The natural history and burden of illness of metachromatic leukodystrophy: a systematic literature review.

BACKGROUND: Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of sulfatides in the nervous system. This systematic literature review aimed to explore the effect of MLD on the lives of patients. METHODS: The Ovid platform was used to search Embase, MEDLINE, and the Cochrane Library for articles related to the natural history, clinical outcomes, and burden of illness of MLD; congress and hand searches were performed using 'metachromatic leukodystrophy' as a keyword. Of the 531 publications identified, 120 were included for data extraction following screening. A subset of findings from studies relating to MLD natural history and burden of illness (n = 108) are presented here. RESULTS: The mean age at symptom onset was generally 16-18 months for late-infantile MLD and 6-10 years for juvenile MLD. Age at diagnosis and time to diagnosis varied widely. Typically, patients with late-infantile MLD presented predominantly with motor symptoms and developmental delay; patients with juvenile MLD presented with motor, cognitive, and behavioral symptoms; and patients with adult MLD presented with cognitive symptoms and psychiatric and mood disorders. Patients with late-infantile MLD had more rapid decline of motor function over time and lower survival than patients with juvenile MLD. Commonly reported comorbidities/complications included ataxia, epilepsy, gallbladder abnormalities, incontinence, neuropathy, and seizures. CONCLUSIONS: Epidemiology of MLD by geographic regions, quantitative cognitive data, data on the differences between early- and late-juvenile MLD, and humanistic or economic outcomes were limited. Further studies on clinical, humanistic (i.e., quality of life), and economic outcomes are needed to help inform healthcare decisions for patients with MLD.

Exploring the relationship between patient-relevant outcomes and Alzheimer's disease progression assessed using the clinical dementia rating scale: a systematic literature review.

Background: People with Alzheimer's disease (AD) have difficulties in performing activities of daily living (ADLs) as the disease progresses, commonly experience neuropsychiatric symptoms (NPS), and often have comorbidities such as cardiovascular disease. These factors all contribute to a requirement for care and considerable healthcare costs in AD. The Clinical Dementia Rating (CDR) scale is a widely used measure of dementia staging, but the correlations between scores on this scale and patient-/care partner-relevant outcomes have not been characterized fully. We conducted a systematic literature review to address this evidence gap. Methods: Embase, MEDLINE, and the Cochrane Library were searched September 13, 2022, to identify published studies (no restriction by date or country) in populations with mild cognitive impairment due to AD or AD dementia. Studies of interest reported data on the relationships between CDR Global or CDR-Sum of Boxes (CDR-SB) scores and outcomes including NPS, comorbidities, ADLs, nursing home placement, healthcare costs, and resource use. Results: Overall, 58 studies met the inclusion criteria (42 focusing on comorbidities, 14 on ADLs or dependence, five on nursing home placement, and six on economic outcomes). CDR/CDR-SB scores were correlated with the frequency of multiple NPS and with total scores on the Neuropsychiatric Inventory. For cardiovascular comorbidities, no single risk factor was consistently linked to AD progression. Increasing CDR/CDR-SB scores were correlated with decline in multiple different measures of ADLs and were also associated with nursing home placement and increasing costs of care. Conclusion: NPS, ADLs, and costs of care are clearly linked to AD progression, as measured using CDR Global or CDR-SB scores, from the earliest stages of disease. This indicates that scores derived from the CDR are a meaningful way to describe the severity and burden of AD for patients and care partners across disease stages.

Prevalence of KRAS G12C Mutation and Co-mutations and Associated Clinical Outcomes in Patients With Colorectal Cancer: A Systematic Literature Review.

PURPOSE: A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically significant KRAS G12C mutation, and to estimate the prognostic significance of these mutations in patients with colorectal cancer (CRC). DESIGN: Relevant English-language publications in the Embase, MEDLINE, and the Cochrane Library databases (from 2009 to 2021) and congress presentations (from 2016 to 2021) were reviewed. Eligible studies were those that reported the prevalence and clinical outcomes of the KRAS G12C mutation in patients with CRC. RESULTS: A total of 137 studies (interventional [n = 8], post hoc analyses of randomized clinical trials [n = 6], observational [n = 122], and longitudinal [n =1]) were reviewed. Sixty-eight studies reported the prevalence of KRAS mutations (KRASm) in 42 810 patients with CRC. The median global prevalence of KRASm was 38% (range, 13.3%-58.9%) and that of the KRAS G12C mutation (KRAS G12C) 3.1% (range, 0.7%-14%). Available evidence suggests that KRASm are possibly more common in tumors that develop on the right side of the colon. Limited evidence suggests a lower objective response rate and inferior disease-free/relapse-free survival in patients with KRAS G12C compared with patients with KRASwt or other KRASm. CONCLUSION: Our analysis reveals that KRAS G12C is prevalent in 3% of patients with CRC. Available evidence suggests a poor prognosis for patients with KRAS G12C. Right-sided tumors were more likely to harbor KRASm; however, their role in determining clinical outcomes needs to be investigated further.