, Stevens-Johnson Syndrome, or toxic epidermal necrolysis using administrative and claims data.

PURPOSE: The Food and Drug Administration's (FDA) Mini-Sentinel pilot program aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of erythema multiforme and related conditions. METHODS: PubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the erythema multiforme HOI. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles that used administrative and claims data to identify erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis and that included validation estimates of the coding algorithms. RESULTS: Our search revealed limited literature focusing on erythema multiforme and related conditions that provided administrative and claims data-based algorithms and validation estimates. Only four studies provided validated algorithms and all studies used the same International Classification of Diseases code, 695.1. Approximately half of cases subjected to expert review were consistent with erythema multiforme and related conditions. CONCLUSIONS: Updated research needs to be conducted on designing validation studies that test algorithms for erythema multiforme and related conditions and that take into account recent changes in the diagnostic coding of these diseases.

A systematic review of validated methods for identifying anaphylaxis, including anaphylactic shock and angioneurotic edema, using administrative and claims data.

PURPOSE: The Food and Drug Administration's Mini-Sentinel pilot program initially aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest from administrative and claims data. This article summarizes the process and findings of the algorithm review of anaphylaxis. METHODS: PubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the anaphylaxis health outcome of interest. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify anaphylaxis and including validation estimates of the coding algorithms. RESULTS: Our search revealed limited literature focusing on anaphylaxis that provided administrative and claims data-based algorithms and validation estimates. Only four studies identified via literature searches provided validated algorithms; however, two additional studies were identified by Mini-Sentinel collaborators and were incorporated. The International Classification of Diseases, Ninth Revision, codes varied, as did the positive predictive value, depending on the cohort characteristics and the specific codes used to identify anaphylaxis. CONCLUSIONS: Research needs to be conducted on designing validation studies to test anaphylaxis algorithms and estimating their predictive power, sensitivity, and specificity.

A systematic review of validated methods for identifying hypersensitivity reactions other than anaphylaxis (fever, rash, and lymphadenopathy), using administrative and claims data.

PURPOSE: The Food and Drug Administration's Mini-Sentinel pilot program aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest from administrative and claims data. This article summarizes the process and findings of the algorithm review of hypersensitivity reactions. METHODS: PubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the hypersensitivity reactions of health outcomes of interest. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify hypersensitivity reactions and including validation estimates of the coding algorithms. RESULTS: We identified five studies that provided validated hypersensitivity-reaction algorithms. Algorithm positive predictive values (PPVs) for various definitions of hypersensitivity reactions ranged from 3% to 95%. PPVs were high (i.e. 90%-95%) when both exposures and diagnoses were very specific. PPV generally decreased when the definition of hypersensitivity was expanded, except in one study that used data mining methodology for algorithm development. CONCLUSIONS: The ability of coding algorithms to identify hypersensitivity reactions varied, with decreasing performance occurring with expanded outcome definitions. This examination of hypersensitivity-reaction coding algorithms provides an example of surveillance bias resulting from outcome definitions that include mild cases. Data mining may provide tools for algorithm development for hypersensitivity and other health outcomes. Research needs to be conducted on designing validation studies to test hypersensitivity-reaction algorithms and estimating their predictive power, sensitivity, and specificity.

A systematic review of validated methods for identifying pulmonary fibrosis and interstitial lung disease using administrative and claims data.

PURPOSE: The Food and Drug Administration's Mini-Sentinel pilot program initially aimed to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of pulmonary fibrosis and interstitial lung disease. METHODS: PubMed and Iowa Drug Information Service Web searches were conducted to identify citations applicable to the pulmonary fibrosis/interstitial lung disease HOI. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify pulmonary fibrosis and interstitial lung disease, including validation estimates of the coding algorithms. RESULTS: Our search revealed a deficiency of literature focusing on pulmonary fibrosis and interstitial lung disease algorithms and validation estimates. Only five studies provided codes; none provided validation estimates. Because interstitial lung disease includes a broad spectrum of diseases, including pulmonary fibrosis, the scope of these studies varied, as did the corresponding diagnostic codes used. CONCLUSIONS: Research needs to be conducted on designing validation studies to test pulmonary fibrosis and interstitial lung disease algorithms and estimating their predictive power, sensitivity, and specificity.

A systematic review of validated methods for identifying acute respiratory failure using administrative and claims data.

PURPOSE: The Food and Drug Administration's (FDA) Mini-Sentinel pilot program initially aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of acute respiratory failure (ARF). METHODS: PubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the anaphylaxis HOI. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify ARF, including validation estimates of the coding algorithms. RESULTS: Our search revealed a deficiency of literature focusing on ARF algorithms and validation estimates. Only two studies provided codes for ARF, each using related yet different ICD-9 codes (i.e., ICD-9 codes 518.8, "other diseases of lung," and 518.81, "acute respiratory failure"). Neither study provided validation estimates. CONCLUSIONS: Research needs to be conducted on designing validation studies to test ARF algorithms and estimating their predictive power, sensitivity, and specificity.