Do physical activity level and body mass index predict recovery from persistent neck pain in men and women of working age? A population-based cohort study.

PURPOSE: The study sought to examine the gender-specific effects of physical activity level and body mass index on recovery from persistent neck pain (PNP) among citizens of working age in Stockholm, Sweden. METHODS: A population-based cohort of 1,730 subjects (18-65) with PNP answered surveys in 2002 and 2007. Prognostic factors were self-reported body mass index (BMI) and physical activity level (PAL) at baseline. Analyses were performed with odds ratios (OR) with corresponding 95 % confidence intervals (95 % CI). RESULTS: Women reporting higher physical activity level had higher odds of recovering from PNP than women with sedentary leisure time (OR of 1.5, 95 % CI 1.0-2.4), but no associations were found in men. No associations were found between BMI and recovery from PNP in any analyses. CONCLUSION: Physical activity seems to be associated with recovery from PNP in women and should therefore be encouraged. Future studies should continue investigating physical activity and lifestyle factors in relation to recovery from persistent neck pain, since these modifiable factors may be considered in interventions.

Use of antidepressant agents and the risk of type 2 diabetes.

PURPOSE: To determine whether there is an association between antidepressant use and the risk of developing type 2 diabetes. METHODS: This study was a retrospective cohort analysis using the Texas Medicaid prescription claims database. Data were extracted for new users of either antidepressant agents (exposed) or benzodiazepines (unexposed) from January 1, 2002 through December 31, 2009. Patients aged 18-64 years without a prior history of diabetes were included. Cox proportional hazards regression was used to examine the association between diabetes incidence among exposed and unexposed groups, while controlling for demographic and clinical covariates. RESULTS: Among the total study population (N = 44,715), the majority were in the exposed (N = 35,552) versus the unexposed (N = 9,163) group. A total of 2,943 patients (6.6%) developed type 2 diabetes during the follow-up period. Antidepressant use was associated with an increase in the risk of diabetes when compared to benzodiazepine use (adjusted hazard ratio [HR] 1.558, 95% confidence interval [CI] 1.401-1.734). The association was observed with tricyclic antidepressants (TCAs; HR 1.759, 95% CI 1.517-2.040), serotonin-norepinephrine reuptake inhibitors (SNRIs; HR 1.566. 95% CI 1.351-1.816), selective serotonin reuptake inhibitors (SSRIs; HR 1.481, 95% CI 1.318-1.665), and "other" antidepressants (HR 1.376; 95% CI 1.198-1.581). CONCLUSIONS: The results of this study suggest that antidepressant use is associated with an increased risk of diabetes. This association was observed with use of TCAs, SNRIs, SSRIs, and "other" antidepressants.

Use of antihypertensive medications among United States veterans newly diagnosed with hypertension.

OBJECTIVES: Most patients with hypertension need combination therapy to reach adequate blood pressure control. The objective of this study was to assess type, duration of, and adherence to antihypertensive therapies among veterans, focusing on the use of combination therapies. RESEARCH DESIGN AND METHODS: The design of the study was a retrospective cohort analysis of electronic medical and pharmacy records from the Central Texas Veterans Health Care System (CTVHCS). Data were extracted for adults newly identified with hypertension between 1995 and 2003. Drug utilization was measured as a time-dependent variable; thus, the use of combination therapies was captured for any given day for each patient in the sample. Medication adherence was assessed using medication possession ratios (MPR), calculated by the number of days of therapy dispensed to a patient divided by the number of days between subsequent prescriptions. RESULTS: The average age of the participants (n = 11 187) was 60.7 (standard deviation (SD): 12.7). Half (50.1%) of the patients could be categorized as having controlled blood pressure. Veterans were followed for an average of 3.6 years (total of 51 549 person-years). Overall, 29 561 treatment episodes were identified, an average of about 2.6 per patient. Over 40% (41.6%) of these episodes involved one medication only, but patients frequently used dual (26.9%) and three or more (15.9%) therapies in combination. The frequency of prescribed antihypertensive therapies, as well as the length of, and adherence to, these therapies were described. Descriptively, medication adherence appeared to be lower among patients who received therapy for longer duration, indicating higher probability of missed doses and more frequent therapy changes. CONCLUSIONS: New information can be gained on the utilization of antihypertensive medications by using time-dependent variables. Understanding the type of combination therapies, the length of and adherence to these therapies, along with the observed blood pressure control rates will provide important new insights into the management of hypertensive patients. Limitations of the study arise primarily from the use of electronic medical records and the information that is contained within the datasource, and generalizability of the findings beyond the study sample.

Sequential administration of dacarbazine and fotemustine in patients with disseminated malignant melanoma--an effective combination with unexpected toxicity.

Resistance to alkylating agents is partly due to the presence of the DNA repair enzyme, termed O6 alkyltransferase (O6AT). Preclinical evidence of the transient restoration of sensitivity of cells resistant to nitrosoureas by pretreatment with a methylating agent, whose role is to deplete cells of O6AT activity and clinical evidence of such a depletion in patients lymphocytes, led us to test the sequential administration of dacarbazine 3 h prior to fotemustine, a chloroethylnitrosourea derivative. 24 patients with measurable advanced melanoma entered the trial and are evaluable. Toxicity was mainly haematological with early neutropenia and/or thrombocytopenia. Clinical activity (33%) was impressive especially on lung metastases with high complete response rate for that site (7/14). Unfortunately, the occurrence of a rapidly fatal pulmonary toxicity precludes further use of the regimen before a plausible explanation for this unexpected toxicity is obtained. Indeed, similar cases have been reported in other trials using the sequential schedule while no lung toxicity was reported in single agent or alternated administrations. Preclinical studies are ongoing to test the hypothesis of a glutathione depletion and the possibility of a rescue treatment.

Nocturnal gastric secretion following treatment with trimipramine (Surmontil).

The study was conducted double blind in 12 healthy volunteers, average age 30 years (23-48). On separate days they were allocated at random to either two tablets of Trimipramine, 25 mg each, or two tablets of Placebo, one and a half hours before introduction of a Levine tube into the stomach. The volunteers had on the day of starting the experiment performed their normal duties, and consumed the last meal, the dinner, at 5 pm. The gastric juice was collected continuously in half hour samples from 11 pm until 7 am the next morning. The average recovery was 87% in 4 tested experiments. The volume of gastric juice was 448 ml/8 h for the series receiving Placebo compared to 418 ml/8 h for those treated with Trimipramine (Table 1). During the first half hour a relative high volume was aspirated, whereas in the following 3 half hours portions the volume decreased to a fairly stable level of about 15-23 ml. A significant lower volume was observed in the Trimipramine treated series in some of the morning portions. A significant lower concentration and output of HCl was found during the middle of the night and in some morning portions in the subjects given Trimipramine. Similarly the concentration and output of pepsin were lower in the Trimipramine series than in the Placebo treated subjects.

Normal and disturbed motility pattern in the duodenum of man. The effect of l-hyoscyamine, trimipramine and ranitidine on the maximal pressure waves.

Eight healthy subjects were examined in random order with an electronic capsule transducer, two capsules being mounted 8 cm from each other in the duodenum. At least two grade III maximal pressure waves were recorded following 0.6 mg l-hyoscyamine (Hässle), 50 mg trimipramine (Surmontil, Rhone Poulenc) or 150 mg ranitidine (Glaxo-Nyegaard & Co.) perorally. A significant prolonged cyclic length (Fig. 1) was observed on the day when l-hyoscyamine was given when compared to results on the day when placebo was given (Table I). No significant differences were observed between placebo and the other drugs given.

Serum concentration of pancreatic polypeptide after infusion of histamine and the effect of cimetidine, trimipramine, and atropine in man.

Histamine was given intravenously to eight human subjects, and the PP concentration in serum increased significantly from 14.8 (7.2-29.3) pM to 27.5 (9.6-39.3) pM and then decreased to the basal level. This histamine-induced PP release was not altered when trimipramine or cimetidine was given in addition to histamine. This PP release could not mediated through histamine-receptor mechanisms, and since atropine prevented this PP release, we conclude that the release of PP after histamine reflects a cholinergic stimulus.

Inhibition of the histamine-stimulated gastric secretion in healthy subjects by the H2-receptor antagonist ranitidine.

The gastric secretion was examined for 30 min before and 120 min during intravenous infusion of 3 microgram/kg/h of histamine dihydrochloride. In eight subjects physiological saline solution was given as infusion in addition to histamine (controls), whereas nine subjects received ranitidine in doses increased every half hour--0.06, 0.12, 0.24, and 0.48 mg/kg/h. The infusion of ranitidine resulted in a significant reduction of volume of gastric juice both when compared with the unstimulated periods before histamine and with those of subjects receiving the saline solution. Similarly, the acid output was reduced still more significantly during infusion of ranitidine, the output being about zero in the last hour. The ranitidine dose used was about five time lower than that previously used of cimetidine. No side effects were observed.

The effect of trimipramine, cimetidine and atropine on gastric secretion.

A comparison was made of increasing doses of trimipramine (0.05-0.40 mg/kg/h), atropine (7-28 microgram/kg/h) and cimetidine (0.30-2.40 mg/kg/h) on the gastric secretion stimulated by 3 microgram/kg/h of histamine dihydrochloride as continuous infusion, each dose step lasting 30 minutes. In 9 healthy subjects it was found that trimipramine had no significant effect on the output of acid. The largest dose of atropine caused a reduction by 77%, and cimetidine a reduction of 89% during the last 15 minutes portions. The study suggests that the healing of peptic ulcer by trimipramine is not linked to the effect on the histamine-stimulated gastric acid secretion.

The effect of trimipramine, cimetidine, and atropine on gastric secretion.

In the present study a comparison was made of the effect of increasing doses of trimipramine (0.05, 0.10, 0.20, 0.40 mg/kg/h), atropine (7, 14, 21, 28 microgram/kg/h), and cimetidine (0.3, 0.6, 1.2, 2.4 mg/kg/h) on the gastric secretion stimulated by 3 microgram/kg/h of histamine dihydrochloride as continuous infusion, each dose step lasting 30 min. In nine healthy individuals it was found that trimipramine had a stimulating effect on the volume and output of acid during one of eight 15-min periods. The largest dose of atropine caused a reduction of the volume and acid output by 68% and 77%, respectively, whereas cimetidine reduced the volume by 74% and the acid output by 89% during the last five 15-min periods, thus having the most pronounced effect. The study may suggest that the healing effect of trimipramine on peptid ulcer is not linked to the effect on submaximal histamine-stimulated secretion and that a different mechanism of action is probably present for the effect of trimipramine, compared with atropine and cimetidine, on the gastric secretion.

Serum concentration of trimipramine (Surmontil) and gastric secretion of acid and pepsin following peroral administration of the drug in healthy humans.

Previous blind studies have shown an increased rate of healing of both duodenal and gastric ulcers following 4 weeks peroral administration of 50 mg trimipramine. The present study shows the effect of 50 mg trimipramine perorally on gastric secretion in relation to that of 25 mg of the drug and placebo. At regular intervals blood specimens were obtained for determination of the serum concentration of trimipramine. In 9 healthy young students it was found that the estimated stabilized values of volume and acid output following 50 mg trimipramine, 33 ml and 3.9 mmol/15 min, respectively, were significantly lower than those following the smallest dose, 37 ml and 4.6 mmol/15 min, respectively. On the other hand, no significant changes of gastric secretion were observed following the peroral administration of 25 mg trimipramine when compared to placebo. Following 50 mg trimipramine the output of pepsin was reduced by about 25%. The values of serum concentration of trimipramine were about 200 nmol/1 at 100 min after administration of 50 mg trimipramine and decreased gradually, whereas the values following the smaller dose were about half of those after the larger one. The results indicate that about 50 mg trimipramine is needed for obtaining a reduction of gastric secretions. Future studies may show whether 25 mg trimipramine, which does not suppress acid secretion when given perorally, is able to promote peptic ulcer healing.