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1.
Int J Biometeorol ; 65(7): 1205-1214, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33751218

ABSTRACT

Changes in ambient temperature have been reported as an important risk factor for respiratory diseases among pre-school children. However, there have been few studies so far on the effects of temperature on children respiratory health in developing countries including Vietnam. This study examined the impact of short-term changes in ambient temperature on hospital admissions for acute lower respiratory infection (ALRI) among children aged less than 5 years old in Ho Chi Minh City (HCMC), Vietnam. Data on daily hospital admissions from 2013 to 2017 were collected from two large paediatric hospitals of the city. Daily meteorological data of the same period were also collected. Time series analysis was performed to evaluate the association between risk of hospitalisations and temperatures categorised by seasons, age, and causes. We found that a 1 °C increase in maximum temperature was associated with 4.2 and 3.4% increase in hospital admission for ALRI among children 3-5 years old during the dry season and the rainy season, respectively. Surprisingly, in the rainy season, a rise of 1°C diurnal temperature range (DTR) was significantly associated with a decrease from 2.0 to 2.5% risk of hospitalisation for ALRI among children <3 years old. These findings suggested that although high temperature is a risk factor for hospital admissions among children in general, other modifiable factors such as age, exposure time, air conditioning usage, wearing protective clothing, socioeconomic status, and behaviour may influence the overall effect of high temperature on hospital admissions of children <5 years old in HCMC. The findings of this study have provided evidence for building public health policies aimed at preventing and minimizing the adverse health effects of temperature on children in HCMC.


Subject(s)
Air Pollution , Air Pollution/analysis , Child , Child, Preschool , Cities , Hospitalization , Hospitals , Humans , Seasons , Temperature , Vietnam/epidemiology
2.
Ann Oncol ; 29(6): 1402-1408, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29659672

ABSTRACT

Background: Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme-arginine deiminase-conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and patients: Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The primary end point was overall survival (OS), with 93% power to detect a 4-5.6 months increase in median OS (one-sided α = 0.025). Secondary end points included progression-free survival, safety, and arginine correlatives. Results: A total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus 7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6 months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in <5% of patients. Two patients on ADI-PEG 20 had ≥grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion. Conclusion: ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway. Clinical Trial number: www.clinicaltrials.gov (NCT 01287585).


Subject(s)
Carcinoma, Hepatocellular/therapy , Hydrolases/therapeutic use , Liver Neoplasms/therapy , Palliative Care , Polyethylene Glycols/therapeutic use , Carcinoma, Hepatocellular/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Prognosis , Survival Rate
3.
Mar Drugs ; 16(11)2018 Nov 01.
Article in English | MEDLINE | ID: mdl-30388774

ABSTRACT

Fucoidans from brown macroalgae have beneficial biomedical properties but their use as pharma products requires homogenous oligomeric products. In this study, the action of five recombinant microbial fucoidan degrading enzymes were evaluated on fucoidans from brown macroalgae: Sargassum mcclurei, Fucus evanescens, Fucus vesiculosus, Turbinaria ornata, Saccharina cichorioides, and Undaria pinnatifida. The enzymes included three endo-fucoidanases (EC 3.2.1.-GH 107), FcnA2, Fda1, and Fda2, and two unclassified endo-fucoglucuronomannan lyases, FdlA and FdlB. The oligosaccharide product profiles were assessed by carbohydrate-polyacrylamide gel electrophoresis and size exclusion chromatography. The recombinant enzymes FcnA2, Fda1, and Fda2 were unstable but were stabilised by truncation of the C-terminal end (removing up to 40% of the enzyme sequence). All five enzymes catalysed degradation of fucoidans containing α(1→4)-linked l-fucosyls. Fda2 also degraded S. cichorioides and U. pinnatifida fucoidans that have α(1→3)-linked l-fucosyls in their backbone. In the stabilised form, Fda1 also cleaved α(1→3) bonds. For the first time, we also show that several enzymes catalyse degradation of S. mcclurei galactofucan-fucoidan, known to contain α(1→4) and α(1→3) linked l-fucosyls and galactosyl-ß(1→3) bonds in the backbone. These data enhance our understanding of fucoidan degrading enzymes and their substrate preferences and may assist development of enzyme-assisted production of defined fuco-oligosaccharides from fucoidan substrates.


Subject(s)
Glycoside Hydrolases/chemistry , Oligosaccharides/chemistry , Phaeophyceae/chemistry , Polysaccharide-Lyases/chemistry , Polysaccharides/chemistry , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , Enzyme Assays , Enzyme Stability , Flavobacterium/chemistry , Flavobacterium/genetics , Glycoside Hydrolases/genetics , Glycoside Hydrolases/isolation & purification , Polymerization , Polysaccharide-Lyases/genetics , Polysaccharide-Lyases/isolation & purification , Protein Engineering/methods , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Substrate Specificity , Sulfates/chemistry
4.
J Viral Hepat ; 24(12): 1089-1097, 2017 12.
Article in English | MEDLINE | ID: mdl-28581644

ABSTRACT

Community-based real-world outcomes on effectiveness of antiviral therapies for chronic hepatitis B virus (CHB) in Asians are limited. Whether hepatitis B surface antigen (HBsAg) loss correlates with undetectable virus and alanine aminotransferase (ALT) normalization on treatment or what predicts risk of seroreversion or detectable virus after stopping therapy is unclear. We aim to evaluate rates and predictors of HBsAg loss, seroconversion, ALT normalization and undetectable HBV DNA, including HBsAg seroreversion or re-emergence of HBV DNA among Asian CHB patients. We retrospectively evaluated 1072 CHB adults on antiviral therapy at two community gastroenterology clinics from 1997 to 2015. Rates of HBsAg loss, ALT normalization, achieving undetectable HBV DNA and developing surface antibody (anti-HBs) were stratified by HBeAg status. Following HBsAg loss, HBsAg seroreversion or re-emergence of detectable HBV DNA was analysed. With median treatment of 76.7 months, the overall rate of HBsAg loss was 4.58%, with similar HBsAg loss rates between HBeAg-positive and HBeAg-negative patients (4.44% vs 4.71%, P=.85) in a predominantly Asian population (98.1%). Among HBsAg loss patients, 33.3% developed anti-HBs, 95.8% achieved undetectable virus and 66.0% normalized ALT. No significant baseline or on-treatment predictors of HBsAg loss were observed. While six patients who achieved HBsAg loss had seroreversion with re-emergence of HBsAg positivity, viral load remained undetectable, demonstrating the sustainability of viral suppression. Among a large community-based real-world cohort of Asian CHB patients treated with antiviral therapy, rate of HBsAg loss was 4.58%. Despite only 33.3% of HBsAg loss patients achieving anti-HBs, nearly all patients achieved sustained undetectable virus.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B Surface Antigens/blood , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Sustained Virologic Response , Adolescent , Adult , Aged , Aged, 80 and over , Alanine Transaminase/blood , Asia , DNA, Viral/blood , Female , Hepatitis B Antibodies , Hepatitis B, Chronic/pathology , Humans , Male , Middle Aged , Retrospective Studies , Seroconversion , Treatment Outcome , Viral Load , Young Adult
5.
J Viral Hepat ; 24(1): 17-21, 2017 01.
Article in English | MEDLINE | ID: mdl-27677786

ABSTRACT

Sofosbuvir/ledipasvir (SOF/LDV) is the first all-oral ribavirin-free treatment approved for chronic hepatitis C virus (HCV) genotype 6, offering a safe and highly efficacious treatment option. Large studies evaluating real-world outcomes of this regimen are lacking. We aim to evaluate real-world treatment outcomes for HCV genotype 6. A retrospective cohort study evaluated 65 adults (age ≥18) with chronic HCV genotype 6 treated with SOF/LDV without ribavirin at a community gastroenterology clinic in the United States from November 2014 to May 2016. Rates of undetectable virus at week 4 on treatment, at end of treatment (EOT) and SVR12 were stratified by the presence of cirrhosis and prior treatment (treatment naïve vs treatment experienced). Among 65 patients with chronic HCV genotype 6 treated with SOF/LDV (52.3% male, mean age 66.3 years [SD 9.7], 41.5% cirrhosis and 15.4% treatment experienced), 97.3% had undetectable virus at week 4 on treatment, 96.9% had undetectable virus at EOT and 95.3% achieved SVR12. SVR12 was 100% in females vs 91.2% in males, P=.096, and 92.3% in patients with cirrhosis vs 97.4% in those without cirrhosis, P=.347. Resistance testing of treatment failures was attempted but unsuccessful due to lack of conforming primers to define the possible resistance mutations. Among the largest U.S. community-based real-world cohort of Asian chronic HCV genotype 6 patients treated with all-oral SOF/LDV without ribavirin, SVR12 was similar to SVR12 reported in clinical trials, confirming the safety and effectiveness of this regimen and validating current HCV genotype 6 treatment guideline recommendations.


Subject(s)
Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Fluorenes/therapeutic use , Genotype , Hepacivirus/classification , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Sofosbuvir/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Asian , Female , Hepacivirus/isolation & purification , Humans , Male , Middle Aged , Retrospective Studies , Sustained Virologic Response , Treatment Outcome , United States , Young Adult
6.
Support Care Cancer ; 22(1): 121-8, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24005884

ABSTRACT

PURPOSE: Indwelling central venous catheters (CVCs) have been increasingly used to enable delivery of intravenous chemotherapy. We aimed to compare the safety and cost of two commonly used CVCs, peripherally inserted central venous catheter (PICCs) and ports, in the delivery of chemotherapy in patients with non-haematological malignancies. METHODS: Seventy patients were randomly assigned to receive either a PICC or a port. The primary endpoint was occurrence of major complications, which required removal of the CVC and secondary endpoints included occurrence of any complications. RESULTS: Port devices were associated with fewer complications compared with PICC lines (hazard ratio of 0.25, CI, 0.09-0.86, P = 0.038). Major complication rate was lower in the port arm compared to the PICC arm (0.047 versus 0.193 major complications/100 catheter days, P = 0.034) with 6 versus 20 % of patients experiencing major complications, respectively. Thrombosis, the most common complication, was significantly higher in the PICC arm compared to the port arm (25 versus 0 %, P = 0.013). Quality of life and cost estimates did not differ significantly between the two arms. CONCLUSIONS: Port devices are associated with a lower risk of complications, with no difference in cost, compared to PICC lines in patients with non-haematological malignancies receiving intravenous chemotherapy.


Subject(s)
Catheterization, Central Venous/adverse effects , Catheterization, Central Venous/economics , Catheterization, Peripheral/adverse effects , Catheterization, Peripheral/economics , Neoplasms/drug therapy , Aged , Antineoplastic Agents/administration & dosage , Australia , Catheterization, Central Venous/instrumentation , Catheterization, Peripheral/instrumentation , Central Venous Catheters/adverse effects , Central Venous Catheters/economics , Female , Humans , Male , Middle Aged , Neoplasms/blood , Neoplasms/economics , Quality of Life , Survival Rate , Thrombosis/economics , Thrombosis/etiology , Vascular Access Devices/adverse effects , Vascular Access Devices/economics
7.
Rev Epidemiol Sante Publique ; 60(2): 103-8, 2012 Apr.
Article in French | MEDLINE | ID: mdl-22424749

ABSTRACT

BACKGROUND: In developing countries, maternal and neonatal mortality is high. Among the causes of death during the neonatal period, low birth weight is crucial. A dose of fluoride beyond 2mg/L causes enamel damage, possibly affecting the fetus. The aim of this study was to search for an association between dental fluorosis in the mother and low birthweight of the newborn. METHODOLOGY: This was a case-control study performed in an endemic area in Senegal (Diourbel). It included 108 mothers who gave birth to newborns weighing less than 2500 g (cases) and 216 mothers with newborns weighing greater or equal to 2500 g (controls). Data on socio-demographic, lifestyle, history and pregnancy variables were collected. Those related to water consumption during pregnancy and dental fluorosis (Dean's index) were measured. The data were analyzed by R software. Logistic regression was used to identify associations and the statistical significance level was set to 0.05. RESULTS: The proportions of mothers consuming well water were 62% among cases versus 43.5% among controls. The score 4 of Dean's Index was reported for 25.9% of cases versus 6.9% of controls. The water consumed and the modal score of Dean's Index were significantly associated with the occurrence of low birthweight adjusted for gender, consanguinity, anemia and hypertension. CONCLUSION: Low birthweight was associated with pregnant women living in endemic areas. Defluoridation programs and access for pregnant women and children to high quality water are necessary in areas of endemic fluorosis.


Subject(s)
Fluorides , Fluorosis, Dental/epidemiology , Infant, Low Birth Weight , Pregnancy Complications/etiology , Case-Control Studies , Endemic Diseases , Female , Fluorosis, Dental/complications , Humans , Infant, Newborn , Logistic Models , Pregnancy , Senegal , Water Quality
8.
Mult Scler Relat Disord ; 60: 103745, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35306241

ABSTRACT

BACKGROUND: Higher levels of moderate to vigorous physical activity (MVPA) associate with disease activity in pediatric multiple sclerosis (MS). Further, measures of retinal integrity associate with lower brain atrophy, yet the relationship of retinal integrity with MVPA has not been investigated. OBJECTIVE: To determine the relationship between MVPA and retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness in patients with MS, myelin oligodendrocyte glycoprotein-associated disorders (MOGAD), neuromyelitis optica spectrum disorder (NMOSD), and monophasic acquired demyelinating syndromes (monoADS). METHODS: 150 consecutive children ≤18 y.o with neuroinflammatory disorders were included. Outcomes included the Godin Leisure Time Activity Questionnaire (GLTEQ) modeled as both a continuous and categorical variable (any vs no MVPA/Strenuous activity), and RNFL and GCIPL using linear mixed models (JASP 0.14.1). RESULTS: An association was identified between MVPA with RNFL thickness (F (1,133) = 8.40, p = .004) and GCIPL thickness (F(1, 131) = 7.68, p = .006). In the MS cohort, any strenuous physical activity was associated with greater RNFL (F(1,35) = 7.30, p = .011) and GCIPL thickness (F(1,35) = 8.73, p =.006). CONCLUSIONS: Any MVPA participation is associated with higher RNFL and GCIPL thickness across neuroinflammatory disorders.


Subject(s)
Multiple Sclerosis , Retinal Ganglion Cells , Adolescent , Benchmarking , Child , Exercise , Humans , Neuroinflammatory Diseases , Tomography, Optical Coherence
9.
Int Arch Occup Environ Health ; 84(5): 513-22, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21431858

ABSTRACT

PURPOSE: This study investigated the association between geographic region and blood lead levels (BLLs) in US children, as well as trends in this relationship, using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: SAS® and SUDAAN® software programs were utilized to develop linear regression models adjusted for several factors associated with BLLs. RESULTS: The largest decline in BLLs was observed in Northeastern children, while the percentage of children with elevated blood lead levels decreased the most for the West and Northeast. Lead levels of Northeastern children were still higher than those of children living in the West. However, levels were not different among children residing in the Northeast, Midwest, and South, and the blood lead concentrations were less than 5 µg/dL for all but one subgroup of children and less than 2 µg/dL for >70% of the subgroups. More importantly, the effects of different risk factors for higher blood lead levels varied by region even after adjusting for all other covariates. CONCLUSIONS: The results of this study not only provide relevant and current blood lead levels for US children that can be used as reference values to evaluate biomonitoring data, but can also be used to help direct prevention and surveillance strategies to reduce lead in the environment of at-risk children.


Subject(s)
Environmental Exposure/statistics & numerical data , Lead Poisoning/blood , Lead Poisoning/epidemiology , Lead/blood , Population Surveillance , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Male , Nutrition Surveys , Reference Values , Risk Factors , United States/epidemiology
10.
Mali Med ; 36(1): 66-69, 2021.
Article in French | MEDLINE | ID: mdl-37973568

ABSTRACT

OBJECTIF: The aim of this study was to describe the results of radiochemotherapy in patients after transurethral resection of muscle invasive bladder tumors. MATERIAL AND METHODS: A retrospective study from May 2014 to May 2016 in the radiotherapy department of the Mali Hospital. Have been included, all patients with bladder cancer infiltrating the muscle. Secondary cancers of the bladder and metastatic forms have been excluded from our study. Transurethral resection of bladder was performed. Neoadjuvant chemotherapy with paclitaxel- carboplatin was administered every three weeks in all patients, then external phototherapy 6 MV at a dose of 66 Gy due to 2 Gy of 5 sessions per week 6MV photon of external beam radiotherapy at a dose of 66 Gy due to 2 Gy of 5 sessions per week associated with concomitant cisplatin at dose of 40mg / m2 / week. RESULTS: Eight patients were included in ourstudy. The average age of 53.75 ± 14.84 years. The male sex was predominant 87.5% (n = 7). The history of chronic smoking wasfound in four patients. The main carcinogenic risk factor identified in our patients was urogenital bilharzia (6 cases / 8).The histological type found was urothelial carcinomain 12.5% (n = 1) and invasive squamous cell carcinomain 87.5% (n = 7). Transurethral resection of the tumor was performed in 62.5% (n = 5). Endoscopic biopsy was performed in 37.5% (n = 3). The tumor was classified pT2N0M0 in 50% (n = 4), pT3aN0M0 in 37.5% (n = 3) and pT3bN0M0 in 12.5% (n = 1). Neoadjuvant chemotherapy with paclitaxel - carboplatin every three weeks was administered to all patients. The results of radiochemotherapy (see Table: evolution). CONCLUSION: Concomitant radiochemotherapy is a conservative curative treatment that can be proposed as a replacement for cystectomy, for non-metastatic infiltrating tumors after the most complete endoscopic resection.


OBJECTIF: Le but de cette étude était de décrire les résultats d'une radiochimiothérapie chez les patients après résection transurétrale des tumeurs de vessie infiltrant le muscle. MATÉRIEL ET MÉTHODES: Une étude rétrospective allant de mai 2014 à mai 2016 au service de radiothérapie de l'hôpital du Mali. Ont été inclus, tous les patients présentant un cancer de vessie infiltrant le muscle. Les cancers secondaires de la vessie ainsi que les formes métastatiques ont été exclus de notre étude. La résection transurétrale de vessie a été réalisée. La chimiothérapie néoadjuvante à base de paclitaxel ­ carboplatine a été administrée toutes les trois semaines. La radiothérapie externe au photon 6MV à la dose de 66 Gy en raison de 2 Gy de 5 séances par semaine associée à la chimiothérapie concomitante à base de cisplatine (CDDP) 40mg/m2/semaine a été réalisée. RÉSULTATS: Au total huit patients ont été inclus dans notre étude. L'âge moyen de 53,75±14,84 ans. Le sexe masculin était prédominant 87.5% (n=7). L'antécédent de tabagisme chronique était retrouvé chez quatre patients. Le principal facteur de risque cancérigène identifié chez nos patients était la bilharziose urogénitale (6cas/8). Le type histologique retrouvé était le carcinome urothelial dans 12.5% (n=1) et le carcinome épidermoïde infiltrant dans 87.5% (n=7). La résection transurétrale de la tumeur a été réalisée dans 62.5% (n=5). La biopsie par voie endoscopique été réalisée dans 37.5% (n=3). La tumeur été classée pT2N0M0 dans 50% (n= 4), pT3aN0M0 dans 37.5% (n=3) et pT3bN0M0 dans 12.5% (n= 1). La chimiothérapie néoadjuvante à base de paclitaxel ­ carboplatine chaque trois semaines a été administrée chez tous les malades.Les résultats de la radiochimiothérapie (cf. Tableau: évolution). CONCLUSION: La radiochimiothérapie concomitante est un traitement curatif conservateur qui peut être proposée en remplacement à la cystectomie pour les tumeurs infiltrantes non métastatiques après une résection endoscopique la plus complète possible.

11.
Transl Psychiatry ; 11(1): 147, 2021 03 02.
Article in English | MEDLINE | ID: mdl-33654078

ABSTRACT

Late-life depression (LLD) is associated with an increased risk of developing dementia; however, it is not known whether individuals with a history of LLD exhibit a more rapid rate of cognitive decline. We aimed to determine whether those with LLD experienced faster cognitive decline compared with never-depressed control (NDC) participants from the community and whether stratification of LLD into early-onset depression (EOD) and late-onset depression (LOD) subtypes revealed differing rates and domain-specific expression of cognitive decline. We conducted a prospective, longitudinal study where 185 participants with LLD (remitted) and 114 NDC were followed for 5 years on average. EOD was defined as having first lifetime depressive episode at <60years and LOD at ≥60years. Every year, participants underwent comprehensive neuropsychological assessment. Composite scores for each cognitive domain were calculated through averaging standardized scores across tests. LLD compared to NDC demonstrated significant baseline impairment but did not decline more rapidly. EOD were significantly impaired in attention/processing speed and global cognitive function at baseline but did not experience more rapid decline as compared to NDC. Those with LOD compared to both NDC and EOD performed worse in all domains at baseline and experienced more rapid decline in verbal skills and delayed memory ability. Our findings suggest that baseline impairment may lower the threshold for those with LLD to develop dementia. EOD and LOD may represent distinct phenotypes of cognitive impairment with differing neural substrates. LOD may represent a distinct phenotype with a more rapid decline in verbal skills and delayed memory.


Subject(s)
Cognitive Dysfunction , Dementia , Age of Onset , Cognitive Dysfunction/epidemiology , Dementia/epidemiology , Depression , Humans , Longitudinal Studies , Neuropsychological Tests , Prospective Studies
12.
Clin Cancer Res ; 27(11): 3050-3060, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33771853

ABSTRACT

PURPOSE: As hypoxia can mediate resistance to immunotherapy, we investigated the safety, tolerability, and efficacy of combining evofosfamide, a prodrug that alleviates hypoxia, with ipilimumab, an immune checkpoint inhibitor, in immunologically "cold" cancers, which are intrinsically insensitive to immunotherapy, as well as in "hot/warm" metastatic cancers that are, atypical of such cancers, resistant to immunotherapy. PATIENTS AND METHODS: In a phase I, 3+3 dose-escalation trial (NCT03098160), evofosfamide (400-640 mg/m2) and ipilimumab (3 mg/kg) were administered in four 3-week cycles. The former was administered on days 1 and 8 of cycles 1-2, while the latter was administered on day 8 of cycles 1-4. Response was assessed using immune-related RECIST and retreatment was allowed, if deemed beneficial, after completion of cycle 4 or at progression. RESULTS: Twenty-two patients were enrolled, of whom 21 were evaluable, encompassing castration-resistant prostate cancer (n = 11), pancreatic cancer (n = 7), immunotherapy-resistant melanoma (n = 2), and human papillomavirus-negative head and neck cancer (n = 1). Drug-related hematologic toxicities, rash, fever, nausea, vomiting, and elevation of liver enzymes were observed in > 10% of patients. The most common drug-related grade 3 adverse event was alanine aminotransferase elevation (33.3%). Two patients discontinued ipilimumab and 4 required evofosfamide deescalation due to toxicity. Of 18 patients with measurable disease at baseline, 3 (16.7%) achieved partial response and 12 (66.7%) achieved stable disease. The best responses were observed at 560 mg/m2 evofosfamide. Preexisting immune gene signatures predicted response to therapy, while hypermetabolic tumors predicted progression. Responders also showed improved peripheral T-cell proliferation and increased intratumoral T-cell infiltration into hypoxia. CONCLUSIONS: No new or unexpected safety signals were observed from combining evofosfamide and ipilimumab, and evidence of therapeutic activity was noted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Head and Neck Neoplasms/drug therapy , Ipilimumab/administration & dosage , Melanoma/drug therapy , Nitroimidazoles/administration & dosage , Pancreatic Neoplasms/drug therapy , Phosphoramide Mustards/administration & dosage , Prostatic Neoplasms/drug therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Aged , Female , Humans , Ipilimumab/adverse effects , Male , Maximum Tolerated Dose , Middle Aged , Nitroimidazoles/adverse effects , Phosphoramide Mustards/adverse effects , Safety , Treatment Outcome
13.
Clin Genet ; 76(4): 326-31, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19917019

ABSTRACT

The purpose of this study was to examine the mental health needs of individuals at risk for adult onset hereditary disorder (AOHD) from the perspective of their genetic service providers, as it is unknown to what extent psychosocial services are required and being met. A mail-out survey was sent to 281 providers on the membership lists of the Canadian Association of Genetic Counsellors and the Canadian College of Medical Geneticists. The survey assessed psychosocial issues that were most commonly observed by geneticists, genetic counsellors (GCs), and nurses as well as availability and types of psychosocial services offered. Of the 129 respondents, half of genetic service providers reported observing signs of depression and anxiety, while 44% noted patients' concerns regarding relationships with family and friends. In terms of providing counselling to patients, as the level of psychological risk increased, confidence in dealing with these issues decreased. In addition, significantly more GCs reported that further training in psychosocial issues would be most beneficial to them if resources were available. As a feature of patient care, it is recommended that gene-based predictive testing include an integrative model of psychosocial services as well as training for genetic service providers in specific areas of AOHD mental health.


Subject(s)
Genetic Services , Mental Health Services/supply & distribution , Anxiety/genetics , Anxiety/therapy , Canada , Counseling , Data Collection , Depressive Disorder/genetics , Depressive Disorder/therapy , Health Services Accessibility , Health Services Needs and Demand , Humans , Mental Disorders/genetics , Mental Disorders/therapy , Mental Health Services/statistics & numerical data
14.
Cancer Invest ; 27(1): 47-51, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19160104

ABSTRACT

The aim of the study was to assess the aspiration risk following postoperative radiation for head and neck cancer. Thirty-seven patients had Modified Barium Swallow before and following treatment. Dysphagia severity was graded from 1 to 7. Before treatment there were sixteen grade 1, seventeen grade 2, three grade 3 and one grade 5. Following postoperative radiation, two patients had grade 1, eleven patients had grade 2, thirteen patients had grade 3, four patients had grade 4, four patients had grade 5, one patients had grade 6, and two patients had grade 7. Nineteen percent (7/37) of the patients developed aspiration (grade 5-7). Aspiration is life-threatening and may develop for all tumor sites and stages.


Subject(s)
Carcinoma, Adenoid Cystic/radiotherapy , Carcinoma, Squamous Cell/radiotherapy , Deglutition Disorders/etiology , Head and Neck Neoplasms/radiotherapy , Respiratory Aspiration/etiology , Aged , Carcinoma, Adenoid Cystic/surgery , Carcinoma, Squamous Cell/surgery , Deglutition Disorders/diagnosis , Female , Fluoroscopy , Head and Neck Neoplasms/surgery , Humans , Male , Middle Aged , Neoplasm Staging , Postoperative Complications , Radiotherapy, Adjuvant , Respiratory Aspiration/diagnosis , Retrospective Studies , Risk Factors
15.
Birth Defects Res A Clin Mol Teratol ; 85(11): 905-13, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19760683

ABSTRACT

BACKGROUND: Few studies have investigated the epidemiologic features of clinically defined subgroups of anotia/microtia. METHODS: Data on cases of anotia and/or microtia among 1999-2005 deliveries were obtained from the Texas Birth Defects Registry, a population-based active surveillance system. We determined crude and adjusted associations between selected factors and seven clinical subgroups of anotia/microtia. RESULTS: In total, 742 cases were diagnosed with anotia and/or microtia, corresponding to a prevalence of 2.86 per 10,000 live births. Of those, 45% had no other major birth defect ("isolated"), 77% were unilateral, and 22% bilateral. Anotia alone made up 6%, whereas microtia made up 94%. Birth prevalence was higher with increasing maternal age and among Mexico-born Hispanics. Compared to white mothers, Hispanic mothers were two-to-three times more likely to have infants with all but the syndromic and bilateral groups (adjusted prevalence ratios [aPRs] = 2.05-2.61). Non-Hispanic blacks had significantly lower risk for total anotia/microtia, and for the isolated, unilateral, and microtia subgroups (aPRs = 0.42-0.64). Less educated mothers were three-to-four times more likely to have children with anotia (aPRs = 2.98 for less than high school, 3.97 for high school graduates). Males were more likely to be born with total anotia/microtia and with syndromic, unilateral, and microtia subtypes (aPRs = 1.27-1.41). CONCLUSIONS: In Texas, most anotia/microtia cases were in the unilateral and microtia groups, and 45% were isolated. Several clinical subgroups exhibited higher prevalence in males and among older mothers. Relative to whites, blacks were at lower risk and Hispanics (especially Mexico-born mothers) were at higher risk for selected types of anotia/microtia.


Subject(s)
Ear/abnormalities , Adult , Congenital Abnormalities/epidemiology , Female , Humans , Male , Prevalence , Registries , Texas/epidemiology
16.
J Affect Disord ; 257: 650-657, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31357162

ABSTRACT

BACKGROUND: Late-life generalized anxiety disorder (GAD) is one of the most common anxiety disorders in older adults. However, its neural markers have received relatively little attention. In this study, we explored the association between worry severity and limbic-prefrontal connectivity during emotional reactivity in late-life GAD. METHODS: We recruited 16 anxious (GAD) and 20 non-anxious (HC) older adults to perform the faces/shapes emotional reactivity task during functional magnetic resonance imaging (fMRI). We investigated the functional connectivity of both the amygdala and the bed nucleus of stria terminalis (BNST) with the prefrontal cortex (PFC) using generalized psychophysiological interaction (gPPI) analysis. We tested for (1) group differences in connectivity, (2) association between worry severity and connectivity, and (3) interaction between group and worry severity and its association with connectivity. RESULTS: Amygdala-PFC and BNST-PFC functional connectivity were associated with worry severity in an inverse U-shape, and was independent of depression severity, global anxiety, neuroticism, and general cognitive function. LIMITATIONS: Our limitations include slightly skewed PSWQ distributions, lack of non-anxious individuals with high worry, small sample size, and low depression comorbidity in a sample of late-life GAD that may not generalize to GAD in younger populations. CONCLUSIONS: This suggests that moderate worry is associated with maximum engagement of the limbic-PFC connectivity, while severe worry is associated with failure of the limbic-PFC emotional regulation circuit. This may explain the aberrant and exaggerated responses to negative stimuli observed in participants with pathological worry.


Subject(s)
Anxiety Disorders/diagnostic imaging , Anxiety Disorders/physiopathology , Emotions/physiology , Magnetic Resonance Imaging , Severity of Illness Index , Aged , Amygdala/physiopathology , Female , Humans , Limbic Lobe/diagnostic imaging , Limbic Lobe/physiopathology , Male , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology
17.
Rev Environ Health ; 34(2): 125-139, 2019 Jun 26.
Article in English | MEDLINE | ID: mdl-30753165

ABSTRACT

Several systematic reviews have been conducted so far to examine the effect of air pollution on respiratory diseases, but there has not been a corresponding meta-analysis to estimate the effect sizes for wheeze-associated diseases/disorders, which is one of the leading causes of emergency department visits and hospitalizations for children worldwide. The aim of this review is to systematically evaluate the relationship between air pollution and risk of wheeze-associated disorders in children in Southeast Asia. We searched the relevant computerized databases (PubMed, EMBASE, Web of Science, Scopus and Cochrane library) for indexed publications up to July 2018. Finally, eight studies were qualified for performing a random-effect meta-analysis to compute the pooled effect sizes. The results show that each increase of 10 µg/m3 in concentrations of PM2.5, PM1 was associated with 1-2% increase in risk of wheeze-associated disorders. Positive associations were found for PM10, SO2, NO2, NOx but no association was found for CO and O3. We confirmed the strong effect of fine particulate matters on respiratory health and recommend an updated meta-analysis should be done when more studies are available.


Subject(s)
Air Pollutants/adverse effects , Air Pollution/adverse effects , Particulate Matter/adverse effects , Respiratory Sounds , Respiratory Tract Diseases/epidemiology , Adolescent , Asia, Southeastern/epidemiology , Child , Child, Preschool , Humans , Incidence , Infant , Infant, Newborn , Prevalence , Respiratory Sounds/etiology , Respiratory Tract Diseases/chemically induced , Respiratory Tract Diseases/mortality , Risk Assessment
18.
Mali Med ; 34(3): 39-43, 2019.
Article in French | MEDLINE | ID: mdl-35897220

ABSTRACT

PURPOSE: Delays to access to radiotherapy are long in our context. The purpose of this study was to analyze the effect of neoadjuvant chemotherapy to concomitant chemoradiotherapy in locally advanced cervical cancers. PATIENTS AND METHODS: We conducted a retrospective study from April 2014 to April 2016 at the radiotherapy center of "Hopital du Mali" in Bamako, Mali. Patients were allocated according to age, histological type, tumor size and the 2002 classification of the FIGO. Experimental protocol was the administration of a neoadjuvante chemotherapy with association of Paclitaxel 175mg/m2 + Carboplatine AUC 5 every 3 weeks and radiothérapy cure with avec linac 6 MV at 70 Gy due to 5 sessions of 2 Gy per week associated with a concomitant chemotherapy with cisplatin at 40 mg/m2/week. The clinical response was assessed at the end of neoadjuvant chemotherapy and of concomitant chemoradiotherapy. RESULTS: Thirty patients were included in the study. The mean age was 53.63 ± 8.9 years. The mean size of the tumor was 5.17 cm (2 to 7 cm). According to the 2002 classification of the FIGO stages IIB were 33% (n = 10); IIIB were 57% (n = 17) and IVA were 10% (n = 3). Clinical evaluation at the end of neoadjuvant chemotherapy found: complete response 17 % (n = 5), partial response 10% (n = 3) and stable disease 73 % (n = 22). Evaluation at the end of the concomitant chemoradiotherapy had found the complete response in 90% (n = 27) and stable disease in 10% (n = 3). CONCLUSION: Neoadjuvant chemotherapy to concomitant chemoradiotherapy in locally advanced cervical cancer allows stabilization of the tumor and improves local control. Due to long delays to access to radiotherapy treatment in our context; neoadjuvant chemotherapy is an alternative to stabilize the disease and prevent distant metastasis from locally advanced cervical cancers.


OBJECTIF: Les délais d'attente pour accéder à la radiothérapie sont longs dans note contexte. L'objet de cette étude était d'analyser le résultat de la chimiothérapie néo adjuvante à la radiothérapie dans les cancers localement avancés du col utérin. PATIENTS ET MÉTHODES: Nous avons réalisé une étude rétrospective allant d'avril 2014 à avril 2016 au centre de radiothérapie de l'hôpital du Mali. Les patients ont été regroupés selon l'âge, le type histologique, la taille de la tumeur, la classification de la FIGO 2002. Le schéma thérapeutique était une chimiothérapie néo adjuvante associant Paclitaxel 175 mg/m2 et Carboplatine AUC 5 toutes les 3 semaines suivie d'une radiothérapie avec linac 6 MV à la dose de 70 Gy en raison de 5 séances de 2 Gy par semaine faite concomitamment à une chimiothérapie avec du cisplatine à la dose de 40 mg/m2/semaine. La réponse clinique était évaluée à la fin de la chimiothérapie néoadjuvante et de la radiochimiothérapie concomitante. RÉSULTATS: Trente patientes ont été incluses dans l'étude. L'âge moyen était de 53.63 ± 8.9 ans. La taille moyenne de la tumeur était de 5,17 cm (2 à 7 cm). Selon la classification FIGO 2002, 10 (33%) étaient en stade IIB distal, 17 (57%) étaient en stade IIIB et 3 (10%) en stade IVA. L'évaluation clinique à la fin de la chimiothérapie néo adjuvante avait retrouvé 17 % de réponses complètes (n=5), 10% de réponses partielles (n=3) 73 % d'évolutions stables (n=22). L'évaluation à la fin de la radiochimiothérapie concomitante avait trouvé une réponse complète chez 27 patientes (90%) et une maladie stable chez 3 (10%). CONCLUSION: La chimiothérapie néo adjuvante à la chimioradiothérapie concomitante dans les cancers localement avancés du col utérin permet la stabilisation de la tumeur et améliore le control local. En raison des délais d'attente longs pour accéder à la radiothérapie, la chimiothérapie néo adjuvante est une alternative pour stabiliser la maladie et réduire le risque de métastases à distance des cancers du col utérin localement avancés.

19.
Environ Sci Pollut Res Int ; 26(3): 2603-2612, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30474814

ABSTRACT

This study examined the effect of short-term changes in ambient temperature on hospital admissions among children aged less than 5 years old in Hanoi, Vietnam. Data on daily hospital admissions from January 2010 to June 2014 were collected from two hospitals. Daily meteorological data were obtained for the same period. We applied time series analysis to evaluate the risk of hospitalisation related to hot and cold weather by age and causes. We found that a 1 °C decrease in minimum temperature during the cold weather months was associated with 2.2% increase in hospital admission for respiratory infection among children 3-5 years old. A 1 °C increase in diurnal temperature range (DTR) in cold weather was associated with an increase of 1.9% and 1.7% in hospitalisation for all causes and respiratory infection, respectively, among children < 3 years old and an increase of 1.8% and 3.4% in hospitalisation for all causes and respiratory infection, respectively, among children of 3-5 years old. Negative associations between hot weather and hospital admissions were demonstrated. These findings suggested that low temperature and DTRs in winter are important risk factors for hospital admissions among children aged < 5 years old in Hanoi. Other factors may have modified the effect of high temperature on hospital admissions of children in Hanoi.


Subject(s)
Hospitalization/statistics & numerical data , Respiratory Tract Infections/therapy , Child, Preschool , Cold Temperature , Female , Hot Temperature , Humans , Infant , Male , Seasons , Temperature , Vietnam
20.
Oncology ; 74(1-2): 25-30, 2008.
Article in English | MEDLINE | ID: mdl-18544956

ABSTRACT

BACKGROUND: Dysphagia and aspiration are long-term complications with life-threatening consequences following treatment of head and neck cancer. We would like to assess the prevalence of aspiration in patients with long-term persistence of dysphagia (1 year or more) following treatment for head and neck cancer and to identify potential risk factors of aspiration. METHODS: Modified barium swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1-7. RESULTS: Between 1992 and 2004, 74 patients with dysphagia underwent MBS 12-152 months following treatment (median 29 months). There were 2 grade 1, 22 grade 3, 21 grade 4, 11 grade 5, 7 grade 6, and 11 grade 7 cases. Twenty-nine patients (39%) had long-term aspiration at a median follow-up of 25 months (range 12-82). Eighteen patients (24%) required permanent gastrostomy because of severe aspiration. Type of treatment and disease stage did not seem to influence long-term aspiration risk. CONCLUSION: Patients with long-term dysphagia after treatment for head and neck cancer are at risk of aspiration. MBS should be performed to identify these patients.


Subject(s)
Deglutition Disorders/etiology , Head and Neck Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Deglutition Disorders/classification , Deglutition Disorders/complications , Female , Head and Neck Neoplasms/complications , Humans , Male , Middle Aged , Neoplasm Staging , Postoperative Complications , Radiation Injuries , Retrospective Studies , Risk Factors
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