RESUMO
Barrow's goldeneyes across western North America have been shown to have a high degree of subpopulation independence using several data types. However, evidence for structured populations based on mitochondrial DNA, band recoveries, and tracking of adults is discordant with evidence from autosomal DNA. We used satellite tracking data from both juveniles and adults marked on natal and breeding grounds, respectively, in British Columbia, Canada to evaluate the hypothesis that male-biased juvenile dispersal maintains genetic panmixia of Pacific Barrow's goldeneyes otherwise structured by migratory movements and high winter and breeding site fidelity of adults. We found that juvenile males traveled to overwintering sites located within the range of the overwintering sites of juvenile females, adult males, and adult females. Juvenile males migrated at the same time, travelled the same distance when moving between natal and overwintering sites, and had the same winter dispersion as juvenile females. Although juveniles did not travel with attendant females, all juveniles overwintered within the wintering range of adults. We tracked some juveniles into the following spring/summer and even second winter. Prospecting juveniles of both sexes travelled from their wintering grounds to potential breeding sites in the proximity of Riske Creek and within the bounds of the breeding locations used by adults. Juveniles tracked for more than a year also showed relatively high winter site fidelity. Because Barrow's goldeneyes pair on wintering grounds, our tracking data are not consistent with the hypothesis that male-biased juvenile dispersal explains the genetic structure in the mitochondrial DNA and panmixia in the autosomal DNA of Barrow's goldeneye. We suggest that uncommon or episodic dispersal of males might be enough to homogenize autosomal DNA but is unlikely to influence demographic population structure relevant to contemporary population management.
RESUMO
During routine cadaveric dissection, accessory hypothenar muscles were incidentally discovered in two cadavers, both males, aged 86 and 92. Both muscles originated from the palmaris longus tendon in the distal portion of the forearm and were identified as accessory abductor digiti minimi (AADM) muscles, based on their association with abductor digiti minimi. While AADM is a common variant in the antebrachium, it is less typical for them to originate from the palmaris longus tendon. The presence of such an AADM could complicate surgical procedures requiring resection of the palmaris longus tendon. Moreover, the surrounding neurovasculature - namely the ulnar nerve as it passes through the ulnar canal between the pisiform and hook of the hamate - could be compressed by contractions of an AADM with such a proximal origin. This can manifest as ulnar neuropathies resulting in pain, weakness, or protracted flexion of the fourth and fifth digits (ulnar claw). Our description of these muscles adds to previous accounts of variation of the palmaris longus and abductor digiti minimi muscles while considering potential clinical implications.
Assuntos
Músculo Esquelético , Anormalidades Musculoesqueléticas , Masculino , Humanos , Músculo Esquelético/inervação , Nervo Ulnar/anatomia & histologia , Antebraço , Punho , CadáverRESUMO
Prevention of respiratory viral infection in stem cell transplant patients is important due to its high risk of adverse outcome. This single-centre, mixed methods study, conducted before the severe acute respiratory syndrome coronavirus-2 pandemic, explored the barriers and facilitators to a policy of universal mask use by visitors and healthcare workers, and examined the impact of the first year of introduction of the policy on respiratory viral infection rates compared with preceding years, adjusted for overall incidence. Education around universal mask use was highlighted as being particularly important in policy implementation. A significant decrease in respiratory viral infection was observed following introduction.
Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Infecções Respiratórias , Humanos , Máscaras , Pandemias , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , SARS-CoV-2 , TransplantadosRESUMO
AbstractThe high energetic costs of both migration and reproduction and the physiological changes to support these costs suggest that these life-history stages should be compartmentalized with little overlap between stages. In contrast, previous studies have shown that male birds can initiate reproductive development during migration before arrival on the breeding grounds with increases in plasma testosterone levels and testis size. However, sex differences in seasonal gonadal function are now recognized as profound, and few studies to date have shown that females can initiate the costly, but critical, estrogen-dependent final stages of gonadal maturation and changes in liver function (yolk precursor synthesis, vitellogenesis) while on migration. Here, we show that female yellow warblers (Setophaga petechia) arrive on the breeding grounds with elevated plasma triglyceride levels compared with males. Some females had plasma triglyceride levels of 5-7 mmol L-1, suggesting that they arrived in a relatively advanced stage of yolk precursor production. Furthermore, we show that females that arrived with higher plasma triglyceride levels took less time to initiate their first clutch. Adaptive plasticity in the timing of the transition from a migratory to a reproductive physiology might help migrant birds buffer against a mismatch between timing of arrival and conditions on the breeding grounds and allow them to advance timing of breeding to maximize breeding productivity.
Assuntos
Migração Animal/fisiologia , Reprodução/fisiologia , Estações do Ano , Aves Canoras/fisiologia , Animais , Feminino , Masculino , Aves Canoras/sangue , Triglicerídeos/sangueRESUMO
It can be a diagnostic challenge to identify patients with coronavirus disease 2019 in whom antibiotics can be safely withheld. This study evaluated the effectiveness of a guideline implemented at Sheffield Teaching Hospitals NHS Foundation Trust that recommends withholding antibiotics in patients with low serum procalcitonin (PCT), defined as ≤0.25 ng/mL. Results showed reduced antibiotic consumption in patients with PCT ≤0.25 ng/mL with no increase in mortality, alongside a reduction in subsequent carbapenem prescriptions during admission. The results support the effectiveness of this guideline, and further research is recommended to identify the optimal cut-off value for PCT in this setting.
Assuntos
Antibacterianos/normas , Antibacterianos/uso terapêutico , Antivirais/normas , Antivirais/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Tratamento Farmacológico da COVID-19 , Pró-Calcitonina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Gestão de Antimicrobianos/métodos , Infecções Bacterianas/sangue , Biomarcadores/sangue , Estudos de Coortes , Coinfecção/sangue , Coinfecção/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Adulto JovemRESUMO
Paranthropus boisei was first described in 1959 based on fossils from the Olduvai Gorge and now includes many fossils from Ethiopia to Malawi. Knowledge about its postcranial anatomy has remained elusive because, until recently, no postcranial remains could be reliably attributed to this taxon. Here, we report the first associated hand and upper limb skeleton (KNM-ER 47000) of P. boisei from 1.51 to 1.53 Ma sediments at Ileret, Kenya. While the fossils show a combination of primitive and derived traits, the overall anatomy is characterized by primitive traits that resemble those found in Australopithecus, including an oblique scapular spine, relatively long and curved ulna, lack of third metacarpal styloid process, gracile thumb metacarpal, and curved manual phalanges. Very thick cortical bone throughout the upper limb shows that P. boisei had great upper limb strength, supporting hypotheses that this species spent time climbing trees, although probably to a lesser extent than earlier australopiths. Hand anatomy shows that P. boisei, like earlier australopiths, was capable of the manual dexterity needed to create and use stone tools, but lacked the robust thumb of Homo erectus, which arguably reflects adaptations to the intensification of precision grips and tool use. KNM-ER 47000 provides conclusive evidence that early Pleistocene hominins diverged in postcranial and craniodental anatomy, supporting hypotheses of competitive displacement among these contemporaneous hominins.
Assuntos
Fósseis/anatomia & histologia , Hominidae/anatomia & histologia , Extremidade Superior/anatomia & histologia , Animais , QuêniaRESUMO
BACKGROUND: Previous research has identified similar prognostic factors in patients with musculoskeletal (MSK) conditions regardless of pain presentation, generating opportunities for management based on prognosis rather than specific pain presentation. METHODS: Data from seven RCTs (2483 participants) evaluating a range of primary care interventions for different MSK pain conditions were used to investigate the course of symptoms and explore similarities and differences in predictors of outcome. The value of pain site for predicting changes in pain and function was investigated and compared with that of age, gender, social class, pain duration, widespread pain and level of anxiety/depression. RESULTS: Over the initial three months of follow-up, changes in mean pain intensity reflected an improvement, with little change occurring after this period. Participants with knee pain due to osteoarthritis (OA) showed poorer long-term outcome (mean difference in pain reduction at 12 months -1.85, 95% CI -2.12 to -1.57, compared to low back pain). Increasing age, manual work, longer pain duration, widespread pain and increasing anxiety/depression scores were significantly associated with poorer outcome regardless of pain site. Testing of interactions showed some variation between pain sites, particularly for knee OA, where age, manual work and pain duration were most strongly associated with outcome. CONCLUSIONS: Despite some differences in prognostic factors for trial participants with knee OA who were older and had more chronic conditions, similarity of outcome predictors across regional MSK pain sites provides evidence to support targeting of treatment based on prognostic factors rather than site of pain. SIGNIFICANCE: Individual patient data analysis of trials across different regional musculoskeletal pain sites was used to evaluate course and prognostic factors associated with pain and disability. Overall, similarity of outcome predictors across these different pain sites supports targeting of treatment based on prognostic factors rather than pain site alone.
Assuntos
Dor Lombar/diagnóstico , Dor Musculoesquelética/diagnóstico , Terapia por Acupuntura , Idoso , Depressão/psicologia , Feminino , Humanos , Dor Lombar/psicologia , Dor Lombar/terapia , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/psicologia , Dor Musculoesquelética/terapia , Modalidades de Fisioterapia , PrognósticoRESUMO
NEW FINDINGS: What is the central question of this study? Endothelium-dependent flow-mediated dilatation (FMD) is impaired during acute (60 min) exposure to moderate hypoxia. We examined whether FMD is impaired to the same degree during exposure to milder hypoxia. Additionally, we assessed whether smooth muscle vasodilatory capacity [glyceryl trinitrate (GTN)-induced dilatation] is impaired during acute hypoxic exposure. What is the main finding and its importance? A graded impairment in FMD and GTN-induced dilatation was evident during acute (≤60 min) exposure to mild and moderate hypoxia. This study is the first to document these graded impairments, and provides rationale to examine the relationship between graded increases in sympathetic nerve activity with hypoxia on FMD and GTN-induced dilatation. Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation [induced with glyceryl trinitrate (GTN)] are impaired at high altitude (5050 m), and FMD is impaired after acute exposure (<60 min) to normobaric hypoxia equivalent to â¼5050 m (inspired oxygen fraction â¼0.11). Whether GTN-induced dilatation is impaired acutely and whether FMD is impaired during milder hypoxia are unknown. Therefore, we assessed brachial FMD at baseline and after 30 min of mild (end-tidal PO2 74 ± 2 mmHg) and moderate (end-tidal PO2 50 ± 3 mmHg) normobaric hypoxia (n = 12) or normoxia (time-control trial; n = 10). We also assessed GTN-induced dilatation after the hypoxic FMD tests and in normoxia on a separate control day (n = 8). Compared with the normoxic baseline, reductions during mild and moderate hypoxic exposure were evident in FMD (mild versus moderate, -1.2 ± 1.1 versus -3.1 ± 1.7%; P = 0.01) and GTN-induced dilatation (-2.1 ± 1.0 versus -4.2 ± 2.0%; P = 0.01); the declines in FMD and GTN-induced dilatation were greater during moderate hypoxia (P < 0.01). When allometrically corrected for baseline diameter and FMD shear rate under the curve, FMD was attenuated in both conditions (mild versus moderate, 0.6 ± 0.9 versus 0.8 ± 0.7%; P ≤ 0.01). After 30 min of normoxic time control, FMD was reduced (-0.6 ± 0.3%; P = 0.02). In summary, there was a graded impairment in FMD during mild and moderate hypoxic exposure, which appears to be influenced by shear patterns and incremental decline in smooth muscle vasodilator capacity (impaired GTN-induced dilatation). Our findings from the normoxic control study suggest the decline in FMD in acute hypoxia also appears to be influenced by 30 min of supine rest/inactivity.
Assuntos
Endotélio Vascular/fisiopatologia , Hipóxia/fisiopatologia , Músculo Liso Vascular/fisiopatologia , Vasodilatação , Doença Aguda , Adulto , Velocidade do Fluxo Sanguíneo , Artéria Braquial/efeitos dos fármacos , Artéria Braquial/fisiopatologia , Colúmbia Britânica , Feminino , Voluntários Saudáveis , Humanos , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Nitroglicerina/farmacologia , Fluxo Sanguíneo Regional , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Adulto JovemRESUMO
Significant racial disparity remains in the incidence of unfavorable outcomes following heart transplantation. We sought to determine which pediatric posttransplantation outcomes differ by race and whether these can be explained by recipient demographic, clinical, and genetic attributes. Data were collected for 80 black and 450 nonblack pediatric recipients transplanted at 1 of 6 centers between 1993 and 2008. Genotyping was performed for 20 candidate genes. Average follow-up was 6.25 years. Unadjusted 5-year rates for death (p = 0.001), graft loss (p = 0.015), acute rejection with severe hemodynamic compromise (p = 0.001), late rejection (p = 0.005), and late rejection with hemodynamic compromise (p = 0.004) were significantly higher among blacks compared with nonblacks. Black recipients were more likely to be older at the time of transplantation (p < 0.001), suffer from cardiomyopathy (p = 0.004), and have public insurance (p < 0.001), and were less likely to undergo induction therapy (p = 0.0039). In multivariate regression models adjusting for age, sex, cardiac diagnosis, insurance status, and genetic variations, black race remained a significant risk factor for all the above outcomes. These clinical and genetic variables explained only 8-19% of the excess risk observed for black recipients. We have confirmed racial differences in survival, graft loss, and several rejection outcomes following heart transplantation in children, which could not be fully explained by differences in recipient attributes.
Assuntos
Biomarcadores/metabolismo , Variação Genética , Rejeição de Enxerto/mortalidade , Transplante de Coração/mortalidade , Grupos Raciais/genética , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Genótipo , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/genética , Sobrevivência de Enxerto , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Estados Unidos/epidemiologiaAssuntos
Citometria de Fluxo , Linfoma de Células T Periférico/terapia , Neoplasia Residual/diagnóstico , Transplante de Células-Tronco , Adulto , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Tempo , Transplante Autólogo , Resultado do TratamentoRESUMO
Supervised exercise reduces liver fat and improves endothelial function, a surrogate of cardiovascular disease (CVD) risk, in nonalcoholic fatty liver disease (NAFLD). We hypothesised that after a 16-week supervised exercise program, patients would maintain longer-term improvements in cardiorespiratory fitness, liver fat and endothelial function. Ten NAFLD patients (5/5 males/females, age 51±13 years, body mass index 31±3 kg m-2 (mean±s.d.)) underwent a 16-week supervised moderate-intensity exercise intervention. Biochemical markers, cardiorespiratory fitness (VO2peak), subcutaneous, visceral and liver fat (measured by magnetic resonance imaging and spectroscopy respectively) and brachial artery flow-mediated dilation (FMD) were assessed at baseline, after 16 weeks of supervised training and 12 months after ending supervision. Despite no significant change in body weight, there were significant improvements in VO2peak (6.5 ml kg-1 min-1 (95% confidence interval 2.8, 10.1); P=0.003), FMD (2.9% (1.5, 4.2); P=0.001), liver transaminases (P<0.05) and liver fat (-10.1% (-20.6, 0.5); P=0.048) immediately after the 16-week supervised training. Nevertheless, 12 months after ending supervision, VO2peak (0.9 ml kg-1 min-1 (-3.3, 5.1); P=0.65), FMD (-0.07% (-2.3, 2.2); P=0.95), liver transaminases (P>0.05) and liver fat (1.4% (-13.0, 15.9); P=0.83) were not significantly different from baseline. At 12 months following cessation of supervision, exercise-mediated improvements in liver fat and other cardiometabolic variables had reversed with cardiorespiratory fitness at baseline levels. Maintenance of high cardiorespiratory fitness and stability of body weight are critical public health considerations for the treatment of NAFLD (Clinicaltrials.gov identifier: NCT01834300).
Assuntos
Endotélio Vascular/fisiopatologia , Terapia por Exercício , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/fisiopatologia , Tecido Adiposo/patologia , Artéria Braquial/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/complicações , Obesidade/terapia , Cooperação do Paciente , Projetos Piloto , Recidiva , Resultado do TratamentoRESUMO
Exercise training ('exercise') and hypocaloric diet ('diet') are frequently prescribed for weight loss in obesity. Whilst body weight changes are commonly used to evaluate lifestyle interventions, visceral adiposity (VAT) is a more relevant and stronger predictor for morbidity and mortality. A meta-analysis was performed to assess the effects of exercise or diet on VAT (quantified by radiographic imaging). Relevant databases were searched through May 2014. One hundred seventeen studies (n = 4,815) were included. We found that both exercise and diet cause VAT loss (P < 0.0001). When comparing diet versus training, diet caused a larger weight loss (P = 0.04). In contrast, a trend was observed towards a larger VAT decrease in exercise (P = 0.08). Changes in weight and VAT showed a strong correlation after diet (R(2) = 0.737, P < 0.001), and a modest correlation after exercise (R(2) = 0.451, P < 0.001). In the absence of weight loss, exercise is related to 6.1% decrease in VAT, whilst diet showed virtually no change (1.1%). In conclusion, both exercise and diet reduce VAT. Despite a larger effect of diet on total body weight loss, exercise tends to have superior effects in reducing VAT. Finally, total body weight loss does not necessarily reflect changes in VAT and may represent a poor marker when evaluating benefits of lifestyle-interventions.
Assuntos
Adiposidade , Restrição Calórica , Dieta Redutora , Exercício Físico , Obesidade/terapia , Sobrepeso/terapia , Peso Corporal , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Chemotherapeutic agents without cross-resistance to prior therapies may enhance PBSC collection and improve patient outcomes by exacting a more potent direct antitumor effect before autologous stem cell transplant. Bendamustine has broad clinical activity in transplantable lymphoid malignancies, but concern remains over the potential adverse impact of this combined alkylator-nucleoside analog on stem cell mobilization. We performed a prospective, nonrandomized phase II study including 34 patients with multiple myeloma (MM) (n=34; International Staging System (ISS) stages I (35%), II (29%) and III (24%); not scored (13%)) to evaluate bendamustine's efficacy and safety as a stem cell mobilizing agent. Patients received bendamustine (120 mg/m2 IV days 1, 2), etoposide (200 mg/m2 IV days 1-3) and dexamethasone (40 mg PO days 1- 4) (bendamustine, etoposide and dexamethasone (BED)) followed by filgrastim (10 µg/kg/day SC; through collection). All patients (100%) successfully yielded stem cells (median of 21.60 × 106/kg of body weight; range 9.24-55.5 × 106/kg), and 88% required a single apheresis. Six nonhematologic serious adverse events were observed in 6 patients including: neutropenic fever (1, grade 3), bone pain (1, grade 3) and renal insufficiency (1, grade 1). In conclusion, BED safely and effectively mobilizes hematopoietic stem cells.
Assuntos
Cloridrato de Bendamustina/administração & dosagem , Dexametasona/administração & dosagem , Etoposídeo/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo , Resultado do TratamentoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Terapia Neoadjuvante , Polietilenoglicóis/administração & dosagem , Recidiva , Transplante de Células-Tronco , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Adulto JovemRESUMO
BACKGROUND: Physical activity reduces cardiovascular mortality and morbidity. The World Health Organisation (WHO) recommends children engage in 60 min daily moderate-to-vigorous physical activity (MVPA). The effect of compliance with this recommendation on childhood cardiovascular risk has not been empirically tested. To evaluate whether achieving recommendations results in reduced composite-cardiovascular risk score (CCVR) in children, and to examine if vigorous PA (VPA) has independent risk-reduction effects. METHODS: PA was measured using accelerometry in 182 children (9-11 years). Subjects were grouped according to achievement of 60 min daily MVPA (active) or not (inactive). CCVR was calculated (sum of z-scores: DXA body fat %, blood pressure, VO2peak, flow mediated dilation, left ventricular diastolic function; CVR score ≥ 1SD indicated 'higher risk'). The cohort was further split into quintiles for VPA and odds ratios (OR) calculated for each quintile. RESULTS: Active children (92 (53 boys)) undertook more MVPA (38 ± 11 min, P < 0.001), had greater VO2peak (4.5 ± 0.8 ml/kg/min P < 0.001), and lower fat % (3.9 ± 1.1 %, P < 0.001) than inactive. No difference were observed between active and inactive for CCVR or OR (P > 0.05). CCVR in the lowest VPA quintile was significantly greater than the highest quintile (3.9 ± 0.6, P < 0.05), and the OR was 4.7 times higher. CONCLUSION: Achievement of current guidelines has positive effects on body composition and cardiorespiratory fitness, but not CCVR. Vigorous physical activity appears to have beneficial effects on CVD risk, independent of moderate PA, implying a more prescriptive approach may be needed for future VPA guidelines.
Assuntos
Doenças Cardiovasculares/epidemiologia , Exercício Físico , Guias como Assunto , Acelerometria , Pressão Sanguínea , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Razão de Chances , Aptidão Física , Fatores de Risco , Comportamento de Redução do Risco , Fatores de TempoRESUMO
We aimed to examine whether doses of melphalan higher than 200 mg/m(2) improve response rates when used as conditioning before autologous transplant (ASCT) in multiple myeloma (MM) patients. Patients with MM, n=131, were randomized to 200 mg/m(2) (mel200) vs 280 mg/m(2) (mel280) using amifostine pretreatment. The primary end point was the proportion of patients achieving near complete response (⩾nCR). No treatment-related deaths occurred in this study. Responses following ASCT were for mel200 vs mel280, respectively, ⩾nCR 22 vs 39%, P=0.03, ⩾PR 57 vs 74%, P=0.04. The hazard of mortality was not statistically significantly different between groups (mel200 vs mel280; hazard ratio (HR)=1.15 (95% confidence interval (CI), 0.62-2.13, P=0.66)) nor was the rate of progression/mortality (HR=0.81 (0.52-1.27, P=0.36)). The estimated PFS at 1 and 3 years were 83 and 46%, respectively, for mel200 and 78 and 54%, respectively, for mel280. Amifostine and mel280 were well tolerated, with no grade 4 regimen-related toxicities and only one grade 3 mucositis (none with mel200) and three grade 3 gastrointestinal (GI) toxicities (two in mel200). Hospitalization rates were more frequent in the mel280 group (59 vs 43%, P=0.08). Mel280 resulted in a higher major response rate (CR+nCR) and should be evaluated in larger studies.
Assuntos
Melfalan/administração & dosagem , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Transplante de Células-Tronco , Condicionamento Pré-Transplante , Adulto , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Taxa de SobrevidaRESUMO
Pharmacogenomic (PGx) information is increasingly being incorporated into US Food and Drug Administration-approved drug labels. We reviewed the data source (adults vs. pediatrics) of PGx information in approved drug labels and assessed the suitability of applying adult-derived PGx information and related prescribing recommendations to the care of pediatric patients. We identified 65 drugs with labels containing PGx information and that have also been evaluated in children and found that in the majority of cases (56/65, 86%), the PGx information described was derived from adult studies. The application of PGx information from adults to pediatrics was deemed suitable for 71.4% (n = 40) of the drugs and unclear for 28.6% (n = 16). An ontogeny effect, limited or conflicting data regarding ontogeny of the genetic biomarker, or a difference in the pathophysiology or progression of the adult vs. pediatric disease were the primary reasons for deeming direct application from adults to pediatrics unclear.
Assuntos
Rotulagem de Medicamentos/legislação & jurisprudência , Marcadores Genéticos , Pediatria/normas , Farmacogenética , United States Food and Drug Administration/normas , Adulto , Criança , Aprovação de Drogas , Prescrições de Medicamentos/normas , Humanos , Educação de Pacientes como Assunto , Testes Farmacogenômicos , Estados UnidosRESUMO
BACKGROUND: High-dose therapy and autologous stem cell transplantation (ASCT) improves outcomes for patients with mantle cell lymphoma (MCL), but relapse ultimately occurs in most patients. Recently presented interim results from a phase III prospective trial suggest maintenance rituximab (MR) after ASCT for MCL improves progression-free survival (PFS). The maturation of these data and any benefit of MR on overall survival (OS) remain to be defined. PATIENTS AND METHODS: In this retrospective study, we examined a cohort of consecutive patients with MCL that underwent ASCT for MCL at our center and evaluated their outcomes according to whether they received MR after ASCT (n = 50) or did not (n = 107). MR was treated as a time-dependent covariate to account for variation in timing of its initiation. RESULTS: MR was associated with an improved PFS [hazard ratio (HR) 0.44; confidence interval (CI) (0.24-0.80), P = 0.007] and overall survival (OS; HR 0.46; CI 0.23-0.93, P = 0.03) following a multivariate adjustment for confounding factors with a median follow-up of â¼5 years. Grade 4 neutropenia was increased (34% versus 18%, P = 0.04) in the MR group, but no effect on the rate of mortality unrelated to relapse was observed. CONCLUSIONS: These data support that MR after ASCT for MCL confers a benefit in PFS and additionally suggest it may improve OS. General application of this strategy will require confirmation of benefit in prospective randomized trials.