Factors for a broad technology assessment of comprehensive genomic profiling in advanced cancer, a systematic review.

Comprehensive Genomic Profiling (CGP) allows for the identification of many targets. Reimbursement decision-making is, however, challenging because besides the health benefits of on-label treatments and costs, other factors related to diagnostic and treatment pathways may also play a role. The aim of this study was to identify which other factors are relevant for the technology assessment of CGP and to summarize the available evidence for these factors. After a scoping search and two expert sessions, five factors were identified: feasibility, test journey, wider implications of diagnostic results, organisation of laboratories, and "scientific spillover". Subsequently, a systematic search identified 83 studies collecting mainly evidence for the factors "test journey" and "wider implications of diagnostic results". Its nature was, however, of limited value for decision-making. We recommend the use of comparative strategies, uniformity in outcome definitions, and the inclusion of a comprehensive set of factors in future evidence generation.

DCIS knowledge of women choosing between active surveillance and surgery for low-risk DCIS.

BACKGROUND: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but often never will. As we cannot predict accurately which DCIS-lesions will or will not progress to IBC, almost all women with DCIS undergo breast-conserving surgery supplemented with radiotherapy, or even mastectomy. In some countries, endocrine treatment is prescribed as well. This implies many women with non-progressive DCIS undergo overtreatment. To reduce this, the LORD patient preference trial (LORD-PPT) tests whether mammographic active surveillance (AS) is safe by giving women with low-risk DCIS a choice between treatment and AS. For this, sufficient knowledge about DCIS is crucial. Therefore, we assessed women's DCIS knowledge in association with socio-demographic and clinical characteristics. METHODS: LORD-PPT participants (N = 376) completed a questionnaire assessing socio-demographic and clinical characteristics, risk perception, treatment choice and DCIS knowledge after being informed about their diagnosis and treatment options. RESULTS: 66 % of participants had poor knowledge (i.e., answered ≤3 out of 7 knowledge items correctly). Most incorrect answers involved overestimating the safety of AS and misunderstanding of DCIS prognostic risks. Overall, women with higher DCIS knowledge score perceived their risk of developing IBC as being somewhat higher than women with poorer knowledge (p = 0.049). Women with better DCIS knowledge more often chose surgery whilst most women with poorer knowledge chose active surveillance (p = 0.049). DISCUSSION: Our findings show that there is room for improvement of information provision to patients. Decision support tools for patients and clinicians could help to stimulate effective shared decision-making about DCIS management.

Methodological guidance for the evaluation and updating of clinical prediction models: a systematic review.

BACKGROUND: Clinical prediction models are often not evaluated properly in specific settings or updated, for instance, with information from new markers. These key steps are needed such that models are fit for purpose and remain relevant in the long-term. We aimed to present an overview of methodological guidance for the evaluation (i.e., validation and impact assessment) and updating of clinical prediction models. METHODS: We systematically searched nine databases from January 2000 to January 2022 for articles in English with methodological recommendations for the post-derivation stages of interest. Qualitative analysis was used to summarize the 70 selected guidance papers. RESULTS: Key aspects for validation are the assessment of statistical performance using measures for discrimination (e.g., C-statistic) and calibration (e.g., calibration-in-the-large and calibration slope). For assessing impact or usefulness in clinical decision-making, recent papers advise using decision-analytic measures (e.g., the Net Benefit) over simplistic classification measures that ignore clinical consequences (e.g., accuracy, overall Net Reclassification Index). Commonly recommended methods for model updating are recalibration (i.e., adjustment of intercept or baseline hazard and/or slope), revision (i.e., re-estimation of individual predictor effects), and extension (i.e., addition of new markers). Additional methodological guidance is needed for newer types of updating (e.g., meta-model and dynamic updating) and machine learning-based models. CONCLUSION: Substantial guidance was found for model evaluation and more conventional updating of regression-based models. An important development in model evaluation is the introduction of a decision-analytic framework for assessing clinical usefulness. Consensus is emerging on methods for model updating.

Is the unstable ataxic hand of Alajouanine and Akerman a distinct contribution?

We discuss from a historical perspective whether the 1931 description of the "unstable ataxic hand" by Théophile Alajouanine, the fifth successor of Charcot at la Salpêtrière, and the Brazilian neurologist Abraham Akerman, then studying in France, merits being considered a distinct contribution vis-à-vis the earlier description by Oppenheim of the "useless hand syndrome". The specific object of the article by Alajouanine and Akerman was a semiologic sign, namely a pseudoathetosis localized in the hand, while the original description by Oppenheim of the symptom-complex that came to be known as useless hand syndrome did not include an abnormal movement. Moreover, as a result of the useless hand syndrome originating from a clinical classification of multiple sclerosis based on the localization of the lesions, it involves topographic and etiologic diagnoses specificities. In contrast, the unstable ataxic hand can be observed in the useless hand syndrome and other syndromes involving predominantly sensory symptoms, such as "numb clumsy hands" due to high cervical spondylosis or extramedullary tumor, and the "cortical sensory syndrome" most commonly due to parietal stroke. Because it had not been thoroughly described in the context of a symptom-complex, Alajouanine and Akerman's unstable ataxic hand merits being considered a distinct and valuable contribution.

A bioactive injectable bulking material; a potential therapeutic approach for stress urinary incontinence.

Stress urinary incontinence (SUI) is a life changing condition, affecting 20 million women worldwide. In this study, we developed a bioactive, injectable bulking agent that consists of Permacol™ (Medtronic, Switzerland) and recombinant insulin like growth factor-1 conjugated fibrin micro-beads (fib_rIGF-1) for its bulk stability and capacity to induce muscle regeneration. Therefore, Permacol™ formulations were injected in the submucosal space of rabbit bladders. The ability of a bulking material to form a stable and muscle-inducing bulk represents for us a promising therapeutic approach to achieve a long-lasting treatment for SUI. The fib_rIGF-1 showed no adverse effect on human smooth muscle cell metabolic activity and viability in vitro based on AlamarBlue assays and Live/Dead staining. Three months after injection of fib_rIGF-1 together with Permacol™ into the rabbit bladder wall, we observed a smooth muscle tissue like formation within the injected materials. Positive staining for alpha smooth muscle actin, calponin, and caldesmon demonstrated a contractile phenotype of the newly formed smooth muscle tissue. Moreover, the fib_rIGF-1 treated group also improved the neovascularization at the injection site, confirmed by CD31 positive staining compared to bulks made of PermacolTM only. The results of this study encourage us to further develop this injectable, bioactive bulking material towards a future therapeutic approach for a minimal invasive and long-lasting treatment of SUI.

Fiber density of collagen grafts impacts rabbit urethral regeneration.

There is a need for efficient and "off-the-shelf" grafts in urethral reconstructive surgery. Currently available surgical techniques require harvesting of grafts from autologous sites, with increased risk of surgical complications and added patient discomfort. Therefore, a cost-effective and cell-free graft with adequate regenerative potential has a great chance to be translated into clinical practice. Tubular cell-free collagen grafts were prepared by varying the collagen density and fiber distribution, thereby creating a polarized low fiber density collagen graft (LD-graft). A uniform, high fiber density collagen graft (HD-graft) was engineered as a control. These two grafts were implanted to bridge a 2 cm long iatrogenic urethral defect in a rabbit model. Histology revealed that rabbits implanted with the LD-graft had a better smooth muscle regeneration compared to the HD-graft. The overall functional outcome assessed by contrast voiding cystourethrography showed patency of the urethra in 90% for the LD-graft and in 66.6% for the HD-graft. Functional regeneration of the rabbit implanted with the LD-graft could further be demonstrated by successful mating, resulting in healthy offspring. In conclusion, cell-free low-density polarized collagen grafts show better urethral regeneration than high-density collagen grafts.

Prediction models for patients with esophageal or gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Clinical prediction models are increasingly used to predict outcomes such as survival in cancer patients. The aim of this study was threefold. First, to perform a systematic review to identify available clinical prediction models for patients with esophageal and/or gastric cancer. Second, to evaluate sources of bias in the included studies. Third, to investigate the predictive performance of the prediction models using meta-analysis. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL, and The Cochrane Library were searched for publications from the year 2000 onwards. Studies describing models predicting survival, adverse events and/or health-related quality of life (HRQoL) for esophageal or gastric cancer patients were included. Potential sources of bias were assessed and a meta-analysis, pooled per prediction model, was performed on the discriminative abilities (c-indices). RESULTS: A total of 61 studies were included (45 development and 16 validation studies), describing 47 prediction models. Most models predicted survival after a curative resection. Nearly 75% of the studies exhibited bias in at least 3 areas and model calibration was rarely reported. The meta-analysis showed that the averaged c-index of the models is fair (0.75) and ranges from 0.65 to 0.85. CONCLUSION: Most available prediction models only focus on survival after a curative resection, which is only relevant to a limited patient population. Few models predicted adverse events after resection, and none focused on patient's HRQoL, despite its relevance. Generally, the quality of reporting is poor and external model validation is limited. We conclude that there is a need for prediction models that better meet patients' information needs, and provide information on both the benefits and harms of the various treatment options in terms of survival, adverse events and HRQoL.

Microfluidic production of bioactive fibrin micro-beads embedded in crosslinked collagen used as an injectable bulking agent for urinary incontinence treatment.

Endoscopic injection of bulking agents has been widely used to treat urinary incontinence, often due to urethral sphincter complex insufficiency. The aim of the study was to develop a novel injectable bioactive collagen-fibrin bulking agent restoring long-term continence by functional muscle tissue regeneration. Fibrin micro-beads were engineered using a droplet microfluidic system. They had an average diameter of 140 µm and recombinant fibrin-binding insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1) was covalently conjugated to the beads. A plasmin fibrin degradation assay showed that 72.5% of the initial amount of α2PI1-8-MMP-IGF-1 loaded into the micro-beads was retained within the fibrin micro-beads. In vitro, the growth factor modified fibrin micro-beads enhanced cell attachment and the migration of human urinary tract smooth muscle cells, however, no change of the cellular metabolic activity was seen. These bioactive micro-beads were mixed with genipin-crosslinked homogenized collagen, acting as a carrier. The collagen concentration, the degree of crosslinking, and the mechanical behavior of this bioactive collagen-fibrin injectable were comparable to reference samples. This novel injectable showed no burst release of the growth factor, had a positive effect on cell behavior and may therefore induce smooth muscle regeneration in vivo, necessary for the functional treatment of stress and other urinary incontinences. STATEMENT OF SIGNIFICANCE: Urinary incontinence is involuntary urine leakage, resulting from a deficient function of the sphincter muscle complex. Yet there is no functional cure for this devastating condition using current treatment options. Applied physical and surgical therapies have limited success. In this study, a novel bioactive injectable bulking agent, triggering new muscle regeneration at the injection site, has been evaluated. This injectable consists of cross-linked collagen and fibrin micro-beads, functionalized with bound insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1). These bioactive fibrin micro-beads induced human smooth muscle cell migration in vitro. Thus, this injectable bulking agent is apt to be a good candidate for regeneration of urethral sphincter muscle, ensuring a long-lasting treatment for urinary incontinence.

Decision support systems for incurable non-small cell lung cancer: a systematic review.

BACKGROUND: Individually tailored cancer treatment is essential to ensure optimal treatment and resource use. Treatments for incurable metastatic non-small cell lung cancer (NSCLC) are evolving rapidly, and decision support systems (DSS) for this patient population have been developed to balance benefits and harms for decision-making. The aim of this systematic review was to inventory DSS for stage IIIB/IV NSCLC patients. METHODS: A systematic literature search was performed in Pubmed, Embase and the Cochrane Library. DSS were described extensively, including their predictors, model performances (i.e., discriminative ability and calibration), levels of validation and user friendliness. RESULTS: The systematic search yielded 3531 articles. In total, 67 articles were included after additional reference tracking. The 39 identified DSS aim to predict overall survival and/or progression-free survival, but give no information about toxicity or cost-effectiveness. Various predictors were incorporated, such as performance status, serum and inflammatory markers, and patient and tumor characteristics. Some DSS were developed for the entire incurable NSCLC population, whereas others were specifically for patients with brain or spinal metastases. Few DSS had been validated externally using recent clinical data, and the discrimination and calibration were often poor. CONCLUSIONS: Many DSS have been developed for incurable NSCLC patients, but DSS are still lacking that are up-to-date with a good model performance, while covering the entire treatment spectrum. Future DSS should incorporate genetic and biological markers based on state-of-the-art evidence, and compare multiple treatment options to estimate survival, toxicity and cost-effectiveness.

Oncologist, patient, and companion questions during pretreatment consultations about adjuvant cancer treatment: a shared decision-making perspective.

OBJECTIVES: To assess the occurrence of questions that foster shared decision making, in particular cancer patients' understanding of treatment decisions and oncologists' understanding of patients' priorities, during consultations in which preference-sensitive decisions are discussed. Specifically, (a) regarding patient understanding, do oncologists ask about patients' preexisting knowledge, information preferences, and understanding and do patients and companions ask about the disease and treatment, and (b) regarding patient priorities, do oncologists ask about patients' treatment- and decision-related preferences and do patients and companions ask about the decision? METHODS: Audiotaped pretreatment consultations of 100 cancer patients with 32 oncologists about (neo)adjuvant treatment were coded and analyzed to document question type, topic, and initiative. RESULTS: The oncologists ascertained prior knowledge in 50 patients, asked 24 patients about preferred (probability) information, and invited questions from 56 patients. The oncologists asked 32 patients about treatment preferences and/or for consent. Respectively, one-third and one-fifth of patients and companions asked about treatment benefits compared with three-quarters of them who asked about treatment harms and/or procedures. CONCLUSIONS: It would be helpful to patients if oncologists more often assessed patients' existing knowledge to tailor their information provision. Also, patients could receive treatment recommendations that better fit their personal situation if oncologists collected information on patients' views about treatments. Moreover, by educating patients to ask about treatment alternatives, benefits, and harms, patients may gain a better understanding of the choice they have.

IGF-1-containing multi-layered collagen-fibrin hybrid scaffolds for bladder tissue engineering.

UNLABELLED: Clinical success of bladder reconstructive procedures could be promoted by the availability of functional biomaterials. In this study, we have developed a multi-layered scaffold consisting of a bioactive fibrin layer laminated between two collagen sheets all having undergone plastic compression. With this construct we performed bladder augmentation in a nude rat model after partial bladder excision and evaluated the morphological and functional behavior of the implant. The fibrin was functionalized with a recombinant human insulin-like growth factor-1 (IGF-1) variant that covalently binds fibrin during polymerization and has a matrix metalloproteinase-cleavage insert to enable cell-mediated release. The purified IGF-1 variant showed similar bioactivity in vitro compared to commercially available wild type (wt) IGF-1, inducing receptor phosphorylation and induction of human smooth muscle cell proliferation. In vivo, the multi-layered bioactive collagen-fibrin scaffolds loaded with the IGF-1 variant triggered dose-dependent functional host smooth muscle cell invasion and bundle formation with re-urothelialization 4weeks after surgery in a rat model. STATEMENT OF SIGNIFICANCE: The design of new bio-functional scaffolds that can be employed for bladder reconstructive procedures is a growing focus in the field of tissue engineering. In this study, a fibrin binding form of human insulin-like growth factor-1 (IGF-1) was produced and used to functionalize a multi-layered collagen-fibrin scaffold consisting of bioactive fibrin layer, sandwiched between two collagen gels. An effective dosage of our IGF-1 variant was successfully determined via a nude rat bladder model, which may play a critical role in estimating its therapeutic dosage in clinical trials. Thus, this new bioactive scaffold may offer an advanced approach to accelerate bladder regeneration.

Timing of risk reducing mastectomy in breast cancer patients carrying a BRCA1/2 mutation: retrospective data from the Dutch HEBON study.

It is expected that rapid genetic counseling and testing (RGCT) will lead to increasing numbers of breast cancer (BC) patients knowing their BRCA1/2 carrier status before primary surgery. Considering the potential impact of knowing one's status on uptake and timing of risk-reducing contralateral mastectomy (RRCM), we aimed to evaluate trends over time in RRCM, and differences between carriers identified either before (predictively) or after (diagnostically) diagnosis. We collected data from female BRCA1/2 mutation carriers diagnosed with BC between 1995 and 2009 from four Dutch university hospitals. We compared the timing of genetic testing and RRCM in relation to diagnosis in 1995-2000 versus 2001-2009 for all patients, and predictively and diagnostically tested patients separately. Of 287 patients, 219 (76%) had a diagnostic BRCA1/2 test. In this cohort, the median time from diagnosis to DNA testing decreased from 28 months for those diagnosed between 1995 and 2000 to 14 months for those diagnosed between 2001 and 2009 (p < 0.001). Similarly, over time women in this cohort underwent RRCM sooner after diagnosis (median of 77 vs. 27 months, p = 0.05). Predictively tested women who subsequently developed BC underwent an immediate RRCM significantly more often than women who had a diagnostic test (21/61, 34%, vs. 13/170, 7.6 %, p < 0.001). Knowledge of carrying a BRCA1/2 mutation when diagnosed with BC influenced decisions concerning primary surgery. Additionally, in more recent years, women who had not undergone predictive testing were more likely to undergo diagnostic DNA testing and RRCM sooner after diagnosis. This suggests the need for RGCT to guide treatment decisions.

Histological variations of the glenoid labrum in dogs.

As the structure and clinical meaning of the canine glenoid labrum are repeatedly disputed up to now, an anatomical histological description of the structure and its varieties in older dogs is carried out. In this study, 20 shoulder joints are histologically and immunohistologically examined. The glenoid labrum (GL) is composed of up to three different zones: a transition zone composed of fibre cartilage with collagen fibres arranged like a fishnet-like pattern, a zone of circularly leading fibre bundles and a meniscoid fold with synovial coverage. A variable recess exists between the GL and the joint surface.

Compressed collagen gel: a novel scaffold for human bladder cells.

Collagen is highly conserved across species and has been used extensively for tissue regeneration; however, its mechanical properties are limited. A recent advance using plastic compression of collagen gels to achieve much higher concentrations significantly increases its mechanical properties at the neo-tissue level. This controlled, cell-independent process allows the engineering of biomimetic scaffolds. We have evaluated plastic compressed collagen scaffolds seeded with human bladder smooth muscle cells inside and urothelial cells on the gel surface for potential urological applications. Bladder smooth muscle and urothelial cells were visualized using scanning electron microscopy, conventional histology and immunohistochemistry; cell viability and proliferation were also quantified for 14 days in vitro. Both cell types tested proliferated on the construct surface, forming dense cell layers after 2 weeks. However, smooth muscle cells seeded within the construct, assessed with the Alamar blue assay, showed lower proliferation. Cellular distribution within the construct was also evaluated, using confocal microscopy. After 14 days of in vitro culture, 30% of the smooth muscle cells were found on the construct surface compared to 0% at day 1. Our results provide some evidence that cell-seeded plastic compressed collagen has significant potential for bladder tissue regeneration, as these materials allow efficient cell seeding inside the construct as well as cell proliferation.

Suspension-adapted Chinese hamster ovary-derived cells expressing green fluorescent protein as a screening tool for biomaterials.

Synthetic biomaterials play an important role in regenerative medicine. To be effective they must support cell attachment and proliferation in addition to being non-toxic and non-immunogenic. We used a suspension-adapted Chinese hamster ovary-derived cell line expressing green fluorescent protein (GFP) to assess cell attachment and growth on synthetic biomaterials by direct measurement of GFP-specific fluorescence. To simplify operations, all cell cultivation steps were performed in orbitally-shaken, disposable containers. Comparative studies between this GFP assay and previously established cell quantification assays demonstrated that this novel approach is suitable for rapid screening of a large number of samples. Furthermore the utility of our assay system was confirmed by evaluation of cell growth on three polyvinylidene fluoride polymer scaffolds that differed in pore diameter and drawing conditions. The data presented here prove the general utility of GFP-expressing cell lines and orbital shaking technology for the screening of biomaterials for tissue engineering applications.

Dimensional ridge alterations following socket preservation using a nanocrystalline hydroxyapatite paste: a histomorphometrical study in dogs.

The aim of the study was to evaluate the histological response and dimensional ridge alterations following application of a nanocrystalline hydroxyapatite paste (NHA) into fresh extraction sockets in dogs. Immediately following vertical tooth separation and extraction, NHA was inserted in the extraction socket of the second molar in the lower jaws of 10 dogs. Untreated extraction sites on the opposite side served as controls. Wounds were closed using resorbable sutures after vertical flap elevation. After three and six months, 5 animals were killed. Lingual and buccal bone height, alveolar wall and total bone width 1, 3 and 5mm underneath the top of the crest were evaluated. Histological analysis revealed a high variability of NHA resorption and osteoconductive properties with different rates of material resorption. No statistically significant differences could be observed between the corresponding aspects of test and control sites. Both groups revealed higher alveolar wall resorption on the buccal than on the lingual side at both time periods. NHA does not seem to be useful for socket preservation procedures since it failed to prevent dimensional ridge alterations while revealing osseous integration but unpredictable material resorption. The role of non-resorbed hydroxyapatite remnants for implant placement is unclear and requires further investigation.

Guided bone regeneration at dehiscence-type defects using biphasic hydroxyapatite + beta tricalcium phosphate (Bone Ceramic) or a collagen-coated natural bone mineral (BioOss Collagen): an immunohistochemical study in dogs.

The aim of this study was to immunohistochemically investigate bone regeneration following application of either hydroxyapatite+beta tricalcium phosphate (BCG) or a collagen-coated natural bone mineral (BOC) in combination with a collagen membrane at dehiscence-type defects in dogs. Standardized buccal dehiscence defects were surgically created following implant bed preparation in six beagle dogs. Defects were randomly filled with either BOC (BioOss Collagen) or BCG (Bone Ceramic) according to a split-mouth design, and covered with a native porcine derived collagen membrane (BioGide). After 1, 4 and 9 weeks of submerged healing, dissected blocks were processed for immunohistochemical (osteocalcin) and histomorphometrical analysis (residual defect length, new bone-implant contact, area of new bone fill, percentage of osseointegrated bone-graft particles). Both groups revealed a significant decrease in mean residual defect length, and increases in mean new bone-implant contact, bone fill and percentage of osseointegrated bone-graft particles after 4 and 9 weeks of healing. Remaining BCG and BOC granules were completely integrated into a secondarily formed network of spongiosa, but there was no osteoclastic activity at the surface of either type of bone-graft particle. Both BCG and BOC may provide an osteoconductive scaffold to support guided bone regeneration procedures at dehiscence-type defects.

A doença de Alzheimer e o impacto nos cuidadores / Alzheimer's diseases and the impact on the caregivers

A doença de Alzheimer (DA) caracteriza-se por um declínio progressivo e inexorável cognitivo, funcional e comportamental dos pacientes atingidos. À medida que o comprometimento ocorre surge a demanda de ajuda, que aumenta com a progressão da doença. Os cuidadores (parentes ou profissionais) vêm para prover os cuidados necessários. Estes desempenham um papel essencial no manejo da vida diária de pacientes com DA, envolvendo-se em praticamente todos os aspectos que dizem respeito aos cuidados da demência. O declínio dos pacientes (cognitivo, dependência nas atividades de vida diária e transtornos de comportamento) e suas demandas representam importantes estressores para os cuidadores levando a tensões como conflitos familiares e problemas econômicos. A carga gerada pela administração de cuidados expressa-se de maneiras mútiplas (emocionais, sociais, econômicas e físicas), que frequentemente se manifestam por altos níveis de problemas de saúde psicológica (ansiedade, depressão, insônia) e física (hipertensão arterial, propensão a infecções). Assim a carga de administrar cuidados é um conceito que integra o nível dos cuidados que o paciente requer com os sentimentos e as dificuldades dos cuidadores em provê-los. Algumas opções terapêuticas atuais para pacientes com DA mostram sucesso, principalmente a utilização de estratégias colinérgica e glutamatérgica, com indicação e utilidade que variam com o estágio da doença, com benefício (melhora, estabilização ou lentificação do declínio) em relação à cognição, função e comportamento. A eficácia do tratamento se relaciona com estabilização ou redução da carga dos cuidadores, oferecendo-lhes a possibilidade de uma melhora de qualidade de vida.

Alzheimer's disease (AD) is characterized by a progressive and relentless cognitive, functional and behavioral decline of the affected patients. As the impairment occurs a demand for help arises, and increases with the progression of the disease. The caregivers (relatives or professionals) come to participative in order to provide the needed assistance or care. They play an essential role in managing the daily life of AD patients under treatment, and are involved in virtually every aspect of dementia care. The patients' decline (cognitive, dependence in activities of daily living and behavioral disturbances) and their demands represent important stressors to the caregivers leading to strains like family conflicts and economic problems. The burden generated by caregiving is expressed in multiple ways (emotional, social, economical and physical), which frequently manifest themselves by high rates of psychological (anxiety, depression, insomnia) and physical (arterial hypertension, propensity to infections) health problems. Thus, caregiving burden is a concept that integrates the level of care the patients require with the caregivers's subjective and objective difficulties about providing it. Several present therapeutic options for patients with AD show some success, mainly the use of cholinergic and glutamatergic strategies, the indciation and utility depending on the stage of the disease, with benefit (improvement, stabilization or slowing of the decline) in relation to cognition, function and behavior. The efficacy of the treatment is related to stabilization or reduction of the burden, offering the caregivers the possibility of a better quality of life.

O mini-exame do estado mental-mais que um instrumento de triagem: uma análise neuropsicológica e neuroanatômica funcional / The mini-mental state examination - more than a screening tool: a neuropsychological and functional neuroanatomic analysis

O Mini-Exame do Estado Mental (MEEM) tem sido amplamente utilizado como instrumento de triagem cognitiva em ambiente de ambulatório e em situação de pesquisa. A obtenção de um ponto de corte para definir se o paciente examinado é suspeito de ser um 'caso' de comprometimento cognitivo / demência é geralmente o objetivo básico. Entretanto, do ponto de vista qualitativo, o MEEM encerra um potencial muito maior do que aparece à primeira vista, permitindo avaliar com relativo detalhe um número apreciável de domínios cognitivos, como atenção, memória, linguagem, gnosia, praxia, esquema corporal, função executiva e outras funções pré-frontais, pensamento. As redes neurais subjacentes a cada domínio são diversas e complexas, envolvendo grande número de áreas / regiões cerebrais, além de conexões hemisféricas e inter-hemisféricas. Dessa maneira o MEEM permite obter muito mais que um simples escore e um ponto de corte dentro de uma avaliação de triagem, mas sim, um mapa de comprometimento de diversos domínios cognitivos relacionados a diversos sistemas funcionais/redes neurais integrando regiões cerebrais determinadas.

Efficacy and safety of risperidone oral solution in agitation associated with dementia in the elderly.

BACKGROUND: Behavioral and psychological symptoms in dementia (BPSD) contribute to caregiver burden and institutionalization of elderly. Neuroleptics are prescribed to control agitation. Side effects of typical neuroleptics are harmful, making atypical neuroleptics an indication. OBJECTIVES: To evaluate efficacy and tolerability of risperidone oral solution (ROS) given once daily to demented elderly outpatients with BPSD (agitation). METHOD: Patients (n=26), 76.35+/-8.63 years, Diagnostic and Statistical Manual of Mental Disorders 4th ed. (DSM-IV) criteria for dementia. RSO was given, starting dose of 0.25 mg and increments of 0.25 mg every week. Mini-Mental State Examination (MMSE) assessed cognitive status, Behavioral and Emotional Activities Manifested in Dementia (BEAM-D) and Clinical Global Impression (CGI) measured BPSD, Extrapiramidal Symptom Rating Scale (ESRS) evaluated extrapyramidal symptoms. Cardiovascular side effects were evaluated clinically. RESULTS: There was a 26% reduction in agitation and no cardiovascular side effects in the range from 1.0 to 1.25 mg. Side effects were more prevalent above 2.5 mg. CONCLUSION: Risperidone oral solution improved agitation with good tolerability from 0.5 to 1.25 mg. A single dose with increments of 0.25 mg may be more acceptable to patients and caregivers.