Trends in intentional and unintentional poisonings among older adults - A national register-based study in Sweden.

BACKGROUND: Among older people intentional poisoning outnumber unintentional ones. While there are indications that time trends differ by poisoning intent, studies are scarce. We assessed how the annual prevalence of intentional and unintentional poisoning changed over time, overall and by demographic groups. METHODS: We conducted a national open cohort study of individuals aged 50-100 years, resident in Sweden during 2005-2016. Individuals were followed up in population-based registers for their demographic and health attributes from 2006-2016. Annual prevalence of hospitalization and death by poisoning intent (unintentional vs. intentional or undetermined; ICD-10 definitions) were compiled for the categories of four demographic attributes (age, sex, marital status, and birth cohort "baby boomers"). The time trends were assessed by multinomial logistic regression with year as an independent variable. RESULTS: The annual overall prevalence of hospitalization and death by intentional poisonings consistently exceeded that of unintentional poisonings. There was a significant downward trend in intentional poisonings but not in unintentional ones. This difference in trends also applied when considering men and women separately, married and unmarried people, the young-old individuals (but not the older- or oldest-old ones), and the baby boomers and non-baby boomers. The largest demographic differences within intent were found between married and unmarried people, and the smallest one between men and women. CONCLUSION: As expected, the annual prevalence of intentional poisonings considerably exceed that of unintentional ones among Swedish older people. The recent trends reveal a significant reduction of intentional poisonings, consistent across a range of demographic attributes. The scope for action regarding this preventable cause of mortality and morbidity remains considerable.

Snus (Swedish smokeless tobacco) use and risk of stroke: pooled analyses of incidence and survival.

BACKGROUND: Snus is a moist smokeless tobacco product with high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear. OBJECTIVE: The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes. METHODS: Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130 485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively. RESULTS: No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) amongst users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61). CONCLUSION: Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared with nonusers, but further studies are needed to determine any possible causal mechanisms.

School performance and the risk of suicide attempts in young adults: a longitudinal population-based study.

BACKGROUND: Poor school performance is strongly associated with attempted suicide, but the mechanisms underlying this association are uncertain. We examined this relationship and the extent to which it is explained by (i) adult health behaviours and (ii) social conditions. Furthermore, we examined the potential modifying role of previous suicidal thoughts in the relationship. METHOD: We conducted a longitudinal cohort study of 6146 individuals aged 18-33 years, recruited in 2002 and 2006 in Stockholm and resurveyed in 2007 and 2010 respectively. We estimated the risk of reported lifetime suicide attempts at follow-up among individuals without a history of suicide attempts at baseline and in relation to compulsory school-leaving grades, controlling for possible confounders and mediators. RESULTS: There were 91 cases of self-reported suicide attempts during the follow-up (5-year incidence of 1.5%). ORs ranged from 3.35 [95% confidence interval (CI) 1.88-5.96] for those in the lowest grade quartile to 2.60 (95% CI 1.48-4.57) and 1.76 (95% CI 0.99-3.13) for those in the second and third quartiles respectively. The relationship between school performance and risk of suicide attempts did not differ by sex. Adult health behaviours and social conditions marginally attenuated, but did not explain, the relationship. The gradient varied with baseline history of suicidal thoughts, and was found only among individuals without such a history. CONCLUSIONS: Poor school performance was found to predict suicide attempts among young adults without a history of suicidal thoughts. Adult health behaviours and social conditions did not explain this relationship. Instead, other factors linked with poor school performance, such as poor coping ability, may increase the risk of suicide attempts.

Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn's disease: a randomised, double-blind, placebo-controlled, phase 2 study.

OBJECTIVE: Although treatment with corticosteroids induces remission in Crohn's disease, prolonged exposure to corticosteroids is undesirable. This randomised clinical trial evaluated the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (sargramostim), an activator of innate immunity, in corticosteroid-dependent patients with Crohn's disease. DESIGN: Patients were randomised in a 2:1 ratio, to sargramostim 6 microg/kg subcutaneously once daily or placebo for up to 22 weeks. The study consisted of (1) an adjunctive phase (weeks 1-4) in which patients received study drug plus corticosteroid therapy; (2) a forced corticosteroid tapering phase (weeks 4-14); and (3) an observation phase (4 weeks) in which patients received study drug plus prednisone < or =7.5 mg. The primary endpoint was corticosteroid-free remission (Crohn's Disease Activity Index (CDAI) < or =150) 4 weeks after corticosteroid elimination. Secondary endpoints were corticosteroid-free response (CDAI decreased by > or =100) and induction of remission in patients who reduced the dose of corticosteroid to 2.5-7.5 mg. RESULTS: Eighty-seven patients were randomised to sargramostim and 42 to placebo. Significantly more sargramostim-treated patients than placebo patients achieved corticosteroid-free remission (18.6% vs 4.9%; p = 0.03). Similar differences were seen for corticosteroid-free response and in patients who tapered corticosteroids to 2.5-7.5 mg/day. Sargramostim treatment was also associated with significant improvements in health-related quality of life. Patients who received sargramostim were more likely to experience musculoskeletal pain, injection site reactions and dyspnoea. CONCLUSIONS: Sargramostim was more effective than placebo for inducing corticosteroid-free remission in patients with Crohn's disease with corticosteroid dependence. Sargramostim may provide significant benefit in this population if these findings are confirmed.

Effect of dietary fiber on the induction of colorectal tumors and fecal beta-glucuronidase activity in the rat.

The purpose of the present study was to investigate whether three different types of dietary fiber, wheat bran, carrot fiber, and citrus pectin, influenced the induction of colorectal tumors produced by 1,2-dimethylhydrazine in rats. In all groups, the tumor yield was high (87 to 97%). In the wheat bran and carrot fiber groups, the incidence of colorectal tumors was not significantly different from that of the group fed on the fiber-free basic diet. The citrus pectin group, however, had a significantly higher incidence of colorectal tumors (p less than 0.001). An increased number of auditory duct tumors was also noted in this group. In a separate experiment, dietary pectin induced a 10-fold increase in fecal beta-glucuronidase activity but did not alter this activity in the bowel wall. It has been suggested that dietary fiber protects against the induction of colorectal tumors, but this was not the case in the experiment. It is possible that the high tumor yield made the demonstration of a weak protective effect of wheat bran impossible. The reason for the increased occurrence of tumors in the citrus pectin group is obscure and will be subjected to further investigation. Fecal beta-glucuronidase activity might be one factor of importance in the activation of the carcinogen.

Effect of two kinds of pectin and guar gum on 1,2-dimethylhydrazine initiation of colon tumors and on fecal beta-glucuronidase activity in the rat.

The effect of 5% low-methoxylated pectin, high-methoxylated pectin, and guar gum on 1,2-dimethylhydrazine initiation of colon cancer was investigated using groups of 30 rats. The growth of the rats in the different groups was very similar to that of control group fed a fiber-free diet. Both kinds of pectin increased the multiplicity of color tumors, whereas guar gum did not significantly influence carcinogenesis. Bacterial beta-glucuronidase activity in feces and colonic content was the same in pectin-fed rats and controls but significantly lower in the guar gum group. Thus, it was not related to the number of tumors in each group.

A three-part study to investigate the incidence and potential etiologies of tadalafil-associated back pain or myalgia.

The potential mechanisms underlying back pain and/or myalgia experienced by men taking tadalafil were investigated. An integrated analysis of 10 placebo-controlled tadalafil clinical trials (N=1846) showed that the incidence of back pain and/or myalgia was 9.4% in patients receiving tadalafil 10 mg (N=394), 8.3% in patients receiving tadalafil 20 mg (N=883) and 3.7% in placebo-treated patients (N=569). One (0.3%) patient receiving tadalafil 10 mg, six (0.7%) patients receiving tadalafil 20 mg, and no patients receiving placebo discontinued treatment due to back pain and/or myalgia. In a prospective study in healthy volunteers, no substantial changes were observed in laboratory markers indicative of inflammation or muscle damage, and tadalafil did not affect renal plasma flow nor produce lumbar or gluteal myositis by positron emission tomography scan or magnetic resonance imaging. Although the mechanism of back pain and/or myalgia remains unknown, these events appear to be self-limiting and a general effect of phosphodiesterase 5 inhibition.

Catamenial insulin reactions treated with a long-acting gonadotropin releasing hormone agonist.

Exacerbation of a variety of symptoms during the menstrual cycle is a well-described phenomenon. The exact causes of these changes are poorly understood, and no specific and efficacious therapy has been described. We successfully treated a patient with severe catamenial insulin reactions with a long-acting gonadotropin releasing hormone agonist to suppress menstrual function and added a combination of estrogen and progestin to offset any adverse effect of the resultant hypoestrogenemia for 1 year.

Insulin autoimmunity as a cause of hypoglycemia.

"Autoimmune" hypoglycemia is a syndrome consisting of fasting hypoglycemia, hyperinsulinemia, and insulin-binding antibodies in a patient who has never been exposed to exogenous insulin. The stimulus for insulin-antibody formation and the mechanism of the hypoglycemia in this condition remain unknown. Three patients with this rare syndrome had severe hypoglycemia of limited duration. Two had received a drug containing a sulfhydryl group (methimazole and penicillamine) as treatment for an autoimmune disorder (Graves' disease and rheumatoid arthritis, respectively). A third patient who underwent surgery for a suspected insulinoma was found to have pancreatic beta cell hyperplasia. Drugs containing a sulfhydryl group may have a role in the etiology of the syndrome. Additionally, our findings suggest a relationship between circulating insulin antibodies and beta cell hyperplasia.

Flocculation and loss of potency of human NPH insulin.

In late 1986, several vials of Humulin N (NPH human insulin, recombinant DNA origin) came to our attention because of a clumped, white coating on the inside of the vials. To determine the frequency of this phenomenon, we surveyed 100 consecutive patients who used Humulin N. Ten patients had encountered 21 vials of flocculated insulin in the previous 12 mo, reflecting an incidence of 1 per 72 vials. Insulin drawn from affected vials was markedly reduced in potency: 20.9 +/- 3.4 U/ml vs. the labeled potency of 100 U/ml. Several patients reporting flocculated insulin, including one hospitalized with ketoacidosis, experienced unusual and unexplained elevation in blood glucose concentration for several days before flocculation was observed. Patients who use NPH human insulin should be aware of this phenomenon and carefully inspect their vials for evidence of insulin precipitation before each injection.

Aldosterone production by isolated adrenal glomerulosa cells: stimulation by physiological concentrations of angiotensin II.

The production of aldosterone by isolated canine zona glomerulosa cells was measured after the incubation of cell suspensions with angiotensin II and ACTH, and during changes in extracellular potassium concentration. Adrenal cell suspensions were prepared by collagenase digestion and physical dispersion of the capsular layer of the dog adrenal cortex, and aldosterone production was determined by direct radioimmunoassay of cell incubation media. The isolated dog adrenal cells were highly responsive to angiotensin II, with aldosterone production significantly stimulated by concentrations of the octapeptide as low as 10(-11)M. Thus, the steroidogenic response of zona glomerulosa cells was consistently observed at peptide concentrations within the physiological range of angiotensin II in dog plasma, i.e., 2.0-5.0 X 5.0 X 10(-11)M. The maximum aldosterone response of 3-8 times the basal level of steroid production was induced by 3 X 10(-10)M angiotensin II, and a decrease in aldosterone production occurred at peptide concentrations above 10(-9)M. The aldosterone response of isolated adrenal cells to ACTH was consistently less sensitive than their response to angiotensin II, by a factor of 10-20 fold. Aldosterone production was significantly increased by 10(-10)M ACTH, and reached a maximum at 10(-8)M ACTH. By contrast with angiotensin II, ACTH usually evoked a higher maximal level of aldosterone production, and did not produce a decline in steroidogenesis at peptide concentrations above the level which caused maximum stimulation of aldosterone formation. Changes in the potassium concentration of cell incubation media were also accompanied by marked effects upon aldosterone synthesis which was abolished in the absence of potassium and became detectable in the presence of 0.5 mM K+. After remaining constant between 2.5 and 4.0 mM K+, aldosterone production rose sharply above 4.5 mM K+ and reached a maximum at 8 mM K+. These observations provide direct evidence that aldosterone production by zona glomerulosa cells is influenced by changes in angiotensin II levels within the normal plasma range.

Actions of angiotensin II antagonists upon aldosterone production by isolated adrenal glomerulosa cells.

The biological activities of angiotensin II antagonists upon basal and angiotensin II-stimulated aldosterone production were evaluated in an isolated canine glomerulosa cell preparation. The most potent competitive antagonist of angiotensin II-stimulated aldosterone production was the [Sar1, Ile8]derivative of angiotensin II. However, this peptide was also a partial agonist at concentrations required to inhibit the steroidogenic effect of angiotensin II on dog adrenal cells, and never reduced aldosterone production to basal levels. On a molar basis, the [Sar1, Ala8] and [Sar1, Gly8]derivatives of angiotensin II were relatively less potent as competitive inhibitors of angiotensin II-stimulated aldosterone production. However, the [Ala8] and [Gly8]-analogues did not exhibit significant agonist activity and were therefore more effective antagonists of angiontensin II-stimulated aldosterone production. These results suggest that increased length of the aliphatic side chain at the C-terminus of angiotensin II antagonists is accompanied by enhanced affinity for the receptor site, but also by increased agonist activity upon aldosterone synthesis. The actions of angiotensin II and [Des-Asp1]angiotensin II upon aldosterone production were inhibited identically and completely by [Sar1, Ala8]angiotensin II, and identically, though incompletely, by lower concentrations of [Sar1, Ile8]angiotensin II. The heptapeptide antagonist [Des-Asp1, Ile8]angiotensin II was much less potent than [Sar1, Ile8]angiotensin II as an inhibitor of the actions of both the heptapeptide and octapeptide agonists. The antagonist activity of six angiotensin II analogues at the adrenal level, determined by the concentration required for 50% inhibition of maximum aldosterone secretion, correlated well with their antagonist activity measured upon isolated smooth muscle. These observations demonstrate that the octapeptide antagonists are more effective than the heptapeptide antagonists upon angiotensin II-stimulated aldosterone production, and that angiotensin II receptors in smooth muscle and adrenal cortex exhibit generally similar responses to angiotensin II antagonists. Also, these results do not support the proposal that the [Des-Asp1]heptapeptide is an important intermediate in the action of angiotensin II upon adolesterone production in the adrenal glomerulosa cells. The production of aldosterone by dispersed zona glomerulosa cells in vitro provides a highly sensitive and biologically appropriate response for evaluation of the agonist and antagonist properties of angiotensin II analogues upon the adrenal gland.

Aldosterone production by isolated glomerulosa cells: modulation of sensitivity to angiotensin II and ACTH by extracellular potassium concentration.

The influence of extracellular potassium concentration on adrenal sensitivity to angiotensin II and ACTH was studied in isolated canine adrenal glomerulosa cells. When potassium was absent from the incubation medium, the aldosterone response to angiotensin II or ACTH was completely abolished. At physiologic angiotensin II concentrations (2.5 x 10(-11) M), aldosterone formation increased 4-fold when potassium concentration was increased from 2.5 to 5.0 mM, and rose 6-fold as potassium was increased from 2.5 to 7.5 mM. In the absence of angiotensin II, the same changes in potassium concentration increased aldosterone production only to 2-fold and 3.5-fold, respectively. The effect of potassium concentration upon the aldosterone response to ACTH was similar but less marked. The concentration and binding affinity of angiotensin II receptor sites in glomerulosa cells were not changed by increasing potassium concentrations from 0 to 7.5 mM. These observations demonstrate that the aldosterone response to the glomerulosa cell to angiotensin II is potassium-dependent within the physiological range for each of these stimuli. Such an interaction suggests that the in vivo effect of potassium upon aldosterone secretion includes a significant modulating action upon adrenal sensitivity to angiotensin II, as well as a direct action of potassium upon the adrenal glomerulosa cell.

Stimulation of aldosterone production by angiotensin II peptides in vitro: enhanced activity of the (1-sarcosine) analogue.

The biological activity of angiotensin agonists has been determined in a highly sensitive in vitro assay system, based upon aldosterone production by isolated dog adrenal cells. The responses to angiotensin II and the heptapeptide [Des-Asp-1]-angiotensin II are identical, while the [Des-Asp-1, Des-Arg-2]-hexapeptide and the [Des-Phe-8]-heptapeptide are almost completely inactive. By contrast, [Sar-1]-angiotensin II, a potent agonist upon vascular smooth muscle, is also about 10 times more active than angiotensin II in stimulating the production of aldosterone by dog adrenal cells. The increased agonist activity of [Sar-1]-angiotensin II is attributable to increased binding affinity as well as increased efficacy at the adrenal receptor site. These results also suggest that conversion to the [Des-Asp-1] heptapeptide is not an important intermediate step in the action of angiotensin II upon the zona glomerulosa.

Self rated health: Is it as good a predictor of subsequent mortality among adults in lower as well as in higher social classes?

STUDY OBJECTIVE: To analyse the predictive power of self rated health for mortality in different socioeconomic groups. DESIGN, SETTING, PARTICIPANTS: Analysis of mortality rates and risk ratios of death during follow up among 170 223 respondents aged 16 years and above in the Swedish Survey of Living Conditions 1975-1997, in relation to self rated health stated at the interview, by age, sex, socioeconomic group, chronic illness and over time. MAIN RESULTS: There was a strong relation between poor self rated health and mortality, greater at younger ages, similar among men and women and among persons with and without a chronic illness. The relative relation between self rated health and subsequent death was stronger in higher than in lower socioeconomic groups, possibly because of the lower base mortality of these groups. However, the absolute mortality risk differences between persons reporting poor and good self rated health were similar across socioeconomic groups within each sex. The mortality risk difference between persons reporting poor and good self rated health was considerably higher among persons with a chronic illness than among persons without a chronic illness. The mortality risk among persons reporting poor health was increased for shorter (<2 years) as well as longer (10+ years) periods of follow up. CONCLUSIONS: The results suggest that poor self rated health is a strong predictor of subsequent mortality in all subgroups studied, and that self rated health therefore may be a useful outcome measure.

Plasma activities of lysosomal enzymes after hepatic dearterialization in man.

Six patients with liver metastases from carcinoid or colon carcinoma underwent hepatic derterialization. This operation, known to cause both tumor necrosis and liver cell damage, caused considerable increases of several lysosomal acid hydrolases in the circulation. Thus, beta-glucosidase showed a small temporary increase during the operation, followed by a slower but higher reaction reaching a maximum 12 to 36 hours postoperatively. Similar reactions were noted for beta-glucuronidase, acid phosphatase, beta-galactosidase, arylsuphatase A, and N-acetyl-beta-glucosaminidase while no reactions were found for cathepsin D. Very high enzyme levels occurred in a patient dying from bleeding complications in the postoperative period.

Localization of abnormal parathyroid glands using thallium-201.

Ectopically located parathyroid adenomas may be difficult to find during initial neck exploration. They account for over 70 percent of missed adenomas found at reexploration. Preoperative localization of parathyroid adenomas would reduce unnecessary dissection and possibly reduce the number of negative results of initial neck exploration. Before reoperative parathyroid surgery is performed, some means of localization is mandatory to detect ectopic adenomas in the neck and mediastinum. Computed tomography and ultrasonography cannot effectively evaluate the mediastinum. Angiography and venous parathyroid hormone sampling are invasive, costly, and tedious to perform. We have shown that thallium-201 will accurately localize ectopic parathyroid adenomas. All 10 adenomas found in positions not immediately adjacent to the thyroid gland were detected by thallium-201 scintigraphy. One was a mediastinal adenoma resected with a median sternotomy. Our results suggest that thallium-201 scintigraphy should be the initial localization procedure of choice before all reexplorations. Its use before initial explorations, as well, will enable the surgeon to immediately direct attention to the area of the localized adenoma. If mediastinal uptake is found to be present, then median sternotomy may be performed during initial surgery provided a thorough neck exploration is performed first.