ABSTRACT
PURPOSE OF REVIEW: Arbovirus infections are a challenge for immunocompromised hosts who travel to or live in endemic regions or who receive organs or tissues from donors who travel or live in such areas. This review addresses Dengue (DENV), Chikungunya (CHIKV), and Zika (ZIKV) infections in hematological patients, hematopoietic cell or solid organ transplant recipients, and people with HIV (PWH). RECENT FINDINGS: Transmission is mainly due through Aedes mosquito bite. DENV and ZIKV may also be transmitted through blood, tissues or donor grafts. Clinical manifestations are quite similar and diagnosis requires laboratory confirmation to provide appropriate management. The best diagnostic method is PCR since serology may present false negative results in immunocompromised patients, or cross-reactivity as in the case of DENV and ZIKV. There is no specific treatment for any of these infections. SUMMARY: Educational and preventive measures are the best strategy: vector control, knowledge of the vector's habits, protection against mosquito bites, avoiding travel to endemic areas or with a current epidemic, and avoiding nonvector transmission according to local recommendations for donor deferral. Vaccination, currently only available for DENV, has not yet been studied in immunocompromised patients and is not currently recommended.
Subject(s)
Chikungunya Fever , Dengue , Immunocompromised Host , Zika Virus Infection , Humans , Dengue/immunology , Dengue/epidemiology , Dengue/transmission , Chikungunya Fever/immunology , Chikungunya Fever/epidemiology , Chikungunya Fever/transmission , Zika Virus Infection/immunology , Zika Virus Infection/transmission , Zika Virus Infection/epidemiology , Endemic Diseases , AnimalsABSTRACT
OBJECTIVE: To identify sociodemographic factors associated with pediatric clinical ethics consultation (CEC). STUDY DESIGN: Matched, case-control study at a single center, tertiary pediatric hospital in the Pacific Northwest. Cases (patients hospitalized January 2008-December 2019 with CEC) were compared with controls (those without CEC). We determined the association of the outcome (CEC receipt) with exposures (race/ethnicity, insurance status, and language for care) using univariate and multivariable conditional logistic regression. RESULTS: Of 209 cases and 836 matched controls, most cases identified as white (42%), had public/no insurance (66%), and were English-speaking (81%); most controls identified as white (53%), had private insurance (54%), and were English-speaking (90%). In univariate analysis, patients identifying as Black (OR: 2.79, 95% CI: 1.57, 4.95; P < .001), Hispanic (OR: 1.92, 95% CI: 1.24, 2.97; P = .003), with public/no insurance (OR: 2.21, 95% CI: 1.58, 3.10; P < .001), and using Spanish language for care (OR: 2.52, 95% CI: 1.47, 4.32; P < .001) had significantly increased odds of CEC, compared with patients identifying as white, using private insurance, and using English for care, respectively. In multivariable regression, Black race (adjusted OR: 2.12, 95% CI: 1.16, 3.87; P = .014) and public/no insurance (adjusted OR: 1.81, 95% CI: 1.22, 2.68; P = .003) remained significantly associated with receipt of CEC. CONCLUSIONS: We found disparities in receipt of CEC by race and insurance status. Further study is needed to determine the causes of these disparities.
Subject(s)
Child, Hospitalized , Ethics Consultation , Healthcare Disparities , Child , Humans , Case-Control Studies , Ethnicity , Hispanic or Latino , Retrospective Studies , White , Black or African AmericanABSTRACT
The aim of this study was to evaluate the prevalence of latent Mycobacterium tuberculosis infection in hematopoietic stem cell transplantation candidates, using tuberculin skin test and QuantiFERON-TB Gold-Plus, in a high-burden tuberculosis country. Adult candidates for hematopoietic stem cell transplantation performed both tests before and those submitted to transplantation were followed up for 12 months. The prevalence of latent Mycobacterium tuberculosis infection was 17.1% and a moderate agreement between QuantiFERON-TB Gold-Plus and tuberculin skin test was observed in this population. Previous tuberculosis exposure was a risk factor for latent Mycobacterium tuberculosis infection. No cases of tuberculosis were diagnosed during follow-up period.
Subject(s)
Hematopoietic Stem Cell Transplantation , Latent Tuberculosis , Mycobacterium tuberculosis , Tuberculosis , Adult , Humans , Interferon-gamma Release Tests , Tuberculin Test , Prevalence , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Latent Tuberculosis/microbiology , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
PURPOSE: The prompt initiation of a betalactam antibiotic in febrile neutropenic patients is considered standard of care, while the empiric use of vancomycin is recommended by guidelines in specific situations, with a low level of evidence. The objective of this study was to assess the utilization of vancomycin in the management of febrile neutropenia within four Brazilian medical centers that implemented more stringent criteria for its administration. METHODS: A comprehensive retrospective analysis was performed encompassing all instances of febrile neutropenia observed during the period from 2013 to 2019. The primary focus was to identify the reasons for initiating vancomycin therapy. RESULTS: A total of 536 consecutive episodes of febrile neutropenia were documented, involving 384 patients with a median age of 52 years (range 18-86). Chemotherapy preceded febrile neutropenia in 59.7% of cases, while 40.3% occurred after hematopoietic stem cell transplantation. The most prevalent underlying diseases were acute myeloid leukemia (26.5%) and non-Hodgkin's lymphoma (22%). According to international guidelines, vancomycin should have been initiated at the onset of fever in 145 episodes (27%); however, it was administered in only 27 cases (5.0%). Three episodes were associated with Staphylococcus aureus bacteremia, two of which were methicillin resistant. The 15-day and 30-day mortality rates were 5.0% and 9.9%, respectively. CONCLUSIONS: The results of this study underscore the notably low utilization rate of vancomycin in cases of febrile neutropenia, despite clear indications outlined in established guidelines. These findings emphasize the importance of carefully implementing guideline recommendations, considering local epidemiological factors, especially when the strength of recommendation is weak.
Subject(s)
Febrile Neutropenia , Vancomycin , Humans , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Vancomycin/therapeutic use , Vancomycin/adverse effects , Anti-Bacterial Agents , Retrospective Studies , Brazil , Fever/etiology , Fever/chemically induced , Febrile Neutropenia/drug therapy , Febrile Neutropenia/chemically inducedABSTRACT
BACKGROUND: The epidemiology of invasive aspergillosis (IA) in patients with acute lymphoid leukemia (ALL) has not been well characterized. OBJECTIVES: To identify potential peculiarities in the natural history, treatment response and outcome of IA diagnosed in patients with ALL and AML. METHODS: This is a retrospective cohort study conducted in seven tertiary-care hospitals between 2009 and 2017 of all consecutive episodes of IA occurring in adult patients with acute leukemia. Demographic characteristics, underlying disease and recent treatment, antifungal prophylaxis, neutropenia, receipt of corticosteroids, clinical and radiological findings, mycological results, antifungal therapy, and 6-week and 12-week survival were recorded. RESULTS: We identified 77 cases of IA in 54 patients with AML and 23 patients with ALL. The majority of patients developed IA in the context of induction chemotherapy for newly diagnosed (48.0%) or relapsed (41.6%) leukemia, with no differences between ALL and AML. Lung involvement was more frequent in AML (96.3% vs. 82.6%, p = 0.06) and rhinosinusitis was more common in ALL (43.5% vs. 24.1%, p = 0.09). Galactomannan was the microbiologic documentation of IA in 76.6%, with similar patterns of positivity in AML and ALL. The 6-week survival of IA in patients with AML and ALL was 63.0% and 56.5%, respectively (p = 0.60). CONCLUSIONS: The epidemiology, clinical presentation, diagnosis and outcome of IA in ALL patients are similar to patients with AML.
Subject(s)
Aspergillosis , Invasive Fungal Infections , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adult , Humans , Antifungal Agents/therapeutic use , Retrospective Studies , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Aspergillosis/epidemiology , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/drug therapy , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/epidemiologyABSTRACT
Bloodstream infection (BSI) caused by carbapenem-resistant P. aeruginosa (CRPA) has high mortality in hematopoietic stem cell transplant (HSCT) recipients. We performed MIC, checkerboard, time-kill assay, PFGE, PCR, and whole genome sequence and described the clinical outcome through Epi Info comparing the antimicrobial combination in vitro. Mortality was higher in BSI caused by CRPA carrying the lasB virulence gene. The isolates were 97% resistant to meropenem displaying synergistic effect to 57% in combination with colistin. Seventy-three percent of the isolates harbored blaSPM-1 and Tn4371 and belonged to ST277. The synergistic effect in vitro with meropenem with colistin appeared to be a better therapeutic option.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Hematopoietic Stem Cell Transplantation , Pseudomonas Infections/drug therapy , Sepsis/drug therapy , Adolescent , Adult , Brazil , Carbapenem-Resistant Enterobacteriaceae , Carbapenems , Colistin/therapeutic use , Female , Humans , Male , Meropenem/therapeutic use , Microbial Sensitivity Tests , Middle Aged , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/isolation & purification , Sepsis/mortality , Young AdultABSTRACT
BACKGROUND: Trichosporon fungaemia (TF) episodes have increased in recent years and mortality rates remain high despite the advances in the management of sepsis. New concepts about its clinical course, treatment and microbiology need to be investigated for the better management of this infection. OBJECTIVES: To describe the aetiology, natural history, clinical management and prognostic factors of TF. METHODS: TF episodes documented between 2005 and 2018 in 23 South American centres were retrospectively investigated by using a standard clinical form. Molecular identification, antifungal susceptibility testing and biofilm production were also performed. RESULTS: Eighty-eight TF episodes were studied. Patients had several underlying conditions, including haematological diseases (47.7%), post-operative status (34%), solid organ transplants (n = 7, 7.9%), among others. Seventy-three (82.9%) patients had a central venous catheter (CVC) at TF diagnosis. The 30 day mortality rate was 51.1%. Voriconazole-based therapy was given to 34 patients (38.6%), with a 30 day mortality rate of 38.2%. Multivariate predictors of 30 day mortality were age (OR 1.036), mechanical ventilation (OR 8.25) and persistent neutropenia (OR 9.299). CVC removal was associated with over 75% decreased risk of 30 day mortality (OR 0.241). Microbiological analyses revealed that 77.7% of the strains were identified as Trichosporon asahii, and voriconazole showed the strongest in vitro activity against Trichosporon spp. Most of the strains (63%) were considered medium or high biofilm producers. CONCLUSIONS: Older age, mechanical ventilation and persistent neutropenia were associated with poor prognosis. CVC may play a role in the pathogenicity of TF and its removal was associated with a better prognosis.
Subject(s)
Fungemia , Trichosporon , Aged , Antifungal Agents/therapeutic use , Basidiomycota , Fungemia/drug therapy , Fungemia/epidemiology , Humans , Microbial Sensitivity Tests , Prognosis , Retrospective Studies , Trichosporon/geneticsABSTRACT
Colorectal cancer (CRC) is a multifactorial disease commonly diagnosed worldwide, with high mortality rates. Several studies demonstrate important associations between differential expression of micro-RNAs (miRs) and the prognosis of CRC. The present study aimed to identify differentially expressed tissue miRs associated with prognostic factors in CRC patients, through a systematic review of the Literature. Using the PubMed database, Cochrane Library and Web of Science, studies published in English evaluating miRs differentially expressed in tumor tissue and significantly associated with the prognostic aspects of CRC were selected. All the included studies used RT-PCR (Taqman or SYBR Green) for miR expression analysis and the period of publication was from 2009 to 2018. A total of 115 articles accomplished the inclusion criteria and were included in the review. The studies investigated the expression of 100 different miRs associated with prognostic aspects in colorectal cancer patients. The most frequent oncogenic miRs investigated were miR-21, miR-181a, miR-182, miR-183, miR-210 and miR-224 and the hyperexpression of these miRs was associated with distant metastasis, lymph node metastasis and worse survival in patients with CRC. The most frequent tumor suppressor miRs were miR-126, miR-199b and miR-22 and the hypoexpression of these miRs was associated with distant metastasis, worse prognosis and a higher risk of disease relapse (worse disease-free survival). Specific tissue miRs are shown to be promising prognostic biomarkers in patients with CRC, given their strong association with the prognostic aspects of these tumors, however, new studies are necessary to establish the sensibility and specificity of the individual miRs in order to use them in clinical practice.
Subject(s)
Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/genetics , Genes, Tumor Suppressor , Lymphatic Metastasis/genetics , MicroRNAs/metabolism , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Disease-Free Survival , Humans , MicroRNAs/genetics , PrognosisABSTRACT
Pediatric hospitalizations for mental health conditions are rapidly increasing, with readmission rates for mental health conditions surpassing those for non-mental health conditions. The objective of this study was to identify reasons for pediatric mental health readmissions from the perspectives of parents and providers. We performed a retrospective content analysis of surveys administered to parents and providers of patients with a 14-day readmission to an inpatient pediatric psychiatry unit between 5/2017 and 8/2018. Open-ended survey items assessed parent and provider perceptions of readmission reasons. We used deductive coding to categorize survey responses into an a priori coding scheme based on prior research. We used inductive coding to identify and categorize responses that did not fit into the a priori coding scheme. All data were recoded using the revised schema and reliability of the coding process was assessed using kappa statistics and consensus building. We had completed survey responses from 89 (64%) of 138 readmission encounters (56 parent surveys; 61 provider surveys). The top three readmission reasons that we identified from parent responses were: discordant inpatient stay expectations with providers (41%), discharge hesitancy (34%), and treatment plan failure (13%). Among providers, the top readmission reasons that we identified were: access to outpatient care (30%), treatment adherence (13%), and a challenging home (11%) and social environment (11%). We identified inpatient stay expectations, discharge hesitancy, and suboptimal access to outpatient care as the most prominent reasons for mental health readmissions, which provide targets for future quality improvement efforts.
Subject(s)
Mental Health , Patient Readmission , Child , Humans , Parents , Reproducibility of Results , Retrospective StudiesABSTRACT
During 2015-2016, Cape Verde, an island nation off the coast of West Africa, experienced a Zika virus (ZIKV) outbreak involving 7,580 suspected Zika cases and 18 microcephaly cases. Analysis of the complete genomes of 3 ZIKV isolates from the outbreak indicated the strain was of the Asian (not African) lineage. The Cape Verde ZIKV sequences formed a distinct monophylogenetic group and possessed 1-2 (T659A, I756V) unique amino acid changes in the envelope protein. Phylogeographic and serologic evidence support earlier introduction of this lineage into Cape Verde, possibly from northeast Brazil, between June 2014 and August 2015, suggesting cryptic circulation of the virus before the initial wave of cases were detected in October 2015. These findings underscore the utility of genomic-scale epidemiology for outbreak investigations.
Subject(s)
Microcephaly , Zika Virus Infection , Zika Virus , Africa, Western , Brazil/epidemiology , Cabo Verde , Disease Outbreaks , Genomics , Humans , Microcephaly/epidemiology , Zika Virus/genetics , Zika Virus Infection/epidemiologyABSTRACT
Glycosyl squaramides were synthesised and evaluated as low molecular weight gelators. Amphiphilic glycosyl squaramides 5 and 6, with a C-16 aliphatic chain, formed thermoreversible gels in polar organic solvents and 1 : 1 ethanol/water mixtures with high efficiency. Rheological analysis showed these gels achieve their structural stability 120 h after gelation and were robust, making them particularly suitable for biomedical applications. The interactions between solvent and gelator strongly influence SAFiN (Self-Assembled Fibrillar Network) formation, critical gelation concentration (CGC) and subsequent gel structure, as evidenced by SEM imaging of xerogels. Spectroscopic studies indicate that H-bonding is involved in the self-assembly of the glycosyl squaramides in organic solvents, while hydrophobic interactions are the major driving force for gel formation in the presence of water. The compounds described herein are the first reported examples of carbohydrate-squaramide conjugates capable of forming supramolecular gels.
ABSTRACT
BACKGROUND: Hepatitis B virus (HBV) infection is a worldwide concern with a broad distribution. In immunosuppressed populations, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients, it can reactivate leading to acute hepatic failure. Different risk factors are known for higher rates of reactivation, and entecavir, tenofovir, and lamivudine are often used for prophylaxis and treatment. However, data regarding the impact of antiviral drugs in neutrophil and platelet engraftment are still unknown and concern the management of viral hepatitis post-HSCT. METHODS: We performed a single-center, retrospective, observational study reviewing medical records of patients referred for hematopoietic stem cell transplant from 2010 to 2017, which were also HBV infected, aiming to describe outcomes related to antiviral treatment and also the impact on platelet and neutrophil recovery after transplant. A secondary goal consisted of analyzing the impact of HBV infection in early and late mortality post-HSCT. The study included patients with positive blood bank screening for hepatitis B infection (HBsAg, Anti-HBc or HBV-NAT), confirmed later on by a laboratory routine serology. RESULTS: A total of 1132 hematopoietic stem cell recipients were assessed between 2010 and 2017. Eighty-six patients were confirmed to have HBV infection, of which six were HBsAg-positive, 20 were isolated anti-HBc-positive, and 60 had resolved infection (anti-HBc-positive and anti-HBs-positive). With regard to prophylaxis, 19 patients underwent HSCT on HBV antiviral therapy or prophylaxis: two were HBeAg-positive, three were HBeAg-negative and HBV-DNA was only detectable in three of them. Moreover, one patient had an occult HBV infection. Regarding therapy, 9 patients were on entecavir, 6 patients on lamivudine, two on tenofovir, and two of them on a combination of tenofovir + lamivudine due to HIV co-infection. Reverse seroconversion was not identified in any patients receiving antiviral therapy or prophylaxis, but it was detected in one patient with occult hepatitis B and another with resolved infection. No severe side effects led to therapy discontinuation in the treated group, which also did not have any significant delay in neutrophil or platelet engraftment when compared to patients without antiviral therapy. In addition, the only factors associated with increased mortality were transplant onset after 50 years, allogeneic transplant and myeloablative conditioning regimens. Interestingly, the presence of HBsAg or detectable HBV-DNA was not related to worse outcomes, neither the use of rituximab. In multivariate analysis, the use of antiviral therapy, the occurrence of graft-versus-host disease or CMV reactivation also was not linked to increased mortality. CONCLUSIONS: To sum up, HBV serology, ALT, and HBV-DNA monitoring are essential to detect hepatic flares earlier, even in populations with chronic inactive hepatitis, due to the possibility of later seroconversion. HBV infection was not related to increased 2-year mortality post-transplant. Antiviral prophylaxis did not cause any important clinical or laboratory side effects that could demand discontinuation, and its use was not associated with later neutrophil and platelet engraftments.
Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Hepatitis B/mortality , Seroconversion , Transplant Recipients/statistics & numerical data , Adult , Aged , Antiviral Agents/therapeutic use , Female , Guanine/analogs & derivatives , Guanine/therapeutic use , Hepatitis B/drug therapy , Hepatitis B/immunology , Hepatitis B virus , Humans , Immunocompromised Host , Lamivudine/therapeutic use , Latin America , Male , Middle Aged , Retrospective Studies , Rituximab/therapeutic use , Virus ActivationABSTRACT
Objective: Asthma carries a high burden of disease for residents of Puerto Rico. We conducted this study to better understand asthma-related healthcare use and to examine potential asthma triggers.Methods: We characterized asthma-related healthcare use in 2013 by demographics, region, and date using outpatient, hospital, and emergency department (ED) insurance claims with a primary diagnostic ICD-9-CM code of 493.XX. We examined environmental asthma triggers, including outdoor allergens (i.e., mold and pollen), particulate pollution, and influenza-like illness. Analyses included descriptive statistics and Poisson time-series regression.Results: During 2013, there were 550,655 medical asthma claims reported to the Puerto Rico Healthcare Utilization database, representing 148 asthma claims/1,000 persons; 71% of asthma claims were outpatient visits, 19% were hospitalizations, and 10% were ED visits. Females (63%), children aged ≤9 years (77% among children), and adults aged ≥45 years (80% among adults) had the majority of asthma claims. Among health regions, Caguas had the highest asthma claim-rate at 142/1,000 persons (overall health region claim-rate = 108). Environmental exposures varied across the year and demonstrated seasonal patterns. Metro health region regression models showed positive associations between increases in mold and particulate matter <10 microns in diameter (PM10) and outpatient asthma claims.Conclusions: This study provides information about patterns of asthma-related healthcare use across Puerto Rico. Increases in mold and PM10 were associated with increases in asthma claims. Targeting educational interventions on exposure awareness and reduction techniques, especially to persons with higher asthma-related healthcare use, can support asthma control activities in public health and clinical settings.
Subject(s)
Allergens/adverse effects , Asthma/epidemiology , Cost of Illness , Environmental Exposure/adverse effects , Patient Acceptance of Health Care/statistics & numerical data , Administrative Claims, Healthcare/statistics & numerical data , Adolescent , Adult , Age Factors , Aged , Allergens/analysis , Asthma/immunology , Asthma/therapy , Child , Child, Preschool , Emergency Service, Hospital/statistics & numerical data , Environmental Exposure/statistics & numerical data , Environmental Monitoring/statistics & numerical data , Female , Geography , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Particulate Matter/adverse effects , Particulate Matter/analysis , Puerto Rico/epidemiology , Risk Factors , Sex Factors , Young AdultABSTRACT
Locoregional lymph node recurrences of primary trunk melanoma can occur in basins not identified during sentinel lymph node biopsy. However, the factors associated with recurrences in non-sentinel lymph node basins are unknown. To evaluate these factors, this observational retrospective study examined the patterns of first lymph node recurrence and the factors associated with recurrence in non-sentinel lymph node basins. A total of 305 patients with primary trunk melanoma who had undergone sentinel lymph node biopsy from 2000 to 2015 were evaluated. Twenty-three patients presented locoregional lymph node recurrence; 8 of which (34.8%) were in non-sentinel lymph node basins. Non-sentinel lymph node recurrences were more frequent in patients with positive sentinel lymph nodes and in those patients whose number of tumour-involved nodes was > 3. These results suggest that clinical examination and ultrasound surveillance should be performed on all potential lymph node drainage basins of trunk melanomas.
Subject(s)
Melanoma , Sentinel Lymph Node , Skin Neoplasms , Humans , Lymph Node Excision , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery , Lymphatic Metastasis , Melanoma/surgery , Neoplasm Recurrence, Local , Retrospective Studies , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Sentinel Lymph Node Biopsy , Skin Neoplasms/surgeryABSTRACT
This in vitro study evaluated the protective effect of fluoride varnishes containing sodium trimetaphosphate (TMP) against dentin erosion and abrasion. Specimens of coronal dentin were divided into: placebo, 2.5% NaF, 5% NaF, 2.5% NaF + 5% TMP, and 5% NaF + 5% TMP groups (n =24/group). After single application of the varnishes, the samples were immersed in citric acid (0.05 mol/L, pH = 3.2, 5 min) followed or not by brushing, and the dentin wear was assessed after 5 days. Varnishes containing fluoride + TMP led to the lowest wear. TMP varnishes showed a superior effect against dentin erosive wear.
Subject(s)
Dentin , Tooth Erosion , Cariostatic Agents , Dental Enamel , Fluorides , Fluorides, Topical , Humans , Sodium Fluoride , Tooth Erosion/prevention & controlABSTRACT
Aromatic antiepileptic drugs (AEDs) are among the drugs most frequently involved in severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS). This study investigated the associations between the genetic polymorphisms of HLA class-I and AED-induced SCARs in the Spanish population. HLA class-I genotypes were determined in AED (phenytoin[PHT],lamotrigine[LTG],carbamazepine[CBZ],phenobarbital[PB])-induced SJS/TEN (n=15) or DRESS (n=12) cases included in the Spanish SCAR registry, PIELenRed. There were 3 control groups: (A)tolerant to a single AED, (B)tolerant to any AED, and (C)Spanish population controls. For SJS/TEN, concomitant HLA-A*02:01/Cw15:02 alleles were significantly associated with PHT-cases compared to control groups B and C [(B)odds ratio(OR):14.75, p=0.009;(C)OR:27.50, p<0.001], and were close to significance with respect to control group A (p=0.060). The genotype frequency of the HLA-B*38:01 was significantly associated with PHT-LTG-cases compared with the 3 groups of controls [(A)OR:12.86, p=0.012;(B)OR:13.81; p=0.002;(C)OR:14.35, p<0.001], and with LTG-cases [(A)OR:147.00, p=0.001;(B)OR:115.00, p<0.001;(C)OR:124.70, p<0.001]. We found the HLA-B*15:02 allele in a Spanish Romani patient with a CBZ-case. The HLA-A*11:01 was significantly associated with CBZ-cases [(A)OR:63.89, p=0.002;(B)OR:36.33, p=0.005;(C)OR:28.29, p=0.007]. For DRESS, the HLA-A*24:02 genotype frequency was statistically significant in the PHT-LTG-cases [(A)OR:22.56, p=0.003;(B)OR:23.50. p=0.001; (C)OR:33.25, p<0.001], and in the LTG-cases [(A),OR:49.00, p=0.015;(B)OR:27.77, p=0.005; (C)OR:34.53, p=0.002]. HLA-A*31:01 was significantly associated with the CBZ-cases [(A)OR:22.00, p=0.047;(B)OR:29.50, p=0.033;(C)OR:35.14, p=0.006]. In conclusion, we identified several significant genetic risk factors for the first time in the Spanish Caucasian population: HLA-A*02:01/Cw*15:02 combination as a risk factor for PHT-induced SJS/TEN, HLA-B*38:01 for LTG- and PHT- induced SJS/TEN, HLA-A*11:01 for CBZ-induced SJS/TEN, and HLA-A*24:02 for LTG- and PHT- induced DRESS. The strong association between HLA*31:01 and CBZ-DRESS in Europeans was confirmed in this study.
Subject(s)
Anticonvulsants/adverse effects , Drug Hypersensitivity Syndrome/genetics , Genes, MHC Class I/genetics , Genetic Predisposition to Disease/genetics , Stevens-Johnson Syndrome/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Drug Hypersensitivity Syndrome/etiology , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Genetic , Risk Factors , Spain , Stevens-Johnson Syndrome/etiology , White People/genetics , Young AdultABSTRACT
AIM: We conducted a prospective evaluation of all eosinophilic drug reactions (EDRs) through the Prospective Pharmacovigilance Program from Laboratory Signals at Hospital to find out the incidence and distribution of these entities in our hospital, their causative drugs, and predictors. METHODS: All peripheral eosinophilia >700 × 106 cells l-1 detected at admission or during hospitalisation, were prospectively monitored over 42 months. The spectrum of the localised or systemic manifestation of EDR, the incidence, the distribution of causative drugs, and the predictors were analysed. RESULTS: The incidence of EDR was 16.67 (95% Poisson confidence interval [CI]: 9.90-25.98) per 10 000 admissions. Of 274 cases of EDR, 154 (56.2%) cases in 148 patients were asymptomatic hypereosinophilia. In the remaining 120 (43.8%) cases, there was other involvement. Skin and soft tissue reactions were detected in 36 (13.1%) cases; visceral EDRs in 19(7.0%) cases; and drug-induced eosinophilic cutaneous and visceral manifestations were detected in the remaining 65 (23.7%) cases, 64 of which were potential drug reaction with eosinophilia and systemic symptoms (DRESS). After adjusting for age, sex, and hospitalisation wards, predictors of symptomatic eosinophilia were earlier onset of eosinophilia (hazard ratio [HR], 10.49; 95%CI: 3.13-35.16) higher eosinophil count (HR, 8.51; 95%CI: 3.28-22.08), and a delayed onset of corticosteroids (HR, 1.34; 95%CI: 1.01-1.73). A higher eosinophil count in patients with DRESS was significantly associated with greater impairment of liver function, prolonged hospitalisation, higher cumulative doses of corticosteroids, and if hypogammaglobinaemia was detected, a reactivation of human-herpesvirus 6 was subsequently detected. CONCLUSIONS: Half (53.3%, 64/120 cases) of symptomatic EDRs were potential DRESS. The main predictor of severity of EDR was an early severe eosinophilia.
Subject(s)
Drug Hypersensitivity Syndrome/epidemiology , Drug-Related Side Effects and Adverse Reactions/epidemiology , Eosinophilia/chemically induced , Pharmacovigilance , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Drug Eruptions/epidemiology , Drug Eruptions/etiology , Drug Eruptions/pathology , Drug Hypersensitivity Syndrome/etiology , Drug Hypersensitivity Syndrome/physiopathology , Eosinophilia/epidemiology , Eosinophilia/physiopathology , Female , Hospitalization , Humans , Incidence , Infant , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Tertiary Care Centers , Young AdultABSTRACT
The term Mycoplasma pneumoniae-induced rash and mucositis (MIRM) was recently proposed to identify the mucocutaneous condition secondary to M. pneumoniae infection that had historically been regarded among the more confusing pathologies of erythema multiforme and Stevens-Johnson syndrome. Based on a number of previous reports, these syndromes require differentiation since they have different prognoses and specific treatment requirements. We report a case of oral and genital erosions that strongly resembled MIRM without rash but were found to be secondary to a Chlamydia pneumoniae infection. After a thorough review of the literature on this subject, we propose that C. pneumoniae should also be considered a potential causative agent of MIRM and that this term should be amended to include C. pneumoniae infection.
Subject(s)
Chlamydophila Infections/diagnosis , Mucositis/etiology , Pneumonia, Mycoplasma/diagnosis , Child , Chlamydophila , Chlamydophila Infections/complications , Diagnosis, Differential , Humans , Male , Mucositis/diagnosis , Mycoplasma pneumoniae , Pneumonia, Mycoplasma/complicationsABSTRACT
Pachyonychia congenita (PC) is a rare genodermatosis caused by a mutation in keratin genes, which can lead to hypertrophic nail dystrophy and focal palmoplantar keratoderma (predominantly plantar), amongst other manifestations. Painful blisters and callosities, sometimes exacerbated by hyperhidrosis, are major issues that can have a significant impact on patient quality of life. Many alternative treatments for this condition have been applied with variable and partial clinical response, but a definitive cure for this disease has yet to be discovered. After obtaining informed consent, two patients with genetically confirmed PC type 1 were treated with plantar injections of botulinum toxin type A. Both patients showed a marked improvement in pain and blistering with an average response time of one week, a six-month mean duration of effectiveness, and a lack of any side effects or tachyphylaxis.
Subject(s)
Botulinum Toxins, Type A/administration & dosage , Foot Dermatoses/drug therapy , Keratoderma, Palmoplantar/drug therapy , Nails, Malformed/drug therapy , Pachyonychia Congenita/drug therapy , Skin/drug effects , Adult , DNA Mutational Analysis , Female , Foot Dermatoses/genetics , Foot Dermatoses/pathology , Genetic Predisposition to Disease , Humans , Injections, Intradermal , Keratin-6/genetics , Keratoderma, Palmoplantar/genetics , Keratoderma, Palmoplantar/pathology , Male , Mutation, Missense , Nails, Malformed/genetics , Nails, Malformed/pathology , Pachyonychia Congenita/genetics , Pachyonychia Congenita/pathology , Phenotype , Remission Induction , Skin/pathology , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVE: To compare motor and cognitive functional independence scores between Hispanic, non-Hispanic black (NHB), and non-Hispanic white (NHW) children with traumatic brain injury (TBI) after discharge from inpatient rehabilitation. DESIGN: Retrospective cohort study using the Uniform Data System for Medical Rehabilitation national dataset from the years 2002 to 2012. SETTING: Inpatient rehabilitation units. PARTICIPANTS: Children (N=10,141) aged 6 months to 18 years who received inpatient rehabilitation for TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Motor and cognitive functional independence after discharge from inpatient rehabilitation, adjusting for age, sex, admission function, length of stay, insurance, and region. RESULTS: Inpatient rehabilitation therapy improved functional independence for all children. Younger age, lower admission functional independence scores, and Medicaid insurance were associated with lower functional independence at discharge. Hispanic and NHB children had lower discharge cognitive scores compared with NHW children; however, differences were small and were partially explained by insurance status and region. Children who received rehabilitation therapy at pediatric facilities had greater cognitive improvement. CONCLUSIONS: While racial/ethnic disparities are small, minority children are more likely to be younger, to have Medicaid, and to be cared for at nonpediatric facilities, factors that increase their risk for lower functional outcomes.