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.     

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.     

Tonic dystonia: an uncommon complication of reflex sympathetic dystrophy syndrome. A review of five cases

Tonic dystonia is an underrecognized complication of reflex sympathetic dystrophy syndrome (RSDS) characterized by an increase in muscle tone at the site of injury. Case-reports.- We describe five cases of tonic dystonia complicating RSDS of the lower extremity. There were four women and one man, with a mean age of 52 years. In addition to the typical features of RSDS, the patients had fixed equinovarus of the foot with hyperextension or hyperflexion of the great toe. In two patients, examination after spinal anesthesia showed that the deformity was reducible. Spontaneous resolution of the dystonia occurred in one patient. Another patient failed to experience meaningful improvement after a motor block followed by botulinic toxin injections. In two patients, the same treatment was followed by a slight improvement. Treatment options are still being evaluated in the last patient. Discussion.- Tonic dystonia is an underrecognized complication of RSDS that often develops after a minor injury yet causes prolonged pain and disability. Spread of the dystonia to other sites is not infrequent. The underlying mechanisms remain unclear but may involve dysfunction of the central or peripheral nervous system or psychogenic factors. Suggested treatments include motor block, intrathecal baclofen, sympathetic block, and sympathectomy. However, none of these treatments has been proved effective. Conclusion.- The five cases described here provide useful information on RSDS-associated tonic dystonia, a condition that runs a protracted course and remains difficult to manage.