Epidemiology and economic burden of amyotrophic lateral sclerosis in the United States: a literature review.

Objective: This review sought to gain a comprehensive, up-to-date understanding of the epidemiology and cost and healthcare resource use (HCRU) burden of amyotrophic lateral sclerosis (ALS) in the US, at a patient and national level. Methods: A targeted literature review (TLR) to identify epidemiological evidence (prevalence, incidence, mortality, survival), and systematic literature review (SLR) to identify cost and HCRU data published since January 2016, were performed. MEDLINE databases and Embase searches were conducted in January 2021. Key congresses (2019-2020) and bibliographies of relevant SLRs were hand-searched. Two high-quality SLRs were reviewed for additional cost data published between January 2001-2015. Registry and database studies were prioritized for epidemiological evidence. To allow comparison between studies in this publication, only evidence from the US was considered, with costs inflated to the 2020/2021 cost-year and converted to US dollars. Results: Eight studies from the epidemiology TLR, and eighteen from the cost and HCRU SLR, were extracted. Reported ALS incidence in the US was ∼1.5 per 100,000 person-years, and point prevalence ranged from 3.84-5.56 per 100,000 population. Total US national costs spanned ∼$212 million-∼$1.4 billion USD/year, and variably consisted of direct costs associated with HCRU and indirect costs. Conclusions: The national cost of ∼$1.02 billion USD/year (estimated using a prevalence of 16,055 cases) best aligns with prevalence estimates found in the TLR (equating to ∼13,000-18,000 cases). However, large-scale, population-based studies are necessary to precisely assess US epidemiology of ALS and capture all costs needed to inform cost-effectiveness models and resource planning.

Antipsychotic-Related Stigma and the Impact on Treatment Choices: A Systematic Review and Framework Synthesis.

BACKGROUND: Antipsychotics are a class of medications primarily used to treat individuals with psychotic disorders. They have also been indicated for patients with other psychiatric conditions, such as post-traumatic stress disorder and major depressive disorder. Non-adherence is prominent amongst individuals prescribed antipsychotics, with medication-related self-stigma and social stigma identified as major factors. No previous reviews have focused on stigma associated specifically with antipsychotic medication. This systematic literature review aimed to synthesise evidence on the prevalence of stigmatising attitudes and behaviours related to antipsychotic treatment and understand their impact on antipsychotic treatment initiation and continuation. METHODS: Two independent reviewers screened studies from databases, congress proceedings, ClinicalTrials.gov, and PsychU.org; relevant studies reported quantitative or qualitative data on antipsychotic-related stigma in adults with psychotic disorders, mood disorders, borderline personality disorder or anxiety disorders, or healthcare providers or caregivers of these patients, and any impact on treatment. Framework synthesis facilitated extraction and synthesis of relevant information; quantitative and qualitative data were coded and indexed against a pre-specified thematic framework by two independent reviewers. RESULTS: Forty-five articles reporting on 40 unique studies were included; 22 reported quantitative data, 16 reported qualitative data, and two reported quantitative and qualitative data relating to antipsychotic-related stigma. Framework synthesis identified four themes: 1) impact of antipsychotic treatment on a) social stigma or b) self-stigma; 2) impact of side effects of antipsychotic treatment on a) social stigma or b) self-stigma; 3) impact of route of administration of antipsychotic treatment on stigma; 4) impact of stigma on the use of antipsychotics. CONCLUSION: This systematic literature review found that antipsychotic-related social and self-stigma is a factor in non-adherence to antipsychotics. Further research should examine stigma in a wider range of patients and the extent to which clinicians' treatment decisions are impacted by the potential stigma associated with antipsychotic medications.

The burden of disease in early schizophrenia - a systematic literature review.

BACKGROUND: Schizophrenia is a heterogeneous disorder with a burden that can vary greatly depending on the severity and the duration. Previous research has suggested that patients in the earlier stages of schizophrenia (typically first-episode schizophrenia) benefit from effective early treatment, however, a comprehensive review of the burden specifically in this population has not been undertaken. A systematic literature review was therefore conducted to characterize the clinical, economic, and humanistic burden, as reported in naturalistic studies of schizophrenia populations specifically at an early stage of disease in comparison with healthy controls, patients with chronic schizophrenia, and patients with other psychiatric disorders. METHODS AND MATERIALS: Searches were conducted in MEDLINE, MEDLINE In-Process, Embase, PsycINFO, and EconLit databases for records published between January 2005 and April 2019, and of relevant conference abstracts published between January 2014 and May 2019. Data were extracted from relevant publications and subjected to qualitative evaluation. RESULTS: Fifty-two publications were identified for inclusion and revealed a considerable burden for early schizophrenia with regards to mortality, psychiatric comorbidities such as substance abuse and depression, poor social functioning, and unemployment. Comparisons with chronic schizophrenia suggested a greater burden with longer disease duration, while comparisons with other psychiatric disorders were inconclusive. This review uncovered various gaps in the available literature, including limited or no data on incarcerations, caregiver burden, and costs associated with early schizophrenia. CONCLUSIONS: Overall, the burden of schizophrenia is apparent even in the early stages of the disease, although further research is required to quantify the burden with chronic schizophrenia and other psychiatric disorders.

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review.

BACKGROUND: Approximately 20% of patients with neuroendocrine tumours (NETs) develop carcinoid syndrome (CS), characterised by flushing and diarrhoea. Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion. Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs (GEP-NETs), other causes to consider include pancreatic enzyme insufficiency (PEI), bile acid malabsorption and small intestinal bacterial overgrowth. If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea, these treatments may be ineffective against the diarrhoea, risking detrimental effects to patient quality of life. AIM: To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs. METHODS: Electronic databases (MEDLINE, Embase and the Cochrane Library) were searched from inception to September 12, 2018 using terms for NETs and diarrhoea. Congresses, systematic literature review bibliographies and included articles were also hand-searched. Any study designs and publication types were eligible for inclusion if relevant data on a cause(s) of diarrhoea in patients with GEP-NETs were reported. Studies were screened by two independent reviewers at abstract and full-text stages. Framework synthesis was adapted to synthesise quantitative and qualitative data. The definition of qualitative data was expanded to include all textual data in any section of relevant publications. RESULTS: Forty-seven publications (44 studies) were included, comprising a variety of publication types, including observational studies, reviews, guidelines, case reports, interventional studies, and opinion pieces. Most reported on PEI on/after treatment with somatostatin analogs; 9.5%-84% of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI. Where reported, 14.3%-50.7% of patients received pancreatic enzyme replacement therapy. Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption (80%), small intestinal bacterial overgrowth (23.6%-62%), colitis (20%) and infection (7.1%). Diagnostic approaches included faecal elastase, breath tests, tauroselcholic (selenium-75) acid (SeHCAT) scan and stool culture, although evidence on the effectiveness or diagnostic accuracy of these approaches was limited. Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation. From the identified evidence, if diarrhoea is assumed to be CS diarrhoea, consequences include uncontrolled diarrhoea, malnutrition, and perceived ineffectiveness of CS treatment. Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team, including gastroenterologists. CONCLUSION: Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use. This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches, to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.

Design study of piezoelectric energy-harvesting devices for generation of higher electrical power using a coupled piezoelectric-circuit finite element method.

This paper presents a design study on the geometric parameters of a cantilever-based piezoelectric energy-harvesting devices (EHD), which harvest energy from motion (vibration), for the purpose of scavenging more energy from ambient vibration energy sources. The design study is based on the coupled piezoelectric-circuit finite element method (CPCFEM), previously presented by Dr. Zhu. This model can calculate the power output of piezoelectric EHDS directly connected to a load resistor and is used in this paper to obtain the following simulation results for variations in geometric parameters such as the beam length, width and thickness, and the mass length, width, and height: 1) the current flowing through and the voltage developed across the load resistor, 2) the power dissipated by the resistor and the corresponding vibrational displacement amplitude, and 3) the resonant frequency. By studying these results, straightforward design strategies that enable the generation of more power are obtained for each geometric parameter, and a physical understanding of how each parameter affects the output power is given. It is suggested that, in designing with the aim of generating more power, the following strategies be used: 1) for the beam, a shorter length, larger width, and lower ratio of piezoelectric layer thickness to total beam thickness are preferred in the case of a fixed mass; 2) for the mass, a shortened mass length and a higher mass height are preferred in the case of variation in the mass length and the mass height with mass width and mass value remain fixed, and a wider width and small mass height are preferred in the case of variation in mass width and height (mass length and value remain fixed; and 3) for the case of a fixed total length, a shorter beam length and longer mass length are preferred. With the design strategies, output powers from the device can reach above 1 to 2 mW/cm(3), much higher than the 200 microW/cm(3) currently achieved in the published literature. This is an encouraging prospect for enabling a wider range of applications of the EHDs. In addition, physical insights into how each parameter influences output power are also discussed in detail.

Analyses of power output of piezoelectric energy-harvesting devices directly connected to a load resistor using a coupled piezoelectric-circuit finite element method.

This paper presents, for the first time, a coupled piezoelectric-circuit finite element model (CPC-FEM) to analyze the power output of a vibration-based piezoelectric energy-harvesting device (EHD) when it is connected to a load resistor. Special focus is given to the effect of the load resistor value on the vibrational amplitude of the piezoelectric EHD, and thus on the current, voltage, and power generated by the device, which are normally assumed to be independent of the load resistor value to reduce the complexity of modeling and simulation. The presented CPC-FEM uses a cantilever with a sandwich structure and a seismic mass attached to the tip to study the following characteristics of the EHD as a result of changing the load resistor value: 1) the electric outputs: the current through and voltage across the load resistor; 2) the power dissipated by the load resistor; 3) the displacement amplitude of the tip of the cantilever; and 4) the shift in the resonant frequency of the device. It is found that these characteristics of the EHD have a significant dependence on the load resistor value, rather than being independent of it as is assumed in most literature. The CPC-FEM is capable of predicting the generated output power of the EHD with different load resistor values while simultaneously calculating the effect of the load resistor value on the displacement amplitude of the tip of the cantilever. This makes the CPC-FEM invaluable for validating the performance of a designed EHD before it is fabricated and tested, thereby reducing the recurring costs associated with repeat fabrication and trials. In addition, the proposed CPC-FEM can also be used for producing an optimized design for maximum power output.