RESUMEN
BACKGROUND: We evaluated the disease and patient characteristics, treatment, and MET testing patterns, predictive biomarkers and survival outcomes in patients with MET-dysregulated metastatic non-small-cell lung cancer (NSCLC) in a real-world setting. PATIENTS AND METHODS: This was a multinational, retrospective, noninterventional chart review study. Data from medical records of patients with advanced/metastatic EGFR wild-type, MET-dysregulated NSCLC (December 2017-September 2018) were abstracted into electronic data collection forms. RESULTS: Overall, 211 patient charts were included in this analysis; 157 patients had MET exon 14 skipping mutations (METex14; with or without concomitant MET amplification) and 54 had MET amplification only. All patients were tested for METex14, whereas MET amplification was evaluated in 168 patients. No overlap was reported between MET dysregulation and ALK, ROS1 or RET rearrangements, or HER2 exon 20 insertions. Overall, 56 of 211 patients (26.5%) received MET inhibitor (METi) therapy in any treatment-line setting (31.2% in the METex14 cohort; 13% in the MET-amplified only cohort). In the METex14 cohort, median OS in patients receiving METi was 25.4 months versus 10.7 months in patients who did not (HR [95% CI]: 0.532 [0.340-0.832]; P = .0055). In the MET-amplified only cohort, median OS was 20.6 months in patients treated with METi compared with 7.6 months in those without METi (HR [95% CI]: 0.388 [0.152-0.991]; P = .0479). CONCLUSIONS: MET alterations in NSCLC typically occur in the absence of other oncogenic driver mutations and are associated with poor survival outcomes. Notably, METi therapies are associated with improved survival outcomes in patients with MET-dysregulated NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Estudios Retrospectivos , Mutación/genética , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas/genética , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Anti-CD19 immunotherapy tafasitamab is used in combination with lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Open-label, phase 1b, First-MIND study assessed safety and preliminary efficacy of tafasitamab + R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) ± lenalidomide as first-line therapy in patients with DLBCL. From December 2019 to August 2020, 83 adults with untreated DLBCL (International Prognostic Index 2-5) were screened and 66 were randomly assigned (33 per arm) to R-CHOP-tafasitamab (arm T) or R-CHOP-tafasitamab-lenalidomide (arm T/L) for 6 cycles. Primary end point was safety; secondary end points included end-of-treatment (EoT) overall response rate (ORR) and complete response (CR) rate. All patients had ≥1 treatment-emergent adverse event, mostly grade 1 or 2. Grade ≥3 neutropenia and thrombocytopenia occurred, respectively, in 57.6% and 12.1% (arm T) and 84.8% and 36.4% (arm T/L) of patients. Nonhematologic toxicities occurred at similar rates among arms. R-CHOP mean relative dose intensity was ≥89% in both arms. EoT ORR was 75.8% (CR 72.7%) in arm T and 81.8% (CR 66.7%) in arm T/L; best ORR across visits was 90.0% and 93.9%. Eighteen-month duration of response and of CR rates were 72.7% and 74.5% (arm T) and 78.7% and 86.5% (arm T/L); 24-month progression-free and overall survival rates were 72.7% and 90.3% (arm T) and 76.8% and 93.8% (arm T/L). Manageable safety and promising signals of efficacy were observed in both arms. Potential benefit of adding tafasitamab + lenalidomide to R-CHOP is being investigated in phase 3 frontMIND (NCT04824092). This study is registered at www.clinicaltrials.gov as #NCT04134936.
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Linfoma de Células B Grandes Difuso , Adulto , Humanos , Lenalidomida/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Rituximab/efectos adversos , Linfoma de Células B Grandes Difuso/patología , Vincristina/efectos adversos , Ciclofosfamida/efectos adversos , Prednisona/efectos adversos , Doxorrubicina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Little is known about biological outcomes for severe psoriasis in trisomy 21 (T21). Our aim was to review outcomes of patients with T21 and severe psoriasis treated with biologic or Janus kinase inhibitors (JAKi). Information on demographics, co-morbidities, and therapeutic responses was retrospectively collated. Twenty-one patients were identified (mean age 24.7 years). Ninety percent (18/20) of TNFα inhibitor trials failed. Almost two-thirds (7/11) of patients achieved an adequate response with ustekinumab. All three patients treated with tofacitinib achieved an adequate response following at least three biologic failures. The mean number of biologic/JAKi therapies received was 2.1 with overall survival of 36%. Eighty-one percent (17/21) of patients required conversion from their index biologic treatment due to failure. In patients with T21 and severe psoriasis, failure of TNFα inhibition is common and ustekinumab therapy should be considered as first-line therapy. The role of JAKi is emerging.
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Productos Biológicos , Síndrome de Down , Inhibidores de las Cinasas Janus , Psoriasis , Humanos , Adulto Joven , Adulto , Ustekinumab/uso terapéutico , Inhibidores de las Cinasas Janus/uso terapéutico , Factor de Necrosis Tumoral alfa , Síndrome de Down/complicaciones , Síndrome de Down/tratamiento farmacológico , Estudios Retrospectivos , Psoriasis/tratamiento farmacológico , Terapia Biológica , Productos Biológicos/uso terapéuticoRESUMEN
BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare genetic syndrome caused by pathogenic or likely pathogenic germline variants in the FLCN gene. Patients with BHD syndrome have an increased risk of fibrofolliculomas, pulmonary cysts, pneumothorax and renal cell carcinoma. There is debate regarding whether colonic polyps should be added to the criteria. Previous risk estimates have mostly been based on small clinical case series. METHODS: A comprehensive review was conducted to identify studies that had recruited families carrying pathogenic or likely pathogenic variants in FLCN. Pedigree data were requested from these studies and pooled. Segregation analysis was used to estimate the cumulative risk of each manifestation for carriers of FLCN pathogenic variants. RESULTS: Our final dataset contained 204 families that were informative for at least one manifestation of BHD (67 families informative for skin manifestations, 63 for lung, 88 for renal carcinoma and 29 for polyps). By age 70 years, male carriers of the FLCN variant have an estimated 19% (95% CI 12% to 31%) risk of renal tumours, 87% (95% CI 80% to 92%) of lung involvement and 87% (95% CI 78% to 93%) of skin lesions, while female carriers had an estimated 21% (95% CI 13% to 32%) risk of renal tumours, 82% (95% CI 73% to 88%) of lung involvement and 78% (95% CI 67% to 85%) of skin lesions. The cumulative risk of colonic polyps by age 70 years old was 21% (95% CI 8% to 45%) for male carriers and 32% (95% CI 16% to 53%) for female carriers. CONCLUSIONS: These updated penetrance estimates, based on a large number of families, are important for the genetic counselling and clinical management of BHD syndrome.
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Síndrome de Birt-Hogg-Dubé , Carcinoma de Células Renales , Pólipos del Colon , Neoplasias Renales , Humanos , Masculino , Femenino , Anciano , Síndrome de Birt-Hogg-Dubé/genética , Síndrome de Birt-Hogg-Dubé/patología , Penetrancia , Proteínas Proto-Oncogénicas/genética , Proteínas Supresoras de Tumor/genética , Neoplasias Renales/epidemiología , Neoplasias Renales/genética , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/genéticaRESUMEN
We present a case of an acute urticated eruption in a child, associated with acral oedema in the setting of recent infection and antibiotic therapy. There are a limited number of differential diagnoses, which we discuss in this article, while also highlighting distinguishing features and management considerations.
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Exantema , Niño , Diagnóstico Diferencial , Exantema/diagnóstico , Exantema/etiología , Familia , HumanosRESUMEN
An 18-year-old presented with an atypical blistering eruption. Direct immunofluorescence microscopy of perilesional skin showed strong linear deposition of IgG and C3 at the dermoepidermal junction. Her presentation was unusual and posed a diagnostic challenge, as this condition is very rare in this age group.
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Enfermedades Cutáneas Vesiculoampollosas , Adolescente , Femenino , Cabeza , Humanos , Cuello , Piel , Enfermedades Cutáneas Vesiculoampollosas/diagnósticoRESUMEN
BACKGROUND: Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor licensed for the treatment of type 2 diabetes mellitus (T2DM), has been reported to improve psoriasis. OBJECTIVE: We compared the effects of sitagliptin treatment, a DPP-4 inhibitor, in combination with narrow-band ultraviolet-B (NB-UVB) phototherapy compared to NB-UVB alone on psoriasis severity, quality of life, cardiovascular disease risk factors and immune parameters in people with moderate psoriasis without T2DM. METHODS: In this 39-week, single-centre, randomised controlled trial, people were allocated randomly to receive sitagliptin for 24 weeks with NB-UVB or NB-UVB alone. The primary endpoint was the change in Psoriasis Area and Severity Index (PASI) from baseline to 24 weeks. We estimated that 120 participants would be needed to have 80% power to find a significant difference between the groups. RESULTS: A total of 118 patients were randomised. The median (IQR) baseline PASI was 8.8 (7.5-11.6). At 24 weeks, the mean difference from baseline in PASI (-1.0 [95% CI -2.0 to 0.0]) was significantly larger in the sitagliptin/NB-UVB arm than in the NB-UVB-alone arm (p = 0.044). There were significant differences in the change in Hospital Anxiety and Depression Scale (-2.5 [95% CI -4.0 to -1.0]; p = 0.002) and EuroQol 5-item questionnaire (0.1 [95% CI 0.0-0.1]; p = 0.036) values from baseline to 24 weeks between the sitagliptin/NB-UVB and the NB-UVB-alone arm. There were no treatment-related serious adverse events. CONCLUSION: Sitagliptin therapy combined with NB-UVB phototherapy significantly improved psoriasis severity, albeit modestly, compared to NB-UVB phototherapy alone in patients with moderate psoriasis without T2DM.
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Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Psoriasis/terapia , Fosfato de Sitagliptina/administración & dosificación , Terapia Ultravioleta/métodos , Adulto , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del TratamientoAsunto(s)
Diabetes Mellitus/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Fosfato de Sitagliptina/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/complicacionesRESUMEN
Secukinumab is a novel anti-interleukin-17A agent that has achieved a 75% decrease from baseline in Psoriasis Area and Severity Index (PASI 75) in 77-81% of patients treated in clinical trials Langley et al. (N Engl J Med 371:326-338, 2014). There is limited data on the use of secukinumab outside of clinical trials. We provide real-world data on the efficacy and safety of secukinumab in patients with severe psoriasis attending an outpatient dermatology service. In our retrospective review, we demonstrate (PASI 75) a response rate of 47% in patients previously treated with multiple systemic and biologics. Our efficacy is comparable to that seen in the Signature study who examined similar populations. Response was maintained at follow-up of almost 1 year with acceptable safety data. Patients with psoriatic arthritis were more likely to remain on secukinumab than those without at last clinic follow-up.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Psoriasis/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales Humanizados/farmacología , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), MET exon 14 skipping mutations occur in 3 to 4% and MET amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation. METHODS: We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients with MET-dysregulated advanced NSCLC. Patients were assigned to cohorts on the basis of previous lines of therapy and MET status (MET exon 14 skipping mutation or MET amplification according to gene copy number in tumor tissue). Patients received capmatinib (400-mg tablet) twice daily. The primary end point was overall response (complete or partial response), and the key secondary end point was response duration; both end points were assessed by an independent review committee whose members were unaware of the cohort assignments. RESULTS: A total of 364 patients were assigned to the cohorts. Among patients with NSCLC with a MET exon 14 skipping mutation, overall response was observed in 41% (95% confidence interval [CI], 29 to 53) of 69 patients who had received one or two lines of therapy previously and in 68% (95% CI, 48 to 84) of 28 patients who had not received treatment previously; the median duration of response was 9.7 months (95% CI, 5.6 to 13.0) and 12.6 months (95% CI, 5.6 to could not be estimated), respectively. Limited efficacy was observed in previously treated patients with MET amplification who had a gene copy number of less than 10 (overall response in 7 to 12% of patients). Among patients with MET amplification and a gene copy number of 10 or higher, overall response was observed in 29% (95% CI, 19 to 41) of previously treated patients and in 40% (95% CI, 16 to 68) of those who had not received treatment previously. The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%); these events were mostly of grade 1 or 2. CONCLUSIONS: Capmatinib showed substantial antitumor activity in patients with advanced NSCLC with a MET exon 14 skipping mutation, particularly in those not treated previously. The efficacy in MET-amplified advanced NSCLC was higher in tumors with a high gene copy number than in those with a low gene copy number. Low-grade peripheral edema and nausea were the main toxic effects. (Funded by Novartis Pharmaceuticals; GEOMETRY mono-1 ClinicalTrials.gov number, NCT02414139.).
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Imidazoles/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Triazinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Benzamidas , Carcinoma de Pulmón de Células no Pequeñas/genética , Edema/inducido químicamente , Exones , Femenino , Dosificación de Gen , Humanos , Imidazoles/efectos adversos , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Proto-Oncogénicas c-met/genética , Triazinas/efectos adversosRESUMEN
BACKGROUND: We report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy. METHODS: Descriptive efficacy analyses were conducted in patients randomised to group A (cycles 1-6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1-3; 500 mg/m2 5-fluorouracil/100 mg/m2 epirubicin/600 mg/m2 cyclophosphamide] then docetaxel [cycles 4-6; 75 mg/m2, escalated to 100 mg/m2 if well tolerated]), B (cycles 1-3: FEC, cycles 4-6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1-6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m2, without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient. This study is registered with ClinicalTrials.gov, number NCT00976989. RESULTS: Three-year Kaplan-Meier survival estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79-95), 88% (80-96) and 90% (82-97) in groups A-C, respectively. Progression-free survival (PFS) rates were 89% (81-96), 89% (81-96) and 87% (80-95). DFS hazard ratio for total pathological complete response (tpCR) versus no tpCR was 0.27 (0.11-0.64). During post-treatment follow-up, 2/72 (2.8%), 3/75 (4.0%) and 4/76 (5.4%) patients in groups A-C had any-grade left ventricular systolic dysfunction; eight (11.1%), 12 (16.0%) and nine (11.8%) patients experienced left ventricular ejection fraction declines ≥10% from baseline to <50%. CONCLUSIONS: Long-term DFS and PFS were similar between groups. Patients who achieved tpCR had improved DFS. No new safety signals were identified.
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Antraciclinas/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Corazón/efectos de los fármacos , Trastuzumab/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antraciclinas/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Volumen Sistólico/efectos de los fármacos , Trastuzumab/efectos adversos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Adipokines are secreted by white adipose tissue, an active endocrine organ, and play a role in the regulation of metabolic functions such as lipid metabolism, inflammation, and vascular homeostasis. Adipokines are secreted in excess in obesity and contribute to the development of associated comorbidities such as metabolic syndrome and atherosclerosis. Psoriasis, a chronic immune-mediated skin disease, is associated with obesity and increased cardiovascular risk. Understanding the role of adipokines in psoriasis may in part explain the association between psoriasis and cardiovascular disease. This review summarizes the data regarding key adipokines in patients with psoriasis and the change in adipokine profiles with psoriasis therapy. Adipokines may be mediators of cutaneous inflammation suggesting a role in the pathophysiology of psoriasis and the development of comorbidities.
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Adipoquinas/sangre , Inflamación/sangre , Obesidad/sangre , Psoriasis/sangre , Psoriasis/terapia , Endotelio/fisiopatología , Humanos , Inflamación/fisiopatología , Obesidad/complicaciones , Obesidad/fisiopatología , Psoriasis/complicaciones , Psoriasis/fisiopatología , Índice de Severidad de la Enfermedad , Pérdida de PesoRESUMEN
We report a patient with psoriasis who developed Mycobacterium marinum (M. marinum) infection after seven years of treatment with adalimumab, a human anti-TNF (tumor necrosis factor) monoclonal antibody. TNF is a pro-inflammatory cytokine that plays a central role in the pathogenesis of psoriasis and a number of other immune-mediated inflammatory diseases. TNF plays an important role in granuloma formation and host defense against mycobacterial infections. Several cases of atypical mycobacterial infections in patients on TNF inhibitors have been reported. To our knowledge, this is the second reported case of M. marinum infection in a patient on adalimumab for the treatment of psoriasis.
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Adalimumab/efectos adversos , Antiinflamatorios/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/inducido químicamente , Psoriasis/tratamiento farmacológico , Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Humanos , Laceraciones/complicaciones , Masculino , Persona de Mediana Edad , Algas MarinasAsunto(s)
Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/terapia , Enfermedades de la Vulva/patología , Adolescente , Canal Anal/patología , Biopsia con Aguja/métodos , Terapia Combinada , Enfermedad de Crohn/patología , Diagnóstico Diferencial , Edema/diagnóstico , Edema/etiología , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Proctoscopía/métodos , Prurito Vulvar/diagnóstico , Prurito Vulvar/patología , Enfermedades Raras , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Enfermedades de la Vulva/diagnósticoRESUMEN
BACKGROUND: Moderate to severe psoriasis is a systemic inflammatory disease associated with insulin resistance, obesity and type 2 diabetes (T2DM). Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that improves glycaemia and has a marketing authorisation for the treatment of T2DM. Non-immunosuppressive therapies that are effective for psoriasis and its associated comorbidities would be a significant advance in the treatment of this chronic disease. METHODS/DESIGN: This is a single centre, 39-week, prospective, randomised, open label, clinical trial of oral sitagliptin (Januvia(®)) in psoriasis patients who are due to undergo a course of narrow-band ultraviolet-B (NB-UVB) phototherapy. We plan to enrol 120 participants and allocate participants on a random and 1:1 basis to receive sitagliptin 100 mg daily for 24 weeks combined with NB-UVB or NB-UVB monotherapy. Participants will be followed up for 12 weeks after sitagliptin therapy is discontinued. The primary endpoint is the change in Psoriasis Area and Severity Index (PASI) 24 weeks after treatment initiation. Secondary endpoints include cumulative NB-UVB dose, number of NB-UVB treatments required to clear psoriasis, proportions of participants who achieve PASI-50 (50 % reduction in PASI from baseline), PASI-75, PASI-90 and the proportion of participants who relapse in each group. We will also analyse changes in cardiovascular disease risk factors, serum cytokine and hormone levels and peripheral blood mononuclear expression of immune proteins at 24 and 36 weeks. A subgroup of participants will have skin biopsies taken and analysed for skin levels and expression of immune cells, receptors, hormones and immune proteins. The genetic or epigenetic profile that predicts best response to DPP-4 inhibitor therapy will be analysed. The safety endpoints include the rate and severity of adverse events. DISCUSSION: This is the first randomised clinical trial assessing dipeptidyl peptidase-4 inhibition therapy in psoriasis. We hypothesise that sitagliptin therapy in combination with NB-UVB improves psoriasis severity compared to NB-UVB monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02347501 (Date of registration: 27 January 2015).
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Protocolos Clínicos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Psoriasis/terapia , Fosfato de Sitagliptina/uso terapéutico , Terapia Ultravioleta/métodos , Humanos , Estudios Prospectivos , Control de Calidad , Tamaño de la Muestra , Fosfato de Sitagliptina/efectos adversosRESUMEN
BACKGROUND: The benefit of patch testing patients with oral lichenoid lesions (OLL) is still debated. OBJECTIVE: We assessed the results of patch testing in patients with multiple amalgams and multiple OLL, where the etiology of the oral mucosal disease was unclear. METHODS: Patients referred from an oral medicine clinic were patch tested to the British Society of Cutaneous Allergy standard series, dental and materials series, and, in 1 patient, the dental methacrylate series also. Patients' responses to amalgam removal were assessed during a mean follow-up of 2.6 (range, 0-4.75) years. RESULTS: Thirty-one patients with OLL were referred for patch testing. Ten (32%) patients tested positively to mercury. Eight patients with positive reactions to mercury had amalgam removal, with complete or partial resolution of the OLL in all cases (100%). CONCLUSIONS: Patients with OLL of unclear etiology adjacent to large amalgam restorations should be investigated for delayed contact hypersensitivity. Removal of amalgams in patients with positive patch test reactions to mercury results in improvement or resolution of the OLL in most patients.
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Alérgenos/efectos adversos , Amalgama Dental/efectos adversos , Dermatitis por Contacto/etiología , Erupciones Liquenoides/etiología , Mercurio/efectos adversos , Enfermedades de la Boca/etiología , Adulto , Anciano , Estudios de Cohortes , Dermatitis por Contacto/diagnóstico , Dermatitis por Contacto/terapia , Remoción de Dispositivos , Femenino , Humanos , Erupciones Liquenoides/diagnóstico , Erupciones Liquenoides/terapia , Masculino , Persona de Mediana Edad , Enfermedades de la Boca/diagnóstico , Enfermedades de la Boca/terapia , Mucosa Bucal , Pruebas del Parche , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
In sub-Saharan Africa (SSA), a rapidly aging population is presenting challenges to health care systems. Doctors need specialized knowledge to be prepared for the increase in age-related medical conditions. This study aims to investigate the current provision of geriatrics education (GE) in SSA medical schools and discover some of the barriers faced in its implementation. Questionnaires were sent to a list of medical schools in SSA, supplied by the sub-Saharan African Medical Schools Study. Responses were received from 25/135 institutions (19%), representing 11 countries in SSA. Of these institutions, 4% taught geriatrics and 40% had no geriatrics teaching. The largest perceived barriers to GE were a lack of staff expertise (72%), lack of funding (52%), and absence of geriatrics in the national curricula (48%). There are still a large number of medical schools in SSA who do not teach geriatrics. Improvements in GE should be implemented through local approaches and national policy, while appreciating the cultural context and economic constraints of each country to prepare future doctors for the increasing challenges of an aging population.
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Educación de Postgrado en Medicina , Educación de Pregrado en Medicina , Geriatría/educación , Servicios de Salud para Ancianos/estadística & datos numéricos , África del Sur del Sahara , Anciano , Curriculum , Educación de Postgrado en Medicina/organización & administración , Educación de Postgrado en Medicina/estadística & datos numéricos , Educación de Pregrado en Medicina/organización & administración , Educación de Pregrado en Medicina/estadística & datos numéricos , Transición de la Salud , Humanos , Evaluación de Necesidades , Encuestas y CuestionariosRESUMEN
IMPORTANCE: There is a need for noninvasive tools to monitor hepatotoxicity in patients with psoriasis who are receiving methotrexate sodium. OBJECTIVE: To evaluate the use of transient elastography (TE) and FibroTest (FibroSURE in the United States), an indirect serum marker of fibrosis, in this population. DESIGN, SETTING, AND PARTICIPANTS: Patients receiving methotrexate therapy for psoriasis between January 2008 and September 2009 were recruited from a dermatology outpatient department. Transient elastography and FibroTest were performed, and patients with abnormal results were considered for liver biopsy. Serial procollagen III peptide (PIIINP) results were recorded. INTERVENTIONS: Transient elastography uses pulse-echo ultrasonography to measure liver stiffness, and this result is an indirect measure of hepatic fibrosis. FibroTest is an indirect serum marker of hepatic fibrosis. MAIN OUTCOMES AND MEASURES: Procollagen III peptide, TE, and FibroTest results, as well as the need for liver biopsy in this cohort. RESULTS: Seventy-seven patients (41 male [53%]) were included. Fifty (65%) patients had a valid TE assessment, and 9 (18%) had an abnormal result (range, 7.1-11.3 kPa). Being overweight or obese increased the possibility of obtaining an invalid TE result significantly (P = .01). On univariate analysis body mass index (r = 0.40, P = .005) and age (r = 0.52, P = .005) were correlated with abnormal TE results. Seventy-one patients received a FibroTest and 11 of 70 analyzed (16%) had an abnormal result (METAVIR score >F1). Age (r = 0.31, P = .009), cumulative methotrexate dose (r = 0.31, P = .01), and duration of methotrexate therapy (r = 0.36, P = .002) were correlated with abnormal FibroTest results. There was no correlation between PIIINP levels and TE results or between PIIINP levels and FibroTest results. Steatosis was demonstrated in all 5 patients who received liver biopsies during the study. Two patients had hepatic fibrosis, with 1 showing a sinusoidal pattern of fibrosis attributed to steatohepatitis. CONCLUSIONS AND RELEVANCE: Transient elastography and FibroTest are effective noninvasive tools for monitoring hepatotoxicity in patients receiving methotrexate for psoriasis. We propose that the need for liver biopsy could be reduced if abnormalities in at least 2 tests (serial PIIINP, TE, or FibroTest) are required before biopsy is considered. This strategy should be evaluated in prospective studies.