Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-small-cell lung cancer

Paclitaxel poliglumex (PPX), a macromolecule drug conjugate linking paclitaxel to polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel. Patients with non-small-cell lung cancer (NSCLC) who had received one prior platinum-based chemotherapy received 175 or 210 mg m−2 PPX or 75 mg m−2 docetaxel. The study enrolled 849 previously treated NSCLC patients with advanced disease. Median survival (6.9 months in both arms, hazard ratio=1.09, P=0.257), 1-year survival (PPX=25%, docetaxel=29%, P=0.134), and time to progression (PPX=2 months, docetaxel=2.6 months, P=0.075) were similar between treatment arms. Paclitaxel poliglumex was associated with significantly less grade 3 or 4 neutropenia (P<0.001) and febrile neutropenia (P=0.006). Grade 3 or 4 neuropathy (P<0.001) was more common in the PPX arm. Patients receiving PPX had less alopecia and did not receive routine premedications. More patients discontinued due to adverse events in the PPX arm compared to the docetaxel arm (34 vs 16%, P<0.001). Paclitaxel poliglumex and docetaxel produced similar survival results but had different toxicity profiles. Compared with docetaxel, PPX had less febrile neutropenia and less alopecia, shorter infusion times, and elimination of routine use of medications to prevent hypersensitivity reactions. Paclitaxel poliglumex at a dose of 210 mg m−2 resulted in increased neurotoxicity compared with docetaxel

Malunion after midshaft clavicle fractures in adults: The current view on clavicular malunion in the literature

This is an overview of the current literature on malunion after midshaft clavicle fracture. Anatomy, trauma mechanism, classification, incidence, symptoms, prevention, and treatment options are all discussed. The conclusion is that clavicle malunion is a distinct clinical entity that can be treated successfully

Validation of the western ontario rotator cuff index in patients with arthroscopic rotator cuff repair: A study protocol

<p>Abstract</p> <p>Background</p> <p>Arthroscopic rotator cuff repair is described as being a successful procedure. These results are often derived from clinical general shoulder examinations, which are then classified as 'excellent', 'good', 'fair' or 'poor'. However, the cut-off points for these classifications vary and sometimes modified scores are used.</p> <p>Arthroscopic rotator cuff repair is performed to improve quality of life. Therefore, disease specific health-related quality of life patient-administered questionnaires are needed. The WORC is a quality of life questionnaire designed for patients with disorders of the rotator cuff. The score is validated for rotator cuff disease, but not for rotator cuff repair specifically.</p> <p>The aim of this study is to investigate reliability, validity and responsiveness of WORC in patients undergoing arthroscopic rotator cuff repair.</p> <p>Methods/Design</p> <p>An approved translation of the WORC into Dutch is used. In this prospective study three groups of patients are used: 1. Arthroscopic rotator cuff repair; 2. Disorders of the rotator cuff without rupture; 3. Shoulder instability.</p> <p>The WORC, SF-36 and the Constant Score are obtained twice before therapy is started to measure reliability and validity. Responsiveness is tested by obtaining the same tests after therapy.</p

Erratum

Barrese V, Miceli F, Soldovieri MV, Ambrosino P, Iannotti FA, Cilio MR, Taglialatela M. Neuronal potassium channel openers in the management of epilepsy: role and potential of retigabine. Clinical Pharmacology: Advances and Applications. 2010;2:225&amp;ndash;236.On page 233, left-hand column, second paragraph, line 17 forward, it says:&amp;ldquo;The most common reasons for discontinuation were dizziness, confusion, somnolence, and asthenia, with the highest proportion of withdrawals in patients receiving retigabine 1200 mg/kg.72 In RESTORE 1, where retigabine was used at 1200 mg/kg, urinary or renal disorders were observed in 12% of patients.&amp;rdquo;In this passage, both instances of &amp;ldquo;retigabine 1200 mg/kg&amp;rdquo; should be &amp;ldquo;retigabine 1200 mg/day.&amp;rdquo;Read original articl

Involvement of KCNQ2 subunits in [3H]dopamine release triggered by depolarization and pre-synaptic muscarinic receptor activation from rat striatal synaptosomes.

KCNQ2 and KCNQ3 subunits encode for the muscarinic-regulated current (IKM), a sub-threshold voltage-dependent K+ current regulating neuronal excitability. In this study, we have investigated the involvement of IKM in dopamine (DA) release from rat striatal synaptosomes evoked by elevated extracellular K+ concentrations ([K+]e) and by muscarinic receptor activation. [3H]dopamine ([3H]DA) release triggered by 9 mmol/L [K+]e was inhibited by the IKM activator retigabine (0.01–30 μmol/L; Emax = 54.80 ± 3.85%; IC50 = 0.50 ± 0.36 μmol/L). The IKM blockers tetraethylammonium (0.1–3 mmol/L) and XE-991 (0.1–30 μmol/L) enhanced K+-evoked [3H]DA release and prevented retigabine-induced inhibition of depolarization-evoked [3H]DA release. Retigabine-induced inhibition of K+-evoked [3H]DA release was also abolished by synaptosomal entrapment of blocking anti-KCNQ2 polyclonal antibodies, an effect prevented by antibody pre-absorption with the KCNQ2 immunizing peptide. Furthermore, the cholinergic agonist oxotremorine (OXO) (1–300 μmol/L) potentiated 9 mmol/L [K+]e-evoked [3H]DA release (Emax = 155 ± 9.50%; EC50 = 25 ± 1.80 μmol/L). OXO (100 μmol/L)-induced [3H]DA release enhancement was competitively inhibited by pirenzepine (1–10 nmol/L) and abolished by the M3-preferring antagonist 4-diphenylacetoxy N-methylpiperidine methiodide (1 μmol/L), but was unaffected by the M1-selective antagonist MT-7 (10–100 nmol/L) or by Pertussis toxin (1.5–3 μg/mL), which uncouples M2- and M4-mediated responses. Finally, OXO-induced potentiation of depolarization-induced [3H]DA release was not additive to that produced by XE-991 (10 μmol/L), was unaffected by retigabine (10 μmol/L), and was abolished by synaptosomal entrapment of anti-KCNQ2 antibodies. Collectively, these findings indicate that, in rat striatal nerve endings, IKM channels containing KCNQ2 subunits regulate depolarization-induced DA release and that IKM suppression is involved in the reinforcement of depolarization-induced DA release triggered by the activation of pre-synaptic muscarinic heteroreceptors