Diagnostic work-up and systemic treatment for advanced non-squamous non-small-cell lung cancer in four Southeast Asian countries.

BACKGROUND: Lung cancer is the second most common cancer and leading cause of cancer mortality worldwide. Recent advances in molecular testing and targeted therapy have improved survival among patients with metastatic non-small-cell lung cancer (NSCLC). We sought to quantify and describe molecular testing among metastatic non-squamous NSCLC cases in selected Southeast Asian countries and describe first-line therapy chosen. PATIENTS AND METHODS: A retrospective study was conducted based on incident lung cancer cases diagnosed between 2017 and 2019 in Lampang (Thailand), Penang (Malaysia), Singapore and Yogyakarta (Indonesia). Cases (n = 3413) were defined using the International Classification of Diseases for Oncology third edition. In Singapore, a clinical series obtained from the National Cancer Centre was used to identify patients, while corresponding population-based cancer registries were used elsewhere. Tumor and clinical information were abstracted by chart review according to a predefined study protocol. Molecular testing of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene rearrangement, ROS1 gene rearrangement and BRAF V600 mutation was recorded. RESULTS: Among 2962 cases with a specified pathological diagnosis (86.8%), most patients had non-squamous NSCLC (75.8%). For cases with staging information (92.1%), the majority presented with metastatic disease (71.3%). Overall, molecular testing rates in the 1528 patients with stage IV non-squamous NSCLC were 67.0% for EGFR, 42.3% for ALK, 39.1% for ROS1, 7.8% for BRAF and 36.1% for PD-L1. Among these patients, first-line systemic treatment included chemotherapy (25.9%), targeted therapy (35.6%) and immunotherapy (5.9%), with 31% of patients having no record of antitumor treatment. Molecular testing and the proportion of patients receiving treatment were highly heterogenous between the regions. CONCLUSIONS: This first analysis of data from a clinically annotated registry for lung cancer from four settings in Southeast Asia has demonstrated the feasibility of integrating clinical data within population-based cancer registries. Our study results identify areas where further development could improve patient access to optimal treatment.

Decreasing incidence of cancer after liver transplantation-A Nordic population-based study over 3 decades.

Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 were extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals of the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2.22 (95% confidence interval [CI], 2.02-2.43). SIRs were especially increased for colorectal cancer in recipients with primary sclerosing cholangitis (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post-LT was observed from the 1980s: 4.53 (95%CI, 2.47-7.60), the 1990s: 3.17 (95%CI, 2.70-3.71), to the 2000s: 1.76 (95%CI, 1.51-2.05). This was observed across age- and indication-groups. The sequential decrease for the SIR of non-Hodgkin lymphoma was 25.0-12.9-7.53, and for nonmelanoma skin cancer 80.0-29.7-10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study.

Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: A case study in haemato-oncology.

Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBR + EHR approach opens a perspective on randomised registry trials.

The role of initial clinical presentation, comorbidity and treatment in multiple myeloma patients on survival: a detailed population-based cohort study.

PURPOSE: This prospective, observational population-based cohort study was performed to determine overall survival (OS) in multiple myeloma (MM) patients in Friesland, the Netherlands, in the era of novel agents and to analyse the influence of first-line treatment, MM-related end-organ damage and comorbidities at initial presentation on OS. METHODS: Detailed clinical information was obtained from the population-based registry 'HemoBase' during the period January 2005 to January 2013, with a follow-up to January 2014. RESULTS: Overall, the symptomatic MM patients (n = 225) had a median OS of 40 months. In the age categories <65, 65-75 and ≥75 years, 99, 94 and 87% of the patients received treatment, with a median OS of 92, 42 and 31 months, respectively. OS for patients with or without treatment was 43 and 3 months, respectively. In multivariable analysis, risk factors for worse OS were increasing age (<65: reference; 65-75: HRadj. = 2.2 (95% CI 1.3-3.7) and ≥75: HRadj. = 2.8 (95% CI 1.7-4.8); P < 0.001), not receiving initial treatment (HRadj. = 4.0 (95% CI 2.1-7.7); P < 0.001), hypercalcaemia (P < 0.001, HRadj. = 1.7 (95% CI 1.2-2.6), P = 0.006) and impaired renal function (HRadj. = 2.6 (95% CI 1.7-4.0); P < 0.001). CONCLUSIONS: Increasing age, not receiving initial treatment, hypercalcaemia and impaired renal function at initial presentation were independent risk factors for worse OS. Comorbidity according to Charlson comorbidity index score was not an independent variable predicting OS.

Skin conductance as a pain assessment tool during chest tube removal: An observational study.

BACKGROUND: Skin conductance variability to assess pain has shown varying results. Skin conductance responses per second (SCR) during a standardized painful stimulus in awake adults may give further understanding of the method's validity. The purpose of this study was to validate the SCR with the visual analogue scale (VAS) for pain (P-VAS) and anxiety (A-VAS) during chest tube removal (CTR). METHODS: Ninety-five patients receiving epidural or non-epidural treatment, scheduled for CTR, were studied. Pain or anxiety was considered when VAS > 30 mm; the SCR cut-off value reflecting pain was ≥0.2 SCR. RESULTS: SCR values could not be recorded in eight cases before CTR, six cases during CTR and seven cases after CTR. CTR induced increases in SCR, P-VAS and A-VAS (p < 0.001). Seventy-seven percent of all pairs of P-VAS and SCR values were well-classified; P-VAS ≤ 30 mm and SCR < 0.2 or P-VAS > 30 mm and SCR ≥ 0.2. SCR obtained before CTR differentiates between patients with and without pain during CTR in all patients (p = 0.04) and in the subgroup of non-anxious patients (p = 0.02), but not in the subgroup of anxious patients. SCR obtained during CTR had similar values in patients with and without pain in all patients and in the subgroup of anxious patients, but in the subgroup of non-anxious patients SCR during CTR differentiates patients with and without pain (p = 0.009). CONCLUSIONS: SCR increases during painful procedures. Preprocedural SCR may help predict reported pain in patients exposed to painful procedures. SCR during CTR differentiates between patients with and without pain only in non-anxious patients. SIGNIFICANCE: Preprocedural SCR may help predict reported pain in patients exposed to painful procedures. Procedural SCR accuracy improves in a subgroup of non-anxious patients. P-VAS is influenced by anxiety different from SCR.

Uses of cancer registries for public health and clinical research in Europe: Results of the European Network of Cancer Registries survey among 161 population-based cancer registries during 2010-2012.

AIM: To provide insight into cancer registration coverage, data access and use in Europe. This contributes to data and infrastructure harmonisation and will foster a more prominent role of cancer registries (CRs) within public health, clinical policy and cancer research, whether within or outside the European Research Area. METHODS: During 2010-12 an extensive survey of cancer registration practices and data use was conducted among 161 population-based CRs across Europe. Responding registries (66%) operated in 33 countries, including 23 with national coverage. RESULTS: Population-based oncological surveillance started during the 1940-50s in the northwest of Europe and from the 1970s to 1990s in other regions. The European Union (EU) protection regulations affected data access, especially in Germany and France, but less in the Netherlands or Belgium. Regular reports were produced by CRs on incidence rates (95%), survival (60%) and stage for selected tumours (80%). Evaluation of cancer control and quality of care remained modest except in a few dedicated CRs. Variables evaluated were support of clinical audits, monitoring adherence to clinical guidelines, improvement of cancer care and evaluation of mass cancer screening. Evaluation of diagnostic imaging tools was only occasional. CONCLUSION: Most population-based CRs are well equipped for strengthening cancer surveillance across Europe. Data quality and intensity of use depend on the role the cancer registry plays in the politico, oncomedical and public health setting within the country. Standard registration methodology could therefore not be translated to equivalent advances in cancer prevention and mass screening, quality of care, translational research of prognosis and survivorship across Europe. Further European collaboration remains essential to ensure access to data and comparability of the results.

Increased stomach cancer risk following radiotherapy for testicular cancer.

BACKGROUND: Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose-response relationship are sparse. METHODS: In a cohort of 22,269 5-year TC survivors diagnosed during 1959-1987, doses to stomach subsites were estimated for 92 patients who developed stomach cancer and 180 matched controls. Chemotherapy details were recorded. Odds ratios (ORs) were estimated using logistic regression. RESULTS: Cumulative incidence of second primary stomach cancer was 1.45% at 30 years after TC diagnosis. The TC survivors who received radiotherapy (87 (95%) cases, 151 (84%) controls) had a 5.9-fold (95% confidence interval (CI) 1.7-20.7) increased risk of stomach cancer. Risk increased with increasing stomach dose (P-trend<0.001), with an OR of 20.5 (3.7-114.3) for ⩾50.0 Gy compared with <10 Gy. Radiation-related risks remained elevated ⩾20 years after exposure (P<0.001). Risk after any chemotherapy was not elevated (OR=1.1; 95% CI 0.5-2.5; 14 cases and 23 controls). CONCLUSIONS: Radiotherapy for TC involving parts of the stomach increased gastric cancer risk for several decades, with the highest risks after stomach doses of ⩾30 Gy. Clinicians should be aware of these excesses when previously irradiated TC survivors present with gastrointestinal symptoms and when any radiotherapy is considered in newly diagnosed TC patients.

Pancreatic cancer risk after treatment of Hodgkin lymphoma.

BACKGROUND: Although elevated risks of pancreatic cancer have been observed in long-term survivors of Hodgkin lymphoma (HL), no prior study has assessed the risk of second pancreatic cancer in relation to radiation dose and specific chemotherapeutic agents. PATIENTS AND METHODS: We conducted an international case-control study within a cohort of 19 882 HL survivors diagnosed from 1953 to 2003 including 36 cases and 70 matched controls. RESULTS: Median ages at HL and pancreatic cancer diagnoses were 47 and 60.5 years, respectively; median time to pancreatic cancer was 19 years. Pancreatic cancer risk increased with increasing radiation dose to the pancreatic tumor location (Ptrend = 0.005) and increasing number of alkylating agent (AA)-containing cycles of chemotherapy (Ptrend = 0.008). The odds ratio (OR) for patients treated with both subdiaphragmatic radiation (≥10 Gy) and ≥6 AA-containing chemotherapy cycles (13 cases, 6 controls) compared with patients with neither treatment was 17.9 (95% confidence interval 3.5-158). The joint effect of these two treatments was significantly greater than additive (P = 0.041) and nonsignificantly greater than multiplicative (P = 0.29). Especially high risks were observed among patients receiving ≥8400 mg/m(2) of procarbazine with nitrogen mustard or ≥3900 mg/m(2) of cyclophosphamide. CONCLUSION: Our study demonstrates for the first time that both radiotherapy and chemotherapy substantially increase pancreatic cancer risks among HL survivors treated in the past. These findings extend the range of nonhematologic cancers associated with chemotherapy and add to the evidence that the combination of radiotherapy and chemotherapy can lead to especially large risks.

Cancer prevalence in United States, Nordic Countries, Italy, Australia, and France: an analysis of geographic variability.

BACKGROUND: The objectives of this study were to quantitatively assess the geographic heterogeneity of cancer prevalence in selected Western Countries and to explore the associations between its determinants. METHODS: For 20 cancer sites, 5-year cancer prevalence, incidence, and survival were observed and age standardised for the mid 2000s in the United States, Nordic European Countries, Italy, Australia, and France. RESULTS: In Italy, 5-year crude prevalence for all cancers was 1.9% in men and 1.7% in women, while it was ∼1.5% in all other countries and sexes. After adjustment for the different age distribution of the populations, cancer prevalence in the United States was higher (20% in men and 10% in women) than elsewhere. For all cancers combined, the geographic heterogeneities were limited, though relevant for specific cancers (e.g., prostate, showing >30% higher prevalence in the United States, or lung, showing >50% higher prevalence in USA women than in other countries). For all countries, the correlations between differences of prevalence and differences of incidence were >0.9, while prevalence and survival were less consistently correlated. CONCLUSION: Geographic differences and magnitude of crude cancer prevalence were more strongly associated with incidence rates, influenced by population ageing, than with survival rates. These estimates will be helpful in allocating appropriate resources.

Nociceptive stimuli responses at different levels of general anaesthesia and genetic variability.

BACKGROUND: Changes in skin conductance (SC), clinical stress score (CSS), the bispectral index spectroscopy (BIS) index and the variation in the BIS index may be used to monitor responses to nociceptive stimuli. We wanted to examine these methods during noxious stimulation during general anaesthesia and if the responses were associated with variability in genes related to pain. METHODS: Sixty patients, given propofol to a BIS level of 40-50, were stimulated with standardised tetanic electrical stimuli during propofol infusion, plasma level of 3 µg/ml alone, or together with remifentanil target plasma level of 3 ng/ml or 10 ng/ml. The CSS, SC, BIS index and the variability of the BIS index were registered. The inter-individual variation in nociceptive responses was analysed for co-variation with genotypes of 89 single nucleotide polymorphisms from 23 candidate genes. RESULTS: During tetanic stimuli, CSS and SC increased significantly and were attenuated with increasing level of remifentanil, different from the BIS index and the variation in the BIS index. Polymorphisms in the P-glycoprotein (ABCB1), tachykinin 1 receptor (TACR1), dopamine receptor D3 (DRD3) and beta arrestin 2 (ARRB2) genes were associated with the co-variation in SC variables or CSS response or both during standardised nociceptive stimuli (P < 0.05). Because of no corrections for multiple testing, the genetic analyses are explorative, and associations must be tested in further studies. CONCLUSION: This exploratory study suggests genes that may be tested further with relation to nociceptive response during anaesthesia. SC and CSS may be useful tools for monitoring nociceptive response during general anaesthesia.

Risk of treatment-related esophageal cancer among breast cancer survivors.

BACKGROUND: Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. DESIGN: Nested case-control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. RESULTS: The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P(trend )< 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). CONCLUSIONS: Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.

Risk of second cancers after the diagnosis of Merkel cell carcinoma in Scandinavia.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumour of the skin that has been associated with a new tumour virus, the MCC polyomavirus. METHODS: To investigate whether MCC may have a shared aetiology with other cancers, we investigated the risk of second cancers after the diagnosis of MCC using the national cancer registries in Denmark, Norway and Sweden. RESULTS: The overall cancer incidence was increased among patients diagnosed with MCC compared with the general population in these countries (79 secondary cancers total, Standardized Incidence Ratio (SIR) 1.38 (95% confidence interval (CI): 1.10-1.72); 49 secondary cancer in females, SIR 1.7 (95% CI: 1.29-2.25); 30 secondary cancers in males and SIR 1.05 (95% CI: 0.73-1.5)). There were significantly increased incidence ratios for non-melanoma skin cancers (34 secondary cancers, SIR 8.35 (95% CI: 5.97-11.68)), melanoma of skin (6 secondary cancers, SIR 4.29 (95% CI: 1.93-9.56)) and laryngeal cancer (2 secondary cancers, SIR 9.51 (95% CI: 2.38-38)). The SIRs for these three cancer sites were also elevated on restricting the follow-up to cancers occurring at least one year after MCC diagnosis. CONCLUSIONS: Patients diagnosed with MCC are at increased risk of a second cancer, particularly, other skin cancers. Conceivable explanations include the impact of increased surveillance of the skin and shared causative factors, for example, ultraviolet light exposure or MCC polyomavirus infection.

Polymorphic MLH1 and risk of cancer after methylating chemotherapy for Hodgkin lymphoma.

BACKGROUND AND OBJECTIVE: Methylating agents are effective chemotherapy agents for Hodgkin lymphoma, but are associated with the development of second primary cancers. Cytotoxicity of methylating agents is mediated primarily by the DNA mismatch repair (MMR) system. Loss of MLH1, a major component of DNA MMR, results in tolerance to the cytotoxic effects of methylating agents and persistence of mutagenised cells at high risk of malignant transformation. We hypothesised that a common substitution in the basal promoter of MLH1 (position -93, rs1800734) modifies the risk of cancer after methylating chemotherapy. METHODS: 133 patients who developed cancer following chemotherapy and/or radiotherapy (n = 133), 420 patients diagnosed with de novo myeloid leukaemia, 242 patients diagnosed with primary Hodgkin lymphoma, and 1177 healthy controls were genotyped for the MLH1 -93 polymorphism by allelic discrimination polymerase chain reaction (PCR) and restriction fragment length polymorphism assay. Odds ratios and 95% confidence intervals for cancer risk by MLH1 -93 polymorphism status, and stratified by previous exposure to methylating chemotherapy, were calculated using unconditional logistic regression. RESULTS: Carrier frequency of the MLH1 -93 variant was higher in patients who developed therapy related acute myeloid leukaemia (t-AML) (75.0%, n = 12) or breast cancer (53.3%. n = 15) after methylating chemotherapy for Hodgkin lymphoma compared to patients without previous methylating exposure (t-AML, 30.4%, n = 69; breast cancer patients, 27.2%, n = 22). The MLH1 -93 variant allele was also over-represented in t-AML cases when compared to de novo AML cases (36.9%, n = 420) and healthy controls (36.3%, n = 952), and was associated with a significantly increased risk of developing t-AML (odds ratio 5.31, 95% confidence interval 1.40 to 20.15), but only in patients previously treated with a methylating agent. CONCLUSIONS: These data support the hypothesis that the common polymorphism at position -93 in the core promoter of MLH1 defines a risk allele for the development of cancer after methylating chemotherapy for Hodgkin lymphoma. However, replication of this finding in larger studies is suggested.

Iron deficiency among children of asylum seekers in the Netherlands.

OBJECTIVES: To investigate, in asylum seekers' children in the Netherlands, biochemical iron status and the prevalence of iron deficiency (ID) and anemia in relation to age, region of origin, length of stay in the Netherlands, body mass index (BMI), and dietary iron intake. PATIENTS AND METHODS: Hemoglobin (Hb) and plasma ferritin concentrations were determined in 122 asylum seekers' children (median age, 7.1 years; range, 2-12 y). ID was defined by plasma ferritin levels <15 microg/L. Anemia was defined by Hb levels <6.8 mmol/L (11 g/dL) for children <6 years of age and Hb levels <7.1 mmol/L (11.5 g/dL) for children between 6 and 12 years of age. Nutritional status of the children was assessed by BMI and dietary intake of iron was estimated by 24-hour recall. RESULTS: Twenty percent of the children had compromised iron status (16% with ID, 4% with ID anemia [IDA]). Another 6% of the children had anemia caused by thalassemia. ID was significantly more prevalent in children <6 years of age and in children of African origin. The iron status was not significantly correlated with the length of stay in the Netherlands (r = 0.6; P = 0.48). Higher BMI z scores were positively correlated with iron status. Adequate or marginal dietary iron intake was not significantly related to the presence of ID (r = 0.02; P = 0.9) or anemia (IDA and thalassemia; r = 0.15; P = 0.9). CONCLUSIONS: Iron deficiency is highly prevalent among the children of asylum seekers in the Netherlands. Our data indicate that systematic biochemical screening for ID is warranted in asylum seekers' children.

The assessment of postoperative pain by monitoring skin conductance: results of a prospective study.

The number of fluctuations of skin conductance per second correlates with postoperative pain. The aim of this prospective study was to test the cut-off value for the number of fluctuations of skin conductance per second obtained from a previous study. Seventy-five patients were asked to quantify their level of pain on a numeric rating scale (0-10) in the recovery room. The number of fluctuations of skin conductance per second was recorded simultaneously. The number of fluctuations of skin conductance per second was different between patients with no (0.07), mild (0.16), moderate (0.28) and severe pain (0.33); p < 0.001. The tested cut-off value for the number of fluctuations of skin conductance per second (0.1) distinguished a numeric rating scale 3 with 88.5% sensitivity and 67.7% specificity. The number of fluctuations of skin conductance per second may be a useful means of assessing postoperative pain.

Skin conductance or entropy for detection of non-noxious stimulation during different clinical levels of sedation.

BACKGROUND: State entropy (SE) measures electroencephalographic signals, whereas response entropy (RE) also includes frontal electromyographic activity. In the presence of electromyographic activity, the RE index is larger than the SE index, the difference being denoted as RE-Delta (RE-Delta= RE - SE). Skin conductance (SC) may be expressed by a slow reacting variable, the mean SC level, the derivate of the mean SC level (D-SC), the number of SC fluctuations (NSCF) or the amplitude of the SC fluctuations (ASCF), which directly shows skin sympathetic nerve activity. The goal of this study was to evaluate whether these SC and entropy variables could differentiate between the responses obtained to load sound stimuli at different sedation levels before the induction of general anaesthesia. METHODS: Twenty women scheduled for gynaecological laparotomy were studied. The modified observer's assessment of alertness sedation (OAAS) was used to classify the patients' hypnotic levels. White sounds (98 dB) were given at OAAS level 5 without propofol, at OAAS levels 4-3 and 3-2 with propofol and at OAAS levels 3-2 and < 2 with propofol and remifentanil. RESULTS: RE and SE showed a steady decline from OAAS level 5 to level < 2 (P < 0.01). RE-Delta did not discriminate between any of the OAAS levels (P= NS). The mean SC level discriminated between OAAS levels 4-3 to < 2 (P < 0.01). D-SC discriminated between all the different OAAS levels (P < 0.01). NSCF discriminated between OAAS levels 5 to 3-2 (P < 0.05), but did not discriminate at OAAS level 3-2 between propofol alone or combined with remifentanil, or between OAAS level 3-2 and < 2. ASCF differentiated between OAAS levels 5 and 4 (P < 0.001) and OAAS levels 3-2 and < 2 (P < 0.05) only. CONCLUSION: RE, SE and D-SC showed a similar discrimination between sound responses at the different sedation levels.

Comparison of skin conductance with entropy during intubation, tetanic stimulation and emergence from general anaesthesia.

BACKGROUND: The number of skin conductance fluctuations (NSCF) expresses sympathetic skin nerve activity. The response entropy (RE) measures electromyographic and electroencephalographic activity in the forehead. The state entropy (SE) measures mainly electroencephalographic activity. When the suppression of frontal muscular activity is complete, RE is equal to SE. RE-Delta is defined as SE minus RE. The purposes of this study were to examine whether NSCF and RE-Delta correlate with signs of clinical stress during intubation and tetanic noxious stimulation and to elucidate how rapidly and accurately entropy and NSCF react during emergence from general anaesthesia. METHODS: Twenty women scheduled for gynaecological laparotomy were studied. During intubation in remifentanil and propofol general anaesthesia, NSCF and RE-Delta were correlated with the clinical stress score. After a wash-out period, two series of tetanic stimuli were given, the first with (R+) and the second without (R-) remifentanil infusion. The tetanic pre-stimuli periods were compared with the tetanic post-stimuli periods, and R+ was compared with R-. During emergence, the responses of entropy and skin conductance were related to the time of extubation. RESULTS: NSCF correlated well with the clinical stress score during intubation (r(2)= 0.73, P < 0.0005). RE-Delta showed a weaker correlation (r(2)= 0.33, P= 0.007). During tetanic stimuli, the NSCF pre-stimuli level was lower than the post-stimuli level (P < 0.001), and the NSCF R+ response was lower than the NSCF R- response (P= 0.002). RE-Delta did not show similar differences. During emergence, RE reacted before NSCF and SE (P= 0.003). CONCLUSION: NSCF was better than RE-Delta for the measurement of clinical stress during intubation, and was sensitive to tetanic stimuli at different opioid analgesic levels, by contrast with RE-Delta. Both modalities were able to predict emergence at the end of anaesthesia, but RE was more rapid.

Monitoring of skin conductance to assess postoperative pain intensity.

BACKGROUND: Pain is known to alter the electrogalvanic properties of the skin. The aim of this pilot study was to investigate the influence of postoperative pain on skin conductance (SC) readings. METHODS: After obtaining ethical approval and written informed consent, 25 postoperative patients were asked to quantify their level of pain on a numeric rating scale (NRS, 0-10) at different time points in the recovery room. As a parameter of SC, the number of fluctuations within the mean SC per second (NFSC) was recorded. Simultaneously, the NRS was obtained from patients by a different observer who was blinded to the NFSC values. RESULTS: Data from 110 readings of 25 patients (14 female, 11 male; 21-67 yr) were included. NFSC showed a significant correlation with the NRS (r=0.625; P<0.01), whereas heart rate and blood pressure showed no or very weak correlation with the NRS. NFSC was significantly different between patients with no (NRS=0), mild (NRS=1-3), moderate (NRS=4-5) and severe (NRS=6-10) pain (no: 0.047, mild: 0.089, moderate: 0.242, severe: 0.263; P<0.0001). Post hoc, a cut-off value for NFSC (0.1) was calculated above which a pain score >3 on the NRS was predicted with sensitivity of 89% and specificity of 74%. CONCLUSIONS: The severity of postoperative pain significantly influences SC. Using cut-off values, NFSC may prove a useful tool for pain assessment in the postoperative period.

Skin conductance monitoring compared with Bispectral Index to assess emergence from total i.v. anaesthesia using propofol and remifentanil.

BACKGROUND: Arousal after sevoflurane anaesthesia has been detectable by monitoring changes in skin conductance (SC) with similar accuracy as monitoring Bispectral Index (BIS). As SC monitoring detects changes in sympathetic tone, the measurements might be confounded by the sympatholytic properties of propofol, a component of total i.v. anaesthesia (TIVA). Therefore in this study, monitoring of SC during emergence from TIVA was compared with the monitoring of BIS. METHODS: Twenty-five patients undergoing plastic surgery were investigated. The number of fluctuations of SC per second (NFSC), BIS and haemodynamic variables [systolic blood pressure (SBP) and heart rate (HR)] were recorded simultaneously. The performance of the monitoring devices in distinguishing between the clinical states 'steady-state anaesthesia', 'first clinical reaction' and 'extubation' were compared using the method of prediction probability (Pk) calculation. RESULTS: BIS((R)) showed the best performance in distinguishing between 'steady-state anaesthesia' and 'first reaction' (Pk BIS 0.99 vs NFSC 0.80; P<0.01), and 'steady-state anaesthesia' and 'extubation' (Pk BIS) 1.00 vs NFSC 0.91; P<0.05); the time from first change of BIS or NFSC to a first clinical reaction was significantly longer for NFSC (median BIS 135 s vs NFSC 191 s; P<0.05). BIS and NFSC performed better in distinguishing between the investigated clinical states than SBP and HR. CONCLUSIONS: In this study, BIS was found to predict arousal with a higher probability but slower response times than NFSC in patients waking after TIVA.