Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours: a multicentre retrospective observational cohort study.

BACKGROUND: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. PATIENTS AND METHODS: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. RESULTS: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). CONCLUSION: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.

Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy: a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and 1H-MR spectroscopy compared with histology (subgroup in the RAXO trial).

BACKGROUND: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. PATIENTS AND METHODS: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusion-weighted imaging and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and Kaplan-Meier estimates of overall survival (OS). RESULTS: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). 1H-MRS revealed steatohepatosis induced by systemic therapy. CONCLUSIONS: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.

Centralized repeated resectability assessment of patients with colorectal liver metastases during first-line treatment: prospective study.

BACKGROUND: Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. METHODS: The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. RESULTS: Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0-1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0-1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. CONCLUSION: Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.

Incidence of lichen sclerosus and subsequent causes of death: a nationwide Finnish register study.

OBJECTIVE: To assess the incidence of lichen sclerosus (LS) in women and the all-cause and cause-specific mortality of women with LS. DESIGN: Population-based descriptive study. SETTING: Finland. POPULATION: All Finnish women, including 7790 women diagnosed with LS during the period 1969-2012. METHODS: Information gathered from the Finnish Hospital Discharge Register on women with LS was combined with dates and causes of death from Statistics Finland and the Finnish Cancer Registry. Population statistics are from Statistics Finland. MAIN OUTCOME MEASURES: Crude and age-adjusted incidence rates of LS and standardised mortality ratios (SMRs). RESULTS: The incidence rate of LS adjusted for age (European Standard Population) increased from 14 per 100 000 woman-years in 2003 to 22 per 100 000 woman-years in 2010-2012. The age-specific incidence rate was highest in postmenopausal women (24-53 per 100 000) but was also elevated in girls aged 5-9 years (seven per 100 000). The all-cause mortality of women with LS was lower than in the general female population (SMR 0.84, 95% CI 0.78-0.90), mostly as a result of decreased mortality from circulatory diseases (SMR 0.80, 95% CI 0.72-0.89) and dementia and Alzheimer's disease (SMR 0.75, 95% CI 0.62-0.88). The cancer mortality equalled that of the population, but the vulvar cancer mortality was increased (SMR 28.1, 95% CI 19.3-39.4). CONCLUSIONS: Lichen sclerosus is a common disease of elderly women. The overall mortality is decreased whereas the mortality as a result of vulvar cancer is increased. TWEETABLE ABSTRACT: The likelihood of getting LS by age 80 years is 1.6%. The mortality of women with LS is reduced compared with that of the population.

Altered TUBB3 expression contributes to the epothilone response of mitotic cells.

BACKGROUND: Epothilones are a novel group of microtubule (mt) targeting cancer drugs that bind to the ß-subunit of the αß-tubulin dimer. Epothilones inhibit cell proliferation and induce cell death by interfering with the normal mt function. In this study, we examined the consequences of altered expression of human ß-tubulin isotypes in terms of the epothilone drug response in human lung and breast cancer cell lines. METHODS: The ß-tubulin isotypes TUBB2A-C, TUBB3 and TUBB were silenced or overexpressed in A549, A549EpoB40 and MCF7 cell lines in the presence or absence of epothilones. The drug effects on cell proliferation, mitosis and mt dynamics were determined using live cell microscopy and immunofluorescence assays. RESULTS: Loss of TUBB3 enhanced the action of epothilones. TUBB3 knockdown increased the severity of drug-induced mitotic defects and resulted in stabilisation of the mt dynamics in cells. Moreover, exogenous expression of TUBB3 in the epothilone resistant cell line conferred the response to drug treatments. In contrast, reduced levels of TUBB2A-C or TUBB had not apparent effect on the cells' response to epothilones. CONCLUSION: Our results show that the expression of TUBB3 contributes to the cellular response to epothilones, putatively by having an impact on the mt dynamics.

Continuous wound infusion with ropivacaine fails to provide adequate analgesia after caesarean section.

BACKGROUND: Continuous wound infusion with local anaesthetic has been used in post-caesarean pain management with conflicting results. We carried out a study comparing three groups: continuous ropivacaine wound infusion, intrathecal morphine with saline wound infusion and saline wound infusion only. METHODS: Sixty-six women undergoing elective caesarean section under combined spinal-epidural anaesthesia were randomly allocated to receive intrathecal morphine with saline wound infusion or 48 h continuous wound infusion with either ropivacaine or saline. All parturients received oral ketoprofen and intravenous oxycodone patient-controlled analgesia. Consumption of oxycodone, visual analogue scale pain scores (0-10 cm), patient satisfaction, side effects and recovery parameters were recorded for 48 h in a double-blind manner. RESULTS: Continuous wound infusion with ropivacaine failed to reduce oxycodone consumption or pain scores compared with saline control. In the first 24 h intrathecal morphine reduced mean oxycodone consumption compared to the ropivacaine wound infusion group (26 mg vs. 48 mg, P=0.007) and saline wound infusion group (26 mg vs. 45 mg, P=0.021). The first 24-h mean pain score was also lower in the intrathecal morphine group vs. the saline wound infusion group (1.3 vs. 2.2, P=0.021). Pain scores were not significantly different between intrathecal morphine and ropivacaine wound infusion groups. Pruritus was more common with intrathecal morphine. CONCLUSION: Compared to saline control, continuous wound infusion with ropivacaine failed to reduce the use of intravenous oxycodone patient-controlled analgesia or pain scores. Intrathecal morphine decreased oxycodone consumption by 46% in the first 24 h after surgery when compared to continuous ropivacaine wound infusion.

Role of cage material, working style and hearing sensitivity in perception of animal care noise.

During daily care, laboratory animals are exposed to a variety of sounds which may have effects on welfare and also cause physiological and behavioural changes. So far, almost no attention has been paid to individual sounds or the sound level caused by animal care or the sound level inside the animal cage. In this study, sounds from selected rat care procedures were recorded: pulling cage out of the rack, placing it onto a table and replacing the cage back into the rack; with measurements made inside the rat cage and in the adjacent cage. Diet was poured into the food hopper and sounds were recorded inside the cage and also the adjacent cage. The work was repeated in a calm and also in a hurried style, using stainless steel and polycarbonate cages. Finally, the sounds produced by running tap water were recorded. Differences between rat and human hearing were compared using novel species-specific sound level weightings: R-weighting for rats dB(R) and H-weighting for human dB(H). Hurried work with steel caused sound exposure levels exceeding 90 dB(R) when the cages were placed into the rack and about 80 dB(R) when pulling them out of the rack or placing onto a table. With polycarbonate, the levels were 10-15 dB(R) lower. Unhurried calm working produced lower sound exposure levels than hurried working in many procedures. When the procedures were repeated with measurements in the adjacent cage, the sound exposure levels were lower, but the results were similar. Pouring food pellets into a hopper above the rat's head caused 15 dB(R) higher sound exposure levels than pouring food to an adjacent cage. In general, humans hear these sounds about 10-15 dB louder than rats. In conclusion, cage material, working style and hearing sensitivity all have an impact on the sound exposure level in the rodent cage. With correct working methods, high sound levels can be efficiently avoided in most cases.

Spacer prostheses in two-stage revision of infected knee arthroplasty.

At present, no consensus exists on the best spacer alternative for the management of two-stage exchange arthroplasty of infected knee arthroplasties. In this retrospective study, patient records of 24 patients, who had undergone two-stage revisions in which resterilised prosthetic components were used as spacers, were reviewed. The outcome was compared to that of operations performed during the same period (1993-2003) using cement spacers (n=10). With an average follow-up of 32 months, control of infection was achieved in 26 cases (76%), with good or excellent clinical outcome in 19 cases (56%). Treatment failed and resulted in amputation at the level of the thigh before reimplantation in one case. Three patients did not undergo reimplantation. In four cases (12%) infection relapsed. The reinfection rate did not differ between the two spacer groups. Patients treated with resterilised components had a superior range of motion during the period between the two stages. Operative time was shorter and there was less blood loss in the reimplantation arthroplasty when a prosthetic spacer was used. We consider resterilised prosthetic components a safe and effective alternative to cement spacers in the management of infected knee arthroplasties.

Ondansetron and tropisetron do not prevent intraspinal morphine- and fentanyl-induced pruritus in elective cesarean delivery.

BACKGROUND: Although intraspinal morphine has been shown to be effective in providing analgesia after cesarean delivery, pruritus as a side-effect remains a common cause of dissatisfaction. The role of ondansetron has been studied in preventing pruritus but the results have been contradictory. METHODS: We randomized 98 parturients undergoing elective cesarean section using combined spinal-epidural anesthesia into a double-blinded trial to receive tropisetron 5 mg (T group) or ondansetron 8 mg (O group) or placebo (NaCl group) after delivery, when intrathecal morphine 160 microg and fentanyl 15 microg were used for post-operative pain control. The patients additionally received ketoprofen 300 mg per day. Post-operative itching, nausea and vomiting, sedation and need for rescue analgesics were registered every 3 h up to 24 h, and all patients were interviewed on the first post-operative day. RESULTS: Seventy-six percent of the parturients in the placebo group, 87% in the ondansetron, and 79% in the tropisetron group had itching. The incidence of post-operative nausea and vomiting was 21%, 20% and 11% of the patients in the placebo, ondansetron and tropisetron groups, respectively. Medication for pruritus was needed by 31%, 23% and 39% of the patients in the placebo, ondansetron and tropisetron groups, respectively. In the post-operative questionnaire, the patients reported less post-operative nausea in the tropisetron group than in the placebo group (P < 0.01). CONCLUSION: Neither ondansetron nor tropisetron prevent itching caused by intrathecal morphine with fentanyl. However, tropisetron reduced post-operative nausea.

Revision total knee arthroplasty with the Total Condylar III system in inflammatory arthritis.

We report a consecutive series of 16 revision total knee arthroplasties using the Total Condylar III system in 14 patients with inflammatory arthritis which were performed between 1994 and 2000. There were 11 women and three men with a mean age of 59 years (36 to 78). The patients were followed up for 74 months (44 to 122). The mean pre-operative Knee Society score of 37 points (0 to 77) improved to 88 (61 to 100) at follow-up (t-test, p < 0.001) indicating very good overall results. The mean range of flexion improved from 62 degrees (0 degrees to 120 degrees) to 98 degrees (0 degrees to 145 degrees) (t-test, p < 0.05) allowing the patients to stand from a sitting position. The mean Knee Society pain score improved from 22 (10 to 45) to 44 (20 to 50) (t-test, p < 0.05). No knee had definite loosening, although five showed asymptomatic radiolucent lines. Complications were seen in three cases, comprising patellar pain, patellar fracture and infection. These results suggest that the Total Condylar III system can be used successfully in revision total knee arthroplasty in inflammatory arthritis.

The C/C-13910 genotype of adult-type hypolactasia is associated with an increased risk of colorectal cancer in the Finnish population.

BACKGROUND AND AIMS: The role of nutrition in the pathogenesis of colorectal cancer is not fully understood. Milk products are an essential part of human nutrition in Western countries. Absorption of lactose, the main sugar of milk, is regulated by the activity of the lactase enzyme in the gut wall. The activity of lactase is genetically determined and is associated with a C/T single nucleotide polymorphism residing 13910 bp upstream of the lactase coding sequence. Here we have studied the relationship between the C/T(-13910) polymorphism and colorectal cancer in Finnish, British, and Spanish populations. PATIENTS AND METHODS: A total of 2766 subjects, including 963 Finnish, 283 British, and 163 Spanish subjects with colorectal cancer, and 773 Finnish, 363 British, and 221 Spanish control subjects, were genotyped for the C/T(-13910) variant by polymerase chain reaction minisequencing. RESULTS: The C/C(-13910) genotype, which is a robust molecular marker of low lactase activity (lactase non-persistence), was found to significantly associate with the risk of colorectal cancer (p = 0.015) in the Finnish subjects, with an odds ratio of 1.40 (95% confidence interval 1.07-1.85). No association was found with site, histology, or stage of the tumour. No significant risk was detected in the British or Spanish populations. CONCLUSION: Low lactase enzyme activity, defined by genotyping of the C/T(-13910) variant, may increase the risk of colorectal cancer. Further studies are warranted to investigate the role of milk and other dairy products in the pathogenesis of colon cancer in different populations.

Patient-controlled epidural technique improves analgesia for labor but increases cesarean delivery rate compared with the intermittent bolus technique.

BACKGROUND: We tested the hypothesis that patient-controlled epidural analgesia for labor (PCEA) provides better analgesia and satisfaction than the intermittent bolus technique (bolus) without affecting the mode of delivery. METHODS: We randomized 187 parturients to receive labor analgesia using either the PCEA or bolus technique. The PCEA group received a starting bolus of 14 mg of bupivacaine and 60 micro g of fentanyl in a 15-ml volume, followed by a background infusion (bupivacaine 0.08% and fentanyl 2 microg ml(-1)) 5 ml h(-1) with a 5-ml bolus and 15-min lock-out interval. The bolus group received boluses of 20 mg of bupivacaine and 75 micro g of fentanyl in a 15-ml volume. RESULTS: Parturients in the PCEA group had significantly (P < 0.05-0.01) less pain during the first and second stages of labor. There was no difference in the spontaneous delivery rate between the groups, but the cesarean delivery rate was significantly (P < 0.05) higher (16.3% vs. 6.7%) in the PCEA group than in the bolus group. Bupivacaine consumption was significantly (P < 0.01) higher (11.2 mg h(-1) vs. 9.6 mg h(-1)) and the second stage of labor was significantly (P < 0.01) longer (70 min vs. 54 min) in the PCEA group than in the bolus group. Patient satisfaction was equally good in both groups. CONCLUSION: The PCEA technique provided better pain relief. This was associated with higher bupivacaine consumption, prolongation of the second stage of labor, and an increased rate of cesarean section.

Prediction of mobilisation failure in patients with non-Hodgkin's lymphoma.

Factors affecting progenitor cell mobilisation in patients with non-Hodgkin's lymphoma (NHL) are incompletely understood. We have analysed factors predicting mobilisation failure in 97 consecutive patients with NHL (59 males, 38 females; median age 49 years) who received mobilisation with intermediate-dose CY (4 g/m(2)) followed by G-CSF. The histology included large cell B (N=50), mantle cell (N=16), follicular (N=16) and other NHL (N=15). The disease status was 1CR/PR/primary refractory in 66 patients and >1 CR/PR in 31 patients. The minimum criterion for successful mobilisation was the collection of >or=1.5 x 10(6)/kg CD34(+) cells. In all, 18 patients (19%) failed to reach this threshold. In univariate analysis, premobilisation factors associated with mobilisation failure included BM involvement at the time of diagnosis (P=0.001) or prior to mobilisation (P=0.001) and low platelet count just prior to mobilisation (P=0.001). In multivariate analysis, only BM involvement at diagnosis (P=0.004) and platelet count just prior to mobilisation (P=0.01) were associated with mobilisation failure. A mathematical model based on these two factors and presented in the form of a receiver operating characteristics curve showed a sensitivity of 0.71 and a specificity of 0.77 in the prediction of mobilisation failure. Patients at a high risk of mobilisation failure may benefit from novel approaches.

Effects of gestational age and prenatal and perinatal events on the coagulation status in premature infants.

OBJECTIVE: To study prospectively the effects of prematurity and perinatal events on the coagulation status of premature infants. PATIENTS AND MAIN OUTCOME MEASURES: Blood samples from premature infants born before 37 gestational weeks were taken for analysis of coagulation factors II, V, VII, and X and platelet count. RESULTS: A total of 125 premature infants, 71 boys, were studied at the median postnatal age of 40 minutes (range 12-100). The lowest median activities of coagulation factors II, V, VII, and X and the platelet count were observed, as expected, in infants (n = 21) born at 24-27 weeks gestation. Twin B (n = 14) had lower median activities of coagulation factors II, V, VII, and X than twin A. Infants with evidence of mild asphyxia (Apgar score at 5 minutes < 7 or cord pH < 7.26) had significantly (p < 0.05) lower levels of coagulation factors II, V, VII, and X and platelet counts than infants without asphyxia. Infants who were small for gestational age (SGA) had significantly (p < 0.05) lower levels of coagulation factors V and VII and platelet counts than infants of appropriate size for gestational age. Other prenatal and perinatal variables examined (sex, maternal hypertension and/or pre-eclampsia, antenatal steroid use, mode of delivery, Apgar scores) did not show any significant associations with coagulation status, which may be explained by the small number of infants studied. CONCLUSIONS: The data strongly suggest that there are distinct differences in specific coagulation tests in different patient populations, which could assist in the identification of extremely preterm, SGA, or asphyxiated preterm infants who may be susceptible to haemorrhagic problems perinatally.

Increased volumetric wear of polyethylene liners with more than 3 years of shelf-life time.

We analyzed 20 retrieved gamma-sterilized polyethylene liners (Biomet Hexloc). The long-term durability varied significantly depending on shelf-life time before implantation. Liners with a shelf-life time of 3 years or more evinced significantly ( P 0.002) higher volumetric wear than those with a shelf life time less than 3 years. Infrared spectroscopy and scanning calorimetry showed that all explanted implants underwent substantial in vivo oxidation and crystallization. The oxidative ageing of polyethylene renders the polyethylene liner susceptible to severe wear. Scanning electron microscopy of the bearing surface of the liner revealed abrasive wear as a dominant mechanism. Moreover, poor acetabular design produces excessively thin liners, substandard locking mechanism, and backside wear of the liner. The primary reason for severe wear in the Hexloc liner was poor modular design and oxidative degradation of the polyethylene.

Investigation of the mechanisms of therapy-related hypoglycaemia in children with acute lymphoblastic leukaemia.

AIM: To determine the mechanisms of fasting hypoglycaemia occurring during maintenance therapy (MT) for childhood acute lymphoblastic leukaemia (ALL). METHODS: Thirty-five children and adolescents with ALL, aged 2.4-17.4 y, were fasted for up to 16 h during MT. Nineteen of the children developed hypoglycaemia after 11 to 16 h of fasting. Blood samples for determination of metabolic changes were taken on completion of fasting. Nineteen patients underwent a glucagon stimulation test after 4 to 16 h of fasting during MT. Erythrocyte concentrations of the metabolites of methotrexate (E-MTX) and 6-mercaptopurine (E-TGN) were measured at the time of fasting. Fifteen out of 19 patients who became hypoglycaemic were re-studied 3 to 4 mo after cessation of therapy. RESULTS: In the hypoglycaemia group, plasma levels of gluconeogenic amino acids alanine and glutamine were lower (medians 117 vs 190 micromol L(-1), p = 0.009, and medians 396 vs 448 micromol L(-1), p = 0.031, respectively) than in the normoglycaemia group. Serum levels of free carnitine were lower (medians 20.3 vs 29.8 micromol L(-1), p = 0.027), free fatty acids higher (medians 3.09 vs 1.23 mmol L(-1), p < 0.001) and marked dicarboxylic aciduria was more common in the patients with hypoglycaemia (in 14/16 vs in 2/14, p < 0.001). Impaired responses to glucagon stimulation occurred in 36% (4/11) in the hypoglycaemia group and in 12.5% (1/8) in the normoglycaemia group (p = 0.243). No significant differences were detected in E-MTX and E-TGN between the groups. Most of the metabolic abnormalities returned to normal after cessation of chemotherapy. CONCLUSIONS: Low levels of gluconeogenic amino acids, especially of alanine, are associated with hypoglycaemia. Reduced hepatic glycogen stores may also be involved in the aetiology.

Emotional reactions and life changes of caregivers of demented patients when home caregiving ends.

Many studies indicate that the cessation of caregiving of demented patients has positive effects on caregivers' lives but contradictory findings have also been reported. The aim of this study was to investigate how the caregivers of demented patients experienced the cessation of caregiving, how caregivers' lives changed after this event, and which factors predicted emotional reactions and life changes. Data were collected from 64 caregivers of demented patients, recruited from a previous controlled intervention study. The semi-structured telephone interviews sought (1) sociodemographic data, (2) emotional reactions the caregivers recalled from the point of cessation of caregiving, and (3) life changes experienced after that time point. At the point of cessation of caregiving, spouse caregivers had higher risk for loneliness, depressive feelings and sorrow than non-spouse caregivers. Feelings of relief were associated with non-spouses. Community care support obtained during the previous intervention study had protected the caregivers from loneliness, depressive feelings and sorrow. After the end of caregiving, spouse caregivers tended to experience more negative life changes. The increased number of leisure activities was associated with the support during community care.

Factors related to non-compliance with antihypertensive drug therapy.

The objectives were to study the associations of perceived health care-related and patient-related factors with self-reported noncompliance with antihypertensive treatment. General practitioners identified all of their hypertensive patients in 26 health centres during 1 week in 1996 (n = 2219). A total of 1782 (80%) patients participated in the study, of whom 1561 were on antihypertensive medication. Based on 82 opinion statements in two questionnaires, 14 problem indices were formed by using factor analysis. Out of these, summary variables concerning problems related to the health care system and the patients were formed. Logistic regression models, including interaction analyses, were used to study the associations with non-compliance. The results were that the majority of patients had at least one perceived health care system-related (88%) and patient-related problem (92%). A high number of both perceived health care system-related problems (adjusted OR 4.77; 95% CI 2.76, 8.26) and patient-related problems (adjusted OR 3.23; 95% CI 1.79, 5.81) were associated with self-reported non-compliance. The experience of adverse drug effects was also associated with non-compliance (adjusted OR 1.41; 95% CI 1.03, 1.94). In conclusion self-reported non-compliance was associated with multiple risks of both perceived health care system-related and patient-related problems.

A double-blinded, randomized comparison of intrathecal and epidural morphine for elective cesarean delivery.

UNLABELLED: We randomized 150 parturients into a double-blinded trial to receive intrathecal (IT) 100 microg (IT 100 group) or 200 microg (IT 200 group) or epidural 3 mg (Epidural group) of morphine for elective cesarean delivery with a combined spinal/epidural technique. The patients additionally received ketoprofen 300 mg/d. Postoperative pain relief and side effects were registered every 3 h up to 24 h, and all patients were interviewed on the first postoperative day. Pain control was equally good, but the parturients in the IT 100 group requested rescue analgesics more often compared with the other groups (P < 0.05). Itching was a common complaint and was reported by 74% of the parturients in the Epidural group and 65% and 91% in the IT 100 and IT 200 groups, respectively (P < 0.01). Medication for itching was requested by 44%, 24%, and 45% of the patients, respectively (P < 0.05). There was no difference in postoperative nausea or vomiting. The pain relief was perceived as good by >90% of the patients in all groups. In conclusion, because of the decreased incidence of and lesser requirements of medication for itching, IT morphine 100 microg with ketoprofen is recommended in cesarean deliveries. Rescue analgesics nevertheless need to be prescribed. IMPLICATIONS: Spinal morphine is an effective analgesic after cesarean delivery, but it has several side effects. The purpose of this study was to compare the prevalence of side effects and the level of analgesia of epidural morphine with two different doses of spinal morphine after elective cesarean delivery. Although rescue analgesics may be required, intrathecal morphine 100 microg is suggested for postoperative analgesia after cesarean delivery.