Practical Insight to Monitor Home NIV in COPD Patients

Home noninvasive ventilation (NIV) is used in COPD patients with concomitant chronic hypercapnic respiratory failure in order to correct nocturnal hypoventilation and improve sleep quality, quality of life, and survival. Monitoring of home NIV is needed to assess the effectiveness of ventilation and adherence to therapy, resolve potential adverse effects, reinforce patient knowledge, provide maintenance of the equipment, and readjust the ventilator settings according to the changing condition of the patient. Clinical monitoring is very informative. Anamnesis focuses on the improvement of nocturnal hypoventilation symptoms, sleep quality, and side effects of NIV. Side effects are major cause of intolerance. Screening side effects leads to modification of interface, gas humidification, or ventilator settings. Home care providers maintain ventilator and interface and educate patients for correct use. However, patient's education should be supervised by specialized clinicians. Blood gas measurement shows a significant decrease in PaCO₂ when NIV is efficient. Analysis of ventilator data is very useful to assess daily use, unintentional leaks, upper airway obstruction, and patient ventilator synchrony. Nocturnal oximetry and capnography are additional monitoring tools to assess the impact of NIV on gas exchanges. In the near future, telemonitoring will reinforce and change the organization of home NIV for COPD patients.     

Alzheimer’s disease treatment: Assessing caregiver preferences for mode of treatment delivery

Introduction  Management of patients with Alzheimer’s Disease (AD) can exert a substantial burden upon caregivers. As new modes of treatment administration are developed, it is important to assess caregiver satisfaction and preference in a standardized manner. This study describes the development of the Alzheimer’s Disease Caregiver Preference Questionnaire (ADCPQ) to assess AD caregivers’ satisfaction with and preference for patch or capsule treatments in AD patients. Methods  Twenty-five published articles (1987-2002) were reviewed to identify potential ADCPQ domains. Three caregiver focus groups (n=24) were conducted to develop a first draft of the questionnaire. After evaluating the acceptance of ADCPQ to caregivers through in-depth interviews (n=10), its psychometric properties were assessed using data from 986 patients enrolled in a multicenter, randomized, double-blind, four-arm, placebo- and active-controlled, 24-week trial. Results  Focus groups indicated that caregivers expressed dissatisfaction with current AD treatment routines including limitations related to: efficacy, administration schedule, number of pills, adherence to treatment, side effects, and taking pills. In-depth interviews with caregivers found the ADCPQ to be comprehensible with an acceptable layout. The resultant ADCPQ comprises three modules: A) baseline, 11 items assessing treatment expectations; B) week 8, 33 items on satisfaction and preferences with treatment options; C) week 24, 10 items assessing overall opinions of treatment options. Missing data per item was low (≤0.3%) and domain internal consistency reliability was good (0.71–0.91). Preference items were also valid when evaluating concordance and discordance between convenience and satisfaction patch and capsule domain scores. Conclusion  AD treatment puts a significant strain on caregivers. New modes of treatment delivery may be less burdensome to caregivers, thereby increasing satisfaction and potential treatment adherence. The ADCPQ was well accepted by AD caregivers and its domains demonstrated satisfactory psychometric properties. The ADCPQ is a useful tool to understand caregiver preferences for patch versus oral therapies in AD.     

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.     

Nutritional factors as predictors of response to radio-chemotherapy and survival in unresectable squamous head and neck carcinoma

BACKGROUND AND PURPOSE: This study sought to evaluate nutritional prognostic factors before treatment in patients with unresectable head and neck cancer treated by concomitant radio-chemotherapy. METHODS AND MATERIALS: Seventy-two consecutive patients were treated. We studied the potential effects of CRP, Alb, preAlb, orosomucoid, weight, weight history, BMI, PINI, OPR and NRI on response to treatment, Event-Free Survival (EFS) and Overall Survival (OS). Effects of potential risk factors on OS and on EFS were analyzed by computing Kaplan-Meier estimates, and curves were compared using the log-rank test. RESULTS: All biological nutritional factors were statistically correlated with the response to radio-chemotherapy. In multivariate analysis, only CRP (p=0.004) remained statistically significant. A statistical correlation was found between Alb and EFS in multivariate analysis (p=0.04). The factors influencing OS in univariate analysis were Alb (p=0.008), CRP (p=0.004), orosomucoid (p=0.01) and NRI (p=0.01), response to radio-chemotherapy (p<0.001) and staging (p=0.04). In multivariate analysis, only the response to radio-chemotherapy (p<0.001) remained significant. CONCLUSIONS: This study illustrates the prognostic value of nutritional status. CRP and Alb may be useful in the assessment of advanced head and neck cancer patients at diagnosis and for stratifying patients taking part in randomized trials.     

An unbinding problem? The disintegration of visible,previously attended objects does not attract attention

In seven experiments, observers searched for a scrambled object among normal objects. The critical comparison was between repeated search in which the same set of stimuli remained present in fixed positions in the display for many (>100) trials and unrepeated conditions in which new stimuli were presented on each trial. In repeated search conditions, observers monitored an essentially stable display for the disruption of a clearly visible object. This is an extension of repeated search experiments in which subjects search a fixed set of items for different targets on each trial (Wolfe, Klempen, & Dahlen, 2000) and can be considered as a form of a "change blindness" task. The unrepeated search was very inefficient, showing that a scrambled object does not "pop-out" among intact objects (or vice versa). Interestingly, the repeated search condition was just as inefficient, as if participants had to search for the scrambled target even after extensive experience with the specific change in the specific scene. The results suggest that the attentional processes involved in searching for a target in a novel scene may be very similar to those used to confirm the presence of a target in a familiar scene.     

Quinacrine increases endothelial nitric oxide release: role of superoxide anion

The effect of acute quinacrine treatment on agonist-induced nitric oxide (NO) release was investigated in cultured human endothelial cells using electrochemical monitoring of the in situ NO concentration. Quinacrine dose-dependently increased NO release with an apparent EC50 of 0.2 microM and a maximal effect at 1 microM. Quinacrine did not modify the dependence of NO release on extracellular L-arginine. Acceleration or deceleration of O2- dismutation, which altered NO release in control cells, did not modify it in quinacrine-treated cells. Quinacrine did not modify NO amperometric signal or reaction with O2- produced by xanthine oxidation. In the presence of quinacrine, agonist-induced NO release became Mg2+ -independent and could not be attributed to an inhibition of phospholipase A2 activity. Quinacrine made NO release insensitive to Cu2+ chelation. The present study demonstrates that acute treatment by low quinacrine concentrations increases endothelial NO release, possibly through an inhibition of O2- production.     

Comparison between macaques' and humans' kinematics of prehension: the role of morphological differences and control mechanisms

Reaching and grasping has been widely studied in both macaques and humans, mainly with the aim of finding similar patterns of behavior in the two species. Little attention has yet been given to how morphological and behavioral differences between the two species might affect the kinematics of the movement. In this study, we present a careful analysis of the similarities and differences between humans' and macaques' prehension movements and discuss these with respect to both the control system and the biomechanics of the arm. Five humans and five macaques performed the same task, namely grasping small feeding objects using a precision grip. Macaques were observed in unconstrained conditions, free to adjust their body posture. The behavioral protocol for macaques revealed a postural preference for sitting and keeping the elbow slightly flexed when applying a precision grip. In agreement with the literature, kinematics revealed general features of movement common to both humans and macaques. However, within a similar timeframe, macaques produced steeper and wider excursion of the elbow and of the wrist, smaller abduction of the shoulder joint and larger displacement of the torso than humans did. The three-joint limb revealed stronger irregularities for the macaques. We hypothesize that the larger kinematic irregularities and the specific elbow--shoulder posture in macaques result in part from an effort of the control system to compensate for different biomechanical constraints, namely for limited shoulder-joint excursion, in order to achieve a similar range of comfort of motion. Finally, we briefly consider the influence of primitive neural circuits responsible for arm motion during locomotion and speculated on their influence on the control of reaching in macaques.     

Can we prevent in-stent restenosis?

Nowadays stent placement has replaced balloon angioplasty as the most commonly performed percutaneous coronary interventional procedure, mainly because of its better acute and chronic outcome. As a result, in-stent restenosis (ISR) has become a widespread problem. The incidence of ISR varies from 10% to 50% and depends on the absence or presence of several risk factors, such as small vessel size, longer lesions, and diabetes. Intravascular ultrasound studies have demonstrated that ISR is mainly caused by neointimal proliferation; consequently, this pathologic process has become the target of many preventive and therapeutic approaches. This article provides an overview of such management strategies, highlighting the rather disappointing experiences with mechanical and systemic drug therapies; the relative merits and disadvantages of intracoronary radiation; and the exciting yet realistic promise, embodied by the recent advancements in drug-eluting stent technology, of potentially eradicating ISR in the near future.     

Absence of FGFR3 mutations in urinary bladder tumours of rats and mice treated with N-butyl-N-(-4-hydroxybutyl)nitrosamine

Frequent activating mutations of FGFR3 (fibroblast growth factor receptor 3) are found in human urothelial cell carcinomas, particularly in superficial papillary tumours (in 74%-84% of pTaG1-G2), but not in carcinomas in situ (CIS) and at a low rate in invasive tumours (in 16%-21% of pT1-4). In mice and rats, BBN (N-butyl-N-(4-hydroxybutyl)nitrosamine) specifically induces bladder tumours. In rats, superficial papillary tumours are mostly observed. In mice, tumour progression follows the CIS pathway: CIS are first observed, followed by tumours that invade surrounding muscle. Therefore, we looked for FGFR3 mutations in these two animal models of bladder cancer. Only the FGFR3b isoform is expressed in human urothelium and derived tumours. We identified the FGFR3b isoform in rats for the first time and showed that this is the main isoform expressed in the bladder urothelium and derived carcinomas in mice and rats, as in humans. SSCP and sequence analysis of FGFR3b showed sequence changes (polymorphisms or silent mutations) in four BBN-induced rat and mouse bladder tumours. The absence of activating mutations of FGFR3 in the mouse model was in agreement with the fact that mouse BBN-induced bladder tumour progression mimics the CIS pathway. The absence of FGFR3 mutations in the rat bladder tumours suggests that, at least at the genetic level, rat superficial papillary tumours differ from their human counterparts.