Preventing Macrovascular Disease in Patients with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (DM) is associated with an increased risk for both micro-and macrovascular complications, and cardiovascular diseases (CVD) are the most common causes of death in these patients, accounting for almost 70% of the deaths. Given the high prevalence of the condition and the expected global increase in the prevalence of type 2 DM, a case is made for prevention of these serious complications in order to reduce the individual morbidity and the economic burden on society. In this review we present the knowledge of how macrovascular disease in patients with type 2 DM may be prevented, and suggest possible strategies for doing so. A thorough search of the published literature was conducted and we first present relevant epidemiological studies demonstrating the impact of important risk factors for CVD in DM, such as dyslipidemia, hyperglycemia, hypertension, smoking, familial premature coronary heart disease and some non-classical risk factors such as hyperinsulinemia, insulin resistance, endothelial dysfunction and inflammation. Secondly, we review the results from published randomized controlled clinical trials and meta-analysis of these, evaluate the findings and suggest strategies for preventing CVD in patients with type 2 DM using non-pharmacological and pharmacological approaches. Present knowledge indicates that most patients with type 2 DM either have manifest CVD or have a high risk for future cardiovascular events, men with DM have a 2- to 4-fold; and women with DM a 3- to 5-fold increased risk for cardiovascular death compared with non-diabetic individuals. Care of patients with type 2 DM should include yearly risk assessment by the use of published risk equations or risk charts. On the background of this assessment, an individual risk reducing strategy should be tailored to each patient’s need, including the treatment of hyperglycemia, hypertension and dyslipidemia together with the use of aspirin (acetylsalicylic acid) and ACE inhibitors. Such measures can reduce the risk of cardiovascular events in patients with type 2 DM.     

Selective referral to high-volume hospitals: estimating potentially avoidable deaths

Context  Evidence exists that high-volume hospitals (HVHs) have lower mortality rates than low-volume hospitals (LVHs) for certain conditions. However, few employers, health plans, or government programs have attempted to increase the number of patients referred to HVHs. Objectives  To determine the difference in hospital mortality between HVHs and LVHs for conditions for which good quality data exist and to estimate how many deaths potentially would be avoided in California by referral to HVHs. Design, Setting, and Patients  Literature in MEDLINE, Current Contents, and FirstSearch Social Abstracts databases from January 1, 1983, to December 31, 1998, was searched using the key words hospital, outcome, mortality, volume, risk, and quality. The highest-quality study assessing the mortality-volume relationship for each given condition was identified and used to calculate odds ratios (ORs) for in-hospital mortality for LVHs vs HVHs. These ORs were then applied to the 1997 California database of hospital discharges maintained by the California Office of Statewide Health Planning and Development to estimate potentially avoidable deaths. Main Outcome Measures  Deaths that potentially could be avoided if patients with conditions for which a mortality-volume relationship had been treated at an HVH vs LVH. Results  The articles identified in the literature search were grouped by condition, and predetermined criteria were applied to choose the best article for each condition. Mortality was significantly lower at HVHs for elective abdominal aortic aneurysm repair, carotid endarterectomy, lower extremity arterial bypass surgery, coronary artery bypass surgery, coronary angioplasty, heart transplantation, pediatric cardiac surgery, pancreatic cancer surgery, esophageal cancer surgery, cerebral aneurysm surgery, and treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). A total of 58,306 of 121,609 patients with these conditions were admitted to LVHs in California in 1997. After applying the calculated ORs to these patient populations, we estimated that 602 deaths (95% confidence interval, 304-830) at LVHs could be attributed to their low volume. Additional analyses were performed to take into account emergent admissions and distance traveled, but the impact of loss of continuity of care for some patients and reduction in the availability of specialists for patients remaining at LVHs could not be assessed. Conclusions  Initiatives to facilitate referral of patients to HVHs have the potential to reduce overall hospital mortality in California for the conditions identified. Additional study is needed to determine the extent to which selective referral is feasible and to examine the potential consequences of such initiatives.      

Cancer risk following appendectomy for acute appendicitis (Denmark)

Objective: Epidemiologic studies have not been able definitely to exclude that appendectomy carries a cancer risk. This study was conducted to clarify whether appendectomy is associated with a subsequent increase in cancer risk, since appendectomy is frequently an elective procedure. Methods: The present study included more than 82,000 persons who underwent appendectomy for acute appendicitis during 1977-89 according to the nation-wide Danish Hospital Discharge Register. During a follow-up interval of up to 17 years, cancer incidence was assessed by linkage to the Danish Cancer Registry and compared with the incidence in the general population of Denmark. Results: The total number of malignancies among appendectomized persons was 1.05 times higher than expected with 95 percent confidence intervals of 0.99-1.11. There was no clear significant excess of any specific cancer type. Conclusion: During a postsurgery period of nearly two decades, results of our study did not support the hypothesis that either appendectomy or acute appendicitis are likely to be associated with malignant neoplasms.     

Improved survival of embryonic porcine dopaminergic neurons in coculture with a conditionally immortalized GDNF-producing hippocampal cell line

Transplantation of embryonic nigral tissue is used as an experimental therapy for patients with Parkinson's disease but is hampered by a limited survival rate of dopaminergic neurons. Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for nigrostriatal dopaminergic neurons, and the present in vitro study aimed at improving the survival of dopaminergic neurons in porcine mesencephalic brain slice cultures by adding transfected, immortalized, temperature-sensitive GDNF-releasing HiB5 cells (HiB5-GDNF). Embryonic (E27/28) porcine ventral mesencephalic brain slices were placed on membrane inserts in six-well plates with serum-containing medium, and HiB5-GDNF, nontransfected HiB5 cells (HiB5-control), or green fluorescent protein-producing HiB5 cells (HiB5-GFP) were seeded onto each tissue slice. The concentration of GDNF in the coculture medium was 0.49 +/- 0.13 ng/ml at day 9 and 0. 22 +/- 0.05 ng/ml at day 19 (mean +/- SEM) as measured by GDNF ELISA. The decrease in release of GDNF over time was paralleled by a gradual reduction in the number of HiB5-GFP cells expressing the reporter gene (EGFP). At day 12, HPLC analysis revealed that medium from HiB5-GDNF cocultures contained 2.0 times more dopamine than medium from HiB5-control cocultures. At day 21 there was 1.6 times more dopamine. Similar results were obtained for the dopamine metabolite 3,4-dihydroxyphenylacetic acid. At day 21, cell counts showed that HiB5-GDNF cocultures contained 1.5 times more tyrosine hydroxylase immunoreactive neurons than HiB5-control cocultures, which must be compared with a 1.8 fold increase after chronic treatment with rhGDNF (10 ng/ml). In conclusion, the better survival of HiB5-GDNF cocultures is promising for the generation of effective cell lines for local delivery of neurotrophic factors to intracerebral nigral grafts.     

Intake of wine, beer and spirits and risk of gastric cancer.

The objective was to study prospectively the relation between quantity and type of alcohol and risk of gastric cancer. In a pooled database from three population studies conducted in 1964-1992, a total of 15,236 men and 13,227 women were followed for a total of 389,051 person-years. During follow-up 122 incident cases of gastric cancer were identified. Total alcohol intake itself was not associated with gastric cancer, but type of alcohol seemed to influence risk. Compared with non-wine drinkers, participants who drank 1-6 glasses of wine had a relative risk ratio of 0.76 (95% confidence interval (CI) 0.50-1.16), whereas those who drank >13 glasses of wine per week had a relative risk ratio of 0.16 (95% CI 0.02-1.18). Linear trend test showed a significant association with a relative risk ratio of 0.60 (95% CI 0.39-0.93) per glass of wine drunk per day. These relations persisted after adjustment for age, gender, educational level, body mass index, smoking habits, inhalation and physical activity. There was no association between beer or spirits drinking and gastric cancer. In conclusion, the present study suggests that a daily intake of wine may prevent development of gastric cancer.     

Prevalence of antibodies against SARS‐CoV‐2 in the Norwegian population,August 2021

BackgroundOne year into the COVID‐19 pandemic, the cumulative number of confirmed COVID‐19 cases in Norway was still low. In January 2021, when the Norwegian COVID‐19 vaccination campaign started, the national seroprevalence estimate of SARS‐CoV‐2 antibodies was 3.2%. We have conducted a nationwide cross‐sectional study in August 2021 to investigate the overall prevalence of SARS‐CoV‐2 antibodies in Norway after 8 months of COVID‐19 mass vaccination and a third wave of SARS‐CoV‐2 infection.MethodsResidual sera were collected from laboratories across Norway in August 2021. In IgG antibodies against the spike protein, the spike receptor binding domain (RBD) and the nucleocapsid protein of SARS‐CoV‐2 were measured by a bead‐based flow cytometric assay.ResultsIn total, 1926 residual sera were collected from individuals aged 0–98 years; 55.1% were from women. The overall national estimated seroprevalence from vaccination and/or infection was 62.6% (credible interval [CrI] 60.1%–65.2%) based on having antibodies against both spike and RBD. Estimated seroprevalence increased with age. Among all samples, 11.7% had antibodies against nucleocapsid. For unvaccinated children <12 years, the seroprevalence estimate due to SARS‐CoV‐2 infection was 12.5% (95% CrI 9.3%–16.1%). Of seropositive samples from the unvaccinated children, 31.9% lacked anti‐nucleocapsid antibodies.ConclusionsThe high overall SARS‐CoV‐2 seroprevalence estimates are in line with Norwegian registry data. Vaccination, not infection, contributed the most to the high seroprevalence in August 2021. Lack of antibodies against nucleocapsid should not automatically be interpreted as absence of previous infection as this could lead to underestimation of COVID‐19 cases in seroprevalence studies.     

Risk for anogenital cancer and other cancer among women hospitalized with gonorrhea

BACKGROUND: We investigated the relationship between infections with Neisseria gonorrhoeae and anogenital and other cancers. METHODS: Nationwide and population based register linkage study utilizing prospectively notified information. The observed numbers of cancers among the women were compared with those expected on the basis of national incidence rates. RESULTS: In a cohort of 4440 women hospitalized for gonorrhea we observed a total of 227 cases of cervical intraepithelial neoplasia grade III (CIN III), with 103 expected (standardized incidence ratio (SIR), 2.2; 95% confidence interval (CI), 1.9-2.5). No significantly increased risk for other anogenital cancers or cancer at other sites was seen. CONCLUSIONS: These results support the view that the observed association between gonorrheal infection and subsequent cervical preneoplasia is due mainly to surveillance bias. However, our results also indicate that women hospitalized with a N. gonorrhoeae infection will benefit from the compliance with the regular Pap smear screening programs.     

Kinetics of antibody and memory B cell responses after MMR immunization in children and young adults

The persistence of antigen-specific memory B-cells (MBCs) in children and young adults long time after vaccination against measles, mumps and rubella (MMR) is not known. Here we have looked at the Swedish immunization program and examined children 1–10 years after the first MMR dose in early childhood, as well as young adults 7–18 years after the second dose of MMR. We show that Ab titers and MBCs against measles and rubella have different kinetics, indicating that the MBC pool and the corresponding Ab titers are regulated independently. These data fit well with other findings that continuous IgG secretion comes from long-lived plasma cells and not MBCs. We also demonstrate that individuals with low post-vaccination Ab titers might have an adequate MBC response. It remains to be shown if memory B-cells provide the same protection as specific antibodies, but our data is a valuable complement to the incomplete knowledge about correlates of protection after vaccination.     

Antibiotic resistance in hospitals: a ward‐specific random effect model in a low antibiotic consumption environment

Association between previous antibiotic use and emergence of antibiotic resistance has been reported for several microorganisms. The relationship has been extensively studied, and although the causes of antibiotic resistance are multi‐factorial, clear evidence of antibiotic use as a major risk factor exists. Most studies are carried out in countries with high consumption of antibiotics and corresponding high levels of antibiotic resistance, and currently, little is known whether and at what level the associations are detectable in a low antibiotic consumption environment. We conduct an ecological, retrospective study aimed at determining the impact of antibiotic consumption on antibiotic‐resistant Pseudomonas aeruginosa in three hospitals in Norway, a country with low levels of antibiotic use. We construct a sophisticated statistical model to capture such low signals. To reduce noise, we conduct our study at hospital ward level. We propose a random effect Poisson or binomial regression model, with a reparametrisation that allows us to reduce the number of parameters. Inference is likelihood based. Through scenario simulation, we study the potential effects of reduced or increased antibiotic use. Results clearly indicate that the effects of consumption on resistance are present under conditions with relatively low use of antibiotic agents. This strengthens the recommendation on prudent use of antibiotics, even when consumption is relatively low. Copyright © 2012 John Wiley & Sons, Ltd.     

Single Gastric Biopsy in Subjects with Low Acid Secretion after Maximal Histamine Stimulation

Examinations of 83 patients and 13 healthy subjects with the augmented histamine test and gastric biopsy show that a maximal acid secretion lower than 10 mEq HCl/hour signifies a diffuse gastritic lesion, the type of which can be verified by a single gastric biopsy. Detailed investigations of the nature and clinical course of gastritis, however, require repeated tests of gastric function and multiple gastric biopsies.