On sparse ensemble methods: An application to short-term predictions of the evolution of COVID-19.

Since the seminal paper by Bates and Granger in 1969, a vast number of ensemble methods that combine different base regressors to generate a unique one have been proposed in the literature. The so-obtained regressor method may have better accuracy than its components, but at the same time it may overfit, it may be distorted by base regressors with low accuracy, and it may be too complex to understand and explain. This paper proposes and studies a novel Mathematical Optimization model to build a sparse ensemble, which trades off the accuracy of the ensemble and the number of base regressors used. The latter is controlled by means of a regularization term that penalizes regressors with a poor individual performance. Our approach is flexible to incorporate desirable properties one may have on the ensemble, such as controlling the performance of the ensemble in critical groups of records, or the costs associated with the base regressors involved in the ensemble. We illustrate our approach with real data sets arising in the COVID-19 context.

Diagnosis and management of pemphigus: Recommendations of an international panel of experts.

BACKGROUND: Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. OBJECTIVE: We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. METHODS: A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. RESULTS: The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. LIMITATIONS: Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. CONCLUSIONS: We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.

Severe Pertussis Infections in the United States, 2011-2015.

BACKGROUND: The incidence of pertussis in the United States has increased in recent years. While characteristics of severe pertussis infection have been described in infants, fewer data are available in older children and adults. In this analysis, we characterize pertussis infections in hospitalized patients of all ages. METHODS: Cases of pertussis with cough onset from 1 January 2011 through 31 December 2015 from 7 US Emerging Infections Program Network states were reviewed. Additional information on hospitalized patients was obtained through abstraction of the inpatient medical record. Descriptive and multivariable analyses were conducted to characterize severe pertussis infection and identify potential risk factors. RESULTS: Among 15942 cases of pertussis reported, 515 (3.2%) were hospitalized. Three hospitalized patients died. Infants aged <2 months accounted for 1.6% of all pertussis cases but 29.3% of hospitalizations. Infants aged 2-11 months and adults aged ≥65 years also had high rates of hospitalization. Infants aged <2 months whose mothers received acellular pertussis during the third trimester and children aged 2 months to 11 years who were up to date on pertussis-containing vaccines had a 43%-66% reduced risk of hospitalization. Among adolescents aged 12-20 years, 43.5% had a history of asthma, and among adults aged ≥65 years, 26.8% had a history of chronic obstructive pulmonary disease. CONCLUSIONS: Individuals at the extreme ends of life may be the most vulnerable to severe pertussis infections, though hospitalization was reported across all age groups. Continued monitoring of severe pertussis infections will be important to help guide prevention, control, and treatment options.

Severe Respiratory Illness Associated with Human Metapneumovirus in Nursing Home, New Mexico, USA.

Human metapneumovirus is an emerging pathogen that causes upper and lower respiratory illness. Nursing home outbreaks of infection with this virus can cause severe illness and lead to poor patient outcomes. We report an outbreak investigation in a nursing home during 2018 and infection control guidelines to assist in disease control.

Analysis of Wait Times and Impact of Real-Time Surveys on Patient Satisfaction.

BACKGROUND: Increasing emphasis is being placed on patient satisfaction, which is linked to reimbursement rates. The Consumer Assessment of Healthcare Providers and Systems (CAHPS) is a national, standardized survey used to assess patient satisfaction. Its limitations include the length of the survey, delay in administration, and generalization to all specialties. Ideal patient satisfaction surveys should collect information in a way that allows for corrective action in a timely manner. OBJECTIVE: To evaluate patient dissatisfaction with wait time using a short, in-office, real-time survey. METHODS: A cross-sectional study in which patients from one provider's office completed a real-time survey. These results were compared with the CAHPS survey data of the same time period. RESULTS: Seven hundred fifty-six patients were seen and 251 surveys were collected. The real-time survey response rate was 33% compared with 9% for the CAHPS survey. Overall, 95.74% of patients who completed the real-time survey were satisfied with their wait times and the duration of their visit, versus 84.2% from the CAHPS survey. CONCLUSION: Implementation of a short in-office survey immediately after patient care can provide better feedback that can be used to ensure that improvement measures are aimed at making significant strides in improving overall health outcomes for patients.

Rickettsia parkeri Rickettsiosis, Arizona, USA.

In the United States, all previously reported cases of Rickettsia parkeri rickettsiosis have been linked to transmission by the Gulf Coast tick (Amblyomma maculatum). Here we describe 1 confirmed and 1 probable case of R. parkeri rickettsiosis acquired in a mountainous region of southern Arizona, well beyond the recognized geographic range of A. maculatum ticks. The likely vector for these 2 infections was identified as the Amblyomma triste tick, a Neotropical species only recently recognized in the United States. Identification of R. parkeri rickettsiosis in southern Arizona demonstrates a need for local ecologic and epidemiologic assessments to better understand geographic distribution and define public health risk. Education and outreach aimed at persons recreating or working in this region of southern Arizona would improve awareness and promote prevention of tickborne rickettsioses.

Differences in Pertussis Incidence by Race and Ethnicity in the United States, 2010-2017.

Background: An increased pertussis burden has been demonstrated among Hispanic or Latino and American Indian or Alaska Native (AI/AN) infants. However, data on potential disparities among other age and racial groups are limited. Methods: We analyzed pertussis cases reported through Enhanced Pertussis Surveillance from 2010 to 2017. Pertussis and severe pertussis incidence were calculated by race (White, Black or African American, AI/AN, and Asian or Pacific Islanders), ethnicity (Hispanic or Latino and non-Hispanic or non-Latino), and age. Results: Compared with White persons, overall incidence was lower among Black or African American (incidence rate ratio [IRR], .57; 95% confidence interval [CI], .53-.61), AI/AN (IRR, 0.65; 95% CI, .58-.72), and Asian or Pacific Islander persons (IRR, 0.39; 95% CI, .35-.43). Overall incidence of pertussis was higher (1.5-fold; 95% CI, 1.37-1.60) among Hispanic or Latino compared with non-Hispanic or non-Latino adults, potentially related to household size or lower pertussis vaccine uptake among adult Hispanic or Latino cases. Severe pertussis incidence was similar among Black or African American and AI/AN persons compared with White persons. Among infants, severe pertussis incidence was 1.4-fold higher (95% CI, 1.03-1.82) among Black or African American infants than among White infants, and 2.1-fold higher (95% CI, 1.67-2.57) among Hispanic or Latino infants than non-Hispanic or non-Latino infants. Conclusions: The contrast between lower reported incidence but similar or higher severe pertussis incidence among Black or African American and AI/AN persons compared with White persons warrants further investigation and may reflect underdiagnosis or underreporting of mild disease.

[Severe skin and soft tissue infection due to Fusarium oxysporum associated with subcutaneous insulin administration]. / Infección grave de piel y partes blandas por Fusarium oxysporum asociado a la administración subcutánea de insulina.

Diabetes mellitus (DM) is a very prevalent chronic disease. Among the treatments for DM, insulin is the most potent antidiabetic agent. However a significant proportion of patients fail to achieve Errors in the application of insulin are an important and correctable factor in many cases. We present the case of a patient with DM who, due to poor insulin application technique and hygiene, develops a skin and soft tissue infection with subsequent appearance of Fusarium oxysporum. It is important to emphasize the relevance of diabetes education in insulinized patients and the role of diabetes educators in their care. On the other hand, it is important to emphasize the importance of taking cultures by soft tissue puncture in case of local signs of infection.

La diabetes mellitus (DM) es una enfermedad crónica muy prevalente. Dentro de los tratamientos para la DM se encuentra la insulina que es el agente antidiabético más potente, sin embargo, una proporción significativa de pacientes no logra alcanzar el objetivo de hemoglobina glicosilada (HbA1c). Los errores en la aplicación de insulina son un factor importante y corregible en muchos casos. Se presenta el caso de una paciente con DM, antecedentes de neuropatía diabética, enfermedad renal crónica estadio V en hemodiálisis, hipertensión arterial, estenosis aórtica con recambio por válvula protésica, y anticoagulada, con escasa adherencia a recomendaciones higiénico dietéticas. Debido a la mala técnica de aplicación de insulina y falta de higiene, desarrolló varias infecciones polimicrobianas de piel y partes blandas, con evolución tórpida de las úlceras y mala respuesta al tratamiento indicado. Durante su internación, de una úlcera se aisló Fusarium oxysporum. Es importante jerarquizar la relevancia de la educación diabetológica en pacientes insulinizados y el rol de los educadores en diabetes en el cuidado de los mismos. Por otro lado, destacar la importancia de la toma de cultivos mediante punción de partes blandas ante la aparición de signos locales de infección.

Effect of exogenous l-carnitine on aortic stiffness in dyslipidemic adolescents: Design of a quadruple-blind, randomized, controlled interventional trial.

Background: Atherosclerotic cardiovascular disease (ASCVD) risk factors including vascular remodeling leading to hypertension and dyslipidemia are prevalent among children and adolescents. Conflicting observational and Mendelian randomization data suggest endogenous carnitine may affect arterial stiffness and lipid traits. Because of this, we developed a study to evaluate the causal role for carnitine in arterial stiffness at a point when the lifecourse trajectory to hypertension can be modified. Methods: This study is a mechanistic, double-blinded, randomized control trial (RCT) in 166 adolescents with dyslipidemia for the effect of 6 months of maximum dose 3 g daily oral l-carnitine supplementation (CS+) versus placebo (CS-) on aortic stiffness measured as carotid-femoral pulse wave velocity (CFPWV) and pulse pressure (PP); lipid concentrations (total cholesterol, HDL-C, triglycerides, and LDL-C) and serum fatty acid oxidation biomarkers by metabolomic analysis. Conclusions: The simultaneous evaluation of endogenous carnitine genetic effects and exogenous l-carnitine supplementation may facilitate future therapies for youth with cardiometabolic derangement to arrest atherosclerotic changes.

High post-exposure prophylaxis (PEP) uptake among household contacts of pertussis patients enrolled in a PEP effectiveness evaluation - United States, 2015-2017.

BACKGROUND: Post-exposure prophylaxis (PEP) for pertussis is recommended for household contacts of pertussis cases in the United States within 21 days of exposure, but data on PEP effectiveness for prevention of secondary cases in the setting of widespread pertussis vaccination are limited. We implemented a multi-state evaluation of azithromycin PEP use and effectiveness among household contacts. METHODS: Culture- or PCR-confirmed pertussis cases were identified through surveillance. Household contacts were interviewed within 7 days of case report and again 14-21 days later. Interviewers collected information on exposure, demographics, vaccine history, prior pertussis diagnosis, underlying conditions, PEP receipt, pertussis symptoms, and pertussis testing. A subset of household contacts provided nasopharyngeal and blood specimens during interviews. RESULTS: Of 299 household contacts who completed both interviews, 12 (4%) reported not receiving PEP. There was no evidence of higher prevalence of cough or pertussis symptoms among contacts who did not receive PEP. Of 168 household contacts who provided at least one nasopharyngeal specimen, four (2.4%) were culture or PCR positive for B. pertussis; three of these received PEP prior to their positive test result. Of 156 contacts with serologic results, 14 (9%) had blood specimens that were positive for IgG anti-pertussis toxin (PT) antibodies; all had received PEP. CONCLUSIONS: Very high PEP uptake was observed among household contacts of pertussis patients. Although the number of contacts who did not receive PEP was small, there was no difference in prevalence of pertussis symptoms or positive laboratory results among these contacts compared with those who did receive PEP.

Seborrheic Dermatitis in Older Adults: Pathogenesis and Treatment Options.

Seborrheic dermatitis is a common and chronic skin disease, which is particularly prevalent in older adults. While a specific cause of seborrheic dermatitis remains largely unelucidated, the currently understood pathogenesis of seborrheic dermatitis revolves around the presence of Malassezia yeast colonies and an inflammatory response in the affected individual. Keratinocyte proliferation resulting from inflammasome response in the host skin leads to the clinically relevant symptoms of seborrheic dermatitis. The increasing number of older adults as a percentage of the population in the USA will lead to an even higher prevalence of the disease in the ensuing decades. Fortunately, there are multiple treatment options based on individual patient situations and preferences. Topical treatment is the gold standard, but oral therapy may be required in certain cases. In order to maximize effectiveness and minimize adverse pharmacologic effects, effective treatment for older adults must take into account changes in lifestyle and metabolism that occur with aging.

Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: A Randomized Clinical Trial.

BACKGROUND: Treatment options are limited for skin disease in dermatomyositis. Lenabasum is a cannabinoid receptor type 2 agonist that triggers the resolution of inflammation. OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of lenabasum in patients with refractory cutaneous dermatomyositis. DESIGN: This study was a single-center, double-blind, randomized, placebo-controlled phase 2 study conducted from July 2015 to August 2017. POPULATION: The population included subjects aged ≥18 years with at least moderately active dermatomyositis skin activity by Cutaneous Dermatomyositis Disease Area and Severity Index activity ≥ 14 and failure or intolerance to hydroxychloroquine. INTERVENTION: Participants received 20 mg lenabasum daily for 28 days and then 20 mg twice per day for 56 days or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was a change in Cutaneous Dermatomyositis Disease Area and Severity Index activity. Safety and other secondary efficacy assessments were performed till day 113. RESULTS: A total of 22 subjects were randomized to lenabasum (n = 11) or placebo (n = 11). No serious or severe adverse events were related to lenabasum, and no participants discontinued the study. The adjusted least-squares mean for Cutaneous Dermatomyositis Disease Area and Severity Index activity decreased more for lenabasum, and the difference was significant on day 113 (least-squares mean [standard error] difference = ‒6.5 [3.1], P = 0.038). Numerically greater improvements were seen in multiple secondary efficacy outcomes and biomarkers with lenabasum. CONCLUSION: Lenabasum treatment was well tolerated and was associated with greater improvement in Cutaneous Dermatomyositis Disease Area and Severity Index activity and multiple efficacy outcomes. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, NCT02466243.

Congenital Heart Diseases: Genetic Risk Variants and Their Methylation Status.

(1) Background: The interaction between single nucleotide variants (SNVs) associated with congenital heart diseases (CHDs) and their gene methylation status has not been well researched. The aim of the present study was to determine if there is a relationship between the methy lation status (MS) of genes and the allelic variants associated with CHDs. (2) Methods: Seven SNVs of the genes AXIN1, TBX1, TBX20, and MTHFR were selected from the literature. DNA extraction, genotyping, and a methylation analysis were performed on healthy subjects and subjects with CHDs. (3) Results: Twenty-two subjects with CHDs were selected as the case group (15 with ventricular septal defects (VSDs) and 7 with atrial septal defects (ASDs)), and 44 healthy subjects comprised the control group. The MTHFR and AXIN1 genes were hypermethylated in the control group when compared to the case group. When analyzed separately, those with atrial septum defects exhibited greater methylation, except for the gene MTHFR where there were no differences. Only the alternate alleles of MTHFR showed a significantly different methylation status in those without cardiopathy. (4) Conclusions: The MTHFR and AXIN genes were hypermethylated in the control group; however, only the alternate alleles of MTHFR (rs1801133 and rs1801131) showed a significantly different methylation status.

Practices and activities among healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection working in different healthcare settings-ten Emerging Infections Program sites, April-November 2020.

Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.

Maternal Folic Acid Intake and Methylation Status of Genes Associated with Ventricular Septal Defects in Children: Case-Control Study.

BACKGROUND: DNA methylation is the best epigenetic mechanism for explaining the interactions between nutrients and genes involved in intrauterine growth and development programming. A possible contributor of methylation abnormalities to congenital heart disease is the folate methylation regulatory pathway; however, the mechanisms and methylation patterns of VSD-associated genes are not fully understood. OBJECTIVE: To determine if maternal dietary intake of folic acid (FA) is related to the methylation status (MS) of VSD-associated genes (AXIN1, MTHFR, TBX1, and TBX20). METHODS: Prospective case-control study; 48 mothers and their children were evaluated. The mothers' dietary variables were collected through a food frequency questionnaire focusing on FA and the consumption of supplements with FA. The MS of promoters of genes was determined in the children. RESULTS: The intake of FA supplements was significantly higher in the control mothers. In terms of maternal folic acid consumption, significant differences were found in the first trimester of pregnancy. Significant differences were observed in the MS of MTHFR and AXIN1 genes in VSD and control children. A correlation between maternal FA supplementation and MS of AXIN1 and TBX20 genes was found in control and VSD children, respectively. CONCLUSIONS: A lower MS of AXIN1 genes and a higher MS of TBX20 genes is associated with FA maternal supplementation.

Infección grave de piel y partes blandas por Fusarium oxysporum asociado a la administración subcutánea de insulina / Severe skin and soft tissue infection due to Fusarium oxysporum associated with subcutaneous insulin administration

Resumen La diabetes mellitus (DM) es una enfermedad crónica muy prevalente. Dentro de los tratamientos para la DM se encuentra la insulina que es el agente antidiabético más potente, sin embargo, una proporción significativa de pacientes no logra alcanzar el objetivo de hemoglobina glicosilada (HbA1c). Los errores en la aplicación de insulina son un factor importante y corregible en muchos casos. Se presenta el caso de una paciente con DM, antecedentes de neuropatía diabética, enfermedad renal crónica estadio V en hemodiálisis, hipertensión arterial, estenosis aórtica con recambio por válvula protésica, y anticoagulada, con escasa adherencia a recomendaciones higiénico dietéticas. Debido a la mala técnica de aplicación de insulina y falta de higiene, desarrolló varias infecciones polimicrobianas de piel y partes blandas, con evolución tórpida de las úlceras y mala respuesta al tratamiento indicado. Durante su internación, de una úlcera se aisló Fusarium oxysporum. Es importante jerarquizar la relevancia de la educación diabetológica en pacientes insulinizados y el rol de los educadores en diabetes en el cuidado de los mismos. Por otro lado, destacar la importancia de la toma de cultivos mediante punción de partes blandas ante la aparición de signos locales de infección.

Abstract Diabetes mellitus (DM) is a very prevalent chronic disease. Among the treatments for DM, insulin is the most potent antidiabetic agent. However a significant proportion of patients fail to achieve Errors in the application of insulin are an important and correctable factor in many cases. We present the case of a patient with DM who, due to poor insulin application technique and hygiene, develops a skin and soft tissue infection with subsequent appearance of Fusarium oxysporum. It is important to emphasize the relevance of diabetes education in insulin ized patients and the role of diabetes educators in their care. On the other hand, it is important to emphasize the importance of taking cultures by soft tissue puncture in case of local signs of infection.

JAG1, MEF2C and BDNF polymorphisms associated with bone mineral density in women from Northern México

Introduction: Osteoporosis is characterized by a low bone mineral density. Genetic composition is one of the most influential factors in determining bone mineral density (BMD). There are few studies on genes associated with BMD in the Mexican population. Objective: To investigate the association of eight single nucleotide polymorphisms (SNP) of JAG1, MEF2C and BDNF genes with BMD in women of Northern México. Materials and methods: This study involved 124 unrelated Mexican women between 40 and 80 years old. BMD was determined by dual X-ray absorptiometry. Genotyping was performed using allelic discrimination by real time PCR. We analyzed the SNP of JAG1 (rs6514116, rs2273061, rs2235811 and rs6040061), MEF2C (rs1366594, rs12521522 and rs11951031), and BDNF (rs6265) and the data using linear regression. Results: The JAG1 SNP rs2235811 was associated with the BMD of the total body under the dominant inheritance model (p=0,024). Although the other SNPs were not associated with BMD in any of the inheritance models studied, a trend was observed. Conclusion: Our results suggest that the SNP rs2235811 in the JAG1 gene might contribute to the variation in BMD in women from northern México.

[Depressive symptoms and serum levels of polyunsaturated fatty acids omega-3 and omega-6 among college students from Northern Mexico]. / Síntomas depresivos y niveles séricos de ácidos grasos poliinsaturados omega-3 y omega-6 en universitarios del norte de México.

INTRODUCTION: Previous studies suggest that low consumption as well as low serum levels of polyunsaturated fatty acids (PUFA) omega-3 and a high omega-6/omega-3 ratio may be implicated in the etiology of depressive disorders, however, epidemiologic evidence is inconclusive. OBJECTIVE: To assess the relationship of serum levels of omega-3 fatty acids (docosahexaenoic [DHA], eicosapentaenoic [EPA], alpha-linolenic fatty acid [ALA]) and the omega-6 (arachidonic acid [AA])/EPA ratio with depressive symptoms among Mexican college students. MATERIAL AND METHODS: A cross-sectional study that included 60 male and female participants (ages 18 to 24 years) with serum levels of EPA, DHA, ALA and AA. Depressive symptoms were ascertained with the Center for Epidemiologic Studies Depression (CES-D) scale validated for Mexican students. Linear regression was used to assess the relationship between depressive symptoms and serum PUFA omega-3 and omega-6. RESULTS: Serum levels of EPA, DHA and EPA/DHA ratio were not related to depressive symptoms, high serum ALA was related with lower depressive symptoms before and after covariate adjustment; however, these results were not statistically significant. Among women, 1% increase in EPA resulted in 5.5. (p = 0.57) increase in the depressive scale scores while 1% increase in ALA resulted in 6.7 decrease (p = 0.39) in the scores. CONCLUSIONS: Our results did not confirm the relationship of serum levels of PUFA omega-3 and omega-6/omega-3 ratio with depressive symptoms; the negative correlation of serum ALA with depressive symptoms remains to be confirmed in prospective studies.