Association of active immunotherapy with outcomes in cancer patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: During the COVID-19 pandemic, there are growing concerns about the safety of administering immunotherapy in cancer patients with COVID-19. However, current clinical guidelines provided no clear recommendation. METHODS: Studies were searched and retrieved from electronic databases. The meta-analysis was performed by employing the generic inverse-variance method. A random-effects model was used to calculate the unadjusted odds ratios (ORs) and adjusted ORs with the corresponding 95% CIs. RESULTS: This meta-analysis included 20 articles with 6,042 cancer patients diagnosed with COVID-19. According to the univariate analysis, the acceptance of immunotherapy within 30 days before COVID-19 diagnosis did not increase the mortality of cancer patients (OR: 0.92; 95% CI: 0.68-1.25; P=0.61). Moreover, after adjusting for confounders, the adjusted OR for mortality was 0.51, with borderline significance (95% CI: 0.25-1.01; P=0.053). Similarly, the univariate analysis showed that the acceptance of immunotherapy within 30 days before COVID-19 diagnosis did not increase the risk of severe/critical disease in cancer patients (OR: 1.07; 95% CI: 0.78-1.47; P=0.66). No significant between-study heterogeneity was found in these analyses. CONCLUSIONS: Accepting immunotherapy within 30 days before the diagnosis of COVID-19 was not significantly associated with a higher risk of mortality or severe/critical disease of infected cancer patients. Further prospectively designed studies with large sample sizes are required to evaluate the present results.

Current Evidence on Nonantibiotic Prevention of Recurrent Urinary Tract Infections.

Clinicians should be aware of the limited evidence on nonantibiotic prophylactic treatment for recurrent urinary tract infections. Owing to the rising antibiotic resistance rates worldwide, nonantibiotic prevention strategies should be considered for patient care. Further research is necessary to evaluate nonantibiotic treatment strategies using a robust randomised controlled trial methodology to contribute to a strong evidence basis.

[Proteomic profile and non-specific immunoprophylaxis of respiratory diseases in frequently sick children].

We have investigated efficacy of meglumine acridonacetate (Cycloferon) infrequently sick children (FSC) on the basis of serum proteomic profile dynamics; we have also studied epidemiologic efficacy of interferon inductor as a mean of non-specific immunoprophylaxis. FSC were subjects to follow up during 4-10 years. We have used recommended regimens of drug administration. Were analyzed: anamneses of FSC, clinical symptoms, infectious index calculation, stratification of children into 5 groups of FSC and separation of children with truly frequent recurrent respiratory viral diseases. On the basis of proteomic blood analyzes the following parameters of efficacy of treatment with meglumine acridonacetate were defined: expression intensity of Rho- and Ras-signaling pathways proteins. Epidemiologic efficacy of the drug was 2,9 (from 2,4 to 3,4), rate of protection--62,8% (58,5-67,1%).

Pertussis epidemiology in Argentina: trends over 2004-2007.

OBJECTIVES: Pertussis continues causing significant morbidity and mortality worldwide. Although its epidemiology has been studied in many developed countries, the current pertussis situation in South America is scarcely known. This review summarizes the most important recent data concerning pertussis in a country of South America, Argentina. METHODS: CDC criteria were used for pertussis diagnosis. Proportion of pertussis cases by age, immunization status, and immunization coverage rate evaluated at the Argentinean National Pertussis Reference Centers was reported. Bordetella pertussis isolates were characterized and compared with vaccine strains. RESULTS: From 2002 to nowadays, a steady increase of pertussis cases was observed. Most of these cases correspond to patients younger than six months old that received less than three doses of vaccine. However, cases in adolescent and adults have also been detected. For this situation, which is not peculiar to Argentina, several explanations have been proposed. Among them, the inability of current vaccines to induce long-lasting immunity is the most widely accepted as a cause of pertussis resurgence. Furthermore, antigenic divergence between local clinical isolates and vaccine strains may have aggravated the effect of waning immunity. CONCLUSIONS: Pertussis is an important problem for public health in Argentina. Divergence between vaccine strains and local isolates could contribute to the described pertussis epidemiology.

Antibody responses, amyloid-beta peptide remnants and clinical effects of AN-1792 immunization in patients with AD in an interrupted trial.

Post mortem examinations of AN-1792-vaccinated humans revealed this therapy produced focal senile plaque disruption. Despite the dispersal of substantial plaque material, vaccination did not constitute even a partial eradication of brain amyloid as water soluble amyloid-beta (Abeta) 40/42 increased in the gray matter compared to sporadic Alzheimer's disease (AD) patients and total brain Abeta levels were not decreased. Significant aspects of AD pathology were unaffected by vaccination with both vascular amyloid and hyper-phosphorylated tau deposits appeared refractory to this therapy. In addition, vaccination resulted in the consequential and drastic expansion of the white matter (WM) amyloid pool to levels without precedent in sporadic AD patients. Although vaccination disrupted amyloid plaques, this therapy did not enhance long-term cognitive function or necessarily halt neurodegeneration. The intricate involvement of vascular pathology in AD evolution and the firm recalcitrance of vessel-associated amyloid to antibody-mediated disruption suggest that immunization therapies might be more effective if administered on a prophylactic basis before vascular impairment and well ahead of any clinically evident cognitive decline. Amyloid-beta is viewed as pathological based on the postmortem correlation of senile plaques with an AD diagnosis. It remains uncertain which of the various forms of this peptide is the most toxic and whether Abeta or senile plaques themselves serve any desirable or protective functions. The long-term cognitive effects of chronic immunotherapy producing a steadily accumulating and effectively permanent pool of disrupted Abeta peptides within the human brain are unknown. In addition, the side effects of such therapy provided on a chronic basis could extend far beyond the brain. Eagerly seeking new therapies, critical knowledge gaps should prompt us to take a more wholistic perspective viewing Abeta and the amyloid cascade as aspects of complex and many-faceted physiological processes that sometimes end in AD dementia.

Human papillomavirus in cervical and head-and-neck cancer.

Cervical cancer is a major cause of cancer mortality in women worldwide and is initiated by infection with high-risk human papillomaviruses (HPVs). High-risk HPVs, especially HPV-16, are associated with other anogenital cancers and a subgroup of head-and-neck cancers. Indeed, HPV infection could account for the development of head-and-neck cancer in certain individuals that lack the classical risk factors for this disease (tobacco and alcohol abuse). This Review summarizes the main events of the HPV life cycle, the functions of the viral proteins, and the implications of HPV infection on their hosts, with an emphasis on carcinogenic mechanisms and disease outcomes in head-and-neck cancer. The demonstration that HPVs have a role in human carcinogenesis has allowed the development of preventive and therapeutic strategies aimed at reducing the incidence and mortality of HPV-associated cancers.

Evaluating a surrogate endpoint at three levels, with application to vaccine development.

Identification of an immune response to vaccination that reliably predicts protection from clinically significant infection, i.e. an immunological surrogate endpoint, is a primary goal of vaccine research. Using this problem of evaluating an immunological surrogate as an illustration, we describe a hierarchy of three criteria for a valid surrogate endpoint and statistical analysis frameworks for evaluating them. Based on a placebo-controlled vaccine efficacy trial, the first level entails assessing the correlation of an immune response with a study endpoint in the study groups, and the second level entails evaluating an immune response as a surrogate for the study endpoint that can be used for predicting vaccine efficacy for a setting similar to that of the vaccine trial. We show that baseline covariates, innovative study design, and a potential outcomes formulation can be helpful for this assessment. The third level entails validation of a surrogate endpoint via meta-analysis, where the goal is to evaluate how well the immune response can be used to predict vaccine efficacy for new settings (building bridges). A simulated vaccine trial and two example vaccine trials are presented, one supporting that certain anti-influenza antibody levels are an excellent surrogate for influenza illness and another supporting that certain anti-HIV antibody levels are not useful as a surrogate for HIV infection.

Children's health and the social theory of risk: insights from the British measles, mumps and rubella (MMR) controversy.

Recent debates in the United Kingdom about the measles, mumps and rubella (MMR) vaccine and its alleged link with autism have centred on contested notions of risk. This paper presents findings from 87 parents' focus group and interview discussions of their decision-making about the vaccine in light of three streams of theoretical literature on risk (cultural theory, risk society, psychometric models of risk perception) and models of vaccination acceptance and resistance. In addition to the risks of infectious disease and autism, parents balanced other risk concerns-both biological and social-in making their decisions. Such decisions, made on behalf of children unable to choose for themselves, and in the midst of contradictory information and uncertainty, symbolised what it means to be a 'good parent'. To cope with uncertainty, parents sought explanations for why some children seem to be more vulnerable to adverse outcomes than others. Debates about children's risks may need special theoretical consideration beyond that offered by the current risk literature. Specific aspects of the MMR debate, namely, selecting between potentially competing risks, making risk judgements on behalf of dependent others, and tensions between private and public good, provide a platform for exploring how social theories of risk might be adapted for children's health controversies.

Addressing immunization barriers, benefits, and risks.

Vaccines have been highly effective in eliminating or significantly decreasing the occurrence of many once-common diseases. Barriers to immunization are a significant factor in the rising incidence rates of some vaccine-preventable diseases. Cost, reduced accessibility to immunizations, increasingly complex childhood and adolescent/adult immunization schedules, and increasing focus on the potential adverse effects of vaccines all contribute to difficulty in meeting the 2010 immunization goals. Physicians must not only be knowledgeable about vaccines but they must incorporate systems in their offices to record, remind, and recall patients for vaccinations. They must also clearly communicate vaccine benefits and risks while understanding those factors that affect an individual's acceptance and perception of those benefits and risks.

[Imogam rage prescription assessment in the rabies prophylaxis center of Poitiers]. / Evaluation de la pertinence de la prescription d'Imogam rage au centre antirabique de Poitiers.

OBJECTIVES: Imogam rage (IgR) prescriptions were assessed in the rabies prophylaxis centre of Poitiers (France). MATERIAL AND METHODS: All medical records closed between January 1 and June 1, 2005 were retrospectively analyzed. An infectious disease specialist examined the pertinence of IgR prescription according to WHO references adapted to the epidemiological situation by the Pasteur Institute French rabies center. The indicator used was the proportion of patients treated by IgR among all patients treated by vaccination or vaccination with IgR. RESULTS: During the study period, 69 medical records have bewereen analyzed: 48 (70%) patients were treated including 22 (46%) with IgR. Imogam rage indication was not appropriate for 21 (95%) patients (one contact with a rodent, 8 low gravity contact, 12 contacts with a French animal) that is to say 86 IgR vials. The direct cost was 8,032 euros. CONCLUSION: This assessment permitted to underline an overprescription of IgR, to adapt guidelines to the local situation, and to improve care quality by adaptating medical record files, improving the prescription decisional tree and the local guidelines, and improving the training of interns.

Screening designs for drug development.

We propose drug screening designs based on a Bayesian decision-theoretic approach. The discussion is motivated by screening designs for phase II studies. The proposed screening designs allow consideration of multiple treatments simultaneously. In each period, new treatments can arise and currently considered treatments can be dropped. Once a treatment is removed from the phase II screening trial, a terminal decision is made about abandoning the treatment or recommending it for a future confirmatory phase III study. The decision about dropping treatments from the active set is a sequential stopping decision. We propose a solution based on decision boundaries in the space of marginal posterior moments for the unknown parameter of interest that relates to each treatment. We present a Monte Carlo simulation algorithm to implement the proposed approach. We provide an implementation of the proposed method as an easy to use R library available for public domain download (http://www.stat.rice.edu/~rusi/ or http://odin.mdacc.tmc.edu/~pm/).

Adjuvanticity of plasmid DNA encoding cytokines fused to immunoglobulin Fc domains.

PURPOSE: Plasmid DNAs encoding cytokines enhance immune responses to vaccination in models of infectious diseases and cancer. We compared DNA adjuvants for their ability to enhance immunity against a poorly immunogenic self-antigen expressed by cancer. EXPERIMENTAL DESIGN: DNAs encoding cytokines that affect T cells [interleukin (IL)-2, IL-12, IL-15, IL-18, IL-21, and the chemokine CCL21] and antigen-presenting cells [granulocyte macrophage colony-stimulating factor (GM-CSF)] were compared in mouse models as adjuvants to enhance CD8+ T-cell responses and tumor immunity. A DNA vaccine against a self-antigen, gp100, expressed by melanoma was used in combination with DNA encoding cytokines and cytokines fused to the Fc domain of mouse IgG1 (Ig). RESULTS: We found that (a) cytokine DNAs generally increased CD8+ T-cell responses against gp100; (b) ligation to Fc domains further enhanced T-cell responses; (c) adjuvant effects were sensitive to timing of DNA injection; (d) the most efficacious individual adjuvants for improving tumor-free survival were IL-12/Ig, IL-15/Ig, IL-21/Ig, GM-CSF/Ig, and CCL21; and (e) combinations of IL-2/Ig+IL-12/Ig, IL-2/Ig+IL-15/Ig, IL-12/Ig+IL-15/Ig, and IL-12/Ig+IL-21/Ig were most active; and (f) increased adjuvanticity of cytokine/Ig fusion DNAs was not related to higher tissue levels or greater stability. CONCLUSIONS: These observations support the potential of cytokine DNA adjuvants for immunization against self-antigens expressed by cancer, the importance of timing, and the enhancement of immune responses by Fc domains through mechanisms unrelated to increased half-life.

An important public health problem: rabies suspected bites and post-exposure prophylaxis in a health district in Turkey.

OBJECTIVE: The aim of this study was to describe rabies suspected animal bites and post-exposure prophylaxis (PEP) practices in Narlidere District in Turkey between 1999 and 2001. METHODS: One thousand five hundred and sixty-nine rabies suspected bite cases reported were identified from the District's rabies surveillance forms. RESULTS: Males comprised 66.7% of the cases, and 43.5% of the total were under 20 years old. In 74% of cases the animal involved in the bite was a dog. Only 70% of the animals had an owner, and only 17% of the animals had a rabies vaccination certificate. In terms of treatment, 68% of the human cases received PEP, and 21% of cases had an extra (sixth) vaccination dose, which is a substantial burden on the healthcare system, costing half a million US dollars per year. The place where the bite occurred (rural areas), the age of the recipient (more than 10 years old), the animal type (animals other than dogs and cats), lack of a vaccination certificate for the animal, and place of wound treatment (hospital) were significantly associated with PEP application. CONCLUSIONS: In addition to the currently recommended strategy of controlling the dog population and of vaccinating domesticated animals, adults and children should be educated about bite prevention to reduce the number of animal bites.

Brote de fiebre amarilla selvatica en el departamento de Santa Cruz-Bolivia, año 1999 / Bud of wild Yellow Fever in departament of Santa Cruz - Bolivia, year 1999

Entre el mes de enero y abril de 1999 se presento un brote de fiebre amarilla selvatica en el departamento de Santa Cruz. CENETROP apoyo a la dirección departamental de salud procesando las muestras de suero recolectadas por el personal de epidemiologia. Se recibieron un total de 175 muestras para ser analizadas en el laboratorio de arbovirosis de CENETROP. De las 175 muestras 51 (29.1 por ciento) fueron positivas para fiebre amarilla. El material enviado a CENETROP principalmente por la Unidad Departamental de Epidemiologia y centros medicos asistenciales, consistio en muestras de suero de pacientes con manifestaciones clinicas compatibles con fiebre amarilla o necropsias de higado de los pacientes fallecidos con manifestaciones clinicas similares. En total se han confirmados por laboratorio 51 casos con 21 (41.2 x ciento) fallecidos. Se indica la regularidad temporal y geografica de los brotes, que deberia inducir actividades de control de programadas. Se destaca la observacion del 20 x ciento de los casos en niños entre 5 a 10 años de edad. Del total de casos el 33 x ciento fueron mujeres. Finalmente, se llama la atencion sobre el peligro de la ocurrencia de casos urbanos de fiebre amarilla, por la presencia de casos selvaticos que son trasladados a la ciudad en fase viremica y la alta infestacion domiciliaria por Aedes aegypti en la ciudad de Santa Cruz