A qualitative evaluation of the oncologists', neurologists', and pain specialists' views on the management and care of chemotherapy-induced peripheral neuropathy in The Netherlands.

PURPOSE: In treating cancer, different chemotherapy regimens cause chemotherapy-induced peripheral neuropathy (CIPN). Despite recent international guidelines, a gold standard for diagnosis, treatment, and care is lacking. To identify the current clinical practice and the physicians' point of view and ideas for improvement, we evaluated CIPN care by interviewing different specialists involved. METHODS: We performed semi-structured, audio-recorded, transcribed, and coded interviews with a purposive sample of oncologists, pain specialists, and neurologists involved in CIPN patients' care. Data is analyzed by a constant comparative method for content analysis, using ATLAS.ti software. Codes, categories, and themes are extracted, generating common denominators and conclusions. RESULTS: With oncologists, pain specialists, and neurologists, nine, nine, and eight interviews were taken respectively (including three, two, and two interviews after thematic saturation occurred). While useful preventive measures and predictors are lacking, patient education (e.g., on symptoms and timely reporting) is deemed pivotal, as is low-threshold screening (e.g., anamnesis and questionnaires). Diagnosis focusses on a temporal relationship to chemotherapy, with adjuvant testing (e.g., EMG) used in severe or atypical cases. Symptomatic antineuropathic and topical medication are often prescribed, but personalized and multidimensional care based on individual symptoms and preferences is highly valued. The limited efficacy of existing treatments, and the lack of standardized protocols, interdisciplinary coordination, and awareness among healthcare providers pose significant challenges. CONCLUSION: Besides the obvious need for better therapeutic options, and multidisciplinary exploration of patients' perspectives, a structured and collaborative approach towards diagnosis, treatment, referral, and follow-up, nurtured by improving knowledge and use of existing CIPN guidelines, could enhance care.

The feasibility and reliability of actigraphy to monitor sleep in intensive care patients: an observational study.

BACKGROUND: Sleep amongst intensive care patients is reduced and highly fragmented which may adversely impact on recovery. The current challenge for Intensive Care clinicians is identifying feasible and accurate assessments of sleep that can be widely implemented. The objective of this study was to investigate the feasibility and reliability of a minimally invasive sleep monitoring technique compared to the gold standard, polysomnography, for sleep monitoring. METHODS: Prospective observational study employing a within subject design in adult patients admitted to an Intensive Care Unit. Sleep monitoring was undertaken amongst minimally sedated patients via concurrent polysomnography and actigraphy monitoring over a 24-h duration to assess agreement between the two methods; total sleep time and wake time. RESULTS: We recruited 80 patients who were mechanically ventilated (24%) and non-ventilated (76%) within the intensive care unit. Sleep was found to be highly fragmented, composed of numerous sleep bouts and characterized by abnormal sleep architecture. Actigraphy was found to have a moderate level of overall agreement in identifying sleep and wake states with polysomnography (69.4%; K = 0.386, p < 0.05) in an epoch by epoch analysis, with a moderate level of sensitivity (65.5%) and specificity (76.1%). Monitoring accuracy via actigraphy was improved amongst non-ventilated patients (specificity 83.7%; sensitivity 56.7%). Actigraphy was found to have a moderate correlation with polysomnography reported total sleep time (r = 0.359, p < 0.05) and wakefulness (r = 0.371, p < 0.05). Bland-Altman plots indicated that sleep was underestimated by actigraphy, with wakeful states overestimated. CONCLUSIONS: Actigraphy was easy and safe to use, provided moderate level of agreement with polysomnography in distinguishing between sleep and wakeful states, and may be a reasonable alternative to measure sleep in intensive care patients. Clinical Trial Registration number ACTRN12615000945527 (Registered 9/9/2015).

Skin temperature measured by infrared thermography after ultrasound-guided blockade of the sciatic nerve.

BACKGROUND: In the present study, we assessed the relationship between subgluteal sciatic nerve blocking and skin temperature by infrared thermography in the lower extremity. We hypothesized that blocking the sciatic nerve will lead to an increase in temperature, and that this will correlate with existing sensory block tests. METHODS: We studied 18 healthy individuals undergoing orthopaedic surgery of the foot under ultrasound-guided subgluteal blockade of the sciatic nerve with 30 ml ropivacaine 7.5 mg/ml. Skin temperature was measured on the toes, the dorsal and plantar side of the foot, the malleoli, and the lateral side of the lower leg, just before sciatic nerve blockade and at 10-min intervals thereafter. RESULTS: Baseline skin temperatures showed a significant distal-to-proximal gradient. After sciatic block, temperatures on the blocked side increased significantly in the toes and foot. When comparing pinprick to skin temperature in a receiver operating curve, there was an AUC of 85.9% (95% confidence interval = 83.7-88.2%, P < 0.001). The medial malleolus (not being innervated by the sciatic nerve) showed no significant difference to the lateral. CONCLUSIONS: After sciatic nerve block, temperatures of the foot increased significantly. There was a good correlation between pinprick testing and infrared temperature measurement. This makes infrared skin temperature measuring a good test in determining block success when sensory testing is impossible.

The relation between skin temperature increase and sensory block height in spinal anaesthesia using infrared thermography.

BACKGROUND AND OBJECTIVES: To evaluate the feasibility of determining the extent of sympathetic blockade by skin temperature measurement with infrared thermography and relate the cranial extent of the temperature increase to that of the sensory block after spinal anaesthesia. METHODS: Before and 5, 10 and 20 min after the administration of spinal anaesthesia, skin temperatures were measured with infrared thermography at the dermatomes T2-L3, in 12 male patients scheduled for lower limb surgery. The most cephalad dermatome at which sensory blockade occurred was related to the dermatome at which the largest temperature jump (corrected for baseline temperature) occurred. RESULTS: The baseline temperatures showed considerable variation across the dermatomes, being lower below T12 than at the thoracic dermatomes. The mean difference between the level of the cephalad skin temperature elevation front (mean 1.03 °C, SD 0.8 °C) and cranial sensory block height was 0.10 dermatomes (SD 1.16), correlation coefficient (0.88, P<0.001). CONCLUSION: The varying baseline temperatures across the trunk, the limited sympathetic block-induced increase in skin temperature at the trunk and the difficult control of influences from the surroundings partly obscured the extent of the skin temperature increase and its correlation to sensory block height. These factors have to be controlled to improve the use of infrared cameras as an easy bedside tool for predicting the cranial extent of (sympathetic blockade during) spinal anaesthesia.

Responsiveness of Noninvasive Continuous Cardiac Output Monitoring During the Valsalva Maneuver.

To describe the baseline hemodynamic variables and response time of hemodynamic changes associated with the Valsalva maneuver using noninvasive continuous cardiac output monitoring (Nexfin). Hemodynamic monitoring provides an integral component of advanced clinical care and the ability to monitor response to treatment interventions. The emergence of noninvasive hemodynamic monitoring provides clinicians with an opportunity to monitor and assess patients rapidly with ease of implementation. However, the responsiveness of this method in tracking dynamic changes that occur has not been fully elucidated. A prospective observational study was conducted involving 44 healthy volunteers (age = 38 ±12 years). Participants performed a Valsalva maneuvers to illicit dynamic changes in blood pressure, cardiac output, cardiac index, systemic vascular resistance index (SVRI), and stroke volume. Changes in these hemodynamic parameters were monitored while performing repeated standardized Valsalva maneuvers. Baseline hemodynamic values were obtained in all 44 participants, and showed an interaction with age, accompanying a significant decline in cardiac index (r = -.66, p < .05) and stroke volume (r = -.68,p < .05), and an increase in SVRI (r = .67, p < .05) with increasing age. The Valsalva maneuver, performed in 20 participants, resulted in a change of 10% from baseline blood pressure and cardiac index, which was detected within 4.53 s (SD = 4.36) and 3.31 s (SD = 2.21), respectively. Noninvasive continuous cardiac monitoring demonstrated the ability to rapidly detect logical and predictable hemodynamic changes. These observations suggest that such Nexfin technology may have useful clinical applications.

Multinational development and validation of an early prediction model for delirium in ICU patients.

RATIONALE: Delirium incidence in intensive care unit (ICU) patients is high and associated with poor outcome. Identification of high-risk patients may facilitate its prevention. PURPOSE: To develop and validate a model based on data available at ICU admission to predict delirium development during a patient's complete ICU stay and to determine the predictive value of this model in relation to the time of delirium development. METHODS: Prospective cohort study in 13 ICUs from seven countries. Multiple logistic regression analysis was used to develop the early prediction (E-PRE-DELIRIC) model on data of the first two-thirds and validated on data of the last one-third of the patients from every participating ICU. RESULTS: In total, 2914 patients were included. Delirium incidence was 23.6%. The E-PRE-DELIRIC model consists of nine predictors assessed at ICU admission: age, history of cognitive impairment, history of alcohol abuse, blood urea nitrogen, admission category, urgent admission, mean arterial blood pressure, use of corticosteroids, and respiratory failure. The area under the receiver operating characteristic curve (AUROC) was 0.76 [95% confidence interval (CI) 0.73-0.77] in the development dataset and 0.75 (95% CI 0.71-0.79) in the validation dataset. The model was well calibrated. AUROC increased from 0.70 (95% CI 0.67-0.74), for delirium that developed <2 days, to 0.81 (95% CI 0.78-0.84), for delirium that developed >6 days. CONCLUSION: Patients' delirium risk for the complete ICU length of stay can be predicted at admission using the E-PRE-DELIRIC model, allowing early preventive interventions aimed to reduce incidence and severity of ICU delirium.

The organization of the reciprocal connections between the subiculum and the entorhinal cortex in the cat: I. A neuroanatomical tracing study.

The connections between the subiculum (SUB) and the entorhinal cortex (EC) were studied in the cat with retrograde and anterograde tracing techniques. Injections of the retrogradely transported tracer WGA-HRP at different levels along the septotemporal axis of the subiculum result in labeled neurons predominantly in the medial entorhinal cortex (MEA) in the superficial layers II and III. In the deep layers labeled cells are found more widespread over the EC. The superficially located labeled EC neurons are topographically distributed in a lateromedial gradient, which corresponds to a septotemporal gradient along the longitudinal axis of the subiculum. This organization of the EC-SUB projection system could be substantiated by the use of injections anterogradely transported radioactively labeled amino acids in EC. The SUB to EC projections were investigated with the anterograde transport of WGA-HRP and with radioactively labeled amino acids that were injected at different levels along the septotemporal axis of the subiculum. This results in a patch of anterogradely labeled fibers and terminals in MEA, predominantly in layers II and III, with a wider band of label in the deep layers. Again, a topographical distribution along the lateromedial axis of the EC corresponding to the septotemporal axis of the SUB was observed. Contralateral reciprocal connections between EC and SUB are also present, and exhibit a similar topographical organization.

[Nutrition and health--enteral nutrition in intensive care patients]. / Voeding en gezondheid--enterale voedingstherapie bij intensivecarepatiënten.

Nutritional therapy in the intensive care unit exerts favourable effects on morbidity and mortality. Enteral nutrition is preferable to parenteral nutrition. Only perforation or total obstruction of the gastrointestinal tract, proven mesenteric ischaemia and toxic megacolon are absolute contra-indications to enteral nutrition. Early enteral nutrition is effective in decreasing infectious complications and reducing the length of stay in the hospital. Nutrition that is enriched with specific ingredients in order to modulate the immune response is referred to as immunonutrition. The use of immunonutrition, notably in surgical intensive care patients, has a favourable effect on the incidence of infectious complications, the duration of artificial respiration and the length of hospital stay. The addition of glutamine to parenteral nutrition may reduce mortality compared to standard parenteral nutrition. Implementation of a simple feeding algorithm in the intensive care unit, with special attention for the treatment of delayed gastric emptying, is cost-effective and leads to an improvement in the nutritional parameters.

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study.

PURPOSE: Recalibration and determining discriminative power, internationally, of the existing delirium prediction model (PRE-DELIRIC) for intensive care patients. METHODS: A prospective multicenter cohort study was performed in eight intensive care units (ICUs) in six countries. The ten predictors (age, APACHE-II, urgent and admission category, infection, coma, sedation, morphine use, urea level, metabolic acidosis) were collected within 24 h after ICU admission. The confusion assessment method for the intensive care unit (CAM-ICU) was used to identify ICU delirium. CAM-ICU screening compliance and inter-rater reliability measurements were used to secure the quality of the data. RESULTS: A total of 2,852 adult ICU patients were screened of which 1,824 (64%) were eligible for the study. Main reasons for exclusion were length of stay <1 day (19.1%) and sustained coma (4.1%). CAM-ICU compliance was mean (SD) 82 ± 16% and inter-rater reliability 0.87 ± 0.17. The median delirium incidence was 22.5% (IQR 12.8-36.6%). Although the incidence of all ten predictors differed significantly between centers, the area under the receiver operating characteristic (AUROC) curve of the eight participating centers remained good: 0.77 (95% CI 0.74-0.79). The linear predictor and intercept of the prediction rule were adjusted and resulted in improved re-calibration of the PRE-DELIRIC model. CONCLUSIONS: In this multinational study, we recalibrated the PRE-DELIRIC model. Despite differences in the incidence of predictors between the centers in the different countries, the performance of the PRE-DELIRIC-model remained good. Following validation of the PRE-DELIRIC model, it may facilitate implementation of strategies to prevent delirium and aid improvements in delirium management of ICU patients.

Gastrointestinal perfusion in septic shock.

Septic shock is characterised by vasodilation, myocardial depression and impaired microcirculatory blood flow, resulting in redistribution of regional blood flow. Animal and human studies have shown that gastrointestinal mucosal blood flow is impaired in septic shock. This is consistent with abnormalities found in many other microcirculatory vascular beds. Gastrointestinal mucosal microcirculatory perfusion deficits have been associated with gut injury and a decrease in gut barrier function, possibly causing augmentation of systemic inflammation and distant organ dysfunction. A range of techniques have been developed and used to quantify these gastrointestinal perfusion abnormalities. The following techniques have been used to study gastrointestinal perfusion in humans: tonometry, laser Doppler flowmetry, reflectance spectrophotometry, near-infrared spectroscopy, orthogonal polarisation spectral imaging, indocyanine green clearance, hepatic vein catheterisation and measurements of plasma D-lactate. Although these methods share the ability to predict outcome in septic shock patients, it is important to emphasise that the measurement results are not interchangeable. Different techniques measure different elements of gastrointestinal perfusion. Gastric tonometry is currently the most widely used technique because of its non-invasiveness and ease of use. Despite all the recent advances, the usefulness of gastrointestinal perfusion parameters in clinical decision-making is still limited. Treatment strategies specifically aimed at improving gastrointestinal perfuision have failed to actually correct mucosal perfusion abnormalities and hence not shown to improve important clinical endpoints. Current and future treatment strategies for septic shock should be tested for their effects on gastrointestinal perfusion; to further clarify its exact role in patient management, and to prevent therapies detrimental to gastrointestinal perfusion being implemented.

Nadroparin-induced Calcinosis cutis in renal transplant recipients.

Low-molecular-weight heparins are routinely used to prevent deep venous thrombosis following renal transplantation in our department. We report 2 patients who developed tender erythematous subcutaneous nodules with induration, ulceration and necrosis at the site of subcutaneous administration of nadroparin. Both patients were renal transplant recipients with impaired graft function and high serum calcium-phosphate products. The diagnosis calcinosis cutis was confirmed by technetium-99m bone scan and by histological examination of biopsies. Both patients showed spontaneous recovery several weeks after discontinuation of nadroparin. Patients with chronic renal failure and hyperphosphatemia may be predisposed to develop calcinosis cutis. In addition, the role of the calcium content of nadroparin is discussed.

Successful treatment of fulminant pneumococcal sepsis with recombinant tissue plasminogen activator.

This case report describes a patient with a rapidly progressive pneumococcal septic shock and purpura fulminans. Despite maximal conventional treatment, the patient developed progressive multiple organ failure with imminent necrosis of the extremities. This extremely rare, but often fatal, disease responded dramatically to the infusion of recombinant tissue plasminogen activator.

Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR.

Ophthalmological and molecular genetic studies were performed in a consanguineous family with individuals showing either retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). Assuming pseudodominant (recessive) inheritance of allelic defects, linkage analysis positioned the causal gene at 1p21-p13 (lod score 4.22), a genomic segment known to harbor the ABCR gene involved in Stargardt's disease (STGD) and age-related macular degeneration (AMD). We completed the exon-intron structure of the ABCR gene and detected a severe homozygous 5[prime] splice site mutation, IVS30+1G->T, in the four RP patients. The five CRD patients in this family are compound heterozygotes for the IVS30+1G->T mutation and a 5[prime] splice site mutation in intron 40 (IVS40+5G->A). Both splice site mutations were found heterozygously in two unrelated STGD patients, but not in 100 control individuals. In these patients the second mutation was either a missense mutation or unknown. Since thus far no STGD patients have been reported to carry two ABCR null alleles and taking into account that the RP phenotype is more severe than the STGD phenotype, we hypothesize that the intron 30 splice site mutation represents a true null allele. Since the intron 30 mutation is found heterozygously in the CRD patients, the IVS40+5G->A mutation probably renders the exon 40 5[prime] splice site partially functional. These results show that mutations in the ABCR gene not only result in STGD and AMD, but can also cause autosomal recessive RP and CRD. Since the heterozygote frequency for ABCR mutations is estimated at 0.02, mutations in ABCR might be an important cause of autosomal recessive and sporadic forms of RP and CRD.

The 2588G-->C mutation in the ABCR gene is a mild frequent founder mutation in the Western European population and allows the classification of ABCR mutations in patients with Stargardt disease.

In 40 western European patients with Stargardt disease (STGD), we found 19 novel mutations in the retina-specific ATP-binding cassette transporter (ABCR) gene, illustrating STGD's high allelic heterogeneity. One mutation, 2588G-->C, identified in 15 (37.5%) patients, shows linkage disequilibrium with a rare polymorphism (2828G-->A) in exon 19, suggesting a founder effect. The guanine at position 2588 is part of the 3' splice site of exon 17. Analysis of the lymphoblastoid cell mRNA of two STGD patients with the 2588G-->C mutation shows that the resulting mutant ABCR proteins either lack Gly863 or contain the missense mutation Gly863Ala. We hypothesize that the 2588G-->C alteration is a mild mutation that causes STGD only in combination with a severe ABCR mutation. This is supported in that the accompanying ABCR mutations in at least five of eight STGD patients are null (severe) and that a combination of two mild mutations has not been observed among 68 STGD patients. The 2588G-->C mutation is present in 1 of every 35 western Europeans, a rate higher than that of the most frequent severe autosomal recessive mutation, the cystic fibrosis conductance regulator gene mutation DeltaPhe508. Given an STGD incidence of 1/10,000, homozygosity for the 2588G-->C mutation or compound heterozygosity for this and other mild ABCR mutations probably does not result in an STGD phenotype.