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Cross-sectional latent class regression models, also known as switching regressions or hidden Markov models, cannot identify transitions between classes that may occur over time. This limitation can potentially be overcome when panel data are available. For such data, we develop a sequence of models that combine features of the static cross-sectional latent class (finite mixture) models with those of hidden Markov models. We model the probability of movement between categories in terms of a Markovian structure, which links the current state with a previous state, where state may refer to the category of an individual. This article presents a suite of mixture models of varying degree of complexity and flexibility for use in a panel count data setting, beginning with a baseline model which is a two-component mixture of Poisson distribution in which latent classes are fixed and permanent. Sequentially, we extend this framework (i) to allow the mixing proportions to be smoothly varying continuous functions of time-varying covariates, (ii) to add time dependence to the benchmark model by modeling the class-indicator variable as a first-order Markov chain and (iii) to extend item (i) by making it dynamic and introducing covariate dependence in the transition probabilities. We develop and implement estimation algorithms for these models and provide an empirical illustration using 1995-1999 panel data on the number of doctor visits derived from the German Socio-Economic Panel.  相似文献   
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BackgroundHydroxychloroquine (HCQ) poisoning is a life-threatening but treatable toxic ingestion. The scale of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) and the controversial suggestion that HCQ is a treatment option have led to a significant increase in HCQ use. HCQ poisoning should be at the top-of-mind for emergency providers in cases of toxic ingestion. Treatment for HCQ poisoning includes sodium bicarbonate, epinephrine, and aggressive electrolyte repletion. We highlight the use of hypertonic saline and diazepam.Case ReportWe describe the case of a 37-year-old man who presented to the emergency department after the ingestion of approximately 16 g of HCQ tablets (initial serum concentration 4270 ng/mL). He was treated with an epinephrine infusion, hypertonic sodium chloride, high-dose diazepam, sodium bicarbonate, and aggressive potassium repletion. Persistent altered mental status necessitated intubation, and he was managed in the medical intensive care unit until his QRS widening and QTc prolongation resolved. After his mental status improved and it was confirmed that his ingestion was not with the intent to self-harm, he was discharged home with outpatient follow-up.Why Should an Emergency Physician Be Aware of This?For patients presenting with HCQ overdose and an unknown initial serum potassium level, high-dose diazepam and hypertonic sodium chloride should be started immediately for the patient with widened QRS. The choice of hypertonic sodium chloride instead of sodium bicarbonate is to avoid exacerbating underlying hypokalemia which may in turn potentiate unstable dysrhythmia. In addition, early intubation should be a priority in vomiting patients because both HCQ toxicity and high-dose diazepam cause profound sedation.  相似文献   
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The Busan partnership adopted at the 4th High Level Forum on Aid Effectiveness at the end of last year is a significant step forward towards the improvement of aid quality and the promotion of development. In particular, the inclusiveness achieved in Busan and the shift in discourse from ‘aid effectiveness’ to ‘development effectiveness’ are emblematic. However, key challenges still remain. Firstly, decision‐making should be more bottom‐up, finding ways to take into account the populations’ needs and experiences and to enhance self‐learning dynamics during the policy process. Today, it is particularly necessary to define what ‘development’ means at country level, according to the aspirations of particular categories of people and meeting operational and local expectations. Secondly, changes in language should be followed by a real change in mindset. Development stakeholders should further adapt their procedures to the reality of complex systems in which development interventions are being dealt with.  相似文献   
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Burkitt's Lymphoma (BL) rarely represents the first clinical manifestation of vertical HIV infection in adolescent in Western Europe. We report the case of a 17 year-old boy with two week history of fever and enlarged cervical lymph nodes firstly misdiagnosed as EBV infection, subsequently diagnosed as Burkitt's Lymphoma and vertical HIV infection.  相似文献   
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The PEDVAC study is the first trial designed to analyze safety and immunogenicity of a therapeutic vaccination with a multiclade multigene HIV DNA vaccine (HIVIS) in infected children. Twenty HIV-1 vertically infected children (6-16 years of age), on stable antiretroviral treatment for at least 6 months with HIV-1 RNA < 50 copies/ml and stable CD4 counts (>400 cells/mm3 or 25%) over 12 months of follow-up, were recruited into the study. Enrolled patients have been randomized into two arms: a control group of 10 children who continued previous antiretroviral treatment (HAART) (arm A) and a group of 10 children immunized intramuscularly with the HIVIS DNA vaccine in addition to previous HAART (arm B). Immunizations took place at week 0, 4, 12 and the boosting dose is planned at week 36. The 10 children in the vaccine group have received the first 3 priming doses of the HIVIS vaccine. Safety data showed good tolerance to the vaccination schedule. Mild cutaneous self-limeted reactions consisted of local irritation, usually itching or erythema +/− swelling at the injection site, were reported. No severe systemic adverse events have been observed. No vaccinated children had a decrease of CD4 T-cell counts from baseline. None experienced virological failure.Analysis of cellular immune responses was scheduled at week 0, 4, 12, 16, 20, 40, 60, 72 and 96 by standard lymphoproliferation assay, intracellular cytokine staining and cell-ELISA, a miniaturized assay to measure antigen-induced IFNγ secretion. Evaluation of these results is in progress and will provide key information on the status and changes of antigen specific immunity during HIV DNA immunization.  相似文献   
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AIDS is inexorably involving all parts of the country and all strata of society, with 10% of the urban and 3% of the rural population infected with HIV. It is increasingly a disease of women and children. The major cofactors for transmission are also sexually transmitted. For most developing countries, in spite of all education efforts, the "silent epidemic" of AIDS continues. AIDS is known but not understood; counselling modifies behavior in only 10-20% of at-risk persons. Under optimal conditions, HIV discordant females have seroconversion rates of 4.7% per year and pregnancy rates of 10.4% per year. The recent political unrest in Zaire and Haiti will further enhance the spread of AIDS in these countries. Despite these difficult periods, the work can and must continue. After all, during our 10th year of collaboration with a Haitian private research group, the Haitian government and Cornell University, Haiti has known seven different political rulers. Finally, I want to make a pledge on behalf of the millions of people who face a certain death from HIV infection and AIDS and who will never make the front page of any newspaper. For these people, you can make a difference. You must give us the tools to carry on this fight. The clinical trials must be done where they are most needed: the developing countries. Vaccines represent the only viable alternative despite the recognized obstacles of viral heterogeneity, immunogenicity, and delivery.  相似文献   
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Anogenital condylomata acuminata are induced by human papillomavirus (HPV) and they rarely manifest in immunocompetent children. Therapeutic options depend on patient's age and general conditions and extension of the lesions. However, management is still a challenge and recurrences are frequent. Cryotherapy, laser, and surgical treatments in children are painful and frequently require general anesthesia. Imiquimod is a topical immune response modifier and constitutes a noninvasive alternative for the treatment of anogenital condylomata acuminata. Here, we report an infant admitted to our hospital with a giant vegetative papillomatous lesion on the perianal region surrounded by small satellites papules. PCR for HPV confirmed the clinical diagnosis of giant condylomata acuminata due to HPV type 6. The child has been successfully treated with topical 5% imiquimod cream without side effects. Although topical imiquimod is not licensed for pediatric age, this report highlights the potential benefits of its use in selected pediatric cases.  相似文献   
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A 79-year-old woman presented with an unusual form of obesity limited to the lower half of the body from the waistline down but sparing the lower legs and feet. The patient was massive (360 lbs) and symmetrical. The superior half of the body was normal with no morbid obesity or lipoatrophy. These findings do not correspond to any classic form of lipodystrophy. The fat distribution is reminiscent of a pair of knickers and qualifies for the name "pantaloon obesity."  相似文献   
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