A systematic review of the association between delayed appropriate therapy and mortality among patients hospitalized with infections due to Klebsiella pneumoniae or Escherichia coli: how long is too long?

BACKGROUND: Temporal relationships between the time to appropriate antibiotic therapy and outcomes are not well described. METHODS: A systematic literature review and meta-analysis was performed to examine this relationship in patients hospitalized with Klebsiella pneumoniae or Escherichia coli infections. RESULTS: Twenty identified studies contained data for patients who received delayed appropriate therapy (DAT) versus appropriate antibiotic therapy for these pathogens. Of the 20 included studies, the majority (19/20) focused on patients with bloodstream infections, and only 1 study evaluated patients with pneumonia. When all DAT results were combined (any delay > 24 h from culture collection or any delay after culture and susceptibility reporting [C& SR]), there was an increased risk of mortality (odds ratio [OR], 1.60 [95% CI, 1.25-2.50]). The risk of mortality was greater when DAT > 48 h from culture collection or DAT > C&SR results were combined (OR, 1.76 [95% CI, 1.27-2.44]). CONCLUSIONS: Our findings suggest there is a need to shift current treatment practices away from antibiotic escalation strategies that contribute to delayed appropriate therapy and toward early, relatively aggressive and comprehensive, antibiotic therapy, especially among patients with bloodstream infections due to K. pneumoniae or E. coli.

OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine over one year of treatment: Pooled results from the PREEMPT randomized clinical trial program.

BACKGROUND: Chronic migraine (CM) is associated with high impact and reduced health-related quality of life (HRQoL). METHODS: Patients with CM from PREEMPT (Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) were randomized (1:1) to receive onabotulinumtoxinA or placebo for two 12-week cycles in the double-blind (DB) phase, followed by three 12-week cycles of open-label (OL) onabotulinumtoxinA (onabotulinumtoxinA/onabotulinumtoxinA (O/O) and placebo/onabotulinumtoxinA (P/O) groups, respectively). HRQoL endpoints were assessed over 56 weeks using the Headache Impact Test (HIT-6) and the Migraine-Specific Quality of Life Questionnaire (MSQ). HIT-6 score reductions ≥2.3 and ≥5 denoted between-group minimally important difference and within-patient clinically meaningful response, respectively. RESULTS: A total of 1236 participants (O/O, n = 607; P/O, n = 629) participated in both phases. The DB phase showed significantly reduced HIT-6 and MSQ for onabotulinumtoxinA versus placebo (all p < 0.001). The OL phase showed significantly reduced HIT-6 for O/O versus P/O at weeks 28, 36, and 48, but not 56. All three MSQ domains showed improved HRQoL relative to baseline, but only the role restrictive domain showed a significant difference between O/O and P/O at week 56. CONCLUSIONS: Benefits of onabotulinumtoxinA on HRQoL versus baseline persisted throughout the OL phase. Statistical superiority in favor of O/O was demonstrated for HIT-6 through 48 weeks and for MSQ (role restrictive) at 56 weeks.

Improving the detection of chronic migraine: Development and validation of Identify Chronic Migraine (ID-CM).

BACKGROUND: Migraine, particularly chronic migraine (CM), is underdiagnosed and undertreated worldwide. Our objective was to develop and validate a self-administered tool (ID-CM) to identify migraine and CM. METHODS: ID-CM was developed in four stages. (1) Expert clinicians suggested candidate items from existing instruments and experience (Delphi Panel method). (2) Candidate items were reviewed by people with CM during cognitive debriefing interviews. (3) Items were administered to a Web panel of people with severe headache to assess psychometric properties and refine ID-CM. (4) Classification accuracy was assessed using an ICHD-3ß gold-standard clinician diagnosis. RESULTS: Stages 1 and 2 identified 20 items selected for psychometric validation in stage 3 (n = 1562). The 12 psychometrically robust items from stage 3 underwent validity testing in stage 4. A scoring algorithm applied to four symptom items (moderate/severe pain intensity, photophobia, phonophobia, nausea) accurately classified most migraine cases among 111 people (sensitivity = 83.5%, specificity = 88.5%). Augmenting this algorithm with eight items assessing headache frequency, disability, medication use, and planning disruption correctly classified most CM cases (sensitivity = 80.6%, specificity = 88.6%). DISCUSSION: ID-CM is a simple yet accurate tool that correctly classifies most individuals with migraine and CM. Further testing in other settings will also be valuable.

The negative impact of spasticity on the health-related quality of life of stroke survivors: a longitudinal cohort study.

BACKGROUND: Spasticity often leads to symptomatic and functional problems that can cause disability for stroke survivors. We studied whether spasticity has a negative impact on health-related quality of life (HRQoL). METHODS: As part of the Greater Cincinnati/Northern Kentucky Stroke Study (NCT00642213), 460 ischemic stroke patients were interviewed during hospitalization and then followed over time. HRQoL was measured by the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the Short Form-12 (SF-12), EuroQol-5 dimension (EQ-5D), and Stroke-Specific Quality of Life (SSQOL) instruments, with lower scores indicating worse health. HRQoL differences between stroke survivors with and without spasticity were compared, adjusting for age, race, stroke severity, pre-stroke function, and comorbidities. RESULTS: Of the 460 ischemic stroke patients, 328 had spasticity data available 3 months after their stroke (mean age of 66 years, 49% were female, and 26% were black). Of these patients, 54 (16%) reported having spasticity. Three months following their stroke, patients who reported spasticity had lower mean scores on the PCS (29.6 ± 1.4 vs 37.3 ± 0.6; P < .001), EQ-5D (0.59 ± 0.03 vs 0.71 ± 0.01; P < .001), and SSQOL (3.57 ± 0.08 versus 3.78 ± 0.03; P = .03) compared with patients who did not report spasticity. Lower HRQoL scores were also observed at the 1-year (PCS, EQ-5D, and SSQOL) and 2-year (EQ-5D and SSQOL) interviews in those with spasticity compared with those without spasticity. CONCLUSIONS: Statistically and clinically meaningful differences in HRQoL exist between stroke survivors with and without spasticity.

Anxiety and depression associated with caregiver burden in caregivers of stroke survivors with spasticity.

OBJECTIVE: To investigate the relationship between anxiety/depression and caregiver burden in informal caregivers of stroke survivors with spasticity. DESIGN: Data were collected via online surveys from informal caregivers 18 years or older who cared for stroke survivors. SETTING: Internet-based survey. PARTICIPANTS: 2007 through 2009 U.S. National Health and Wellness Survey database or Lightspeed Research general panel respondents (N=153). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Anxiety and depression were self-reported by the caregiver as a physician diagnosis. Depression severity was measured by the Patient Health Questionnaire-9 (PHQ-9). Caregiver burden was measured by the Oberst Caregiving Burden Scale (OCBS) and the Bakas Caregiving Outcomes Scale (BCOS). Logistic regression analyses were conducted with anxiety, depression, and the PHQ-9 depression severity categories as a result of each caregiver burden scale. RESULTS: Data were analyzed for 153 informal caregivers; they were mostly women (70.6%) and white (78.4%), with a mean age of 51.6 years. For every 1-point increase in the OCBS Difficulty Scale, the odds of anxiety or depression were 2.57 times as great (P<.001) and 1.88 times as great (P=.007), respectively. The odds of PHQ-9 severe depression versus all other categories combined were 2.48 times as great (P<.001). For every 1-point decrease in the BCOS, the odds of anxiety or depression were 2.43 times as great (P<.001) and 2.27 times as great (P=.002), respectively. The odds of PHQ-9 severe depression versus all other categories combined were 4.55 times as great (P<.001). CONCLUSIONS: As caregiver burden increases, caregivers are more likely to have anxiety and depression. Depression severity also increases. Providing treatment to stroke survivors with spasticity that lessens the time and more importantly, the difficulty of caregiving may lead to a reduction in caregiver anxiety and depression.

Mapping from disease-specific measures to health-state utility values in individuals with migraine.

OBJECTIVE: The objective of this study was to develop empirical algorithms that estimate health-state utility values from disease-specific quality-of-life scores in individuals with migraine. METHODS: Data from a cross-sectional, multicountry study were used. Individuals with episodic and chronic migraine were randomly assigned to training or validation samples. Spearman's correlation coefficients between paired EuroQol five-dimensional (EQ-5D) questionnaire utility values and both Headache Impact Test (HIT-6) scores and Migraine-Specific Quality-of-Life Questionnaire version 2.1 (MSQ) domain scores (role restrictive, role preventive, and emotional function) were examined. Regression models were constructed to estimate EQ-5D questionnaire utility values from the HIT-6 score or the MSQ domain scores. Preferred algorithms were confirmed in the validation samples. RESULTS: In episodic migraine, the preferred HIT-6 and MSQ algorithms explained 22% and 25% of the variance (R(2)) in the training samples, respectively, and had similar prediction errors (root mean square errors of 0.30). In chronic migraine, the preferred HIT-6 and MSQ algorithms explained 36% and 45% of the variance in the training samples, respectively, and had similar prediction errors (root mean square errors 0.31 and 0.29). In episodic and chronic migraine, no statistically significant differences were observed between the mean observed and the mean estimated EQ-5D questionnaire utility values for the preferred HIT-6 and MSQ algorithms in the validation samples. CONCLUSIONS: The relationship between the EQ-5D questionnaire and the HIT-6 or the MSQ is adequate to use regression equations to estimate EQ-5D questionnaire utility values. The preferred HIT-6 and MSQ algorithms will be useful in estimating health-state utilities in migraine trials in which no preference-based measure is present.

The Impact of Acute Kidney Injury on the Risk of Mortality and Health Care Utilization Among Patients Treated With Polymyxins for Severe Gram-Negative Infections.

BACKGROUND: With the rise of antibiotic resistance, polymyxin use has re-emerged but with a concern of renal toxicity. This study aims to assess mortality, length of stay, and total hospitalization cost associated with acute kidney injury (AKI) among recipients of intravenous (IV) sodium colistimethate (CMS) or IV polymyxin B (PMB). METHODS: We conducted a retrospective database analysis using the Premier database from January 1, 2012, through September 30, 2015. Adults ≥18 years of age who were admitted for inpatient treatment with ≥3 consecutive days of CMS or PMB were included. Generalized linear models compared patients who developed AKI with those who did not. Models were adjusted for patient and clinical characteristics. RESULTS: A total of 4886 patients were included; 4103 patients received CMS, and 783 received PMB. In the multivariable analyses, the presence of AKI was associated with higher in-hospital mortality in both the CMS cohort (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.9-2.7; P < .001) and the PMB cohort (aOR, 2.7; 95% CI, 1.8-4.2; P < .001). In both cohorts, patients who developed AKI experienced longer hospital stays (9.7 days and 11.6 days in the CMS and PMB cohorts, respectively; P < .001). The mean total hospitalization costs for patients who developed AKI were $47 820 higher (95% CI, $34 918-$60 722) in the CMS cohort and $35 244 higher (95% CI, $17 561-$52 928) in the PMB cohort. CONCLUSIONS: The clinical and economic burden of AKI in the context of polymyxin use is substantial. The use of effective antibiotics with limited toxicity should remain a priority.

A Screening Tool to Identify Spasticity in Need of Treatment.

OBJECTIVE: To develop a clinically useful patient-reported screening tool for health care providers to identify patients with spasticity in need of treatment regardless of etiology. DESIGN: Eleven spasticity experts participated in a modified Delphi panel and reviewed and revised 2 iterations of a screening tool designed to identify spasticity symptoms and impact on daily function and sleep. Spasticity expert panelists evaluated items pooled from existing questionnaires to gain consensus on the screening tool content. The study also included cognitive interviews of 20 patients with varying spasticity etiologies to determine if the draft screening tool was understandable and relevant to patients with spasticity. RESULTS: The Delphi panel reached an initial consensus on 21 of 47 items for the screening tool and determined that the tool should have no more than 11 to 15 items and a 1-month recall period for symptom and impact items. After 2 rounds of review, 13 items were selected and modified by the expert panelists. Most patients (n = 16 [80%]) completed the cognitive interview and interpreted the items as intended. CONCLUSIONS: Through the use of a Delphi panel and patient interviews, a 13-item spasticity screening tool was developed that will be practical and easy to use in routine clinical practice.

Caregiver burden, productivity loss, and indirect costs associated with caring for patients with poststroke spasticity.

OBJECTIVE: Many stroke survivors experience poststroke spasticity and the related inability to perform basic activities, which necessitates patient management and treatment, and exerts a considerable burden on the informal caregiver. The current study aims to estimate burden, productivity loss, and indirect costs for caregivers of stroke survivors with spasticity. METHODS: Internet survey data were collected from 153 caregivers of stroke survivors with spasticity including caregiving time and difficulty (Oberst Caregiver Burden Scale), Work Productivity and Activity Impairment measures, and caregiver and patient characteristics. Fractional logit models examined predictors of work-related restriction, and work losses were monetized (2012 median US wages). RESULTS: Mean Oberst Caregiver Burden Scale time and difficulty scores were 46.1 and 32.4, respectively. Employed caregivers (n=71) had overall work restriction (32%), absenteeism (9%), and presenteeism (27%). Caregiver characteristics, lack of nursing home coverage, and stroke survivors' disability predicted all work restriction outcomes. The mean total lost-productivity cost per employed caregiver was US$835 per month (>$10,000 per year; 72% attributable to presenteeism). CONCLUSION: These findings demonstrate the substantial burden of caring for stroke survivors with spasticity illustrating the societal and economic impact of stroke that extends beyond the stroke survivor.

Poststroke spasticity: sequelae and burden on stroke survivors and caregivers.

Among the estimated 20% to 40% of stroke survivors who develop spasticity, the burden of this condition on patients, caregivers, and society is substantial. Stroke survivors with spasticity may experience reductions in their ability to perform activities of daily living and in their health-related quality of life. The occurrence of spasticity in stroke survivors may also result in an increased burden on their caregivers, who exhibit poorer physical and emotional health as compared with the general population. The responsibilities that caregivers have to the stroke survivor--in terms of providing medical care, protecting from falls, and assisting with feeding and hygiene, among other tasks of daily living--must be balanced with their responsibilities to other family members and to themselves. Caregivers of stroke survivors often report a feeling of confinement with little opportunity for relief, and although social support can be helpful, it is frequently limited in its availability. In terms of the socioeconomic burden of spasticity after stroke, recent data point to a 4-fold increase in health care costs associated with stroke survivors with spasticity compared with stroke survivors without spasticity. Thus, it is important to reduce the burden of spasticity after stroke. Consequently, effective spasticity treatment that reduces spasticity and the level of disability experienced by stroke survivors will likely increase their functioning and their health-related quality of life and will also result in a diminished burden on their caregivers.

Relationship between disability and health-related quality of life and caregiver burden in patients with upper limb poststroke spasticity.

OBJECTIVE: To evaluate the relationship between disability and both health-related quality of life (HRQoL) and caregiver burden in patients with upper limb poststroke spasticity. DESIGN: Multicenter open-label study. SETTING: Thirty-five sites in North America. PARTICIPANTS: Patients (N = 279) with upper limb poststroke spasticity. METHODS: Post hoc analyses of data from an open-label study were performed to estimate HRQoL and caregiver burden at study baseline across levels of disability in 4 problem domains: hygiene, dressing, limb posture, and pain. Disability severity in these areas was determined by using the 4-point Disability Assessment Scale rated by the physicians. MAIN OUTCOME MEASUREMENTS: HRQoL measured by the patient-reported EuroQol 5 Dimensions questionnaire and the Stroke-Adapted Sickness Impact Profile and caregiver burden. RESULTS: At study baseline, increasing disability in the hygiene, dressing, and pain domains of the Disability Assessment Scale was associated with diminishing HRQoL scores (P < .002) measured by the EuroQol 5 Dimensions. By using the Stroke-Adapted Sickness Impact Profile, greater disability scores in all problem domains were significantly associated with higher overall dysfunction scores (P ≤ .05). Within the physical dimension of the Stroke-Adapted Sickness Impact Profile, significant associations also were observed in all domains. At baseline, caregiver burden was significantly related to increasing levels of hygiene and dressing domain severity (P ≤ .05). Caregiver assistance requirement increased from approximately 9.0-28.2 hours per week in the hygiene domain and 3.3-32.1 hours per week in the dressing domain as disability increased from "none" to "severe." CONCLUSIONS: In patients with upper limb poststroke spasticity, increasing disability in the hygiene, dressing, and pain domains of the Disability Assessment Scale were associated with diminishing HRQoL. Furthermore, these patients required caregiver assistance proportionally related to the severity of their disability in the hygiene and dressing domains.