Concomitant dysregulation of androgen secretion and dysfunction of adipose tissue induced insulin resistance

Hyperandrogenism and hyperinsulinemia have resulted from dysfunction of the theca cell of the ovary and adipose tissue and each one potentiates the other in patients with androgen excess disorders e.g., polycystic ovary disease and idiopathic hirsutism. Possible external and/or internal triggers can produce such cellular dysfunction. There is evidence that sodium valproate acts as a trigger of cellular dysfunction and produces both hyperinsulinemia and hyperandrogenism. Therefore, the elimination of these triggers can help the patients to recover from hyperinsulinemia, insulin resistance and hyperandrogenism.     

Propionibacterium acnes: an under-appreciated cause of post-neurosurgical infection

BACKGROUND: Propionibacterium acnes is increasingly recognized as a cause of post-neurosurgical infection. This review of patients with P. acnes neurosurgical infection was carried out in order to determine clinical characteristics and outcomes in relation to duration of antimicrobial treatment. METHODS: We retrospectively reviewed the charts of consecutive patients with P. acnes isolated from neurosurgical specimens from 1 January 1999 to 30 June 2005. We defined P. acnes neurosurgical infection as isolation of P. acnes alone from a sterile neurosurgical site in a patient who clinically improved following treatment with an appropriate antibiotic. RESULTS: We identified 28 patients with definite P. acnes neurosurgical infection; median age 49 years (range 23-77); 15 (54%) male. All patients had prior neurosurgical procedures: 27 (96%) post-craniotomy. The median time from surgery to presentation was 54 days (range 12-1,578). Eighteen out of 28 (64%) patients who met the definition of neurosurgical infection had Gram-positive bacilli seen in at least one surgical specimen compared with only 2/56 (4%) patients who did not meet the definition (P < 0.0001). Intravenous benzyl penicillin +/- oral penicillin VK was the most common treatment. The median duration of antibiotic treatment for intracranial infection was 29 days. Five of nine patients who had extracranial bone-flap-associated infection had 相似文献   

Demolition experts: management of the parafunctional patient: 2. Restorative management strategies

The second part of this paper discusses strategies for providing restorative dental care for the parafunctional patient.These include direct composite resin restorations, cast metal resin-retained restorations and dentine-bonded crowns, design features for porcelain fused to metal crowns and denture design. Specific features can help enhance predictability in the hostile environment of increased occlusal loading and parafunction. CLINICAL RELEVANCE: Appropriate planning, design and execution of restorative procedures can reduce the chance of failure. Patients may have to accept a compromise between appearance and restoration survival/maintenance.     

Local and regional anaesthetic techniques in wound management

Adequate pain control is vital in perioperative care. Pain affects respiratory and cardiovascular function with knock-on effects on many other organs and systems. Surgery is also recognized as one of the most frequent causes of chronic pain with surgical approach and level of pain experienced being modifiable risk factors for the development of chronic post-surgical pain.     

Cost-Effectiveness Models for Chronic Obstructive Pulmonary Disease: Cross-Model Comparison of Hypothetical Treatment Scenarios

ObjectivesTo compare different chronic obstructive pulmonary disease (COPD) cost-effectiveness models with respect to structure and input parameters and to cross-validate the models by running the same hypothetical treatment scenarios.MethodsCOPD modeling groups simulated four hypothetical interventions with their model and compared the results with a reference scenario of no intervention. The four interventions modeled assumed 1) 20% reduction in decline in lung function, 2) 25% reduction in exacerbation frequency, 3) 10% reduction in all-cause mortality, and 4) all these effects combined. The interventions were simulated for a 5-year and lifetime horizon with standardization, if possible, for sex, age, COPD severity, smoking status, exacerbation frequencies, mortality due to other causes, utilities, costs, and discount rates. Furthermore, uncertainty around the outcomes of intervention four was compared.ResultsSeven out of nine contacted COPD modeling groups agreed to participate. The 5-year incremental cost-effectiveness ratios (ICERs) for the most comprehensive intervention, intervention four, was €17,000/quality-adjusted life-year (QALY) for two models, €25,000 to €28,000/QALY for three models, and €47,000/QALY for the remaining two models. Differences in the ICERs could mainly be explained by differences in input values for disease progression, exacerbation-related mortality, and all-cause mortality, with high input values resulting in low ICERs and vice versa. Lifetime results were mainly affected by the input values for mortality. The probability of intervention four to be cost-effective at a willingness-to-pay value of €50,000/QALY was 90% to 100% for five models and about 70% and 50% for the other two models, respectively.ConclusionsMortality was the most important factor determining the differences in cost-effectiveness outcomes between models.     

Cost-effectiveness of roflumilast as an add-on treatment to long-acting bronchodilators in the treatment of COPD associated with chronic bronchitis in the United Kingdom

Objective

To estimate the cost-effectiveness of adding a selective phosphodiesterase-4 inhibitor, roflumilast, to a long-acting bronchodilator therapy (LABA) for the treatment of patients with severe-to-very severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis with a history of frequent exacerbations from the UK payer perspective.

Methods

A Markov model was developed to predict the lifetime cost and outcomes [exacerbations rates, life expectancy, and quality-adjusted life years (QALY)] in patients treated with roflumilast, which showed a reduction in the exacerbation rates and lung function improvement in a pooled analysis from two clinical trials, M2-124 and M2-125. Sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness.

Results

The addition of roflumilast to concomitant LABA reduced the number of exacerbations from 15.6 to 12.7 [2.9 (95 % CI 0.88–4.92) exacerbations avoided] and increased QALYs from 5.45 to 5.61 [0.16 (95 % CI 0.02–0.31) QALYs gained], at an incremental cost of £3,197 (95 % CI £2,135–£4,253). Cost in LABA alone and LABA + roflumilast were £16,161 and £19,358 respectively. The incremental cost-effectiveness ratios in the base case were £19,505 (95 % CI £364–£38,646) per quality-adjusted life-year gained and 18,219 (95 % CI £12,697–£49,135) per life-year gained. Sensitivity analyses suggest that among the main determinants of cost-effectiveness are the reduction of exacerbations and the case fatality rate due to hospital-treated exacerbations. Probabilistic sensitivity analysis suggests that the probability of roflumilast being cost-effective is 82 % at willingness-to-pay £30,000 per QALY.

Conclusions

The addition of roflumilast to LABA in the treatment of patients with severe-to-very severe COPD reduces the rate of exacerbations and can be cost-effective in the UK setting.