Agitation in patients with dementia: a systematic review of epidemiology and association with severity and course.

OBJECTIVES: More than 90% of individuals with Alzheimer's disease (AD) experience behavioral and neuropsychiatric symptoms (NPS), such as agitation. However, little is known regarding the specific burden of agitation for Alzheimer's patients. DESIGN: A global systematic literature review was conducted in MEDLINE and Embase for studies of clinical, humanistic, and economic burden of agitation in AD/dementia published from 2006-2016. References of identified papers and related literature reviews were examined. Studies meeting predetermined inclusion criteria for burden of agitation/NPS were summarized. RESULTS: Eighty papers met the inclusion criteria for burden of agitation in dementia. Wide ranges of agitation prevalence were reported, but few papers provided information on incidence. The association of agitation with AD severity was presented in multiple studies; a few suggested positive association of agitation with mortality. CONCLUSIONS: High prevalence of agitation is consistent with earlier reports, but several gaps in understanding of agitation in AD need further exploration.

Psychometric validation and meaningful change thresholds of the Worst Itching Intensity Numerical Rating Scale for assessing itch in patients with chronic kidney disease-associated pruritus.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is characterized by persistent itch that often leads to substantially impaired quality of life. The Worst Itching Intensity Numerical Rating Scale (WI-NRS) is a single-item patient-reported outcome measure in which patients indicate the intensity of the worst itching they experienced over the past 24 h. Here, we evaluated the content validity and psychometric properties of the WI-NRS and confirmed the threshold of meaningful change in hemodialysis patients with moderate-to-severe CKD-aP. METHODS: Content validity interviews were conducted in 23 patients. Psychometric properties of the WI-NRS were assessed using data from one phase 2 (N = 174) and two phase 3 (N = 848) clinical trials investigating an anti-pruritic treatment. Anchor-based methods were used to confirm meaningful within-patient change score thresholds in the phase 3 trial patients and mixed-method exit interviews (N = 70) contributed further insight. RESULTS: Content validity interviews indicated patients considered the WI-NRS to be straightforward, comprehensive, and relevant. Test-retest reliability was strong in both trial cohorts (intraclass correlation coefficients > 0.75). Construct validity analyses indicated high correlation between the WI-NRS and other measures of itch. Anchor-based analyses showed a reduction of ≥ 3 points from baseline score represented an appropriate clinically meaningful within-patient change on the WI-NRS. In the exit interviews, all patients with a reduction ≥ 3 points considered the change meaningful. CONCLUSIONS: The WI-NRS is a reliable, valid, and responsive measure of itch intensity for patients with moderate-to-severe CKD-aP. These results support its use to assess treatment efficacy and in clinical evaluation and management of pruritus in hemodialysis patients.

Itching is a distressing medical condition common in patients with chronic kidney disease, especially those undergoing hemodialysis. The itch often leads to skin damage due to a continuous and uncontrollable urge to scratch. It affects about 60% of hemodialysis patients and can be severe enough to seriously affect quality of life. At present, there are no approved therapies. To evaluate whether new treatments for itch are effective, clinicians need to assess if the intensity of itch decreases over time. However, because itch intensity can only be measured accurately by the person experiencing it, a measure is required that can be easily understood and used by patients. This study evaluated a scale in which patients mark a number between '0' (corresponding to no itch) and '10' (the worst itching imaginable), to describe the worst itch intensity they experienced over the last 24 hours. Using data from three clinical trials of a novel treatment for itch in patients undergoing hemodialysis with moderate-to-severe pruritus, we found that the scale was reliable in repeat-testing experiments, and mirrored other methods of measuring changes in itch. In interviews, patients said they found the scale straightforward and easy to complete. Our analysis and patients' opinions showed a 3-point reduction in itch intensity on the scale represented a meaningful improvement. These findings support the use of this scale to assess the efficacy of new treatments and in clinical evaluation and management of pruritus in patients with chronic kidney disease.

Impact of Respiratory Syncytial Virus-Confirmed Hospitalizations on Caregivers of US Preterm Infants.

This study assessed the impact of respiratory syncytial virus-confirmed hospitalizations (RSVH) on caregivers of high-risk preterm infants. Caregivers for infants born at 29 to 35 weeks' gestational age and hospitalized for confirmed RSV disease responded to measures of self-rated and perceived infant stress (1-7; 7 = very stressful), perceived infant health (0-100; 100 = best imaginable health), and productivity impairment. Data were collected at hospital discharge through 1 month post-discharge. Caregiver responses indicated high stress levels, poor health, and productivity loss were reported at discharge; however, steady improvements were seen through 1 month post-discharge: caregiver-rated stress (from 6 to 2), infant stress (5 to 1), caregiver-perceived infant health (64 to 84), and productivity loss (mothers: 91% to 31%; fathers: 81% to 18%). Qualitative results indicated emotional impact, family routine disruption, financial concerns, and medical concerns persisted at 1 month post-discharge. This study found the caregiver burden of RSVH persists at least 1 month beyond discharge.

A Scale to Assess Activities of Daily Living in Pantothenate Kinase-Associated Neurodegeneration.

OBJECTIVE: Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal-recessive, neurodegenerative disorder with a mixed-motor phenotype caused by a defective PanK2 enzyme, for which there are few adequate treatment options. Clinimetrically sound measures of patient-reported outcomes are necessary to facilitate therapeutic development for this debilitating disease. This study's objective was to develop such a scale and assess its clinimetric properties. METHODS: A conceptually driven, iterative, content development process incorporating input from experts, caregivers, and patients was used. Scale items were initially adapted from the Unified Parkinson's Disease Rating Scale (UPDRS) Part II resulting in the 12-item Pantothenate Kinase-Associated Neurodegeneration Activities of Daily Living (PKAN-ADL). The PKAN-ADL scale was administered to caregivers (n = 37) and patients (n = 2) twice over 2 weeks, along with selected Quality of Life in Neurological Disorders (Neuro-QoL) measures, selected attributes of the Health Utilities Index (HUI)-2/3, and the Stroke Aphasia Depression Questionnaire (SADQ-10) to assess construct validity. RESULTS: Internal consistency was 0.93, with excellent test-retest reliability (intraclass correlation coefficient = 0.99). Of the 12 items, 25% (n = 3) showed a ceiling effect >30% (range, 31-54) and 42% (n = 5) showed a floor effect >30% (range, 31-46), reflecting disease heterogeneity. Convergent validity was shown with Neuro-QoL measures (rs > 0.90) and HUI-2/3 attributes (rs ≥ 0.48); divergent validity was demonstrated with the SADQ-10 (r = 0.11). Participants reported a high level of comprehension (98%), and average item relevance ratings (0-10 scale) ranged from 7.0 to 9.9. CONCLUSION: The PKAN-ADL scale demonstrated acceptable content validity, with evidence of construct validity and excellent reliability. Overall results support the use of the PKAN-ADL scale in clinical trials.

Diagnostic and clinical experience of patients with pantothenate kinase-associated neurodegeneration.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder with brain iron accumulation (NBIA). OBJECTIVES: To assess PKAN diagnostic pathway, history, and burden across the spectrum of PKAN severity from patient and/or caregiver perspectives. METHODS: Caregivers of patients (n = 37) and patients themselves (n = 2) were interviewed in a validation study of the PKAN-Activities of Daily Living (ADL) scale. The current study used quartiles of the PKAN-ADL total score to divide patients by severity of impairment (Lowest, Second Lowest, Third Lowest, Highest). Diagnostic and treatment history, healthcare utilization, disease burden, and caregiver experience were compared between groups. RESULTS: The analyses included data from 39 patients. Mean age at PKAN symptom onset (P = 0.0007), initial MRI (P = 0.0150), and genetic testing (P = 0.0016) generally decreased across the PKAN severity spectrum. The mean duration of illness did not differ among PKAN severity groups (range, 9.7-15.2 years; P = 0.3029). First MRI led to diagnosis in 56.4% of patients (range, 30.0-90.0%). A mean (SD) of 13.0 (13.1) medical and 55.2 (78.5) therapy visits (eg, physical, speech) occurred in the past year. More patients in the higher PKAN severity groups experienced multiple current functional losses and/or earlier onset of problems (P-values < 0.0500). Over half (56.8%) of caregivers experienced a change in employment because of caregiving. The percentage of patients requiring full-time caregiving increased across the PKAN severity spectrum (range, 11.1-100%; P = 0.0021). CONCLUSIONS: PKAN diagnosis was often delayed, most probably due to low awareness. Considerable burden of functional impairment and high healthcare utilization were found across the PKAN severity spectrum.