Patient-initiated follow up affects fear of recurrence and healthcare use: a randomised trial in early-stage endometrial cancer.

OBJECTIVE: To test the hypothesis that patient-initiated follow up reduces the fear of cancer recurrence (FCR) and healthcare use when compared with traditional hospital-based follow up. DESIGN: Pragmatic, multicentre randomised trial. SETTING: Four Danish departments of gynaecology between May 2013 and May 2016. POPULATION: One hundred and fifty-six women diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I low-intermediate risk endometrial carcinoma. METHODS: Women allocated to the control group attended hospital-based follow up consisting of regular outpatient visits for 3 years after primary treatment. Women in the intervention group were instructed in patient-initiated follow up, which included careful instruction in alarm symptoms and options for self-referral rather than a schedule of examinations. MAIN OUTCOME MEASURES: The primary end point was FCR as measured by the Fear of Cancer Recurrence Inventory (FCRI) after 10 months of follow up. Secondary end points included cancer-related use of primary and secondary health care during the first 10 months after treatment. RESULTS: In the primary analysis, FCR decreased significantly more in the control group from baseline to 10 months of follow up (difference -5.9, 95% CI -10.9 to -0.9). The majority of this improvement happened after only 3 months of follow up. Women receiving the intervention had fewer examinations at the department compared with the control group (0 versus 2 median visits, P < 0.01) and 58% of these examinations were scheduled because of vaginal bleeding. CONCLUSIONS: Hospital-based follow up alleviates FCR significantly more than patient-initiated follow up, though the estimated difference was small. Patient-initiated follow up is a feasible, potentially cost-reducing follow-up approach in a population of endometrial cancer survivors with low risk of recurrence. The decision to use patient-initiated follow up should balance these benefits and harms. TWEETABLE ABSTRACT: Patient-initiated follow up reduces healthcare use but maintains fear of recurrence in endometrial cancer. PLAIN LANGUAGE SUMMARY: Why and how was the study carried out? Follow up of women with endometrial cancer is resource consuming and previous research suggests that it is not effective. Even though the women benefit from reassurance at follow up, routine examinations may also remind the women of the disease and induce fear of cancer recurrence. Furthermore, routine follow up may delay recurrence diagnosis, because the women do not report their symptoms until the next scheduled visit. In the research explained in this article, patient-initiated follow up was evaluated as an alternative to traditional follow up. The women were randomly assigned to one of two follow-up programmes: regular gynaecological examinations at the department of gynaecology or self-referral with careful instruction in alarm symptoms, that is, patient-initiated follow up. The level of fear of cancer recurrence in the two groups was obtained by questionnaires. Information on healthcare use was obtained by questionnaires and a chart review. What were the main findings? Regular examinations at the department of gynaecology reduced the fear of cancer recurrence significantly more than patient-initiated follow up, though the difference was small. Women who were instructed in alarm symptoms, under self-referral, were able to monitor their symptoms, and this approach significantly reduced the number of examinations at the department of gynaecology. What are the limitations of the work? Participants in the self-referral group knew that they were examined less than other women, and this may have induced fear of cancer recurrence. Similarly, the regular completion of questionnaires regarding fear of cancer recurrence may have reminded the women of the disease and diminished the difference between the two groups. What are the implications for patients Patient-initiated follow up reduced healthcare use but maintained fear of cancer recurrence in women who had survived early-stage endometrial cancer. Future analyses on quality of life and cost-effectiveness are needed to balance the benefits and harms of patient-initiated follow up.

The effect of an attachment-oriented couple intervention for breast cancer patients and partners in the early treatment phase: A randomised controlled trial.

OBJECTIVE: Patients and partners both cope individually and as a dyad with challenges related to a breast cancer diagnosis. The objective of this study was to evaluate the effect of a psychological attachment-oriented couple intervention for breast cancer patients and partners in the early treatment phase. METHODS: A randomised controlled trial including 198 recently diagnosed breast cancer patients and their partners. Couples were randomised to the Hand in Hand (HiH) intervention in addition to usual care or to usual care only. Self-report assessments were conducted for both patients and partners at baseline, postintervention (5 months), and follow-up (10 months), assessing cancer-related distress, symptoms of anxiety and depression, and dyadic adjustment. Patients' cancer-related distress was the primary outcome. RESULTS: Cancer-related distress decreased over time in both patients and partners, but the intervention did not significantly affect this decrease at postintervention (P = .08) or follow-up (P = .71). A significant positive effect was found on dyadic adjustment at follow-up for both patients (P = .04) and partners (P = .02). CONCLUSIONS: There was no significant effect of the HiH intervention cancer-related distress. The results suggest that most couples can cope with cancer-related distress in the context of usual care. However, the positive effect on dyadic adjustment implies that the HiH intervention benefitted both patients and partners. Future studies should investigate how to integrate a couple focus in usual cancer care to improve dyadic coping in the early treatment phase.

Who are the cancer survivors? A nationwide study in Denmark, 1943-2010.

BACKGROUND: No nationwide studies on social position and prevalence of comorbidity among cancer survivors exist. METHODS: We performed a nationwide prevalence study defining persons diagnosed with cancer 1943-2010 and alive on the census date 1 January 2011 as cancer survivors. Comorbidity was compared by social position with the non-cancer population. RESULTS: Cancer survivors composed 4% of the Danish population. Somatic comorbidity was more likely among survivors (OR 1.59, 95% CI 1.57-1.60) and associated with higher age, male sex, short education, and living alone among survivors. CONCLUSIONS: Among cancer survivors, comorbidity is common and highly associated with social position.

Socio-economic status influences blood pressure control despite equal access to care.

OBJECTIVE: Denmark has a health care system with free and equal access to care irrespective of age and socio-economic status (SES). We conducted a cross-sectional study to investigate a possible association between SES and blood pressure (BP) control of hypertensive patients treated in general practice. METHODS: We enrolled 184 general practices and 5260 hypertensive patients. The general practitioners reported information about BP and diagnosis of diabetes. Information about education, income, antihypertensive drug treatment and other co-morbidity was retrieved from relevant registers from Statistics Denmark. The outcome measure was BP control defined as BP <140/90 mmHg in general and <130/80 mmHg in diabetics. RESULTS: Patients <65 years and with an educational level of 10-12 years had increased odds ratio (OR) of BP control compared to patients with an educational level <10 years. Patients ≥65 years had increased OR of BP control if they were married/cohabiting as compared to being single, whereas education and income had no impact in this age group. Diabetics had significantly reduced odds of BP control irrespective of age, educational or income level. CONCLUSIONS: Despite equal access to care for all patients, SES had significant impact on BP control in this survey. Diabetes and cardiovascular disease also had a substantial influence irrespective of age, educational and income level.

Treatment of 5413 hypertensive patients: a cross-sectional study.

BACKGROUND: Most hypertensive patients are managed in primary care in Denmark, but previous studies have shown that only 21-43% of hypertensive patients achieve optimal blood pressure (BP) control. Antihypertensive drug treatment, risk factors and cardiovascular disease (CVD) are some of the important factors to consider when optimizing the individual treatment strategy in hypertensive patients. OBJECTIVE: To examine treatment of BP according to Danish guidelines (BP < 140/90 mmHg generally and <130/80 mmHg for diabetics) in a population from general practice in relation to risk factors, CVD and diagnosis of diabetes. METHODS: A cross-sectional study comprising 184 practices and 5413 hypertensive patients was carried out in Denmark. The general practitioners filled in information on each patient's risk factors, CVD and antihypertensive drug treatment. Patients filled in a questionnaire on risk factors. The outcome measures were optimal BP control according to Danish guidelines and antihypertensive drug treatment. RESULTS: Mean patient age was 65.9 years [95% confidence interval (CI): 65.6-66.1]. Optimal BP control was achieved in 29.1% (95% CI: 27.9-30.3) of the study population. Among 842 diabetics with or without CVD, optimal BP control was achieved in 10.9% (95% CI: 8.8-10.3), while 38.7% (35.5-41.9) of patients with CVD achieved optimal BP control. The majority of all patients were treated with 1 (32.5%, 95% CI: 32.5 (31.3-33.8)) or two antihypertensive drugs (39.0%, 95% CI: 38.2-40.8). In hypertensive diabetics, 17.7% were not treated with an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. CONCLUSION: In general practice, the proportion of hypertensive patients achieving optimal BP control is inadequate. The majority of hypertensive patients are treated with only one or two antihypertensive drugs.

Frequency of opioid use in a population of cancer patients during the trajectory of the disease.

AIMS: Bearing in mind that Denmark has one of the world's highest legal uses of strong opioids per capita, the aim of the present study was to describe the frequency of opioid use in a complete, population-based cohort of cancer patients at different time points during the trajectory of the disease, and to analyse the influence of different factors on opioid use close to death. MATERIALS AND METHODS: All incident cancer patients registered in 1997-1998 (n=4006) from a population of 470,000 were followed individually from diagnosis to death (non-survivors) or for 5 years (survivors). The use of opioids was obtained from a prescription database covering the whole population. RESULTS: Among the 43% cancer patients who survived for 5 years, 12% used opioids at diagnosis, 38% during follow-up and 10% after 5 years. For the non-survivors, 80% used opioids sometime during follow-up. At diagnosis, use related inversely to the cancer type's 5-year survival, and ranged from 20 to 46%; before death 64-76% used opioids. The odds ratios for opioid use at death were smaller for breast cancer (0.53; confidence interval 0.33-0.85), haemopoietic cancer (0.28; confidence interval 0.17-0.44) and the group of miscellaneous cancers (0.54; confidence interval 0.36-0.83) compared with colorectal cancer. Older age, longer disease duration and male gender (0.76; confidence interval 0.59-0.99) reduced the odds of opioid use at death. CONCLUSIONS: Judged by the use of opioids, moderate to severe pain is frequent throughout the trajectory of the cancer disease. The frequency of opioid use was in accordance with the frequency of moderate to severe cancer-related pain described in published studies. This completely population-based data set enables analyses of the actual practice regarding cancer patients' use of opioids, and it can serve as a more effective template for the management of cancer pain than the traditional measures, such as opioid consumption per capita, for international comparisons.

Socio-economic inequalities in first-time use of antidepressants: a population-based study.

OBJECTIVE: To analyse whether first-time use of antidepressants (incidence) and selection of TCAs (tricyclic antidepressants) versus new-generation drugs are associated with socio-economic status and psychiatric history. METHOD: We conducted a population-based cohort study using registry data covering Funen County, Denmark. A total of 305,953 adult residents without antidepressant prescriptions 5 years prior to the study period (1998) were included. RESULTS: The 1-year incidence rate of antidepressant prescription (1.7%) increased with age. It was higher in people who were female, less educated, unemployed, those receiving old-age or disability pension, low-income groups, and singles. The proportion prescribed new-generation antidepressants (82%) showed no difference according to socio-economic variables (education, annual income and socio-economic group), but was higher among the young and single. Admission to psychiatric hospital within 4 years prior to the study period was associated with high-incidence rate of antidepressant prescription and overall a preference for the new-generation antidepressants. CONCLUSION: Socio-economic status did not seem to influence the selection of TCAs versus new-generation antidepressants. Compatible with the general epidemiology of depression, low socio-economic status was associated with a high number of first-time users of antidepressants in the population, and the incidence rate increased with age.

[General practitioners want continuing education. Audit registrations among 369 physicians in Copenhagen]. / Praktiserende laeger ønsker efteruddannelse. Auditregistrering blandt 369 laeger i København.

The purpose of the study was to evaluate general practitioners' (GPs') interest in CME. A medical audit comprising 369 GPs in three counties was conducted in 1996. During 28,550 consultations the participating GPs recorded clinical subject, handling of the consultation, problems in the consultation and perceived need for training in relation to the consultation. The interest in CME varied from GP to GP and from one clinical subject to another. Desire for CME was expressed in relation to 16% of the consultations, most frequently in relation to psychiatry, community medicine and musculoskeletal diseases. Theoretical courses were the learning style most often preferred, especially for subjects requiring biomedical knowledge. Newer educational methods were also listed. Organisers of CME for general practitioners should be aware of the wide range of needs and wishes for CME among general practitioners.

Dapsone intoxication: two case reports.

Two patients with dapsone intoxication, an adult and a 16-month-old child, are reported. Both developed symptomatic methemoglobin concentrations, of 35% and 37%, respectively, and improved with intravenous methylene blue. Methemoglobin levels subsequently rose in both cases to 25% at 24 and 37 hours, respectively. The recurrence of elevated methemoglobin levels resulted from either continued absorption of dapsone or its toxic metabolite from the gastrointestinal tract. Both patients were begun on serial oral activated charcoal and the child received a second methylene blue treatment. During the intoxication, serum hemoglobin concentrations dropped 2 gm with an increase in the reticulocyte count. Review of 20 cases of dapsone overdose from the literature showed that the major toxic manifestations are methemoglobinemia and hemolysis. Delayed sulfhemoglobinemia, reported in only one case, resolved spontaneously. The treatment of dapsone intoxication is intravenous methylene blue for symptomatic methemoglobinemia, gastric decontamination, and early administration of serial oral activated charcoal. Hemolysis is mild but transfusions may be required for patients with a glucose-6-phosphate dehydrogenase deficiency.

Aspirin can inhibit gastric mucosal cyclo-oxygenase without causing lesions in rat.

Dose-response relationships between aspirin-induced cyclo-oxygenase inhibition and gastric mucosal injury were studied in rats. Oral or parenteral aspirin, 25 mg/kg, inhibited prostaglandin generation by 87%-95% at 1, 3, and 6 h with no lesion formation. Aspirin, 100 mg/kg, inhibited prostaglandin generation by 95%-98% at 1, 3, and 6 h, but lesions were observed only when aspirin was given orally. Three-hour pretreatment with intraperitoneal aspirin, 12.5 mg/kg, did not enhance the mucosal injury caused by 10 mM acidified taurocholate, although prostaglandin generation was inhibited by 80%. Pretreatment with 25 mg/kg aspirin inhibited prostaglandin generation by 89% and was associated with significant mucosal injury by acidified taurocholate. We conclude that aspirin-induced 95% inhibition of gastric mucosal cyclo-oxygenase is not, by itself, sufficient to produce lesions and inhibition by greater than 80% is required to predispose the gastric mucosa to injury by otherwise mild irritants.

Salicylic acid blocks indomethacin- and aspirin-induced cyclo-oxygenase inhibition in rat gastric mucosa.

Salicylic acid reduces gastric mucosal lesions induced by aspirin and indomethacin. Aspirin and indomethacin reduce gastric mucosal cyclo-oxygenase activity. These studies were designed to determine whether or not salicylic acid interacts with gastric mucosal cyclo-oxygenase, decreasing the inhibitory effect of aspirin and indomethacin as has been observed in platelets and vascular tissue. The interaction between salicylic acid and two cyclo-oxygenase inhibitors, indomethacin and aspirin, was assessed on ex vivo prostaglandin generation in the rat gastric mucosa. Salicylic acid (100 mg/kg) was administered orally 30 min before the subcutaneous injection of either indomethacin (0.5-10 mg/kg) or aspirin (5.0-20 mg/kg). Pretreatment produced a shift of the mean 50% inhibitory dose for PGF2 alpha formation from 0.92 to 7.6 mg/kg for indomethacin and from 7.8 to 20 mg/kg for aspirin. Similar results were achieved with ex vivo prostacyclin synthesis as measured by the level of 6-keto-PGF 1 alpha. These data are consistent with competitive enzyme kinetics, and may, in part, explain the protective effect of salicylic acid against the ulcerogenicity of aspirin and indomethacin on the gastric mucosa.

Comparison of human urine gastric inhibitor (HUGI) and bacterial endotoxin as inhibitors of acid secretion.

In conscious cats with gastric fistulas, 10 micrograms . kg-1 of human urinary gastric inhibitor (HUGI) given as an intravenous bolus injection increased mean rectal temperature 1.4 degree C and inhibited mean gastrin-stimulated acid secretion by 64%. The sample of HUGI contained an amount of beta-hydroxymyristic acid corresponding to a 5% contamination of the HUGI with bacterial endotoxin. Injection of bacterial endotoxin in an amount corresponding to the beta-hydroxymyritic acid content of HUGI mimicked, both in magnitude and time course, the increase in body temperature and the inhibition of acid secretion produced by HUGI. We conclude that inhibition of acid secretion by HUGI may be due to the presence of an endotoxin-like contaminant.

Histamine augments gastric ulceration produced by intravenous aspirin in cats.

In unanesthetized cats, continuous intravenous infusion of aspirin for 36 hr did not produce gastric ulcers when given alone but did when combined with 160 microgram kg-1 hr-1 of histamine-2HCl intravenously. The ulcers were mainly antral in location. The incidence and severity of ulcers increased with duration of the infusion up to 36 hr and with dose of aspirin up to 4 mg kg-1 hr-1. With the highest doses and longest durations some of the antral ulcers perforated. Antral ulcers occurred in more than half of the cats getting 0.25 mg kg-1 hr-1 or more of aspirin for 36 hr or getting 4 mg kg-1 hr-1 of aspirin for 6 or more hr. Intravenous aspirin plus intragastric infusion of 40 ml hr-1 of 150 mM HCl for 16 hr also produced gastric ulcers. Plasma salicylate concentrations were less than 350 microgram ml-1 with all doses and durations of aspirin used (400 microgram ml-1 is regarded as the upper limit of the therapeutic range in man). These studies show that when the stomach is acidified by giving histamine intravenously or HCl intragastrically, intravenous aspirin produces large deep gastric ulcers. The mechanism of the ulcerogenic action of intravenous aspirin is not known.