The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta‐Analysis of Randomized Controlled Trials

Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta‐analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta‐analyses. We, therefore, undertook a meta‐analysis of randomized controlled trials with placebo or no‐treatment control groups to determine if these supplements increase all‐cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random‐effects meta‐analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96–1.09; p = 0.51). Seventeen trials contributed all‐cause mortality data with pooled RR of 0.96 (95% CI, 0.91–1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I² = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92–1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95–1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73–1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all‐cause mortality risk in elderly women. © 2014 American Society for Bone and Mineral Research.     

Implementation of prehospital thrombolysis in Sweden: components of delay until delivery of treatment and examination of treatment feasibility

OBJECTIVE: To evaluate the feasibility of prehospital thrombolysis in Sweden in terms of safety and to examine the various components of the delay between onset of symptoms and start of treatment. SETTING: A total of 16 hospitals in Sweden in both urban and less populated areas and the associated ambulance organisations. DESIGN: Prospective evaluation of patients with an ST-elevation infarction treated with reteplase. An ECG was recorded and transmitted to hospital. The ambulances were staffed by a physician in 1% of cases, a nurse in 67% and a staff nurse in 32%. RESULTS: Of the 148 patients who received treatment prior to hospital admission, six (4%) had a cardiac arrest prior to hospital admission and two (1%) died prior to arrival at hospital. One patient was given treatment despite an exclusion criterion (previous stroke) and died on the 1st day in hospital due to a cerebral haemorrhage. The overall 30-day mortality was 7.1% and 1-year mortality 9.8%. Treatment was initiated within 2 h after the onset of symptoms in 53% of patients and within 1 h in 17% of patients. The median interval between the arrival of the ambulance and sending an ECG was 13 min and the median interval between sending an ECG and the start of thrombolysis was 18 min. The delay was similar regardless of ambulance staff. CONCLUSION: Implementation of prehospital thrombolysis on a national basis in Sweden appears to be safe. More than half the patients can be given treatment less than 2 h after the onset of symptoms. There is potential for reducing this time still further.     

The NUGGET study: NIR ultra gold-gilded equivalency trial.

This study should clarify whether the gold-coated NIROYAL stent is equivalent to the stainless steel NIR stent. Patients were randomized to either NIR stent (n = 298) or a NIROYAL stent (n = 305). The primary endpoint was the minimum lumen diameter of the target lesion at 6 months postprocedure. Secondary endpoints focused on clinical events. At 30 days, adverse events were similar in both groups. At 6 months, the minimal lumen diameter was 1.83/1.64 mm (P < 0.001; 95% CI = 0.08-0.30) and the angiographic restenosis rate was 20.6%/37.7% (P < 0.001; 95% CI = -24.7 to -9.3) for NIR/NIROYAL. The 6-month MACE rates were NIR 7.4% and NIROYAL 10.5% (95% CI = -7.7 to 1.4). Compared to stainless steel stent, the NIROYAL stent demonstrated a smaller minimal lumen diameter, a higher late loss (i.e., higher neointimal hyperplasia in spite of a significantly better initial gain), with higher restenosis and similar MACE rates at 6 months.     

The risk of revision in total knee arthroplasty is not affected by previous high tibial osteotomy: A 15-year follow-up of 32,476 total knee arthroplasties in the Norwegian Arthroplasty Register

Background and purpose — Previous studies have found different outcomes after revision of knee arthroplasties performed after high tibial osteotomy (HTO). We evaluated the risk of revision of total knee arthroplasty with or without previous HTO in a large registry material.Patients and methods — 31,077 primary TKAs were compared with 1,399 TKAs after HTO, using Kaplan-Meier 10-year survival percentages and adjusted Cox regression analysis.Results — The adjusted survival analyses showed similar survival in the 2 groups. The Kaplan-Meier 10-year survival was 93.8% in the primary TKA group and 92.6% in the TKA-post-HTO group. Adjusted RR was 0.97 (95% CI: 0.77–1.21; p = 0.8).Interpretation — In this registry-based study, previous high tibial osteotomy did not appear to compromise the results regarding risk of revision after total knee arthroplasty compared to primary knee arthroplasty.High tibial osteotomy (HTO) is a well-established joint preserving procedure for the treatment of medial knee osteoarthritis. The goal is to achieve unloading of the affected medial compartment of the knee to prevent or postpone the need for an artificial knee joint. This is performed by slightly overcorrecting the knee joint from varus malalignment to valgus or neutral position. Osteotomy was a standard treatment option for unicompartmental knee osteoarthritis in earlier years before knee arthroplasty was a surgical option, but osteotomy lost importance in the 1980s because of the success of knee replacement surgery (Smith et al. 2013). However, there has been an increase in osteotomies during the last 15 years, especially in younger patients in some countries (Seil et al. 2013). National arthroplasty registers have demonstrated higher risk of revision for knee arthroplasty in younger patients (under the age of 60) (NAR 2014, SKAR 2013). The 2 most commonly used methods for HTO are lateral closing wedge and medial opening wedge osteotomy. Both methods have shown improvement in knee pain and function (Naudie et al. 1999, van Raaij et al. 2008, Efe et al. 2011, W-Dahl et al. 2012). Nevertheless, some patients later require a second procedure, a total knee arthroplasty (Naudie et al. 1999), depending on the degree of osteoarthritis, their level of pain and function, and the degree of correction achieved. Although total knee arthroplasty appears to be technically more challenging after HTO in cases with severe overcorrection, bone stock loss, altered joint line (Figures 1 and ​and2),2), or patella infera, only a few studies have found inferior results compared to primary TKA (Windsor et al. 1988, Parvizi et al. 2004, Haslam et al. 2007, Farfalli et al. 2012). The aim of this study was to evaluate the risk of revision after TKA, comparing primary TKA with and without previous high tibial osteotomy using data from the Norwegian Arthroplasty Register (NAR).Open in a separate windowFigure 1.Example of extra-articular malalignment after high tibial osteotomy (HTO) with opening wedge technique. The red line on the left radiograph (a) indicates the mechanical axis lateral to the knee joint. The radiograph to the right (b) indicates the extra-articular angulation of the tibia in the osteotomy area.Open in a separate windowFigure 2.Example of intra-articular malalignment after high tibial osteotomy (WTO) with closing wedge technique. The solid red line indicates that the tibial plateau has been elevated medially and is not perpendicular to the tibial axis.     

Activated pancreatic stellate cells can impair pancreatic islet function in mice

Background

Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets.

Methods

Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.

Results

PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets co-cultured with PSCs for 24–48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

Conclusion

Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes.     

Nerve function varies with hemoglobin A1c in controls and type 2 diabetes

Aims

To determine the cross-sectional threshold at which hemoglobin A1c (HbA1c) is associated with polyneuropathy in healthy controls, and the values associated with the most pronounced decline in nerve function in patients with diabetes.

Sex differences in neuropathic pain in longstanding diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes

Aim

Neuropathy and neuropathic pain are common complications of type 1 diabetes (T1D). We aimed to determine if sex-specific differences in neuropathic pain are present in adults with longstanding T1D.