Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoporosis: a systematic review and meta-analysis.

SUMMARY: We aimed to systematically review observational studies evaluating use of bisphosphonates (BPs) and risk of osteonecrosis of jaw (ONJ) or other sites among non-cancer patients. INTRODUCTION: PubMed, EMBASE, and Cochrane Library were screened from database inception to Dec 2012. METHODS: Two reviewers independently identified cohort and case-control studies evaluating the use of oral or intravenous (IV) BPs and the risk of ONJ and extracted the characteristics of the studies and risk estimates. Pooled estimates of odds ratios and 95 % confidence intervals (CI) were derived by random effects meta-analysis. Subgroup analyses were carried according to patients' characteristics and route of BP use. RESULTS: We identified 12 studies, including 2,652 cases and 1,571,997 controls. Use of BPs was associated with a significantly increased risk of ONJ or ON of other sites [odds ratio (OR) 2.32; 95 % CI 1.38-3.91; I (2) = 91 %]. The summary OR was 2.91 (95 % CI 1.62-5.22; I (2) = 85.9 %) for adjusted studies. Use of BPs were associated with higher risk on ONJ (OR 2.57; 95 % CI 1.37-4.84; I (2) = 92.2 %) than ON of other sites (OR 1.79; 95 % CI 0.71-4.47; I (2) = 83.3 %). Meta-regression analysis did not find design characteristics or outcome definitions to be significant sources of heterogeneity. CONCLUSION: The available evidence suggests that use of BPs in cancer patients is associated with a substantial risk for ONJ. Patients receiving IV BP are at highest risk.

Diagnostic value of procalcitonin for bacterial infection in elderly patients - a systemic review and meta-analysis.

OBJECTIVE: To summarise evidence for the diagnostic accuracy of procalcitonin (PCT) tests for identifying systemic bacterial infections in elderly patients. METHODS: Major databases, including MEDLINE, EMBASE and the Cochrane Library, were searched for studies published from 1975 to March 2013 that evaluated PCT as a marker for diagnosing systemic bacterial infections in elderly patients and that provided sufficient data to construct two-by-two tables. RESULTS: Four studies were available for quantitative meta-analysis. The area under a summary receiver operating characteristic curve was 0.89 (95% CI: 0.86-0.92). The overall sensitivity and specificity estimates for PCT tests were 0.83 (95% CI: 0.38-0.98) and 0.83 (95% CI: 0.60-0.94), respectively. These studies reported heterogeneous sensitivity estimates ranging from 0.24 to 0.96. The positive likelihood ratio for PCT (LR+ = 4.77; 95% CI: 2.49-9.13) was not sufficiently high for its use as a rule-in diagnostic tool, while its negative likelihood ratio was acceptably low for its use as a rule-out diagnostic tool (LR- = 0.20; 95% CI: 0.04-0.97). CONCLUSIONS: Existing data suggest that PCT tests may add to the diagnosis of sepsis in elderly patients. We did not observe the performance of the PCT test in elderly patients inferior to adult patients. Given the imperfect accuracy, we do not recommend that the PCT test be used in isolation; instead, we suggest that it be interpreted in the context of clinical findings.

Brain structural changes in patients with chronic myofascial pain.

BACKGROUND: Myofascial trigger points (MTrPs) are a highly prevalent source of musculoskeletal pain. Prolonged ongoing nociceptive input from MTrPs may lead to maladaptive changes in the central nervous system. It remains, however, unknown whether pain from MTrPs is associated with brain atrophy. In addition, stress, which may contribute to the formation of MTrPs, is also known to affect brain structures. Here, we address whether structural brain changes occur in patients with chronic pain originating from MTrPs and whether such changes are related to pain or stress. METHODS: Voxel-based morphometry was used to compare grey-matter (GM) volumes in 21 chronic pain patients, with MTrPs in the bilateral upper trapezius muscles, with 21 healthy controls. Hyperalgesia was assessed by pressure pain thresholds, and stress was assessed by cortisol levels and anxiety questionnaires. RESULTS: Patients exhibited normal stress levels but lowered pain thresholds. GM atrophy was found in dorsal and ventral prefrontal regions in patients. The GM density of the right dorsolateral prefrontal cortex correlated with pain thresholds in patients, i.e. the more atrophy, the lower pain threshold. GM atrophy was also found in the anterior hippocampus, but the atrophy was neither related to pain nor stress. CONCLUSIONS: Patients with chronic myofascial pain exhibit GM atrophy in regions involved in top-down pain modulation and in processing of negative affect. The relationship between the dorsolateral prefrontal cortex and pain thresholds suggests the presence of pain disinhibition. No evidence was found for the involvement of stress. It remains unclear whether the observed atrophy contributes to the development of the chronic pain state or is caused by the ongoing nociceptive input. SIGNIFICANCE: Chronic myofascial pain, caused by myofascial trigger points, is associated with localized brain atrophy in areas involved in pain processing and modulation, among others. These findings extend previous knowledge about peripheral and spinal changes to the supraspinal level.

Yttrium-90 delivered via a centering catheter and afterloader, given both before and after stent implantation, inhibits neointima formation in porcine coronary arteries.

Background: Intracoronary radiation (IR) studies have shown reduction of neointima formation (NF). Extrapolation of animal studies with beta-radiation to clinical trials have shown variable results, which may be related to dosimetry, centering issues, and/or shielding of beta-rays by the stent metal. We examined the effect of yttrium-90 (90Y), a pure beta-emitter delivered via an automatic afterloader to a centering catheter, on the inhibition of NF in balloon-injured (BI) porcine coronary arteries as well as in arteries receiving 90Y either prior to or following stent implantation (SI).Methods: Twenty-three swine (44 coronary arteries) were studied. In the first study, IR (18 Gy at 1.2 mm from the balloon surface) was administered in 17 arteries following BI, while eight control arteries were subjected to BI only. In the second study, 10 swine (19 coronary arteries) underwent SI. IR (18 Gy) was administered in six arteries before and in eight arteries after SI, while five control arteries received SI only. The animals were sacrificed 2 weeks after BI and 4 weeks after SI. Their coronaries were perfusion fixed and stained, and vessel parameters (intimal area [IA] and medial fracture length [FL]) were analyzed by computer-aided histomorphometry.Results: Arteries subjected to IR following BI had less NF compared to controls (IA/FL=0.14+/-0.2 mm vs. 0.49+/-0.2 mm; P=0.003). IA was reduced significantly in the arteries receiving radiation before and after SI compared to controls (0.92+/-0.98 and 0.00+/-0/00 vs. 2.72+/-1.2 mm(2); P=0.014), despite similar SI in all groups.Conclusions: IR with 90Y delivered via a centering catheter is safe and effective with complete and homogenous inhibition of NF in the context of BI or SI in the porcine coronary model.