Long-term opioid therapy in Denmark: A disappointing journey.

BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long-term opioid users. METHODS: Data were obtained from the national representative Danish Health and Morbidity Surveys and The Danish National Prescription Registry. Respondents with no dispensed opioids the year before the survey were followed from 2000 and from 2005 until the end of 2012 (n = 12,145). A nationally representative subsample of individuals (n = 2015) completed the self-administered questionnaire in both 2000 and 2013. Collected information included chronic pain (≥6 months), health behaviour, self-rated health, pain interference with work activities and physical activities. Long-term users were defined as those who were dispensed at least one opioid prescription in six separate months within a year. RESULTS: The incidence of L-TOT was substantially higher in CNCP patients at baseline than in others (9/1000 vs. 2/1000 person-years). Smoking behaviour and dispensed benzodiazepines were significantly associated with initiation of L-TOT in individuals with CNCP at baseline. During follow-up, L-TOT in CNCP patients increased the likelihood of negative changes in pain interference with work (OR 9.2; 95% CI 1.9-43.6) and in moderate activities (OR 3.7; 95% CI 1.1-12.6). The analysis of all individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long-term opioid therapy does not seem to provide pain relief, improvement in HRQOL and physical capacity in CNCP patients in a general population.

Chronic non-cancer pain and the epidemic prescription of opioids in the Danish population: trends from 2000 to 2013.

BACKGROUND: Chronic pain has serious consequences for individuals and society. In addition, opioid prescription for chronic non-cancer pain (CNCP) has become more frequent. This study aims to examine the trends regarding the prevalence of CNCP, dispensed opioids, and concurrent use of benzodiazepine (BZD)/BZD-related drugs in the Danish population. METHODS: Data from the cross-sectional national representative Danish Health and Morbidity Surveys (2000, 2005, 2010, and 2013) were combined with The Danish National Prescription Registry at an individual level. The study populations varied between 5000 and 13,000 individuals ≥16 years (response rates: 51-63%). Respondents completed a self-administered questionnaire, which included the analyzed items on identification of chronic pain (≥6 months). RESULTS: From 2000 to 2013, the prevalence of CNCP increased and subsequently the annual prevalence of opioid use from 4.1% to 5.7% among CNCP individuals. Higher CNCP prevalence was related to female gender, no cohabitation partner, short education, non-Western origin, and overweight/obesity. In addition, women with CNCP, especially >65 years, became more frequent users of opioids and used higher doses than men. Concurrent use of BZD/BZD-related drugs decreased (13%) from 2010 to 2013, still one-third of long-term opioid user were co-medicated with these drugs. CONCLUSIONS: The use of opioids has increased in Denmark, especially among elderly women. The concurrent use of BZD/BZD-related drugs has decreased from 2010 to 2013, but still one-third of long-term opioid users were co-medicated.

Benefits and harms of cervical screening from age 20 years compared with screening from age 25 years.

BACKGROUND: To quantify the benefits (cancer prevention and down-staging) and harms (recall and excess treatment) of cervical screening starting from age 20 years rather than from age 25 years. METHODS: We use routine screening and cancer incidence statistics from Wales (for screening from age 20 years) and England (screening from 25 years), and unpublished data from the National Audit of Invasive Cervical Cancer to estimate the number of: screening tests, women with abnormal results, referrals to colposcopy, women treated, and diagnoses of micro-invasive (stage 1A) and frank-invasive (stage IB+) cervical cancers (under three different scenarios) in women invited for screening from age 20 years and from 25 years. RESULTS: Inviting 100,000 women from age 20 years yields an additional: 119,000 screens, 20,000 non-negative results, 8000 colposcopy referrals, and an extra 3000 women treated when compared with inviting from age 25 years. Screening from age 20 years prevents between three and nine frank invasive cancers and between 0 and 23 cancers in total (depending on the scenario). A cumulative increase of nine stage IB+ cancers corresponds to an annual rate increase of 0.9 per 100,000 women aged 20-29 years. CONCLUSIONS: To prevent one frank invasive cancer, one would need to do between 12,500 and 40,000 additional screening tests in the age group 20-24 years and treat between 300 and 900 women.

A randomised trial of weekend and evening breast screening appointments.

BACKGROUND: There is a need to research interventions that improve access to and convenience of breast cancer screening services. METHODS: We conducted a randomised trial comparing invitations to out-of-hours appointments with standard office hour appointments. Women who were to be invited for routine breast screening were randomised (3 : 1 : 1 : 1) to one of these screening invitations: standard office hour appointment, office hour appointment with the option to change to an out-of-hours appointment, weekday evening appointment, or weekend appointment. RESULTS: A total of 9410 women were invited to an office hour, 3519 to an office hour with the option to change, 3271 to a weekday evening, and 3162 to a weekend appointment. The offer of an initial out-of-hours appointment was associated with a non-significant decrease in attendance rates (73.7% vs 74.1%). The highest attendance was observed in the group offered an initial office hour appointment with the option to change to out-of-hours (76.1% vs 73.3% for standard office hour, P=0.001), with 7% of invitees exercising the option to change. CONCLUSION: The optimum strategy for improving attendance at breast screening is to offer a traditional office hour appointment and including in the letter of invitation an option to change to an evening or weekend appointment if wished.

[The content of ascorbic acid in tissues of swine fetuses and newborn piglets and in the blood plasma and tissue of swine of different ages with regard to the effect of the restriction of suckling time]. / Der Gehalt an Ascorbinsäure in Geweben von Schweinefeten und von neugeborenen Ferkeln sowie der im Blutplasma und in Geweben von Schweinen unterschiedlichen Alters, unter Berücksichtigung des Einflusses der Beschränkung der Säugezeit.

In 55, 75, 95 and 110 days old pig-fetuses as well as in newborn piglets the weight of different tissues and their content of ascorbic acid were analysed. The time for suckling of the piglets of 2 sows was restricted to 12 hours per day (= group A); the piglets of 2 sows were used as a control (= group B). The restriction of the milk intake did not influence the content of the blood plasma and of the tissues in ascorbic acid. After weaning the pigs of group A had a compensatory growth and on the 214th day after birth the same slaughter mass as that of the group B. There was no difference in the content of ascorbic acid of the tissues of the 2 groups of pigs. The significance of changes in the content of ascorbic acid in the tissues during the fetal and the postnatal growth is described.

Trophic effects of different enteral diets in the rat intestine.

The trophic effect of 4 commercial diets compared to chow was studied in 50 rats. The 4 commercial diets were: a free amino acid diet, a diet based on soy protein hydrolysate and two diets based on intact protein with and without extra fibre added. Bowel weight, mucosa weight and DNA content were measured after 7 days of treatment. The enteral formula based on a soy protein hydrolysate had a significant growth stimulating effect on the proximal small bowel compared to rat chow. In the ileum and in the colon all diets without fibre supplementation caused significantly lower bowel weights than rat chow.

Microcirculatory and trophic effects of short chain fatty acids in the human rectum after Hartmann's procedure.

Short chain fatty acids (acetic, propionic and butyric) were instilled into the rectum of patients who had undergone Hartmann's procedure. The following parameters were examined before and after a 2-week treatment period with short chain fatty acids (100 ml twice daily at a total concentration of 150 mM): (1) microcirculatory effects in vivo using a laser Doppler flow technique, and (2) morphometrical changes in mucosal biopsies. The following parameters were significantly increased in all patients after treatment: (1) mucosal blood flow, (2) the fractional crypt cell epithelium plus surface epithelium volume in relation to total tissue volume down to the muscularis mucosa, (3) nuclear volume in the crypt and the surface epithelium, and (4) the fractional nuclear volume to total cell volume in the crypt and the surface epithelium. These data suggest that short chain fatty acids in the human colon have trophic and vasodilatory effects.

Treatment of ureteric colic. Intravenous versus rectal administration of indomethacin.

A randomised multicentre clinical trial was undertaken to compare the effect on pain of indomethacin administered either intravenously or rectally to 116 patients with ureteric colic. Adverse reactions were also assessed. Of the patients receiving the intravenous injection, 48/53 (91%) achieved good pain relief (i.e. no supplementary analgesia was required) 30 min after administration, compared with 46/63 (73%) receiving the enema. Significantly more side effects occurred in the group treated intravenously. It was concluded that indomethacin administered as an enema was less effective than the intravenous form, but it should be regarded as a good alternative in the treatment of ureteric colic.

Fixation of displaced femoral neck fractures. A comparison between sliding screw plate and four cancellous bone screws.

In a prospective, randomized trial, 104 consecutive patients with displaced femoral neck fractures were allocated either to fixation with a sliding screw plate or 4 ASIF cancellous bone screws. The patients were reexamined at fixed intervals to determine the time of union. The 2-year-cumulated rate of union was 64 per cent in the plate group and 84 per cent in the screw group.