Newer antiepileptic drugs in the treatment of status epilepticus: impact on prognosis

Background: Newer antiepileptic drugs (AED) are increasingly prescribed, and seem to have a comparable efficacy as the classical AED, but are better tolerated. Very scarce data exist regarding their prognostic impact in patients with status epilepticus (SE). We therefore analyzed the evolution of prescription of newer AED between 2006-2010 in our prospective SE database, and assessed their impact on SE prognosis.¦Methods: We found 327 SE episodes occurring in 271 adults. The use of older versus newer AED (levetiracetam, pregabalin, topiramate, lacosamide) and its relationship to outcome (return to clinical baseline conditions, new handicap, or death) were analyzed. Logistic regression models were applied to adjust for known SE outcome predictors.¦Results: We observed an increasing prescription of newer AED over time (30% of patients received them at the study beginning, vs. 42% towards the end). In univariate analyses, patients treated with newer AED had worse outcome than those treated with classical AED only (19% vs 9% for mortality; 33% vs 64% for return to baseline, p<0.001). After adjustment for etiology and SE severity, use of newer AED was independently related to a reduced likelihood of return to baseline (p<0.001), but not to increased mortality.¦Conclusion: This retrospective study shows an increase of the use of newer AED for SE treatment, but does not suggest an improved prognosis following their prescription. Also in view of their higher price, well-designed, prospective assessments analyzing their impact on efficacy and tolerability should be conducted before a widespread use in SE.

Five Years Of Denosumab Treatment In Women With Postmenopausal Osteoporosis: Preliminary Results From The Freedom Extension Study

Aims: The pivotal FREEDOM study evaluated the effi cacy and safety of 3 years' denosumab treatment in women with postmenopausal osteoporosis (PMO).1 Since osteoporosis is a chronic condition requiring long-term therapy, FREEDOM was extended to further elucidate the safety and effi cacy of long-term denosumab administration. We present data from the fi rst 2 years of this extension, representing up to 5 years' continuous exposure to denosumab.Methods: Patients who completed FREEDOM were eligible for the extension. Women continued to receive (long-term group), or started after 3 years' placebo (cross-over group), denosumab 60 mg sc every 6 months and daily calcium and vitamin D. These data refl ect 5 years' (long-term) or 2 years' (cross-over) continuous denosumab treatment. Effi cacy measures include changes in BMD from extension study baseline and bone turnover markers (BTM). P-values are descriptive.Results: Of the 83.0% of subjects who completed FREEDOM, 70.2% (N = 4550) agreed to participate in the extension (long-term: 2343; cross-over: 2207). In the long-term group, there were further signifi cant gains (P < 0.0001) in BMD in years 4 and 5: 1.9% and 1.7% at the lumbar spine to a total of 13.7% from FREEDOM baseline and 0.7% and 0.6% at the total hip to a total of 7.0%. During their fi rst 2 years' denosumab treatment, women in the cross-over group had signifi cant improvements in lumbar spine (7.9%) and total hip BMD (4.1%) (P < 0.0001). Serum C-telopeptide (CTX) was rapidly reduced following denosumab dosing in both groups, with the characteristic attenuation of CTX reduction observed at the end of the dosing interval. A low incidence of new vertebral and nonvertebral fractures was reported for both groups. The denosumab safety profi le did not change over time.Conclusions: Denosumab treatment for up to 5 years in women with PMO remains well tolerated, maintains reduction of BTMs and continues to significantly increase BMD.Reference1. Cummings. NEJM 2009;361:756.

Surgical treatment of ingrown toenail without matricectomy.

BACKGROUND: Partial excision of the nail matrix (matricectomy) is generally considered necessary in the surgical treatment of ingrown toenail. Recurrences may occur, however, and poor cosmetic results are frequently observed. OBJECTIVE: The objective is to present a new surgical procedure for ingrown toenail with complete preservation of the nail matrix. METHODS: Twenty-three patients with ingrown toenail were included in this study. The surgical excision was performed 1 week after the completion of treatment of the initial infection. A large volume of soft tissue surrounding the nail plate was removed under local anesthesia. No matrix excision was performed. RESULTS: Short-term results were excellent. No recurrences or severe complications were observed during the minimum 12-months follow-up period. Cosmetic results were remarkable. CONCLUSIONS: Ingrown toenail results from the compression of the lateral nail folds on the nail plate. This study shows that ingrown toenail can be surgically treated without matricectomy. A large volume of soft tissue surrounding the nail plate should be removed to decompress the nail and reduce inflammation. Cosmetic results are excellent and superior to the classical Emmert plasty. Postoperative nail dystrophies and spicule formation are not observed. The main advantage of this surgical approach is the complete preservation of the anatomy and function of the nail to improve both therapeutic and cosmetic results.

Intérêt des faibles doses de rt-PA dans les syndromes inflammatoires et hémorragiques du segment antérieur: étude clinique et revue de la littérature [Treatment of anterior segment fibrinous reactions and hemorrhage with intracameral low dose rt-PA: clinical study and review of the literature].

PURPOSE: to evaluate the efficacy and the safety of low dose intraocular tissue plasminogen activator (rt-PA) in the treatment of traumatic hyphema and postoperative fibrinous membrane. METHODS: Six microg to 10 microg of rt-PA was injected into the anterior chamber to treat severe fibrinous postoperative membranes and total traumatic hyphemae. RESULTS: Thirteen eyes of 13 patients were treated. Four cases of traumatic hyphema and 9 cases of fibrinous membranes were included. Complete fibrinolysis within 24 hours was observed in 4 cases (30.8%). A partial success was noted in 7 eyes (53.8%). No beneficial effect was observed in two cases of traumatic hyphema associated with intravitreal hemorrhage after penetrating trauma. No side effect attributable to rt-PA occurred. CONCLUSION: Low dose intraocular rt-PA appears to be safe and effective in the treatment of postoperative fibrinous membrane and endocular hemorrhage limited to the anterior chamber.

Is lean body mass decreased after obesity treatment by adjustable gastric banding?

BACKGROUND: There is concern that surgically-induced weight loss in obese subjects is associated with a disproportionate decrease in lean body mass (LBM) and in skeletal muscle mass (SMM), a major constituent of LBM. To address this issue, 1) we measured total and regional body composition following gastric banding in a group of obese subjects, and 2) we compared these data to those of a non-surgical control group of similar age and body size. METHODS: Body composition was assessed by dual-energy X-ray absorptiometry (DEXA) before and after laparoscopic adjustable silicone gastric banding (LAGB) in 32 women (after 1 year: age 43.7+/-8.4 years, BMI 36.4+/-5.9 kg/m2, mean+/-SD), and in 117 control women (age 44.5+/-7.5 years; BMI 36.7+/-5.5 kg/m2) referred for non-surgical weight management, prior to weight loss. SMM was estimated using a published equation based on LBM of the extremities (appendicular LBM). RESULTS: 1 year after LAGB, body weight loss (-23.7+/-11.6 kg, P<10(-6)) was mainly due to decreased fat mass (-21.2+/-11.2 kg, P<10(-6)), and total LBM was modestly, although significantly, decreased (-2.1+/-4.2 kg, P=0.01). Appendicular LBM (-0.7+/-2.7 kg) and total SMM (-0.9+/-3.0 kg) were not significantly modified. None of the body composition variables was significantly decreased in weight-reduced subjects compared to the control group, especially appendicular LBM and total SMM. CONCLUSIONS: Results provide no evidence for a decrease in appendicular LBM and total SMM with weight loss following LAGB. Follow-up of these obese patients revealed a very favorable pattern of change in total and regional body composition, with preservation of muscle mass.

Elevated serum f erritin is an independent predictor of severe liver fibrosis, steatosis, and treatment failure in chronic hepatitis C

Background: Infection with the hepatitis C virus (HCV) i s associatedwith hepatic iron accumulation. We performed a comprehensive analysisof serum ferritin levels and of their genetic determinants in thepathogenesis and treatment of patients with chronic hepatitis C enrolledin the Swiss Hepatitis C Cohort Study (SCCS).Methods: Serum ferritin levels at baseline o f therapy with p egylatedinterferon-α ( PEG-IFN-α) and ribavirin or b efore liver biopsy werecorrelated with clinical features of c hronic HCV infection, includingnecroinflammatory activity (N=970), fibrosis (N=980), steatosis (N=886)and response to treatment (N=876). The association b etween highferritin levels (> median) and the endpoints w as assessed b y logisticregression. In addition, a candidate gene analysis as well as a genomewideassociation study (GWAS) of serum ferritin levels were performed.Results: S erum ferritin > sex-specific median was one of the strongestpre-treatment predictors of failure to achieve SVR (P<0.0001, OR=0.46,95% CI=0.34-0.60). This association remained highly significant in amultivariate analysis (P=0.0001, OR=0.32, 95% CI=0.18-0.57), with anodds ratio c omparable to that of IL28B g enotype, and persisted afteradjustment for duration of infection. Additional independent predictors ofnonresponse were viral load, HCV genotype, presence of diabetes, andliver fibrosis stage. Higher serum ferritin levels were also independentlyassociated with severe liver fibrosis (P<0.0001, OR=2.67, 95% CI=1.66-4.28) a nd steatosis (P=0.0034, OR=2.34, 95% CI=1.33-4.12), but n otwith necroinflammatory a ctivity (P=0.3). No significant g eneticdeterminants of serum ferritin levels were identified.Conclusions: Elevated serum ferritin levels are associated withadvanced liver fibrosis, hepatic steatosis, and poor r esponse to IFN-α-based therapy in c hronic hepatitis C, i ndependently from IL28Bgenotype.

REDUCTION OF MIGRAINES AFTER TREATMENT OF HEREDITARYHEMORRHAGIC TELANGIECTASIA (HHT)

Background: Pulmonary arteriovenous malformations (PAVMs) due to hereditaryhemorrhagic telangiectases (HHT) is associated with paradoxical strokes, brainabcesses, and increased prevalence of migraines. We report a patient in whom wefound a relationship between PAMVs and a reduction in frequency of migrainewith aura after the treatment of the first pulmonary malformation.Patient and methods: A 67-year-old woman developed migraine with visual auraand major epistaxis during childhood. A PAVM is discovered and surgically removedin 1969. Migraines nearly disappeared during several years, after which theystarted to reappear progressively. A HHT syndrome is diagnosed based on recurrentepistaxis, the development of cutaneous telangiectases and a positive family history.She suffered a left subcortical stroke in 2008. Perfusion CT, chest radiography,thoracic CT-angiography, contrast echocardiography, contrast transcranial Dopplerand cerebral MRI were performed.Results: Perfusion CT showed previous asymptomatic strokes in cerebellum andbasal ganglia. 4 PAMVs were confirmed on the chest x-ray whose structural conformationis identified on thoracic CT. Contrast echocardiography and transcranialDoppler showed a massive right to left shunt. It is planned to embolize the 4PAVMs, and migraine frequency will now be prospectively assessed.Conclusion: This patient with a pulmonary arteriovenous malformation showeda reduced migraine frequency after resection of her lung lesion. This suggests acausal relationship between a right to left shunt and migraine, as discussed inpatients with patent foramen ovale.

Treatment with tumor necrosis factor inhibitors in axial spondyloarthritis: comparison between private rheumatology practices and academic centers in a large observational cohort.

OBJECTIVE: To evaluate the initiation of and response to tumor necrosis factor (TNF) inhibitors for axial spondyloarthritis (axSpA) in private rheumatology practices versus academic centers. METHODS: We compared newly initiated TNF inhibition for axSpA in 363 patients enrolled in private practices with 100 patients recruited in 6 university hospitals within the Swiss Clinical Quality Management (SCQM) cohort. RESULTS: All patients had been treated with ≥ 1 nonsteroidal antiinflammatory drug and > 70% of patients had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 before anti-TNF agent initiation. The proportion of patients with nonradiographic axSpA (nr-axSpA) treated with TNF inhibitors was higher in hospitals versus private practices (30.4% vs 18.7%, p = 0.02). The burden of disease as assessed by patient-reported outcomes at baseline was slightly higher in the hospital setting. Mean levels (± SD) of the Ankylosing Spondylitis Disease Activity Score were, however, virtually identical in private practices and academic centers (3.4 ± 1.0 vs 3.4 ± 0.9, p = 0.68). An Assessment of SpondyloArthritis international Society (ASAS40) response at 1 year was reached for ankylosing spondylitis in 51.7% in private practices and 52.9% in university hospitals (p = 1.0) and for nr-axSpA in 27.5% versus 25.0%, respectively (p = 1.0). CONCLUSION: With the exception of a lower proportion of patients with nr-axSpA newly treated with anti-TNF agents in private practices in comparison to academic centers, adherence to ASAS treatment recommendations for TNF inhibition was equally high, and similar response rates to TNF blockers were achieved in both clinical settings.

An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia.

OBJECTIVE: To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States. METHODS: This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function. RESULTS: Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events. CONCLUSION: Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registry NCT00333866).

Impact of previous virological treatment failures and adherence on the outcome of antiretroviral therapy in 2007.

BACKGROUND: Combination antiretroviral treatment (cART) has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort. METHODS: Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence. Starting ART in the mono/dual era before HIV-1 RNA assays became available was counted as one failed regimen. Logistic regression was used to identify risk factors for virological failure between the two consecutive visits. RESULTS: Of 4541 patients 31.2% and 68.8% had initiated therapy in the mono/dual and cART era, respectively, and been on treatment for a median of 11.7 vs. 5.7 years. At visit 1 in 2007, the mean number of previous failed regimens was 3.2 vs. 0.5 and the viral load was undetectable (<50 copies/ml) in 84.6% vs. 89.1% of the participants, respectively. Adjusted odds ratios of a detectable viral load at visit 2 for participants from the mono/dual era with a history of 2 and 3, 4, >4 previous failures compared to 1 were 0.9 (95% CI 0.4-1.7), 0.8 (0.4-1.6), 1.6 (0.8-3.2), 3.3 (1.7-6.6) respectively, and 2.3 (1.1-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. From the cART era, odds ratios with a history of 1, 2 and >2 previous failures compared to none were 1.8 (95% CI 1.3-2.5), 2.8 (1.7-4.5) and 7.8 (4.5-13.5), respectively, and 2.8 (1.6-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. CONCLUSIONS: A higher number of previous virologically failed regimens, and imperfect adherence to therapy were independent predictors of imminent virological failure.

Changes in antihypertensive drug treatment in the general population: the Colaus Study

Background and aims: there is little information regar ding changes in antihypertensive drug treatment in Switzerland. We aimed at assessing those changes in a population-based, prospective study. Methods: 768 hypertensive subjects (372 women, 397 men) followed for 5 years. Subjects were defined as continuers (no change), switchers (one antihypertensive class replace by another), combiners (one antihypertensive class added) and discontinuers (stopped treatment). Results: Analysis of all patients (mono or combination therapy) showed that 54.6% were continuers, 27.2% combiners, 12.9% switchers and 5.3 % discontinuers. Similar findings were obtained for participants on monotherapy only: 42.2% continuers, 36.7% combiners, 13.4% switchers and 7.7% discontinuers. Combiners had higher systolic and diastolic blood pressure values at baseline than the other groups (p<0.001), while no difference were found for personal and family history and other clinical and biological variables. Compared to continuers, combiners and switchers improved their blood pressure status at follow-up: 26.7% of combiners and 26.3% of switchers improved, versus 17.7% of continuers and 7.3% of discontinuers (p<0.001). Among participants on monotherapy at baseline, continuation was greatest for angiotensin II type 1 receptor blocking agents (ARBs, 53.1%), angiotensin-converting enzyme inhibitors (44.4%) and β-blockers (41.8%). Only one quarter of participants treated with diuretic or calcium channel blockers at baseline remained so at follow-up. Conclusion: Antihypertensivedrug treatment is very stable in Switzerland. There are no big differences in persistence between antihypertensive classes, even if ARBs had the most favorable utilization pattern. Changes are only due to blood pressure level and improve blood pressure status.

Antiretroviral treatment during pregnancy.

OBJECTIVE: Virologic failure of HIV-positive patients is of special concern during pregnancy. We compared virologic failure and the frequency of treatment changes in pregnant and non-pregnant women of the Swiss HIV Cohort Study. METHODS: Using data on 372 pregnancies in 324 women we describe antiretroviral therapy during pregnancy. Pregnant women on HAART at conception (n = 131) were matched to 228 non-pregnant women (interindividual comparison) and to a time period of equal length before and after pregnancy (intraindividual comparison). Women starting HAART during pregnancy (n = 145) were compared with 578 non-pregnant women starting HAART. FINDINGS: The median age at conception was 31 years, 16% (n = 50) were infected through injecting drug use and the median CD4 cell count was 489 cells/microl. In the majority of pregnancies (n = 220, 59%), women had started ART before conception. When ART was started during pregnancy (n = 145, 39%), it was mainly during the second trimester (n = 100, 69%). Two thirds (n = 26) of 35 women starting in the third trimester were diagnosed with HIV during pregnancy. The risk of virologic failure tended to be lower in pregnant than in non-pregnant women [adjusted odds ratio 0.52 (95% confidence interval 0.25-1.09, P = 0.08)], but was similar in the intraindividual comparison (adjusted odds ratio 1.04, 95% confidence interval 0.48-2.28). Women starting HAART during pregnancy changed the treatment less often than non-pregnant women. CONCLUSION: Despite the physiological changes occurring during pregnancy, HIV infected pregnant women are not at higher risk of virologic failure.

Oral mucosal melanoma: conservative treatment including laser surgery.

Objective: To discuss the convenience of laser surgery as optimal treatment for melanoma of the oral mucosa.Patients and methods: A retrospective evaluation of four patients with primary oral melanomas treated at a single Cancer Institution in Mexico City.Results: Two patients were treated with resection of the melanoma with CO2 laser together with extraction of the involved dental organs and curettage of the alveolar walls. These two cases had melanoma in situ with multiple isolated foci. The third patient had a lesion with vertical growth, who was submitted to partial maxillectomy along with selective dissection of bilateral neck levels I-V with a negative report and the fourth patient had a history of oral nodular melanoma and presented with lymph node metastasis. According to follow-up status, there was no distant metastasis in any of the patients reported here.Conclusion: In our experience, conservative management with CO2 laser is adequate for melanomas of the oral mucosa with extraction of the dental organs and curettage of the alveoli to achieve complete surgical resection microscopically without sacrifice of the quality of life. Management of the neck is controversial. We recommend selective therapeutic resection of the neck only if it is found to be clinically positive. Elective dissection has not shown to have an impact in overall survival.

Clinical characteristics, prognosis, and treatment of pelvic cryptorchid seminoma.

PURPOSE: To analyze the clinical characteristics, prognosis, and treatment outcome of pelvic cryptorchid seminoma (PCS), and to determine whether whole abdominal-pelvic irradiation for Stage I disease is necessary. METHODS AND MATERIALS: From 1958 to 1991, 60 patients with PCS were treated at the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing. They presented with a lower abdominal mass and showed a predominance for the right side. A high proportion of patients with PCS [26 of 60 (43%)] had metastatic disease, compared to 20% of those with scrotal seminoma, and there was a tendency toward a higher frequency of pelvic nodal metastases. There were 34 Stage I, 6 Stage IIA, 11 Stage IIB, 5 Stage III, and 4 Stage IV patients. Of these 60 patients, 56 underwent laparotomy with or without cryptorchiectomy (37 radical orchiectomy, 7 partial orchiectomy, and 12 biopsy of the primary or cervical node), and 4 cervical node biopsy only. All patients were further treated with radiotherapy, chemotherapy, or a combination of both. Patients with Stage I and II disease received radiotherapy, whereas patients with Stage III and IV were treated with chemotherapy. RESULTS: The overall and disease-free survivals at 5 and 10 years were 92% and 87%, and 88% and 84%, respectively. The 5- and 10-year survivals were 100% for Stage I, 94% and 87% for Stage II, and 56% and 42% for Stage III/IV, respectively (p < 0.05). Volume of irradiation, i.e., whole abdominal-pelvic radiotherapy (10 patients), versus hockey-stick encompassing paraaortic, ipsilateral iliac nodes and the primary tumor or tumor bed (17) did not influence outcome in Stage I patients. Five patients relapsed within 2-12 years after treatment, and four of these patients were successfully salvaged. Four patients developed a second malignant tumor and died. CONCLUSION: Stage I and II PCS can be adequately controlled by radiotherapy regardless of the surgical procedure. Whole abdominal-pelvic irradiation for Stage I and IIA disease is not required, and fields can be limited to the paraaortic, ipsilateral iliac nodes and primary tumor or tumor bed. We recommend platinum-based chemotherapy for Stage IIB-IV PCS.