Differences in cardiovascular safety with non‐steroidal anti‐inflammatory drug therapy—A nationwide study in patients with osteoarthritis

Osteoarthritis (OA) and the non‐steroidal anti‐inflammatory drugs (NSAIDs) used to relieve OA‐associated pain have been linked independently to increased cardiovascular risk. We examined the risk of cardiovascular events associated with NSAID use in patients with OA. We employed linked nationwide administrative registers to examine NSAID use between 1996 and 2015 by Danish patients with OA aged ≥18 years. Using adjusted Cox proportional hazard analyses, we calculated the risk of the composite outcome of cardiovascular death, non‐fatal myocardial infarction and non‐fatal ischaemic stroke/TIA, and of each outcome separately, up to 5 years after OA diagnosis. Of 533 502 patients included, 64.3% received NSAIDs and 38 226 (7.2%) experienced a cardiovascular event during follow‐up. Compared with non‐use, all NSAIDs were associated with increased risk of the composite outcome: hazard ratio (HR) for rofecoxib, 1.90 (95% confidence interval, 1.74‐2.08); celecoxib, 1.47 (1.34‐1.62); diclofenac, 1.44 (1.36‐1.54); ibuprofen, 1.20 (1.15‐1.25); and naproxen, 1.20 (1.04‐1.39). Similar results were seen for each outcome separately. When celecoxib was used as reference, ibuprofen (HRs: 0.81 [CI: 0.74‐0.90]) and naproxen (HRs: 0.81 [0.68‐0.97]) exhibited a lower cardiovascular risk, even when low doses were compared. Low‐dose naproxen and ibuprofen were associated with the lowest risks of the composite outcome compared to no NSAID use: HRs: 1.12 (1.07‐1.19) and 1.16 (0.92‐1.42), respectively. In patients with OA, we found significant differences in cardiovascular risk among NSAIDs. Naproxen and ibuprofen appeared to be safer compared to celecoxib, also when we examined equivalent low doses. In terms of cardiovascular safety, naproxen and ibuprofen, at the lowest effective doses, may be the preferred first choices among patients with OA needing pain relief.     

Dominant GDAP1 founder mutation is a common cause of axonal Charcot-Marie-Tooth disease in Finland

We describe a founder mutation in the gene encoding ganglioside-induced differentiation associated-protein 1 (GDAP1), leading to amino acid change p.H123R, as a common cause of autosomal dominant axonal Charcot-Marie-Tooth (CMT2) neuropathy in Finland. The mutation explains up to 14 % of CMT2 in Finland, where most patients with axonal neuropathy have remained without molecular diagnosis. Only three families out of 28 were found to carry putative disease mutations in the MFN2 gene encoding mitofusin 2. In addition, the MFN2 variant p.V705I was commonly found in our patients, but we provide evidence that this previously described mutation is a common polymorphism and not pathogenic. GDAP1-associated polyneuropathy caused predominantly a mild and slowly progressive phenotype. Besides distal leg muscle weakness, most patients showed mild proximal weakness, often with asymmetry and pes cavus. Our findings broaden the understanding of GDAP1 mutations in CMT2 phenotypes and provide support for the use of whole-exome sequencing in CMT gene diagnostics.     

Cauda Equina Intradural Extramedullary Cavernous Haemangioma: Case Report and Review of the Literature

Cavernous haemangioma (cavernoma) is a benign vascular lesion, exceptionally located in cauda equina. We report a case, diagnosed and operated in the Department of Neurosurgery from Pitesti County Emergency Hospital, of a 60-year-old woman with history of lumbar region distress, who presented with low back pain, paravertebral muscle contracture, and bilateral lumbar radiculopathy, with sudden onset after lifting effort. The preoperative diagnosis was done using computed tomography (CT) and magnetic resonance imaging (MRI), and the patient underwent surgery—two level laminectomy, dural incision, and tumor dissection from the cauda equina nerve roots under operatory microscope. Histopathological examination confirmed the positive diagnosis of cavernoma of cauda equina. The patient''s outcome was favorable, without postoperative neurological deficits.     

Antibiotic prophylaxis in total hip arthroplastyEffects of antibiotic prophylaxis systemically and in bone cement on the revision rate of 22,170 primary hip replacements followed 0-14 years in the Norwegian Arthroplasty Register

We studied the effects of antibiotic prophylaxis, systemically and in bone cement, on the revision rate of cemented total hip arthroplasties (THAs) in data from the Norwegian Arthroplasty Register during the period 1987-2001. To have comparable groups, only THAs performed because of primary osteoarthritis, using cemented implants with documented good results, and high-viscosity cement were included. If systemic antibiotic prophylaxis had been given, only operations with cephalosporin or penicillin were selected. Cox-estimated survival relative revision risks (RR) are presented with adjustment for differences among groups in gender, age, cement brand, type of systemic antibiotic prophylaxis, type of prosthesis, type of operating room, and duration of the operation. Of 22,170 THAs studied, 696 THAs (3.1%) were revised, 440 (2.0%) for aseptic loosening and 102 (0.5%) for deep infection. We found the lowest risk of revision when the antibiotic prophylaxis was given both systemically and in the cement (15,676 THAs). Compared to this combined regime, patients who received antibiotic prophylaxis only systemically (5,960 THAs) had a 1.4 times higher revision rate with all reasons for revision as endpoint (p= 0.001), 1.3 times higher with aseptic loosening (p= 0.02) and 1.8 times higher with infection as the endpoint (p= 0.01). With the combined antibiotic regime, the results were better if antibiotics were given 4 times on the day of surgery (2,194 THAs), as compared to once (1,424 THAs) (p<0.001), twice (2,680 THAs) (p<0.001), or 3 times (5,522 THAs) (p= 0.02). Those who received systemic prophylaxis a single day 1, 2 or 3 times, as compared to 4 times, had a revision rate 1.8-3.5 times higher with all reasons for revision as endpoint, 1.5-3.1 times higher with aseptic loosening, and 2.7-6.8 times higher with infection. When we compared systemic prophylaxis 4 times in 1 day, no further improvement resulted in those given systemic prophylaxis for 2 days (1,928 THAs) or 3 days (717 THAs). In a subset of data including only the Charnley prosthesis, we obtained similar results. This observational study shows that the best results were recorded when antibiotic prophylaxis was given both systemically and in the bone cement, and if the systemic antibiotic was given 4 times on the day of surgery.