RESUMO
BACKGROUND: Primary hyperoxalurias (PHs) are rare genetic diseases that increase the endogenous level of oxalate, a waste metabolite excreted predominantly by the kidneys and also the gut. Treatments aim to improve oxalate excretion, or reduce oxalate generation, to prevent kidney function deterioration. Oxalobacter formigenes is an oxalate metabolizing bacterium. This Phase III, double-blind, placebo-controlled randomized trial investigated the effectiveness of orally administered Oxabact™, a lyophilized O. formigenes formulation, at reducing plasma oxalate levels in patients suffering from PH. METHODS: Subjects (≥ 2 years of age) with a diagnosis of PH and maintained but suboptimal kidney function (mean estimated glomerular filtration rate at baseline < 90 mL/min/1.73 m2) were eligible to participate. Subjects were randomized to receive Oxabact or placebo twice daily for 52 weeks. Change from baseline in plasma oxalate concentration at Week 52 was the primary study endpoint. RESULTS: Forty-three subjects were screened, 25 were recruited and one was discontinued. At Week 52, O. formigenes was established in the gut of subjects receiving Oxabact. Despite decreasing plasma oxalate level in subjects treated with Oxabact, and stable/increased levels with placebo, there was no significant difference between groups in the primary outcome (Least Squares mean estimate of treatment difference was - 3.80 µmol/L; 95% CI: - 7.83, 0.23; p-value = 0.064). Kidney function remained stable in both treatments. CONCLUSIONS: Oxabact treatment may have stabilized/reduced plasma oxalate versus a rise with placebo, but the difference over 12 months was not statistically significant (p = 0.06). A subtle effect observed with Oxabact suggests that O. formigenes may aid in preventing kidney stones. A higher resolution version of the Graphical abstract is available as Supplementary information.
Assuntos
Hiperoxalúria Primária , Hiperoxalúria , Cálculos Renais , Humanos , Hiperoxalúria/terapia , Hiperoxalúria Primária/terapia , Oxalobacter formigenes/metabolismo , Oxalatos , Cálculos Renais/metabolismoRESUMO
BACKGROUND: In primary hyperoxaluria Type 1 (PH1), endogenous oxalate overproduction significantly elevates urinary oxalate excretion, resulting in recurrent urolithiasis and/or progressive nephrocalcinosis and often early end-stage renal disease (ESRD). In ESRD, dialysis cannot sufficiently remove oxalate; plasma oxalate (Pox) increases markedly, inducing systemic oxalate deposition (oxalosis) and often death. Interventions to reduce Pox in PH1 subjects with ESRD could have significant clinical impact. This ongoing Phase II, open-label trial aimed to evaluate whether long-term Oxabact™ (Oxalobacter formigenes, OC5, OxThera Intellectual Property AB, Sweden) lowers Pox in PH1 ESRD subjects, ameliorating clinical outcome. METHODS: PH1 ESRD subjects on stable dialysis regimens were examined. Subjects were administered one OC5 capsule twice daily for up to 36 months or until transplantation. Total Pox values, cardiac function and safety were evaluated. Free Pox was evaluated in a comparative non-treated PH1 dialysis group using retrospective chart reviews and analyses. RESULTS: Twelve subjects enrolled in an initial 6-week treatment phase. Following a washout of up to 4 weeks, eight subjects entered a continuation study; outcomes after 24 months of treatment are presented. After 24 months, all subjects had reduced or non-elevated Pox compared with baseline. Cardiac function improved, then stabilized. No treatment-related serious adverse events were reported. CONCLUSIONS: Compared with an untreated natural control cohort, 24 months OC5 administration was beneficial to PH1 ESRD subjects by substantially decreasing Pox concentrations, and improving or stabilizing cardiac function and clinical status, without increasing dialysis frequency. OC5 was safe and well-tolerated.
Assuntos
Hiperoxalúria Primária , Hiperoxalúria , Falência Renal Crônica , Humanos , Hiperoxalúria Primária/complicações , Falência Renal Crônica/terapia , Oxalatos , Oxalobacter formigenes , Diálise Renal , Estudos RetrospectivosRESUMO
BACKGROUND: In patients with primary hyperoxaluria (PH), endogenous oxalate overproduction increases urinary oxalate excretion, leading to compromised kidney function and often kidney failure. Highly elevated plasma oxalate (Pox) is associated with systemic oxalate deposition in patients with PH and severe chronic kidney disease (CKD). The relationship between Pox and estimated glomerular filtration rate (eGFR) in patients with preserved kidney function, however, is not well established. Our analysis aimed to investigate a potential correlation between these parameters in PH patients from three randomized, placebo-controlled trials (studies OC3-DB-01, OC3-DB-02, and OC5-DB-01). METHODS: Baseline data from patients with a PH diagnosis (type 1, 2, or 3) and eGFR > 40 mL/min/1.73 m2 were analyzed for a correlation between eGFR and Pox using Spearman's rank and Pearson's correlation coefficients. Data were analyzed by individual study and additionally were pooled for Studies OC3-DB-02 and OC5-DB-01 in which the same Pox assay was used. RESULTS: A total of 106 patients were analyzed. A statistically significant inverse Spearman's correlation between eGFR and Pox was observed across all analyses; correlation coefficients were - 0.44 in study OC3-DB-01, - 0.55 in study OC3-DB-02, - 0.51 in study OC5-DB-01, and - 0.49 in the pooled studies (p < 0.0064). CONCLUSIONS: Baseline evaluations showed a moderate and statistically significant inverse correlation between eGFR and Pox in patients with PH already at early stages of CKD (stages 1-3b), demonstrating that a correlation is present before substantial loss in kidney function occurs.
Assuntos
Hiperoxalúria Primária , Insuficiência Renal Crônica , Taxa de Filtração Glomerular , Humanos , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/diagnóstico , Hiperplasia , Rim , OxalatosRESUMO
PURPOSE: This paper reports prescribing patterns for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in six Asia Pacific countries. METHODS: In a prospective noninterventional study, 31 sites in Australia, China, India, Singapore, South Korea, and Taiwan recorded details of CINV prophylaxis for the acute phase (first 24 h) and delayed phase (days 2-5) after single-day HEC or MEC for adult patients. Additional information on CINV prophylactic medications was collected from 6-day patient diaries. Primary antiemetic therapies were defined as corticosteroids, the 5-hydroxytryptamine-3 receptor antagonists (5HT3-RAs), and neurokinin-1 receptor antagonists (NK1-RAs). RESULTS: Evaluable patients in cycle 1 numbered 648 (318 [49%] HEC and 330 [51%] MEC) of mean (SD) age of 56 (12) years, including 58% women. For the acute phase after HEC, overall (and country range), 96% (91-100%) of patients received a 5HT3-RA, 87% (70-100%) a corticosteroid, and 43% (0-91%) an NK1-RA. CINV prophylaxis for the HEC delayed phase was more variable: including 22% (7-65%) 5HT3-RA, 52% (12-93%) corticosteroid, and 46% (0-88%) NK1-RA. For the MEC acute phase, 97% (87-100%) of patients received 5HT3-RA and 86% (73-97%) a corticosteroid. For the MEC delayed phase, 201 patients (61%) received a primary antiemetic, including 5HT3-RA (41%), corticosteroid (37%), and/or NK1-RA (4%). CONCLUSIONS: The 5HT3-RAs were prescribed consistently in all countries, while prescribing of other antiemetic therapies was variable, and corticosteroids were under-prescribed for CINV prophylaxis, particularly in the delayed phase.
Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Náusea/tratamento farmacológico , Padrões de Prática Médica , Vômito/tratamento farmacológico , Corticosteroides/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Ásia , Protocolos Clínicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Pacientes , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Qualidade da Assistência à Saúde , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Vômito/induzido quimicamente , Vômito/prevenção & controleRESUMO
PURPOSE: We sought to describe the impact of chemotherapy-induced nausea and vomiting (CINV) in prior cycles on CINV and chemotherapy regimen modification in subsequent cycles. METHODS: Eligible patients in this multinational prospective observational study were adults (≥18 years old) receiving their first single-day highly or moderately emetogenic chemotherapy (HEC or MEC). Multivariate logistic regression was used to assess the impact of CINV in prior cycles on CINV in subsequent cycles. Other independent variables included in the model were the cycle number, age, sex, and emetogenicity of regimen. RESULTS: There were 598 evaluable patients in cycle 2 and 533 in cycle 3, half receiving HEC and half MEC. Patients who experienced complete response (no emesis or rescue antiemetics) in earlier cycles, relative to those with no complete response, had an adjusted odds ratio (OR) of 5.9 (95% confidence interval (CI), 4.14-8.50) for experiencing complete response in subsequent cycles. Prior CINV was a significant and consistent predictor of subsequent CINV for all CINV endpoints: for emesis, OR 12.7 (95% CI, 8.47-18.9), for clinically significant nausea, OR 7.9 (95% CI, 5.66-10.9), and for clinically significant nausea and/or vomiting, OR 7.2 (5.17-10.1). Modifications to chemotherapy were recorded for 26-29% of patients in cycles 2 and 3, with CINV as the major reason for the modification for 5-9% of these patients. CONCLUSIONS: CINV in prior cycles was a strong and consistent predictor of CINV in subsequent cycles, while the incidence of chemotherapy regimen modification due to CINV was low in individual cycles.
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Náusea/epidemiologia , Neoplasias/tratamento farmacológico , Vômito/epidemiologia , Adulto , Distribuição por Idade , Idoso , Antieméticos/uso terapêutico , Ásia/epidemiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Pacientes , Estudos Prospectivos , Distribuição por Sexo , Inquéritos e Questionários , Vômito/induzido quimicamente , Vômito/tratamento farmacológicoRESUMO
PURPOSE: Some patients experience nausea and/or vomiting (NV) before receipt of chemotherapy. Our objective was to evaluate the impact of prior chemotherapy-induced NV (CINV) on the incidence of anticipatory NV in later cycles. METHODS: This multicenter, prospective non-interventional study enrolled chemotherapy-naïve adults scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC) for cancer in six Asia Pacific countries, excluding those with emesis within 24 h before cycle 1 chemotherapy. On day 1 before chemotherapy, patients answered four questions regarding emesis in the past 24 h, nausea, expectation of post-chemotherapy nausea, and anxiety in the past 24 h, the latter three scored from 0-10 (none-maximum). Multivariate logistic regression was used to assess the impact of prior CINV on anticipatory NV in cycles 2 and 3. RESULTS: Five hundred ninety-eight patients (59% female) were evaluable in cycle 2 (49% HEC, 51% MEC). The incidence of anticipatory emesis was low before cycles 2 and 3 (1.5-2.3%). The incidence of clinically significant anticipatory nausea (score of ≥3) was 4.8, 7.9, and 8.3% before cycles 1, 2, and 3, respectively, with adjusted odds ratio (OR), 3.95 (95% confidence interval (CI), 2.23-7.00; p < 0.001) for patients with clinically significant nausea in prior cycles, compared with none. The adjusted ORs for other anticipatory NV endpoints ranged from 4.54-4.74 for patients with prior CINV. The occurrence of clinically significant anxiety in the prior cycle also resulted in a significantly increased likelihood of anticipatory nausea. CONCLUSIONS: These findings highlight the importance of preventing CINV in cycle 1 to reduce anticipatory NV in subsequent cycles.
Assuntos
Antineoplásicos/efeitos adversos , Náusea/epidemiologia , Vômito Precoce/epidemiologia , Vômito/epidemiologia , Idoso , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Ásia/epidemiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Inquéritos e Questionários , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito Precoce/tratamento farmacológico , Vômito Precoce/prevenção & controleRESUMO
BACKGROUND: Integument-related toxicities are common during epidermal growth factor receptor (EGFR)-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT) KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial. METHODS: Integument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity. RESULTS: 154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59); most (98%) experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 vs. 0.78), health rating scores (72.5 vs. 71.0) and QLQ-C30 global health status scores (65.8 vs. 66.7) were comparable at baseline vs. safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity. CONCLUSIONS: First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00508404.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Dermatopatias/induzido quimicamente , Pele/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Genes ras , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Panitumumabe , Qualidade de Vida , Pele/patologia , Dermatopatias/genética , Dermatopatias/patologia , Adulto JovemRESUMO
BACKGROUND: Vascular endothelial growth factor (VEGF) has a crucial role in angiogenesis, and is a valid target in metastatic breast cancer. Motesanib is an investigational oral inhibitor of VEGF receptors. We aimed to determine whether treatment with motesanib plus paclitaxel is better than placebo plus paclitaxel in patients with HER2-negative locally recurrent or metastatic breast cancer. METHODS: Between Dec 1, 2006, and July 4, 2008, patients with untreated HER2-negative metastatic breast cancer were randomly assigned (using a randomisation list created by personnel not associated with the study) in a 1:1:1 ratio to paclitaxel (90 mg/m(2) on days 1, 8, and 15 every 3 weeks) plus either masked motesanib 125 mg orally once per day (n=91), masked placebo orally once per day (n=94), or open-label bevacizumab 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle (n=97), after stratification according to adjuvant or neoadjuvant chemotherapy (taxane-containing regimens vs other regimens vs none), number of metastatic sites (<3 vs ≥3), and hormone receptor status (positive vs negative). Placebo was provided as a replica of motesanib 25 mg tablets. The primary endpoint was objective response rate (ORR) based on the population as assigned to treatment. This trial is registered with ClinicalTrials.gov, number NCT00356681. FINDINGS: ORRs for the motesanib group and the placebo group did not differ significantly (49%vs 41%; absolute difference 8% [95% CI -6 to 22]; p=0.31). The ORR in the bevacizumab group (52%) was similar to that in the motesanib group. The most common grade 3 or higher adverse events included diarrhoea (18 of 92 patients in the motesanib group, none of 89 patients in the placebo group, and four of 96 patients in the bevacizumab group), fatigue (11, eight, and six), hypertension (11, one, and seven), and peripheral sensory neuropathy (ten, seven, and 19). More patients in the motesanib group had serious adverse events than did those in the placebo or bevacizumab groups (34, 26, and 21 patients, respectively); the most common of these in the motesanib group were gastrointestinal in nature. INTERPRETATION: Data from this trial do not support the further investigation of motesanib at this dose and schedule in this population. FUNDING: Amgen.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Indóis/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Niacinamida/análogos & derivados , Paclitaxel/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Método Duplo-Cego , Feminino , Humanos , Indóis/administração & dosagem , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Oligonucleotídeos , Paclitaxel/administração & dosagem , Receptor ErbB-2/análiseRESUMO
Preterm labor is a common obstetric complication. Clinical evaluation of cervical ripening to predict preterm labor is very inaccurate. We used frequency-domain near-infrared spectroscopy (FD-NIRS) to non-invasively investigate the changes of the optical properties (i.e., absorption and scattering of light) in the uterine cervix during regular pregnancies. Optical properties of uterine cervices were measured in 13 patients at various time points of regular pregnancies. For each gestational trimester, mean values with 95% confidence intervals were calculated for oxy-, deoxy-, and total hemoglobin concentration (O(2)Hb, HHb, tHb), tissue oxygen saturation and water content and statistically significant differences between the trimesters were determined. The wavelength-dependent scattering (scatter power) was calculated by an exponential fit. O(2)Hb, and tHb and the scatter power showed an increase as a function of the gestational age. Differences between the second and the third trimester were statistically significant. HHb and the water content showed no significant change over time. Our results show that FD-NIRS is a promising diagnostic tool for providing information about cervical content of hemoglobin, water, and extracellular matrix proteins. We propose this technology to assess the cervical ripening and eventually to predict preterm labor.
Assuntos
Maturidade Cervical/metabolismo , Colo do Útero/química , Trabalho de Parto Prematuro/diagnóstico , Espectroscopia de Luz Próxima ao Infravermelho , Adulto , Colo do Útero/fisiologia , Feminino , Hemoglobinas/análise , Humanos , Oxigênio/análise , Gravidez , Água/análise , Adulto JovemRESUMO
BACKGROUND: The use and effectiveness of cinacalcet in 'real-world' clinical practice was investigated in a pan-European observational study in dialysis patients with secondary hyperparathyroidism (SHPT) of varying severity. METHODS: Adult patients with chronic kidney disease on dialysis who had initiated cinacalcet treatment were enrolled. Data were collected 6 months before initiating cinacalcet, at baseline (initiation of cinacalcet) and up to 12 months after cinacalcet initiation. RESULTS: A total of 1865 patients [mean (SD) age 58 (15) years] were enrolled from 187 sites in 12 countries. Most patients had a dialysis vintage of > or =1 year (1-5 years, n = 833; >5 years, n = 748 versus <1 year, n = 265). The patients generally had severely uncontrolled intact parathyroid hormone (iPTH) serum levels (median 721 pg/ml) and elevated phosphorus (median 5.9 mg/dl) and calcium (median 9.6 mg/dl) at baseline, despite being prescribed conventional therapies. The proportions of patients achieving the recommended [NKF-K/DOQI(TM) (KDOQI(TM))] targets increased from baseline [4%, 39%, 40% and 46% for iPTH, phosphorus, calcium and calcium-phosphorus product (Ca x P), respectively] to Month 12 (28%, 48%, 51% and 68%, respectively). At Month 12, 18% of patients had achieved the combined target for iPTH + Ca x P compared with 2% at baseline. Most patients (65%) received <60 mg/day cinacalcet at Month 12. Vitamin D sterol use remained fairly stable throughout the study. There was a 13% decrease in prescribed sevelamer; use of calcium-based phosphate binders increased by 5.6%. There was no unexpected safety or tolerability concerns. CONCLUSION: This analysis of current European clinical practice shows that-consistent with findings from randomized controlled trials and retrospective observational studies-cinacalcet improves attainment of KDOQI bone metabolism targets in dialysis patients with various stages of SHPT.
Assuntos
Osso e Ossos/metabolismo , Hiperparatireoidismo Secundário/tratamento farmacológico , Minerais/metabolismo , Naftalenos/uso terapêutico , Diálise Renal , Adulto , Idoso , Cálcio/sangue , Cinacalcete , Europa (Continente) , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/metabolismo , Falência Renal Crônica/complicações , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Hormônio Paratireóideo/sangue , Fósforo/sangue , Vitamina D/metabolismoRESUMO
The influence of sex hormones on the human uterine cervix is likely to be important in the process of cervical ripening. Frequency domain near-infrared spectroscopy (FD-NIRS) was used to investigate non-invasively the changes in the optical properties that reflect physiologic parameters and tissue composition of the uterine cervix in the different phases of the menstrual cycle. Twenty premenopausal and nine postmenopausal women were examined. Optical properties of the uterine cervix were measured, and physiological parameters [concentration of water, oxyhemoglobin (O(2)Hb) and deoxyhemoglobin (HHb), total hemoglobin (tHb), oxygen saturation (StO(2)), water, and scattering power] were calculated. Analysis of variance (ANOVA) was used to test for statistical significance. The optical properties of the anterior cervical lip did not differ from those of the posterior lip. HHb was significantly lower in cervices during menstrual bleeding than during the follicular, luteal, or postmenopausal phases. The ratio of O(2)Hb to HHb was highly significantly increased by a factor of 2 when cervices during the menstrual bleeding were compared with those during the follicular, luteal, or postmenopausal phases. The scattering power was significantly lower during menstrual bleeding than during the follicular or postmenopausal phases. We demonstrated that withdrawal of sex hormones during menstrual bleeding is associated with a significant decrease in HHb and scattering power, with stable values of O(2)Hb, tHb, StO(2), and H(2)O compared with the values during the follicular, luteal or postmenopausal phases of the menstrual cycle. Cervical softening during menstrual bleeding seems to be different from cervical softening for labor.
Assuntos
Colo do Útero/fisiologia , Hormônios Esteroides Gonadais/fisiologia , Adulto , Maturidade Cervical/fisiologia , Feminino , Hemoglobinas/metabolismo , Humanos , Ciclo Menstrual/fisiologia , Pessoa de Meia-Idade , Trabalho de Parto Prematuro/etiologia , Trabalho de Parto Prematuro/fisiopatologia , Trabalho de Parto Prematuro/prevenção & controle , Fenômenos Ópticos , Oxiemoglobinas/metabolismo , Pós-Menopausa/fisiologia , Gravidez , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Mastodynia is correlated with the menstrual cycle. Using frequency-domain near-infrared spectroscopy (FD-NIRS), we investigated changes in breast perfusion in women who were or were not using hormonal contraception. Healthy volunteers, on or not on hormonal contraception, were examined. Optical properties were measured in all quadrants of both breasts, and physiological parameters were calculated. Measurements were repeated every other day during one complete menstrual cycle. Measurements were comparable in all quadrants. Data remained unchanged during the entire cycle in patients using hormonal contraception. However, a biphasic variation of deoxyhemoglobin, oxyhemoglobin, total hemoglobin (tHb), and water content (H(2)O) was observed in women not using contraception. tHb and H(2)O distinctly increased during the ovulation period and remained elevated throughout the luteal phase. It was concluded that FD-NIRS allows accurate measurement of optical properties of human breasts. As opposed to the menstrual cycles of persons using oral contraception, spontaneous menstrual cycles exhibit biphasic variations of tissue perfusion parameters. These findings are important for the investigation of mastodynia.
Assuntos
Mama/irrigação sanguínea , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Mama/efeitos dos fármacos , Mama/fisiologia , Anticoncepcionais Orais/administração & dosagem , Feminino , Hemoglobinas/metabolismo , Humanos , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/fisiologia , Fenômenos Ópticos , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Adulto JovemRESUMO
In order to have a rational approach to necessary preventive measures it is essential to know the health risks. The 80 million travellers each year with destinations in Africa, Asia, Latin America, Pacific Islands and remote areas in Eastern Europe are exposed to a broad range of pathogens that are rarely encountered at home. The risk depends on the degree of endemicity in the area visited, the duration of stay, the individual behaviour and the preventive measures taken. Travellers' diarrhoea (TD) is the most frequent ailment of visitors to countries with poor hygiene. The incidence rate is 25-90% in the first 2 weeks abroad. The risk of TD is far less in travellers originating in a high risk country, as some immunity develops. Malaria is an important risk for travellers going to endemic areas. Without chemoprophylaxis, the monthly incidence is high in some destinations, among them frequently visited tropical Africa where 80-95% of the infections are due to Plasmodium falciparum. The incidence rates are lower in most endemic areas of Asia and Latin America where Plasmodium vivax predominates. The risk is nil in all capital cities of South America and SE Asia, as well as in many frequently visited tourist destinations. The diseases preventable by immunization will be discussed in a separate paper (Vaccination priorities; page 175). Sexually transmitted diseases occur frequently, as some travellers (5% of Europeans) engage in casual sex, approximately half of them without being protected by a condom. The prevalence for HIV-infection, syphilis, gonorrhoea, etc. often exceeds 50% in prostitutes. In some European countries, a major proportion of heterosexuals with newly acquired HIV-infection have acquired it while abroad.
Assuntos
Epidemiologia , Viagem , Acidentes , Doenças Transmissíveis/epidemiologia , Diarreia/epidemiologia , Feminino , Humanos , Malária Falciparum/epidemiologia , Masculino , Saúde Pública , Fatores de Risco , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/transmissãoRESUMO
Selection of immunizations should be based on requirements and on risk of infection. According to the International Health Regulations, many countries require yellow fever vaccination and proof thereof as the International Certificate of vaccination. Additionally selected countries require proof of vaccination against cholera and meningococcal disease. A consultation for travel health advice is always an opportunity to ascertain that routine immunizations have been performed. Recommended immunizations often are more important for traveller's health than the required or routine ones. The most frequent vaccine preventable infection in non-immune travellers to developing countries is hepatitis A with an average incidence rate of 0.3% per month; in high risk backpackers or foreign-aid-volunteers this rate is 2.0%. Many immunizations are recommended for special risk groups only: there is a growing tendency in many countries to immunize all young travellers to developing countries against hepatitis B, as it is uncertain who will voluntarily or involuntarily get exposed. The attack rate of influenza in intercontinental travel is estimated to be 1%. Immunity against poliomyelitis remains essential for travel to Africa and parts of Asia. Many of the 0.2-0.4% who experience an animal bite are at risk of rabies. Typhoid fever is diagnosed with an incidence rate of 0.03% per month among travellers to the Indian subcontinent, North and West Africa (except Tunisia), and Peru, elsewhere this rate is 10-fold lower. Meningococcal disease, Japanese encephalitis, cholera and tuberculosis have been reported in travellers, but these infections are rare in this population. Although no travel health vaccine is cost beneficial, most professionals will offer protection against the frequent risks, while most would find it ridiculous to use all available vaccines in every traveller. It is essentially an arbitrary decision made on the risk level one wishes to recommend protection--but the priorities need to be set correctly.
Assuntos
Viagem , Vacinação , Fatores Epidemiológicos , Hepatite A/epidemiologia , Hepatite A/prevenção & controle , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Humanos , Fatores de Risco , Febre Amarela/epidemiologia , Febre Amarela/prevenção & controleRESUMO
Background. The calcimimetic, cinacalcet, is approved for treating secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on dialysis. Biochemical profiles and clinical outcomes in patients discontinuing cinacalcet at kidney transplantation have not been previously described.Methods. We performed a retrospective observational study evaluating post-transplant biochemical profiles and clinical outcomes in patients who had enrolled in phase 2 or 3 randomized, placebo-controlled studies of cinacalcet before receiving a kidney transplant.Results. The study included 28 former cinacalcet and 10 former placebo patients. Post-kidney transplant, there were no obvious differences between the two groups in levels of serum intact parathyroid hormone, calcium or phosphorus. One patient in each group underwent post-transplant parathyroidectomy. Kidney transplant failure was apparent in one former cinacalcet-treated patient (4%) and three former placebo patients (30%). The duration of hospitalization (mean +/- standard error) immediately post-transplant in these two groups was 2.3 +/- 0.3 and 3.4 +/- 0.8 weeks, respectively.Conclusions. Using cinacalcet to treat SHPT in patients with CKD awaiting kidney transplantation does not appear to modify SHPT-related post-transplant biochemical profiles, or clinical outcomes, compared with placebo.
RESUMO
OBJECTIVE: Preterm labor is a common obstetric complication. Clinical evaluation of cervical ripening to predict preterm labor has a substantial inter- and intraobserver variability. We used frequency domain near-infrared spectroscopy (FD-NIRS) to non-invasively investigate the changes of the optical properties (i.e., absorption and scattering of light) in the uterine cervix during drug-induced cervical ripening. METHODS: Ten volunteers scheduled for abortion were examined. Optical properties of the uterine cervix were measured and physiological parameters were calculated prior to and after induction of cervical ripening using topical misoprostol. Mean relative changes, +/-standard error of the mean as well as statistical significance using the t-test were calculated for oxy- and deoxyhemoglobin, total hemoglobin, oxygen-saturation, and water. The wavelength-dependent decrease of scattering (scatter power) was calculated by an exponential fit and tested with the Wilcoxon test. RESULTS: Misoprostol induced a decrease in total hemoglobin of 21 +/- 6% (P < 0.05), a decrease in oxyhemoglobin of 22 +/- 6% (P < 0.05), a decrease in deoxyhemoglobin of 16 +/- 11% and an increase of 36 +/- 8% (P < 0.005) in water content. The scatter power was significantly lower (P < 0.05) after cervical ripening. CONCLUSION: Our results show that FD-NIRS is a promising diagnostic tool to detect changes in cervical concentrations of hemoglobin and water. A severe tissue edema, probably due to a hormone-induced inflammatory process, seems to be important for cervical ripening. The reduction in total hemoglobin is likely to be a consequence of the increased water content of the tissue resulting in a dramatic increase of the distance between vessels. We propose this technology to assess the cervical ripening and eventually to predict preterm labor.