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Patients with cancer experience high rates of alterations in mental status. The mechanisms for altered mental status (AMS) in this population are manifold. The cancer itself may cause AMS through direct invasion of the central nervous system or as metastatic leptomeningeal spread. However, cancer patients are also vulnerable to tumor-associated complications such as seizures, cerebral edema, strokes, or cancer treatment-related complications such as infections, direct neural injury from radiation or chemotherapy, edema, or dysregulated autoimmune response from immunotherapies. Both during treatment and as sequelae, patients may suffer neurocognitive complications from chemotherapy and radiation, medications or opportunistic infections, as well as toxic-metabolic, nutritional, and endocrine complications. In this review, we describe a clinical approach to the cancer patient presenting with AMS and discuss the differential drivers of AMS in this patient population. While common etiologies of AMS in noncancer patients (toxic-metabolic or infectious encephalopathy, delirium) are also applicable to cancer patients, we additionally provide a cancer-specific differential diagnosis that warrants special consideration in the cancer patient with AMS.
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BACKGROUND: Fewer than 1 in 20 people on the African continent in need of palliative care receive it. Malawi is a low-income country in sub-Saharan Africa that has yet to achieve advanced palliative care integration accompanied by unrestricted access to pain and symptom relieving palliative medicines. This paper studied the impact of Malawi's Waterloo Coalition Initiative (WCI) - a local project promoting palliative care integration through service development, staff training, and increased service access. METHODS: Interdisciplinary health professionals at 13 hospitals in southern Malawi were provided robust palliative care training over a 10-month period. We used a cross-sectional evaluation to measure palliative care integration based on 11 consensus-based indicators over a one-year period. RESULTS: 92% of hospitals made significant progress in all 11 indicators. Specifically, there was a 69% increase in the number of dedicated palliative care rooms/clinics, a total of 253 staff trained across all hospitals (a 220% increase in the region), substantive increases in the number of patients receiving or assessed for palliative care, and the number of hospitals that maintained access to morphine or other opioid analgesics while increasing the proportion of referrals to hospice or other palliative care programs. CONCLUSION: Palliative care is a component of universal health coverage and Sustainable Development Goal 3. The WCI has made tremendous strides in establishing and integrating palliative care services in Malawi with notable progress across 11 project indicators, demonstrating that increased palliative care access is possible in severely resource-constrained settings through sustained models of partnership at the local level.
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Cuidados Paliativos al Final de la Vida , Cuidados Paliativos , Humanos , Malaui , Estudios Transversales , DolorRESUMEN
BACKGROUND: In recent years, the subspecialty of neuropalliative care has emerged with the goal of improving the quality of life of patients suffering from neurological disease, though gaps remain in neuropalliative care education and training. E-learning has been described as a way to deliver interactive and facilitated lower-cost learning to address global gaps in medical care. We describe here the development of a novel, international, hybrid, and asynchronous curriculum with both self-paced modules and class-based lectures on neuropalliative care topics designed for the neurologist interested in palliative care, the palliative care physician interested in caring for neurological patients, and any other physician or advanced care providers interested in neuropalliative care. METHODS: The course consisted of 12 modules, one per every four weeks, beginning July 2022. Each module is based on a case and relevant topics. Course content was divided into three streams (Neurology Basics, Palliative Care Basics, and Neuropalliative Care Essentials) of which two were optional and one was mandatory, and consisted of classroom sessions, webinars, and an in-person skills session. Evaluation of learners consisted of multiple choice questions and written assignments for each module. Evaluation of the course was based on semi-structured qualitative interviews conducted with both educator and learner, the latter of which will be published separately. Audio files were transcribed and underwent thematic analysis. For the discussion of the results, Khan's e-learning framework was used. RESULTS: Ten of the 12 participating educators were interviewed. Of the educators, three identified as mid-career and seven as senior faculty, ranging from six to 33 years of experience. Nine of ten reported an academic affiliation and all reported association with a teaching hospital. Themes identified from the educators' evaluations were: bridging the global gap, getting everybody on board, defining the educational scope, investing extensive hours of voluntary time and resources, benefiting within and beyond the curriculum, understanding the learner's experience, creating a community of shared learning, adapting future teaching and learning strategies, and envisioning long term sustainability. CONCLUSIONS: The first year of a novel, international, hybrid, and asynchronous neuropalliative care curriculum has been completed, and its educators have described both successes and avenues for improvement. Further research is planned to assess this curriculum from the learner perspective.
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Curriculum , Cuidados Paliativos , Investigación Cualitativa , Humanos , Instrucción por Computador , Neurología/educación , Educación a DistanciaRESUMEN
BACKGROUND: CREBBP and EP300 mutations occur at a frequency of 15% and 13%, respectively, in small cell lung cancer (SCLC), and preclinical models demonstrated susceptibility to targeting with HDAC inhibitors. METHODS: Patients with treatment-naïve extensive-stage SCLC, ECOG ≤2 were enrolled and treated with entinostat orally weekly (4 dose levels, DL) in combination with standard dose carboplatin, etoposide, and atezolizumab. Cohort allocation was determined by Bayesian optimal interval (BOIN) design targeting an MTD with a DLT rate of 20%. RESULTS: Three patients were enrolled and treated at DL1 with entinostat 2 mg. Patients were aged 69-83; 2 male, 1 female; 2 were ECOG 1, and 1 was ECOG 0. The most common adverse events (AEs) were anemia (3), neutropenia (3), thrombocytopenia (2), leukopenia (2), and hypocalcemia (2). Two experienced DLTs during cycle 1: (1) grade (Gr) 4 febrile neutropenia, and (1) Gr 5 sepsis. BOIN design required stopping accrual to DL1, and the trial was closed to further accrual. Entinostat and atezolizumab pharmacokinetics were both comparable to historical controls. CONCLUSION: Addition of entinostat to atezolizumab, carboplatin, and etoposide is unsafe and resulted in early onset and severe neutropenia, thrombocytopenia. Further exploration of entinostat with carboplatin, etoposide, and atezolizumab should not be explored. (ClinicalTrials.gov Identifier: NCT04631029).
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Anemia , Neoplasias Pulmonares , Neutropenia , Carcinoma Pulmonar de Células Pequeñas , Trombocitopenia , Humanos , Masculino , Femenino , Etopósido , Carboplatino , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Teorema de Bayes , Neutropenia/inducido químicamente , Trombocitopenia/inducido químicamente , Anemia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients. METHODS: Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS). RESULTS: Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p < 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p < 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006). CONCLUSIONS: Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management.
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Adenocarcinoma Mucinoso , Neoplasias del Apéndice , Neoplasias Peritoneales , Seudomixoma Peritoneal , Humanos , Seudomixoma Peritoneal/genética , Seudomixoma Peritoneal/terapia , Seudomixoma Peritoneal/metabolismo , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/terapia , Neoplasias del Apéndice/genética , Neoplasias del Apéndice/terapia , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Serina-Treonina Quinasas TOR/genética , Procedimientos Quirúrgicos de CitorreducciónRESUMEN
PURPOSE OF REVIEW: While the benefits of palliative care for patients with cancer are well established, palliative care in neuro-oncology is still in its early stages. However, in recent years, there has been increasing attention drawn to the need for better palliative care for patients with brain tumors. RECENT FINDINGS: There is a growing body of literature demonstrating the high symptom burden and significant supportive care and information needs of these patients and their caregivers. In the area of caregiver needs, the last 3 years has seen a more rapid growth in recognizing and characterizing these needs. However, there remains a knowledge gap regarding the optimal means of addressing these needs. In this article, we outline important recent advances in the literature on palliative care for patients with brain tumors and highlight areas in need of greater attention and investigation.
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Neoplasias Encefálicas , Cuidados Paliativos , Humanos , Calidad de Vida , Neoplasias Encefálicas/terapia , CuidadoresRESUMEN
Immune checkpoint inhibitors (ICIs) have been associated with neurological immune related adverse events (irAE-N) and patients with ICI toxicity may present with neurological or ocular symptoms. Furthermore, patients on ICI may initially present to oncology or neurology. We report a case series of 3 patients treated with ICIs presenting with diplopia or ptosis, found to have concurrent myocarditis in addition to immune-related myopathy (irMyopathy) or myasthenia gravis (irMG). None of the patients described cardiac symptoms, underscoring the importance of screening for myocarditis in patients presenting with diplopia and/or other neuromuscular symptoms which may suggest either irMyopathy or irMG.
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Miastenia Gravis , Miocarditis , Diplopía , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Miastenia Gravis/inducido químicamente , Miastenia Gravis/tratamiento farmacológico , Miocarditis/inducido químicamente , Miocarditis/diagnósticoRESUMEN
BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8th edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Endosonografía , Humanos , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Pancreatectomía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: Delirium is common among patients with acute stroke and associated with worse outcomes. However, it is unclear which stroke locations or types are most associated with delirium. MATERIALS AND METHODS: We systematically reviewed studies of patients with acute stroke that reported stroke locations and types by delirium status. We included papers in any language, through a combined search from January 2010 to June 2021. Case studies with less than 20 patients, case-control studies, and randomized controlled trials were excluded. MEDLINE, EMBASE, PsycINFO, CINAHL, and Alois databases were searched. Pooled relative risks were calculated using bivariate random effects models or network meta-analysis. Methodological quality was assessed across 8 factors. RESULTS: 31 patient samples representing 8329 patients were included. Delirium was more common in patients with supratentorial lesions than infratentorial (RR [Relative Risk] 2.01, CI [Confidence Interval] 1.49-2.72); anterior circulation lesions than posterior (RR 1.41, CI 1.13-1.78); and cortical lesions than subcortical (RR 1.54, CI 1.25-1.89). Stroke side was not associated with delirium (right vs. left: RR 0.99, CI 0.77-1.28). Delirium was more common in patients with hemorrhagic strokes than ischemic (RR 1.74, CI 1.42-2.11) and patients with preexisting qualitative atrophy (RR 1.66, CI 1.21-2.27). CONCLUSION: Several brain localizations and types of strokes were associated with delirium. Conclusions were in part limited by the heterogeneity of studies and broad or qualitative lesion descriptions. These results may assist in anticipating the risk of delirium in acute stroke and highlight brain networks and pathologies that may be involved in the pathophysiology of delirium.
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Delirio , Accidente Cerebrovascular , Delirio/epidemiología , Humanos , Metaanálisis en Red , Riesgo , Accidente Cerebrovascular/epidemiologíaRESUMEN
AIMS: National studies have demonstrated disparities in the treatment and survival of pancreatic cancer patients based on socioeconomic status (SES). This study aimed to identify specific differences in perioperative management and outcomes based on patient SES and to study the role of a multidisciplinary clinic (MDC) in mitigating any variations. METHODS: The study analyzed patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma in a large hospital system. The patients were categorized into groups of high and low SES and whether they were managed by the authors' pancreatic cancer MDC or not. The study compared differences in disease characteristics, receipt of multimodality therapy, perioperative outcomes, and recurrence-free and overall survival. RESULTS: Of the 162 low-SES patients and 119 high-SES patients, 54% were managed in the MDC. Outside the MDC, low-SES patients were less likely to receive neoadjuvant chemotherapy and had less minimally invasive surgery, a longer OR time, less enhanced recovery participation, and more major complications (p < 0.05). No SES disparities were observed among the MDC patients. Despite similar tumor characteristics, the low-SES patients had inferior median overall survival (21 vs 32 months; p = 0.005), but the MDC appeared to eliminate this disparity. Low SES correlated with inferior survival for the non-MDC patients (17 vs 32 months; p < 0.001), but not for the MDC patients (24 vs 25 months; p = 0.33). These findings persisted in the multivariable analysis. CONCLUSION: A pancreatic cancer MDC standardizes treatment decisions, eliminates disparities in surgical outcomes, and improves survival for low-SES patients.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/cirugía , Disparidades en Atención de Salud , Humanos , Recurrencia Local de Neoplasia , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Clase SocialRESUMEN
BACKGROUND: Palliative care (PC) development cannot only be assessed from a specialized provision perspective. Recently, PC integration into other health systems has been identified as a component of specialized development. Yet, there is a lack of indicators to assess PC integration for pediatrics, long-term care facilities, primary care, volunteering and cardiology. AIM: To identify and design indicators capable of exploring national-level integration of PC into the areas mentioned above. METHODS: A process composed of a desk literature review, consultation and semi-structured interviews with EAPC task force members and a rating process was performed to create a list of indicators for the assessment of PC integration into pediatrics, long-term care facilities, primary care, cardiology, and volunteering. The new indicators were mapped onto the four domains of the WHO Public Health Strategy. RESULTS: The literature review identified experts with whom 11 semi-structured interviews were conducted. A total of 34 new indicators were identified for national-level monitoring of palliative care integration. Ten were for pediatrics, five for primary care, six for long-term care facilities, seven for volunteering, and six for cardiology. All indicators mapped onto the WHO domains of policy and education while only pediatrics had an indicator that mapped onto the domain of services. No indicators mapped onto the domain of use of medicines. CONCLUSION: Meaningful contributions are being made in Europe towards the integration of PC into the explored fields. These efforts should be assessed in future regional mapping studies using indicators to deliver a more complete picture of PC development.
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Enfermería de Cuidados Paliativos al Final de la Vida , Cuidados Paliativos , Niño , Europa (Continente) , Humanos , Salud Pública , Derivación y ConsultaRESUMEN
Mutations in RAS occur in 30-50% of metastatic colorectal carcinomas (mCRCs) and correlate with resistance to anti-EGFR therapy. Consequently, mCRC biomarker guidelines state RAS mutational testing should be performed when considering EGFR inhibitor treatment. However, a small subset of mCRCs are reported to harbor RAS amplification. In order to elucidate the clinicopathologic features and anti-EGFR treatment response associated with RAS amplification, we retrospectively reviewed a large cohort of mCRC patients that underwent targeted next-generation sequencing and copy number analysis for KRAS, NRAS, HRAS, BRAF, and PIK3CA. Molecular testing was performed on 1286 consecutive mCRC from 1271 patients as part of routine clinical care, and results were correlated with clinicopathologic findings, mismatch repair (MMR) status and follow-up. RAS amplification was detected in 22 (2%) mCRCs and included: KRAS, NRAS, and HRAS for 15, 5, and 2 cases, respectively (6-21 gene copies). Patients with a KRAS-amplified mCRC were more likely to report a history of inflammatory bowel disease (p < 0.001). In contrast, mutations in KRAS were associated with older patient age, right-sided colonic origin, low-grade differentiation, mucinous histology, and MMR proficiency (p ≤ 0.017). Four patients with a KRAS-amplified mCRC and no concomitant RAS/BRAF/PIK3CA mutations received EGFR inhibitor-based therapy, and none demonstrated a clinicoradiographic response. The therapeutic impact of RAS amplification was further evaluated using a separate, multi-institutional cohort of 23 patients. Eight of 23 patients with KRAS-amplified mCRC received anti-EGFR therapy and all 8 patients exhibited disease progression on treatment. Although the number of KRAS-amplified mCRCs is limited, our data suggest the clinicopathologic features associated with mCRC harboring a KRAS amplification are distinct from those associated with a KRAS mutation. However, both alterations seem to confer EGFR inhibitor resistance and, therefore, RAS testing to include copy number analyses may be of consideration in the treatment of mCRC.
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Adenocarcinoma/complicaciones , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias del Colon/complicaciones , Resistencia a Antineoplásicos/genética , Enfermedades Inflamatorias del Intestino/complicaciones , Proteínas Proto-Oncogénicas p21(ras)/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Receptores ErbB/antagonistas & inhibidores , Femenino , Amplificación de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/patología , Masculino , Persona de Mediana Edad , Panitumumab/uso terapéutico , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Service provision is a key domain to assess national-level palliative care development. Three editions of the European Association for Palliative Care (EAPC) Atlas of Palliative Care monitored the changes in service provision across Europe since 2005. AIM: To study European trends of specialized service provision at home care teams, hospital support teams, and inpatient palliative care services between 2005 and 2019. DESIGN: Secondary analysis was conducted drawing from databases on the number of specialized services in 2005, 2012, and 2019. Ratios of services per 100,000 inhabitants and increase rates on number of services for three periods were calculated. Analysis of variance (ANOVA) analyses were conducted to determine significant changes and chi-square to identify countries accounting for the variance. Income-level and sub-regional ANOVA analysis were undertaken. SETTING: 51 countries. RESULTS: Forty-two countries (82%) increased the number of specialized services between 2005 and 2019 with changes for home care teams (104% increase-rate), inpatient services (82%), and hospital support teams (48%). High-income countries showed significant increase in all types of services (p < 0.001), while low-to-middle-income countries showed significant increase only for inpatient services. Central-Eastern European countries showed significant improvement in home care teams and inpatient services, while Western countries showed significant improvement in hospital support and home care teams. Home care was the most prominent service in Western Europe. CONCLUSION: Specialized service provision increased throughout Europe, yet ratios per 100,000 inhabitants fell below the EAPC recommendations. Western Europe ratios' achieved half of the suggested services, while Central-Eastern countries achieved only a fourth. High-income countries and Western European countries account for the major increase. Central-Eastern Europe and low-to-middle-income countries reported little increase on specialized service provision.
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Servicios de Atención de Salud a Domicilio , Cuidados Paliativos , Europa (Continente) , Humanos , Pacientes Internos , Organización Mundial de la SaludRESUMEN
OBJECTIVES: Adenotonsillectomy (AT) is commonly used to treat upper airway obstruction in children, but selection of patients who will benefit most from AT is challenging. The need for diagnostic evaluation tools without sedation, radiation, or high costs has motivated the development of long-range optical coherence tomography (LR-OCT), providing real-time cross-sectional airway imaging during endoscopy. Since the endoscope channel location is not tracked in conventional LR-OCT, airway curvature must be estimated and may affect predicted airway resistance. The study objective was to assess effects of three realistic airway curvatures on predicted airway resistance using computational fluid dynamics (CFD) in LR-OCT reconstructions of the upper airways of pediatric patients, before and after AT. METHODS: Eight subjects (five males, three females, aged 4-9 years) were imaged using LR-OCT before and after AT during sedated endoscopy. Three-dimensional (3D) airway reconstructions included three airway curvatures. Steady-state, inspiratory airflow simulations were conducted under laminar conditions, along with turbulent simulations for one subject using the k-ω turbulence model. Airway resistance (pressure drop/flow) was compared using two-tailed Wilcoxon signed rank tests. RESULTS: Regardless of the airway curvatures, CFD findings corroborate a surgical end-goal with computed post-operative airway resistance significantly less than pre-operative (P < 0.01). The individual resistances did not vary significantly for different airway curvatures (P > 0.25). Resistances computed using turbulent simulations differed from laminar results by less than â¼5%. CONCLUSIONS: The results suggest that reconstruction of the upper airways from LR-OCT imaging data may not need to account for airway curvature to be predictive of surgical effects on airway resistance. Lasers Surg. Med. 51:150-160, 2019. © 2018 Wiley Periodicals, Inc.
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Obstrucción de las Vías Aéreas/diagnóstico por imagen , Obstrucción de las Vías Aéreas/cirugía , Esofagoscopía , Procedimientos de Cirugía Plástica , Tomografía de Coherencia Óptica , Tonsila Faríngea/patología , Obstrucción de las Vías Aéreas/etiología , Resistencia de las Vías Respiratorias , Niño , Preescolar , Simulación por Computador , Femenino , Humanos , Hidrodinámica , Hipertrofia , Masculino , Tonsila Palatina/patologíaRESUMEN
BACKGROUND: The objective of this study was to investigate the prevalence of pathogenic germline variants (PGVs) in 32 cancer susceptibility genes in individuals with newly diagnosed pancreatic ductal adenocarcinoma (PDAC). A key secondary objective was to evaluate how often PGVs would have been undetected with existing genetic testing criteria. METHODS: From May 2016 through May 2017, this multicenter cohort study enrolled consecutive patients aged 18 to 89 years with histologically confirmed PDAC diagnosed within the previous 12 weeks. Demographics, medical histories, and 3-generation pedigrees were collected from participants who provided samples for germline DNA analysis. RESULTS: Four hundred nineteen patients were deemed eligible, 302 were enrolled, and 298 were included in the final cohort. Clinically actionable variants were reported in 29 PDAC patients (9.7%), with 23 (7.7%) having a PGV associated with an increased risk for PDAC. Six of 23 individuals (26%) with PDAC-associated gene mutations did not meet currently established genetic testing criteria. According to guideline-based genetic testing, only 11 of the 23 PGVs (48%) in known PDAC genes would have been detected. Six additional patients (2%) had PGVs associated with an increased risk for other cancers. CONCLUSIONS: These findings support the significant prevalence of PGVs associated with PDAC and the limitations of current paradigms for selecting patients for genetic testing, and they thereby lend support for universal germline multigene genetic testing in this population.
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Adenocarcinoma/genética , Pruebas Genéticas/métodos , Células Germinativas/metabolismo , Mutación de Línea Germinal , Neoplasias Pancreáticas/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , Estudios Prospectivos , Adulto JovenRESUMEN
The cortical bone trajectory (CBT) screw technique yields effective mechanical and clinical results, improving the holding screw strength with a less invasive exposure. Accurate and safe screw placement is crucial. A patient-specific drill template with a preplanned trajectory was considered a promising solution; however, it is critical to assess the efficacy and safety of this technique. This study aims to evaluate the accuracy of patient-specific computed tomography (CT)-based rapid prototype drill guide templates for the CBT technique. CT scanning was performed in 7 cadaveric thoracolumbar spines, and a 3-dimensional reconstruction model was generated. By using computer software, we constructed drill templates that fit onto the posterior surface of thoracolumbar vertebrae with drill guides to match the CBT. In total, 80 guide templates from T11 to L5 were created from the computer models by using rapid prototyping. The drill templates were used to guide the drilling of CBT screws without any fluoroscopic control, and CT images were obtained after fixation. The entry point and direction of the planned and inserted screws were measured and compared. In total, 80 screws were inserted from T11 to L5. No misplacement or bony perforation was observed on postoperative CT scan. The patient-specific prototype template system showed the advantage of safe and accurate cortical screw placement in the thoracolumbar spine. This method showed its ability to customize the patient-specific trajectory of the spine, based on the unique morphology of the spine. The potential use of drill templates to place CBT screws is promising.
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Since the last comprehensive review on the development of national palliative care in Africa was undertaken 12 years ago, in 2005, we did a scoping review of peer-reviewed, published articles on palliative care development between 2005-16 for each African country. The scoping review was conducted by assessing the medical literature and including local expert recommendations of suggested articles. We did a basic quality assessment of the articles using the journals' impact factor, journal quartile, and the number of citations as suitable metrics for quality consideration. Articles published in English, Spanish, Portuguese, and French that mentioned at least one dimension of WHO's palliative care public health strategy (implementation of services, education, policies, or medicine availability) and vitality (activity by professionals or advocates) were included. Of the 518 articles found, 49 met the inclusion criteria. Information on 26 (48%) of 54 African countries was found. Most services were concentrated in Kenya, South Africa, and Uganda, and 14 (26%) countries showed an increase in services during this timeframe. Stand-alone palliative care policies exist in Malawi, Mozambique, Rwanda, Swaziland, Tanzania, and Zimbabwe. Postgraduate diplomas in palliative care are available in Kenya, South Africa, Uganda, and Tanzania. Restricted access to opioids, prescriber restriction laws, and a low prevalence of morphine use remain common barriers to adequate palliative care provision. Although information on palliative care is unevenly distributed, the available information showed an increased development of palliative care services in a subset of African countries. Despite this growth, however, there is still minimal to no identified palliative care development in most African countries.
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Cuidados Paliativos/organización & administración , África , HumanosRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV) and certain antiretrovirals are associated with diabetes. Few studies have examined the prevalence of and factors associated with diabetes among HIV-infected individuals on combination antiretroviral therapy (cART) in sub-Saharan Africa; some report prevalence estimates between 3.5-26.5% for diabetes in Cameroon and 20.2-43.5% for prediabetes in sub-Saharan Africa. METHODS: In a cross-sectional study, HIV-infected individuals (16-65 years old) were screened for diabetes using haemoglobin A1c (HbA1c ). We further categorized HbA1C as normoglycemia (HbA1c < 5.7%), prediabetes (HbA1c 5.7-6.4%) or diabetes (HbA1c ≥ 6.5%). Dysglycemia was defined as HbA1c ≥ 5.7%. Logistic regression modelling was used to assess factors associated with having dysglycemia. RESULTS: Of 500 participants, 363 (72.6%) were female. Median age was 42.5 years [interquartile range (IQR): 36.5-49.5]. Nineteen patients (3.8%) had diabetes and 170 patients (34%) were classified as having prediabetes. One hundred nine (22%) had a CD4+ count <200 cells/mm(3) , and 464 (93%) had received >28 days of ART at time of screening. Median abdominal circumference for women was 79.5 cm (IQR: 75.5-85.3) and for men, 86.5 cm (IQR: 81.7-90.5). Adjusting for age, sex, socio-economic status, CD4 cell count, being on cART >28 days, body mass index, hypertension, history of hypertension, abdominal circumference and duration of HIV infection, larger abdominal circumference was associated with higher prevalence of prediabetes or diabetes (adjusted odds ratio = 1.07, 95% confidence interval: 1.03-1.11), while being on cART (adjusted odds ratio = 0.46, confidence interval: 0.22-0.99) was associated with lower prevalence. CONCLUSIONS: There was a high prevalence of dysglycemia among Cameroonian HIV-infected adults. Larger abdominal circumference was associated with higher prevalence, while cART was associated with lower prevalence. Copyright © 2016 John Wiley & Sons, Ltd.