Diabetes in treated hypertension is common and carries a high cardiovascular risk: results from a 28-year follow-up

OBJECTIVE: The objective of this study was to analyse predictive factors for development of type 2 diabetes during life-long therapy for hypertension and the alleged additional cardiovascular risk this constitutes. METHODS: The study group (n = 754) comprised the hypertensive subgroup of a randomized population sample of 7500 men, aged 47-54 years, screened for cardiovascular risk factors and followed for 25-28 years. The patients were treated with thiazide diuretics and beta-adrenergic blocking drugs with the addition of hydralazin during the first decade. Calcium antagonists were substituted for hydralazin and, if needed, angiotensin-converting enzyme inhibitors were added when these drugs became available. RESULTS: A total of 148 (20.4%) treated hypertensive patients developed diabetes during 25 years, and in multivariate Cox regression analysis body mass index, serum triglycerides and treatment with beta-blockers were positively related with this complication. New-onset diabetes implied a significantly increased risk for stroke [hazard ratio (HR): 1.67; 95% confidence interval (95% CI): 1.1-2.6; P < 0.05], myocardial infarction (OR: 1.66; 95% CI: 1.1-2.5; P < 0.05) and mortality (OR: 1.42; 95% CI: 1.1-1.9; P < 0.05). The greatest risk for stroke was new-onset diabetes, followed by smoking (OR: 1.46; 95% CI: 1-2.2; P = 0.07) and the greatest risk for myocardial infarction was new-onset diabetes, followed by smoking (HR: 1.64; 95% CI: 1.1-2.4; P < 0.01). The greatest risk for mortality was smoking (HR: 1.73; 95% CI: 1.3-2.2; P < 0.005). Achieved systolic and diastolic blood pressure were not predictive of cardiovascular complications or death. The mean observation time from onset of diabetes mellitus to a first stroke was 9.1 years and to a first myocardial infarction 9.3 years. CONCLUSION: Diabetes in treated hypertensive patients is alarmingly common and carries a high risk for cardiovascular complications and mortality.     

Late psychological symptoms after awareness among consecutively included surgical patients

BACKGROUND: Awareness during general anesthesia can cause late psychological symptoms. Selection bias may have affected the results in previous retrospective studies. The authors used prospective consecutive collection to recruit patients with previous awareness. METHODS: In a cohort of 2,681 consecutive patients scheduled to undergo general anesthesia, 98 considered themselves to have been aware during previous surgery. Six patients died before inclusion, and another 13 were excluded (4 cases of stroke or dementia, 7 declined to participate, and 2 could not be located). Seventy-nine patients were interviewed by telephone, and medical records were checked in uncertain cases. The interview followed a structured protocol, including seven late symptoms (anxiety, chronic fear, nightmares, flashbacks, indifference, loneliness, and lack of confidence in future life). Three persons independently assessed the interviews for classification, to determine whether awareness had occurred. RESULTS: Four cases were performed using regional anesthesia, and another 29 were not considered as awareness by the assessors. Therefore, the final analyses included 46 patients. Twenty (43%) had experienced pain, and 30 (65%) described acute emotional reactions during the awareness episode. Fifteen (33%) patients had experienced late psychological symptoms afterward. In 6 of those cases, the symptoms lasted for more than 2 months, and 1 patient had a diagnosis of post-traumatic stress disorder. Acute emotional reactions were significantly related to late psychological symptoms (P<0.05). CONCLUSION: The method for recruiting awareness cases in studies on late psychological symptoms may affect the result. The authors found fewer and milder problems, despite a similar degree of initial problems as in previous studies.     

Generation of immunosuppressive mesenchymal stem cells in allogeneic human serum

Mesenchymal stem cells (MSC) may be used to treat acute graft-versus-host disease and for tissue repair. In vitro expansion of MSC has been achieved in the presence of fetal calf serum (FCS). For safety and regulatory reasons, we explored if FCS could be replaced by human blood group AB serum. Proliferation and fold increase of MSC was higher in the presence of AB-serum, compared to FCS. Similar to cells generated in FCS media, MSC from AB-serum media were more than 95% positive for CD90, CD105 and human leukocyte antigen (HLA) class I, and negative for hematopoietic and endothelial markers CD14, CD31, CD34, CD45, and CD80. HLA class II expression was higher in MSC generated in AB-serum, but decreased with higher passage numbers. MSC generated in AB-serum suppressed lymphocyte proliferation in mixed lymphocyte cultures and after stimulation with phytohemagglutinin. MSC expanded in AB-serum and FCS have similar in vitro properties.     

Membrane prostaglandin E synthase-1: a novel therapeutic target

Prostaglandin E(2) (PGE(2)) is the most abundant prostaglandin in the human body. It has a large number of biological actions that it exerts via four types of receptors, EP1-4. PGE(2) is formed from arachidonic acid by cyclooxygenase (COX-1 and COX-2)-catalyzed formation of prostaglandin H(2) (PGH(2)) and further transformation by PGE synthases. The isomerization of the endoperoxide PGH(2) to PGE(2) is catalyzed by three different PGE synthases, viz. cytosolic PGE synthase (cPGES) and two membrane-bound PGE synthases, mPGES-1 and mPGES-2. Of these isomerases, cPGES and mPGES-2 are constitutive enzymes, whereas mPGES-1 is mainly an induced isomerase. cPGES uses PGH(2) produced by COX-1 whereas mPGES-1 uses COX-2-derived endoperoxide. mPGES-2 can use both sources of PGH(2). mPGES-1 is a member of the membrane associated proteins involved in eicosanoid and glutathione metabolism (MAPEG) superfamily. It requires glutathione as an essential cofactor for its activity. mPGES-1 is up-regulated in response to various proinflammatory stimuli with a concomitant increased expression of COX-2. The coordinate increased expression of COX-2 and mPGES-1 is reversed by glucocorticoids. Differences in the kinetics of the expression of the two enzymes suggest distinct regulatory mechanisms for their expression. Studies, mainly from disruption of the mPGES-1 gene in mice, indicate key roles of mPGES-1-generated PGE(2) in female reproduction and in pathological conditions such as inflammation, pain, fever, anorexia, atherosclerosis, stroke, and tumorigenesis. These findings indicate that mPGES-1 is a potential target for the development of therapeutic agents for treatment of several diseases.     

Reflecting peer-support groups in the prevention of stress and burnout: randomized controlled trial

Title.  Reflecting peer-support groups in the prevention of stress and burnout: randomized controlled trial.
Aim.  This paper is a report of a study to test the effect of participating in a reflecting peer-support group on self-reported health, burnout and on perceived changes in work conditions.
Background.  Stress-related conditions are one of the most common causes for long-term sick-leave. There is limited evidence for the effectiveness of person-directed interventions aimed at reducing stress levels in healthcare workers. Prior research in the relationship between support and burnout show somewhat inconsistent results.
Method.  A randomized controlled trial with peer-support groups as the intervention was conducted with 660 healthcare workers scoring above the 75th percentile on the exhaustion dimension of the Oldenburg Burnout Inventory. One hundred and fifty-one (22·9%) agreed to participate. The intervention started in 2002 with 51 participants (96·1% were women), 80 of whom constituted the control group. Potential differences in outcome measures 12 months after the intervention were compared using ancova , and data collected was completed in 2004. Qualitative content analyses were used to analyse reported experiences from group participation.
Results.  Statistically significant intervention effects were found for general health, perceived quantitative demands at work, participation and development opportunities at work and in support at work. Seven categories of experiences from participating were identified: talking to others in a similar situation, knowledge, sense of belonging, self-confidence, structure, relief of symptoms and behavioural change.
Conclusion.  Peer-support groups using a problem-based method could be a useful and comparatively inexpensive tool in alleviating work-related stress and burnout.     

Concomitant injuries may not reduce the likelihood of achieving symmetrical muscle function one year after anterior cruciate ligament reconstruction: a prospective observational study based on 263 patients

Purpose

A better understanding of patient characteristics and the way common concomitant injuries affect the recovery of muscle function after surgery should help providers to treat patients with anterior cruciate ligament (ACL) injuries. The aim of this study was to determine whether patient characteristics, concomitant injuries and graft choice at ACL reconstruction were associated with symmetrical knee muscle function at one year. The hypothesis was that the presence of concomitant injuries would negatively influence the opportunity to achieve symmetrical knee function at the one-year follow-up.

Methods

Data was extracted from the Swedish National Knee Ligament Register and a rehabilitation outcome register between August 2012 and December 2016. The patients had been evaluated with a battery of tests comprising knee extension and flexion strength, vertical jump, hop for distance and the side-hop test one year after ACL reconstruction. Univariable and multivariable logistic regression analyses were performed with achieving a limb symmetry index (LSI) of ≥?90% in all tests of muscle function as primary outcome.

Results

A total of 263 patients with a mean age of 26.7?±?10.3 years were included in the study (47% females). No patient demographic or intra-operative predictors were found to be significant when attempting to predict the achievement of a symmetrical muscle function. Lateral meniscus injury and a patellar tendon autograft reduced the odds of achieving an LSI of ≥?90% in knee extension strength, OR?=?0.49 [(95% CI 0.25–0.97), p?=?0.039] and OR?=?0.30 [(95% CI 0.14–0.67), p?=?0.0033] respectively. In addition, reduced odds of recovering knee extension strength were found in older patients, OR?=?0.76 [(95% CI 0.60–0.98), p?=?0.034]. A higher pre-injury level of physical activity increased the odds of recovering knee flexion strength, OR?=?1.14 [(95% CI 1.01–1.29), p?=?0.037].

Conclusion

Intra-operatively identified concomitant injuries or graft choice did not affect the likelihood of recovering symmetrical performance in five different tests of muscle function one year after ACL reconstruction. However, fewer than one in four patients achieved an LSI of ≥?90% in all tests.

Level of evidence

Prospective observational study: Level 2.

     

Lipoprotein particle abnormalities and the impaired lipolysis in renal insufficiency.

BACKGROUND: Increased concentrations of very low- (VLDL) and intermediate-density (IDL) lipoproteins in chronic renal failure (CRF) are thought to result from a defect(s) in degradation of plasma triglyceride (TG)-rich lipoproteins. The purpose of this study was to identify lipoprotein abnormalities associated with the reduced lipolytic rate constant, k1, of combined VLDL and IDL substrate from renal patients and asymptomatic controls. METHODS: The VLDL + IDL were isolated from 18 predialytic patients (CRF-I), 8 patients on hemodialysis (CRF-II) and 10 asymptomatic controls. The lipolytic rate constant (k1) of VLDL + IDL was measured by an assay using bovine milk lipoprotein lipase and determination of TG before and after incubation by gas chromatography (GC). Neutral lipids were measured by GC and apolipoproteins by electroimmunoassays; the apolipoprotein-defined TG-rich lipoproteins including Lp-B:C, Lp-B:C:E and Lp-A-II:B:C:D:E were determined by immunoaffinity chromatography. RESULTS: The k1 values of VLDL + IDL were significantly (P < 0.001) lower in CRF-I and CRF-II patients (0.0341 and 0.0352 min-1, respectively) than controls (0.0515 min-1). The levels of apolipoproteins B, C-III and E, and TG-rich Lp-B:C, Lp-B:C:E and Lp-A-II:B:C:D:E particles normalized to 100 mg TG per VLDL + IDL were significantly higher in both groups of CRF patients than in controls. All three TG-rich lipoproteins were characterized by significantly increased percent contents of free (FC) and esterified (CE) cholesterol and a decreased percentage of TG. The k1 values of the combined CRF-I and CRF-II patient groups showed significant negative correlations (P < 0.001) with FC (r=-0.81) and CE (r=-0.63) and a positive correlation with TG (r=0.72). Among lipoprotein particles, only Lp-A-II:B:C:D:E levels showed a significant negative correlation with k1 values (r=-0.47, P < 0.03). CONCLUSIONS: This study shows that the abnormal neutral lipid composition of all three TG-rich lipoprotein particles and increased concentrations of Lp-A-II:B:C:D:E particles represent the main factors affecting the in vitro lipolytic rates of VLDL + IDL substrate in both the CRF patients before dialysis and patients on hemodialysis.     

No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease.

In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels 相似文献   

Adult bacterial meningitis: aetiology, penicillin susceptibility, risk factors, prognostic factors and guidelines for empirical antibiotic treatment

Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibility occurred in 21 (23%) of 92 cases of known aetiology, compared to an estimated 6% in nationally notified cases (p < 0.001). Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of ABM cases in the study population, and in 99.6% of nationally notified cases. The notification rate was 75% for penicillin-susceptible episodes, and 24% for penicillin-non-susceptible episodes (p < 0.001). Cases involving staphylococci, Pseudomonas spp. and Enterobacteriaceae were under-reported. Among 51 ABM cases with no identified risk factors, nine of 11 cases with penicillin-non-susceptible bacteria were community-acquired. Severe sequelae correlated independently with age, penicillin non-susceptibility, mechanical ventilation and non-transferral to a tertiary hospital (p < 0.05; logistic regression). Other factors that correlated with severe sequelae by univariate analysis only were inappropriate clinical handling, abnormal consciousness, convulsions and nosocomial infection. Overall, the data indicated that neither age alone, community-acquired infection nor absence of identified risk factors can predict susceptibility to penicillin accurately. Recommendations for empirical antibiotic treatment for ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting.