Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process.

OBJECTIVES: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care. METHODS: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice. RESULTS: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years. CONCLUSIONS: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.

Treating schizophrenia with cariprazine: from clinical research to clinical practice. Real world experiences and recommendations from an International Panel.

BACKGROUND: Management of schizophrenia is sub-optimal in many patients. Targeting negative symptoms, among the most debilitating aspects of schizophrenia, together with positive symptoms, can result in significant functional benefits and dramatically improve quality of life for patients and their carers. Cariprazine, a partial agonist of the dopamine receptors D2/D3 has demonstrated effectiveness across symptom domains in clinical trials, particularly on negative symptoms. OBJECTIVE: To obtain a broader insight from clinicians with specific experience with cariprazine, on how it affects patient populations outside the clinical trial setting. METHODS: The panel addressed a series of psychopharmacologic topics not comprehensively addressed by the evidence-based literature, including characteristics of patients treated, dosing and switching strategies, duration of therapy, role of concomitant medications and tolerability as well as recommendations on how to individualize cariprazine treatment for patients with schizophrenia. RESULTS: Patients recommended for cariprazine treatment are those with first episodes of psychosis, predominant negative symptoms (maintenance/acute phase) and significant side effects (metabolic side effects, hyperprolactinemia, sedation) with other antipsychotics. When the long-term treatment of a lifetime illness is adequately weighted, cariprazine becomes one of the first-line medications, not only for patients with predominant negative symptoms but also for those with relatively severe positive symptoms, especially if they are at the first episodes and if a specific medication is added for symptoms such as agitation or insomnia. For instance, patients with agitation may also benefit from the combination of cariprazine and a benzodiazepine or another sedating agent. Cariprazine may be prescribed as add-on to medications such as clozapine, when that medication alone is ineffective for negative symptoms, and sometimes the first may be discontinued or its dose lowered, after a period of stability, leaving the patient on a better tolerated antipsychotic regimen. CONCLUSIONS: Based on real-world clinical experience, the panel considered that cariprazine, with its distinct advantages including pharmacokinetics/pharmacodynamics, good efficacy and tolerability, represents a drug of choice in the long-term management of schizophrenia not only for patients with predominant negative symptoms but also for those with positive symptoms.

Zebrafish xenografts as a fast screening platform for bevacizumab cancer therapy.

Despite promising preclinical results, average response rates to anti-VEGF therapies, such as bevacizumab, are reduced for most cancers, while incurring in remarkable costs and side effects. Currently, there are no biomarkers available to select patients that can benefit from this therapy. Depending on the individual tumor, anti-VEGF therapies can either block or promote metastasis. In this context, an assay able to predict individual responses prior to treatment, including the impact on metastasis would prove of great value to guide treatment options. Here we show that zebrafish xenografts are able to reveal different responses to bevacizumab in just 4 days, evaluating not only individual tumor responses but also the impact on angiogenesis and micrometastasis. Importantly, we perform proof-of-concept experiments where clinical responses in patients were compared with their matching zebrafish Patient-Derived Xenografts - zAvatars, opening the possibility of using the zebrafish model to screen bevacizumab therapy in a personalized manner.

Modafinil in schizophrenia: is the risk worth taking?

Schizophrenia is a severe mental disorder characterised by positive and negative symptoms. Negative symptoms are difficult to treat and there is no specific treatment. In small trials, modafinil has been studied in association with antipsychotic treatment. We present three cases of its use; two have developed positive symptoms and one developed renal impairment. Further studies are needed to assess its usefulness in schizophrenia and safety in this group of patients.

The Mental Health Recovery Measure Can Be Used to Assess Aspects of Both Customer-Based and Service-Based Recovery in the Context of Severe Mental Illness.

Within clinical psychiatry, recovery from severe mental illness (SMI) has classically been defined according to symptoms and function (service-based recovery). However, service-users have argued that recovery should be defined as the process of overcoming mental illness, regaining self-control and establishing a meaningful life (customer-based recovery). Here, we aimed to compare customer-based and service-based recovery and clarify their differential relationship with other constructs, namely needs and quality of life. The study was conducted in 101 patients suffering from SMI, recruited from a rural community mental health setting in Portugal. Customer-based recovery and function-related service-based recovery were assessed, respectively, using a shortened version of the Mental Health Recovery Measure (MHRM-20) and the Global Assessment of Functioning score. The Camberwell Assessment of Need scale was used to objectively assess needs, while subjective quality of life was measured with the TL-30s scale. Using multiple linear regression models, we found that the Global Assessment of Functioning score was incrementally predictive of the MHRM-20 score, when added to a model including only clinical and demographic factors, and that this model was further incremented by the score for quality of life. However, in an alternate model using the Global Assessment of Functioning score as the dependent variable, while the MHRM-20 score contributed significantly to the model when added to clinical and demographic factors, the model was not incremented by the score for quality of life. These results suggest that, while a more global concept of recovery from SMI may be assessed using measures for service-based and customer-based recovery, the latter, namely the MHRM-20, also provides information about subjective well-being. Pending confirmation of these findings in other populations, this instrument could thus be useful for comprehensive assessment of recovery and subjective well-being in patients suffering from SMI.

Pulmonary metastasis as sole manifestation of relapse in previously treated localised prostate cancer: three exceptional case reports.

Metastatic prostate cancer recurrence after definitive local therapy can occur in any tissue. Usually, the first affected site is the bone. Lung metastases without bone or lymph node involvement are extremely rare in patients with prostate cancer, and only a handful of cases are reported in the literature. In several other malignancies, such as breast cancer, sarcomas, colorectal cancer, and renal cell carcinoma, long-term disease-free survival has been reported after resection of solitary pulmonary metastases. We present three unusual cases of isolated pulmonary recurrence of prostate cancer after initial definitive local therapy. One of the patients underwent resection of the lung metastasis, resulting in a long-term disease-free survival. Both surgical excision of solitary and oligometastatic lung secondary lesions and systemic therapy can play an important role in long-term disease control. Surgery should be considered for selected and well-informed patients with pulmonary metastasis after primary localised treatment for prostate cancer.

[Cognition, social cognition and functioning in schizophrenia]. / Cognição, cognição social e funcionalidade na esquizofrenia.

The major reviews of the literature support the idea that a significant proportion of patients with schizophrenia present cognitive deficits in several domains, more marked in the domains of verbal memory, vigilance and attention, memory, intellectual quotient, language and executive functioning. Such deficits appear to be one of the main determinants of these patients' functional outcome. More recently, social cognition deficits have been described. Social cognition may be understood as a separate and independent dimension of neurocognition or non-social cognition and may constitute a mediator between the neurocognition and functioning. However, there has been controversy concerning the real meaning of deficits observed due to the diversity of analysis methodologies employed and the fact that the available neuropsychological tests and batteries have not been specifically designed to evaluate cognitive deficits in patients with schizophrenia. In this paper, the Working Group on Schizophrenia (GTE) describes and highlights the existing clinical and scientific evidence, performs a critical review of cognitive functioning, social cognition and its impact on functional outcome, in patients with schizophrenia. The authors review definitions of (neuro)cognition, social cognition and functioning, analyze the existing methods for its assessment, describe the treatments available in this context and summarize the evidence of dysfunctions in these three concepts, taking into account their interconnection. Overall, the GTE considered the need for a standardized battery of tests to measure neurocognition, social cognition and functioning, consensually accepting the use of MATRICS as the standard tool for assessing neurocognition in schizophrenia. It was also recognized that verbal memory and vigilance deficits may be the best predictors of functional outcome in schizophrenia. In addition, the GTE has established social cognition as a priority area in the study of schizophrenia, however, the limitations in terminology and assessment methodologies do not allow a consensus in this area. The GTE considers that further longitudinal studies with larger samples are needed, so that a more adequate therapeutic armamentarium becomes available for patients with schizophrenia.