Marta Seretny

Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis

ABSTRACT Chemotherapy‐induced peripheral neuropathy (CIPN) is a disabling pain condition resulting from chemotherapy for cancer. Severe acute CIPN may require chemotherapy dose reduction or cessation. There is no effective CIPN prevention strategy; treatment of established chronic CIPN is limited, and the prevalence of CIPN is not known. Here we used a systematic review to identify studies reporting the prevalence of CIPN. We searched Embase, Medline, CAB Abstracts, CINAHL, PubMed central, Cochrane Library, and Web of Knowledge for relevant references and used random‐effects meta‐regression to estimate overall prevalence. We assessed study quality using the CONSORT and STROBE guidelines, and we report findings according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidance. We provide a qualitative summary of factors reported to alter the risk of CIPN. We included 31 studies with data from 4179 patients in our analysis. CIPN prevalence was 68.1% (57.7–78.4) when measured in the first month after chemotherapy, 60.0% (36.4–81.6) at 3 months and 30.0% (6.4–53.5) at 6 months or more. Different chemotherapy drugs were associated with differences in CIPN prevalence, and there was some evidence of publication bias. Genetic risk factors were reported in 4 studies. Clinical risk factors, identified in 4 of 31 studies, included neuropathy at baseline, smoking, abnormal creatinine clearance, and specific sensory changes during chemotherapy. Although CIPN prevalence decreases with time, at 6 months 30% of patients continue to suffer from CIPN. Routine CIPN surveillance during post‐chemotherapy follow‐up is needed. A number of genetic and clinical risk factors were identified that require further study.

Surviving Intensive Care: A Systematic Review of Healthcare Resource Use After Hospital Discharge*

Objectives:Intensive care survivors continue to experience significant morbidity following acute hospital discharge, but healthcare costs associated with this ongoing morbidity are poorly described. As the demand for intensive care increases, understanding the magnitude of postacute hospital healthcare costs is of increasing relevance to clinicians and healthcare planners. We undertook a systematic review of the literature reporting major healthcare resource use by intensive care survivors following discharge from the hospital and identified factors associated with increased resource use. Data Sources:Seven electronic databases (1990 to August 2012), conference proceedings, and reference lists were searched. Study Selection:Studies published in English were included that reported postacute hospital discharge healthcare resource use at the individual level for survivors of intensive care. Data Extraction:Two reviewers screened abstracts and one abstracted data using standardized templates. Study quality was assessed using recognized appraisal methods specific to economic evaluation, epidemiological studies, and randomized trials. Data Synthesis:From 4,909 articles, 18 articles representing 14 cohorts fulfilled inclusion criteria. There was substantial variation in methodology, especially the resource categories included in the studies. Following standardization to a common currency and year, variation in cost of resource use was evident (range 2011 US

Anesthesia-induced Suppression of Human Dorsal Anterior Insula Responsivity at Loss of Volitional Behavioral Response.

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Therapy for Chemotherapy-Induced Peripheral Neuropathy

148,454 for year 1 postdischarge). Studies undertaken within the United States reported the highest costs; those in the United Kingdom reported substantially lower costs. Factors associated with increased resource use included increasing age, comorbidities, organ dysfunction score, and previous resource use. Conclusions:Wide variation in methodological approaches limited study comparability and external validity of findings. We found substantial variation in the cost of resource use, especially among countries. Careful description of patient cohorts and healthcare systems is required to maximize generalizability. We give recommendations for a more standardized approach to improve design and reporting of future studies.

Brainstem processing of peripheral punctate stimuli in patients with and without chemotherapy-induced peripheral neuropathy: a prospective cohort functional MRI study

Background:It has been postulated that a small cortical region could be responsible for the loss of behavioral responsiveness (LOBR) during general anesthesia. The authors hypothesize that any brain region demonstrating reduced activation to multisensory external stimuli around LOBR represents a key cortical gate underlying this transition. Furthermore, the authors hypothesize that this localized suppression is associated with breakdown in frontoparietal communication. Methods:During both simultaneous electroencephalography and functional magnetic resonance imaging (FMRI) and electroencephalography data acquisition, 15 healthy volunteers experienced an ultraslow induction with propofol anesthesia while a paradigm of multisensory stimulation (i.e., auditory tones, words, and noxious pain stimuli) was presented. The authors performed separate analyses to identify changes in (1) stimulus-evoked activity, (2) functional connectivity, and (3) frontoparietal synchrony associated with LOBR. Results:By using an FMRI conjunction analysis, the authors demonstrated that stimulus-evoked activity was suppressed in the right dorsal anterior insula cortex (dAIC) to all sensory modalities around LOBR. Furthermore, the authors found that the dAIC had reduced functional connectivity with the frontoparietal regions, specifically the dorsolateral prefrontal cortex and inferior parietal lobule, after LOBR. Finally, reductions in the electroencephalography power synchrony between electrodes located in these frontoparietal regions were observed in the same subjects after LOBR. Conclusions:The authors conclude that the dAIC is a potential cortical gate responsible for LOBR. Suppression of dAIC activity around LOBR was associated with disruption in the frontoparietal networks that was measurable using both electroencephalography synchrony and FMRI connectivity analyses.

P51 Surviving intensive care: a systematic review of health care resource use after hospital discharge

In Reply Drs Abbott and Zee comment on the possibility of lower urinary melatonin levels serving as a marker for underlying circadian misalignment related to cumulative shift work. We have also contemplated the possibility that melatonin levels are simply a reporter of circadian alignment rather than a marker for abnormal glucose metabolism. Melatonin levels among individuals in the NHS have been shown to be inversely associated with the number of night shifts performed in the 2 weeks preceding the measurement,1 whereas no association was found between melatonin levels and the total number of years of previous shift work for individuals in the NHS.2 This suggests that shift work likely does not have a sustained effect on melatonin secretion. Additionally, the association of increased shift work with increased risk of incident type 2 diabetes shown in the NHS cohort appeared to be largely mediated by increased body mass index,3 whereas the association of melatonin with incident type 2 diabetes in our study was independent of body mass index. Nevertheless, we think that Abbott and Zee raise an important issue about the relationship between other forms of chronic circadian misalignment and melatonin secretion. If the low levels of nocturnal melatonin secretion within our cohort were indeed attributable to circadian misalignment due to factors other than prior or current shift work, then the association between low melatonin secretion and incident type 2 diabetes could simply represent an association of circadian misalignment and incident type 2 diabetes. Careful studies are needed to delineate which circadian intervention may be suited to beneficially affect glucose metabolism and whether melatonin levels are a modifiable risk factor.

CN-16INCIDENCE, PREVALENCE AND PREDICTORS OF CHEMOTHERAPY INDUCED PERIPHERAL NEUROPATHY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Background Chemotherapy-induced peripheral neuropathy affects 30% of cancer survivors. Findings from animal studies suggest that brainstem descending inhibitory pathways are important in chronic neuropathic pain. An aberrant descending pain modulation system has been implicated in human neuropathic pain. Whether aberrant descending pain modulation before chemotherapy is associated with development of chemotherapy-induced peripheral neuropathy is unclear. We aimed to assess descending pain modulation systems using functional MRI (fMRI) in chemotherapy-naive patients with cancer to determine whether differences are associated with subsequent development of the neuropathy. Methods In this multicentre prospective cohort study, adult patients with cancer and no chronic pain, neuropathy, or risk factors for neuropathy were recruited from the oncology clinic before onset of chemotherapy. After patients had given written informed consent, descending inhibitory pathways were challenged (jittered punctate stimuli 256 mN Somedic von Frey filament) during a 3T fMRI scan, and images analysed with FSL software. Sample size was based on published fMRI estimates. Chemotherapy-induced peripheral neuropathy was diagnosed with the CIPN20 questionnaire. Findings 30 patients were recruited (mean age 60·4 years [SD 7·9]). We report a preliminary analysis of the first 12 patients (60·6 [8·3], six women); six had colorectal cancer, four gynaecological cancer, and two lung cancer. Seven patients (three men, four women) developed chemotherapy-induced peripheral neuropathy. After data brain extraction, registration, B0 unwarping, and motion correction, FEAT was used for first and second level analysis. Mean group level comparisons between patients with and without the neuropathy were conducted with mixed-effects analysis (z threshold 2·3, regions considered significant at p Interpretation These preliminary results suggest that baseline differences exist, before peripheral nerve injury, in the descending pain modulation system of patients who go on to develop chemotherapy-induced peripheral neuropathy. These differences might aid development of biomarkers to guide chemotherapy choices. Limitations of the study include the small sample size for the present analysis, the observational nature of the study, and the possibility of unknown confounders. Strengths include the prospective design in a unique patient cohort and the high sensitivity of fMRI. Funding Wellcome Trust via Scottish Translational Medicine and Therapeutics Initiative (STMTI).

Incidence, Prevalence and Predictors of Chemotherapy Induced Peripheral Neuropathy

Background Intensive care units (ICUs) are an expensive resource. However, this expense does not end at hospital discharge. ICU survivors continue to experience significant morbidity. As the demand for ICU is likely to increase substantially, there is a need to establish how much health care resource survivors consume following discharge from hospital. This will enable appropriate service planning and policy development to meet the needs of these patients, and will improve the precision of economic evaluations relating to ICU. Aims We conducted a systematic review to determine the reported use of major health care resource by ICU survivors following discharge from hospital and to identify factors associated with increased resource use. Methods Studies were included if the study population derived from an adult, general ICU population, health care resource use was reported at the patient level and the publication was in the English language. Two reviewers independently screened abstracts, rejecting those clearly not meeting inclusion criteria. A single reviewer then retrieved the full texts and assessed them for inclusion. Costs were inflated to 2009 using the consumer price index and converted to US dollars using the purchasing power parity method. Results From 3522 articles, nine fulfilled criteria for inclusion. Two studies were conducted in the UK; three in Canada and four in the USA. Six studies used a cohort design; the remaining three collected data as part of a trial. The number of patients for which resource use was reported ranged from 66 to 963. Mean age ranged from 40 to 66. There was substantial variation in the cost categories included in each study. Following standardisation to a common currency and year, variation in resource use was apparent (range

Validation of potential assessment tools for diagnosis of neuropathic pain in endometriosis: a pilot study

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Assessment tools for diagnosis of neuropathic pain in women with chronic pelvic pain: a pilot study.

45 173). Studies undertaken within the USA reported the highest costs; those in the UK reported substantially lower costs. The larger proportion of resource was consumed in secondary care (range 53–96%). Factors associated with increased resource use included increasing age, co-morbidities and organ dysfunction score. Conclusion This review is the first to bring together the literature relating to post-hospital discharge health care resource use for survivors of ICU. There was substantial variation in the cost of resource use between studies. Given the paucity of identified studies and their relatively short time horizons, there is a clear need for longer term studies to investigate resource use of ICU survivors. Our findings should help to inform the design and reporting of such studies.