Fatigue in people with localized colorectal cancer who do and do not receive chemotherapy: a longitudinal prospective study.

BACKGROUND: Fatigue is associated with cancer and chemotherapy and may be sustained. Here, we describe a prospective longitudinal study evaluating fatigue and putative mechanisms in people with colorectal cancer (CRC). PATIENTS AND METHODS: People with localized CRC completed the Functional Assessment of Cancer Treatment-Fatigue (FACT-F) questionnaire at baseline (before chemotherapy, if given), 6, 12, and 24 months. Healthy controls (HCs) were assessed at the first three time points. Fatigue was defined by standardized FACT-F scores ≤68/100. Quality-of-life (QoL, assessed by the FACT-G questionnaire), affective, and cognitive symptoms were evaluated. Associations were sought between fatigue, baseline factors, and blood tests (including hemoglobin, cytokines, and sex hormones). Regression analyses, Fisher's exact tests, and Wilcoxon rank-sum tests assessed levels of fatigue at each time point and change in fatigue from baseline. A repeated-measures analysis investigated prognostic factors of fatigue across all time points. RESULTS: A total of 289 subjects with localized CRC (173 received chemotherapy) and 72 HCs were assessed. More CRC patients had fatigue than HCs at baseline (52% versus 26%, P < 0.001). Fatigue was increased in the chemotherapy (CTh) group at 6 months [CTh+ 70% versus CTh- 31% (P < 0.001), HCs 22%] and remained more common at 12 [CTh+ 44% versus CTh- 31% (P = 0.079)] and 24 months [CTh+ 39% versus CTh- 24% (P = 0.047)]. There was no significant difference between those not receiving chemotherapy and HCs at follow-up assessments. Fatigue was associated with poor QoL, affective and cognitive symptoms, but not consistently with cytokine levels. Predictors for sustained fatigue were baseline fatigue, treatment group, cognitive and affective symptoms, poorer QoL, and comorbidities. CONCLUSIONS: CRC patients have more fatigue than HCs at baseline. Fatigue peaks immediately after adjuvant chemotherapy, but remains common for 2 years in those who receive chemotherapy. Cognitive and affective symptoms, QoL, comorbidities, chemotherapy, and baseline fatigue predict for longer term fatigue.

Cognitive function and fatigue after diagnosis of colorectal cancer.

BACKGROUND: Cognitive impairment and fatigue have been associated with cancer and its treatment. We present baseline data from a large longitudinal study that evaluates cognitive function, fatigue, and potential underlying mechanisms following diagnosis of colorectal cancer (CRC). PATIENTS AND METHODS: We evaluated CRC patients with stage I-III disease before or after surgery, participants with limited metastatic disease and healthy controls (HC). Neuropsychological evaluation included clinical and computerised tests. Participants completed questionnaires for fatigue and quality of life (QOL)-(FACT-F), anxiety/depression, and cognitive symptoms (FACT-Cog). Ten cytokines, clotting factors, sex hormones, carcinoembryonic antigen (CEA), and apolipoprotein E genotype were evaluated. Primary end points were cognitive function on clinical tests evaluated by a Global Deficit score (GDS) and fatigue. Associations between test results, demographic, and disease related factors were explored. RESULTS: We assessed 291 participants with early-stage disease [median age 59 (23-75) years, 63% men], 72 with metastatic disease, and 72 HC. Using GDS, 45% (126/281) of participants with early-stage CRC had cognitive impairment versus 15% (11/72) of HC (odds ratio 4.51, 95% confidence interval 2.28-8.93; P < 0.001), with complex processing speed, attention/working memory, and verbal learning efficiency being most affected. Women with early-stage CRC had greater cognitive impairment than men [55/105 (52%) versus 71/176 (40%), P < 0.050]. Cognitive symptoms were self-reported by 21% (59/286) of early-stage patients versus 17% (12/72) of HC; fatigue by 52% (149/287) of early-stage patients and 26% (19/72) of HC (P < 0.0001). Women reported more fatigue than men (P = 0.003). Fatigue, QOL, anxiety/depression, and cognitive symptoms were associated with each other (r = 0.43-0.71), but not with neuropsychological performance. Most cytokines were elevated in cancer patients. Cognitive function was not associated with cytokines, sex hormones, clotting factors, CEA, or apolipoprotein E genotype. CONCLUSIONS: The incidence of cognitive impairment was three to five times higher in CRC patients than HC, with women having higher impairment rates than men. The cognitive impairment profile suggests dysfunction primarily in fronto-subcortical brain systems. TRIAL REGISTRATION: NCT00188331.

Seventy-five years ago: insulin treatment in Hereford General Hospital.

This year, 1998, marks the 75th anniversary of the general availability of insulin in the United Kingdom. To mark the occasion, Diabetic Medicine publishes this account of the early days of insulin therapy in one of Britain's district general hospitals, Hereford General Hospital. The authors describe the first tentative use of insulin and draw some interesting parallels with the issues which still concern the introduction of novel therapies in endocrinology today.

Elevations of complex partial epileptic-like experiences during increased geomagnetic activity for women reporting "premenstrual syndrome".

Responses to the frequency of complex partial epileptic-like experiences were recorded every second day by 12 women for at least two months per individual. Five (41%) of the women displayed significant increases (effect sizes between 6% and 17%) in the numbers of these experiences when the daily geomagnetic activity exceeded 40 nT. The results were consistent with the hypothesis that a spectrum of experiences and behaviours, associated with limbic lability, can be enhanced by environmental stimuli correlated with perturbations of the geomagnetic field.

Influence of change from grouped to individual housing on a T-cell-dependent immune response in mice: antagonism by diazepam.

Transferring CD-1 mice from grouped to individual housing and then maintaining them individually resulted in a decline in the peak IgM plaque-forming cell (PFC) response to sheep red blood cells (SRBCs). However, the immunosuppression was dependent on the amount of time mice were maintained individually. In particular, individual housing for 5-10 days prior to SRBC inoculation and for 4 days following inoculation resulted in a suppression of the splenic PFC response and serum antibody titers. Shorter periods of individual housing (4 days following inoculation) did not provoke the immunosuppression. Likewise, following more protracted individual housing (15-30 days prior to inoculation) the immunosuppression was not evident. Inasmuch as daily treatment with an anxiolytic, diazepam (1.0 mg/kg), antagonized the suppression induced by 5 days of individual housing, it was suggested that the change from group to individual housing and then maintenance of animals individually acted much like a stressor to induce the immunosuppression.

Some aspects of the epidemiology and control of Salmonella typhimurium infection in outwintered suckler cows.

Two outbreaks of Salmonella typhimurium infections affected outwintered, spring-calving suckler cows in late pregnancy. The infections spread rapidly both within and between groups of stock on the affected farms, with morbidity in the infected groups varying from 14.5 per cent to over 60 per cent, and mortality in adult cattle varying from 0 to 14.3 per cent. Prophylactic measures included the use of antibiotics and killed vaccines against Escherichia coli, Salmonella dublin, S typhimurium, and Pasteurella multocida. In one outbreak, use was also made of a polyvalent serovaccine and hyperimmune serum against E coli, S typhimurium, and S dublin. In both outbreaks no new cases were reported in the affected groups after the administration of the second dose of vaccine, and there was no resurgence of disease on the affected farms within 18 months of the primary outbreaks.

Mobility after major limb amputation for arterial occlusive disease.

This study is concerned with the degree of mobility achieved by patients following major amputation for arterial occlusive disease of the legs and its relationship to the level of amputation. Eighty-four out of a possible 85 consecutive amputees form the basis of the study and the degree of mobility was assessed and graded in survivors six months after amputation. Of the 69 survivors 74% were mobile to some degree and 57% walked daily with a prosthesis. Sixty-five per cent of all the amputations were below-knee. Seventeen per cent of below-knee stumps in patients surviving two weeks failed to heal. In amputees who attained a unilateral mobile healed stump 78% with below-knee amputations and 50% with above-knee amputations walked daily with a prosthesis. To obtain maximum mobility the knee should be retained whenever practical even though this results in some unhealed stumps requiring revision.

Septicaemia, encephalitis and abortions in a housed flock of sheep caused by Listeria monocytogenes type 1/2.

One hundred and ninety-six housed pregnant ewes were fed poor quality silage for two days. Ewes are reluctant to eat the silage and within 48 hours they became dull and developed diarrhoea and lameness. Despite treatment with antibiotics and calcium borogluconate 19 ewes died, more than 60 developed vaginal discharges and at lambing 94 ewes were barren. Six developed nervous signs and two of these died, one with lesions typical of listeric encephalitis. Post mortem lesions and the isolation of Listeria monocytogenes type 1/2 from lung, liver, spleen and kidney are described. L monocytogenes was also isolated from blood samples from live ewes. The estimated gross financial loss to the farmer was 5130 pounds or, for the flock, 26 pounds per ewe.