Comparison of psychosocial outcomes in head and neck cancer patients receiving a coping strategies intervention and control subjects receiving no intervention

This feasibility study aimed at comparing psychosocial outcomes in head and neck cancer patients receiving the Nucare program with a group of control subjects receiving no intervention. A prospective, nonrandomized study design was used. The Nucare program, a short-term psychoeducational coping strategies intervention, was the test intervention. Control subjects were matched to intervention subjects by cancer stage and time since cancer diagnosis. Outcomes were quality of life and depressive symptoms evaluated at baseline and 3 to 4 months later. One hundred thirty-eight subjects were recruited, and outcome data were available on 101 subjects. At outcome evaluation, compared with their baseline scores, the intervention group had improved physical and social functioning, global quality of life, fatigue, sleep disturbance, and depressive symptoms; the control group showed no changes in quality of life or depressive symptoms. The results suggest that the Nucare program may improve quality of life and reduce depressive symptoms in head and neck cancer patients.     

In vivo pharmacodynamic profiling of doripenem against Pseudomonas aeruginosa by simulating human exposures

Doripenem is a new broad-spectrum carbapenem with activity against a range of gram-negative pathogens, including nonfermenting bacteria such as Pseudomonas aeruginosa. The objective of this study was to evaluate simulated human exposures to doripenem using a neutropenic murine thigh infection model against 24 clinical P. aeruginosa isolates with a wide range of MICs. Dosing regimens in mice were designed to approximate the free time above MIC (fT>MIC) observed with 500 mg doripenem every 8 h given as either a 1-h or 4-h intravenous infusion in humans. Maximal antibacterial killing was associated with doripenem exposures of > or =40% fT>MIC; bacteriostatic effects were noted at approximately 20% fT>MIC. The simulated 1-h infusion provided bactericidal effects for isolates with MICs of < or =2 microg/ml, while variable killing was noted for isolates with MICs of 4 to 8 microg/ml and regrowth for isolates with an MIC of 16 microg/ml. The 4-h infusion regimen displayed similar killing for isolates with MICs of < or =2 microg/ml and enhanced activity for two of the four isolates with an MIC of 4 microg/ml. Given that the 4-h regimen yields negligible fT>MIC for MICs of > or =8 microg/ml, regrowth was generally observed. Simulated doses of 500 mg doripenem every 8 h infused over 1 h demonstrated antibacterial killing for P. aeruginosa isolates with MICs of 0.125 to 8 microg/ml. Exposures of > or =40% fT>MIC resulted in the most pronounced bactericidal effects, while killing was variable for 20 to 30% fT>MIC. Infusing doses over 4 h enhanced efficacy against selected pseudomonal isolates with an MIC of 4 microg/ml.     

Differences in the inflammatory response between patients with and those without diabetes mellitus after coronary stenting

Background: Patients with diabetes mellitus who undergo coronary stenting are at increased risk of restenosis. It is known that inflammation plays a crucial role in restenosis. Objective: We assessed the inflammatory response to elective coronary stent implantation (CSI) in stable diabetic and nondiabetic patients. Methods: C‐reactive protein (CRP), soluble (s) P‐selectin, and soluble intercellular adhesion molecule (sICAM)‐1 plasma levels were determined in diabetic (n = 51) and nondiabetic (n = 56) patients before and 48 hours and 4 weeks after bare metal stenting (BMS). Results: Diabetic patients presented significantly higher inflammatory marker levels before and after CSI. Nonetheless, diabetic and nondiabetic patients had postintervention peak of markers attained within 48 hours. At baseline, diabetic and nondiabetic patients presented CRP levels of 5.0 ± 20.1 (P ≤ 0.04) and 3.8 ± 9.4 μg/ml and, at 48 hours postintervention, 22.0 ± 20.2 (P = 0.001; P = 0.002) and 12.6 ± 11.3 (P ≤ 0.0001) μg/ml. Regarding sP‐selectin, diabetic and nondiabetic patients obtained levels of, at baseline, 182 ± 118 (P ≤ 0.04) and 105 ± 48 ng/ml and, at 48 hours, 455 ± 290 (P = 0.001; P ≤ 0.01) and 215 ± 120 (P ≤ 0.04) ng/ml. For diabetic and nondiabetic patients, sICAM‐1 levels were, at baseline, 248 ± 98 (P ≤ 0.04) and 199 ± 94 ng/ml and, at 48 hours, 601 ± 201 (P = 0.001; P ≤ 0.01) and 283 ± 220 (P = 0.001) ng/ml. At 4 weeks, for all patients, markers returned to preprocedural levels: versus before PCI: *P = 0.001, ^§P ≤ 0.0001; versus nondiabetic patients: ^#P ≤ 0.04, ^¶P = 0.002, ^?P ≤ 0.01. Conclusions: Diabetic and nondiabetic patients exhibited a temporal inflammatory response after an elective BMS. However, diabetic patients present higher preprocedural levels of CRP, sP‐selectin, and sICAM‐1 and reveal a further exacerbated inflammatory response after intervention. The differences in inflammatory response may have implications in restenosis within these two sets of patients.     

NSAID-induced deleterious effects on the proximal and mid small bowel in seronegative spondyloarthropathy patients

AIM:To investigate the small bowel of seronegative spondyloarthropathy(SpA) patients in order to ascertain the presence of mucosal lesions.METHODS:Between January 2008 and June 2010,54 consecutive patients were enrolled and submitted to avideo capsule endoscopy(VCE) examination.Historyand demographic data were taken,as well as the history of non-steroidal anti-inflammatory drug(NSAID) consumption.After reading each VCE recording,a capsule endoscopy scoring index for small bowel mucosal inflammatory change(L...     

Influence of cortical bone anchorage on the primary stability of dental implants

Purpose

This retrospective chart review study assessed patient records to determine implant insertion torque (IT) and implant stability quotient (ISQ) values during implant placement to evaluate the correlation with cortical bone anchorage (mono- or bicortical).

Methods

Primary stability data (IT during implant placement surgery and ISQ values immediately after implant placement) and cone beam computed tomography of 33 patients (165 implants) were assessed. Patients were divided into the following groups: G1, implants with apical cortical bone contact; G2, implants with bicortical bone contact (apical and cervical regions); and G3, implants with cervical cortical bone contact.

Results

Sixty-eight implants were excluded due to cortical bone contact on regions other than implant apical or cervical. Ninety-seven implants were therefore assessed for this study. No implant failure was found after a mean 70.42-month follow-up time. Implants with bicortical anchorage (G2) showed higher IT (64.1 Ncm) during implant placement and higher ISQ values (76) (p?<?0.05). Monocortical implants (G1, apical, and G3, cervical) showed similar IT (G1 52.3 and G3 54.3) and ISQ values (G1 71.9 and G3 73) (p?>?0.05). No correlation (Pearson correlation coefficient) was found between the two stability measurement devices for the different cortical bone anchorages that were analyzed (G1 0.190, G2 0.039, and G3 ??0.027) (p?>?0.05).

Conclusions

Insertion torque values and implant stability quotients were influenced by cortical bone contact. No significant correlation was found between IT and ISQ values—higher insertion torque values do not necessarily lead to higher implant stability quotients.

     

Pharmacokinetics of oritavancin in plasma and skin blister fluid following administration of a 200-milligram dose for 3 days or a single 800-milligram dose

Oritavancin is a novel glycopeptide currently being developed for the treatment of complicated skin and skin structure infections (cSSSI), including those caused by multidrug resistant gram-positive pathogens. The disposition of oritavancin in skin structures was investigated using a cantharide-induced blister fluid model. Seventeen healthy male subjects received oritavancin, but only 16 subjects were evaluated after one subject discontinued study drug. Each subject (eight per dose group) received 200 mg of oritavancin once a day for 3 days (group A) or 800 mg as one single dose (group B). Group A plasma samples and exudates from blister fluid were collected on days 3, 4, 7, 9, and 12 and on days 3, 4, 7, and 9, respectively. Group B samples and exudates were collected on days 1, 2, 5, 7, and 10 and on days 1, 2, 5, and 7, respectively. Drug concentrations were determined using a liquid chromatography-tandem mass spectrometry assay and, subsequently, pharmacokinetic analysis was performed. Differences between treatment groups in ratios for area under the concentration-time curve for blister fluid and plasma (AUC(blister fluid)/AUC(plasma) ratios) were evaluated using a t test (alpha = 0.05). Mean maximum concentration of drug in plasma or blister fluid was approximately 8-fold and 11-fold higher in plasma than in blister fluid following the 200- or 800-mg doses of oritavancin, respectively. Mean AUC(blister fluid)/AUC(plasma) ratios at 24 h were 0.190 (standard deviation [SD], 0.052) and 0.182 (SD, 0.062) for groups A and B, respectively (P = 0.791). To place these results in a clinical context, mean drug concentrations in blister fluid exceed the oritavancin MIC at which 90% of strains are inhibited of Staphylococcus aureus (2 microg/ml) by approximately 2- to 5.5-fold at 12 h and 1.5- to 3-fold at 24 h following administration of both dosing regimens. These results support the potential use of oritavancin for the treatment of cSSSI.     

Use of Monte Carlo simulation to assess the pharmacodynamics of beta-lactams against Pseudomonas aeruginosa infections in children: a report from the OPTAMA program

BACKGROUND: Assessing the likelihood of achieving bactericidal pharmacodynamic exposures against Pseudomonas aeruginosa with intravenous antimicrobial regimens would provide insights into the selection of empiric therapy in the pediatric population. OBJECTIVE: The objective of this study was to use pharmacodynamic modeling to determine the likelihood of various pediatric antibiotic regimens achieving bactericidal exposures against P aeruginosa in children. METHODS: Minimum inhibitory concentrations (MICs) were determined for meropenem (20 and 40 mg/kg q8h), imipenem (15 and 25 mg/kg q6h), ceftazidime (50 mg/kg q8h), cefepime (50 mg/kg q8h), and piperacillin/tazobactam (75 mg/kg q6h) against P aeruginosa isolates from 2 pediatric institutions. A 5000-patient Monte Carlo simulation was performed to predict attainment of pharmacodynamic targets against P aeruginosa for each of these regimens in a population of 10-year-olds. Optimal regimens were defined as those that had a > or =90% likelihood of attaining target exposures. RESULTS: At institution 1, high-dose imipenem, high-dose meropenem, and ceftazidime achieved bactericidal pharmacodynamic exposures (likelihood of target attainment: 94%, 92%, and 92%, respectively). No other regimen was associated with a high probability of attaining bactericidal exposure (low-dose imipenem, 87%; cefepime, 85%; low-dose meropenem, 84%; piperacillin/tazobactam, 60%). At institution 2, no regimen was associated with a high likelihood of attaining bactericidal exposure; the calculated probabilities were cefepime, 78%; ceftazidime, 65%; high-dose meropenem, 58%; high-dose imipenem, 57%; low-dose imipenem, 54%; low-dose meropenem, 47%; and piperacillin/tazobactam, 47%. A lack of agreement between attainment of bactericidal exposures and percent susceptibility was apparent for many of the regimens. CONCLUSIONS: Few regimens demonstrated a high likelihood of achieving bactericidal exposures against P aeruginosa at these institutions. Importantly, percent susceptibility overestimated attainment of the bactericidal target for some regimens, suggesting that further study is necessary in pediatric patients. The findings of this study highlight differences in target attainment and MIC distributions between institutions, emphasizing the importance of using institution-specific data when selecting empiric antimicrobial therapy.     

Late coronary artery recanalization effects on left ventricular remodelling and contractility by magnetic resonance imaging.

AIMS: To assess the recanalization effects of post-myocardial infarction (MI) on left ventricular (LV) remodelling and contractility in relation to conservative therapy. METHODS AND RESULTS: Thirty-six patients with occluded infarct-related artery between 12 h and 14 days post-anterior MI were randomized to percutaneous coronary intervention (PCI group) or conservative therapy (no-PCI group). Magnetic resonance imaging was performed at enrollment and after 6 months. The left ventricle was divided into infarct, adjacent, and remote segments. There was no difference in relation to LV volume between groups at the 6 month follow-up. Change in LV ejection fraction was favourable to the PCI group: 5.00% vs. -0.76%, P=0.012. Change in circumferential shortening (Ecc) of the remote segments in the PCI group was significantly better than in the no-PCI group: -1.67+/-6.30% vs. 0.29+/-6.02%, P<0.001. Infarct size and LV mass were similar between groups. CONCLUSIONS: Late recanalization improved LV ejection fraction and myocardial contractility in late follow-up, but did not change the ventricular volumes. Improvement in the left ventricle global and regional contractility may benefit the long-term outcome in post-MI patients with sustained patency of the infarct-related artery.     

Age related changes in the activity-rest circadian rhythms and c-fos expression of ring doves with aging. Effects of tryptophan intake

Age related changes in the circadian rhythms and sleep quality has been linked with impairment in the function of the suprachiasmatic nucleus (SCN) and melatonin secretion. The precursor of melatonin, serotonin (5-HT) is a neurotransmitter involved in the synchronisation of the circadian clock located in SCN, which shows decreased levels with age. The present work studied the effects of L-tryptophan, the precursor of 5-HT, on the circadian activity-rest rhythm and c-fos expression in the SCN of young and old ring doves, animals diurnal and monocyclic as humans. Two hours before the onset of dark phase, animals housed in cages equipped for activity recording and maintained under 12/12 L/D conditions, received orally L-tryptophan (100 and 240 mg/kg) and, for comparative purposes, melatonin (2.5 and 5 mg/kg). The administration of both L-tryptophan and melatonin reduced the nocturnal activity of all ring doves although only the highest doses were effective in old ones. A reduced amplitude in the activity-rest rhythm was observed in old animals in comparison to youngest, but it was increased after the treatments. Sleep parameters, calculated from the activity data, indicated a worsened sleep quality in old animals but it was improved with the treatments. In addition, the expression of c-fos in the SCN was reduced after both mentioned treatments. The results point to the SCN as a target for the observed nocturnal effects of L-tryptophan and melatonin, and support the supplemental administration of the essential amino acid L-tryptophan to reverse the disturbances of the circadian activity-rest cycle related with ageing.