Drug monitoring detects under- and overdosing in patients receiving 5-fluorouracil-containing chemotherapy-results of a prospective, multicenter German observational study.

INTRODUCTION: Body surface area (BSA)-based dosing of 5-fluorouracil (5-FU) results in marked inter-individual variability in drug levels, whereas determination of plasma 5-FU concentration and area under the curve (AUC) is a more precise dosing method but has not been integrated into clinical routine. We conducted a multicenter, prospective study to study 5-FU AUC distributions and assess clinical factors predicting therapeutic dosing in patients receiving BSA-dosed 5-FU. METHODS: Between June 2017 and January 2018, a total of 434 patients receiving continuous, infusional BSA-dosed 5-FU from 37 sites in Germany were included. Plasma 5-FU concentration and AUC were measured in venous blood samples at steady state. The primary objective was to determine 5-FU AUC distributions in relation to the target range, which is defined as 20-30 mg × h/l. The second objective was to explore clinical parameters that correlate with achievement of 5-FU AUC target range. RESULTS: The primary tumor was mainly located in the gastrointestinal tract (96.3%), with colorectal cancer being the most common (71.2%) tumor entity. 5-FU was administered as monotherapy (8.1%) or as part of FOLFOX (33.2%), FOLFIRI (26.3%), or other regimens (12.4%). Treatment setting was adjuvant (31.3%) or metastatic (64.5%). The median AUC was 16 mg × h/l. Only 20.3% of patients received 5-FU treatment within the target range, whereas the majority of patients (60.6%) were underdosed and 19.1% of patients were overdosed. In the univariate logistic regression, treatment setting was the only clinical parameter that significantly correlated with achievement of the target range. Patients treated in the metastatic setting had a 2.1 (95% confidence interval 1.186-3.776, P = 0.011) higher odds to reach the target range compared with patients treated in the adjuvant setting. CONCLUSIONS: The majority of patients received suboptimal doses of 5-FU using BSA dosing. Therapeutic drug monitoring of 5-FU is an option for optimized individualized cancer therapy and should be integrated into the clinical practice.

[What are the effects of different places of death of old people?] / Welche Auswirkungen zeigen unterschiedliche Sterbeorte betagter Menschen?: Eine Analyse Münchner Todesbescheinigungen.

Background: Inadequate quality of medical postmortem examinations has been discussed in the forensic medical literature for many years. It is known that older deceased persons are less likely to have a non-natural cause of death certified and autopsies are performed less frequently compared to younger deceased persons. Methods: Death certificates of all deaths that occurred in Munich with an age of ≥ 75 years during the death period 01/01/2013-31/12/2014 were analyzed. Standardized, anonymized data entry was performed. The collected data were analyzed descriptively. Results: A total of 26,303 persons died during the study period. Of these deaths, 16,146 (60.7%) were ≥ 75 years. Most common places of death for the aged were hospital (56.1%), private address (21.8%), and nursing home (20.0%). A natural mode of death was reported in 88.5%, unexplained in 8.8%, and non-natural in 2.7%. Most common immediate causes of death were diseases of the circulatory system (23.5%), inaccurately designated or unknown causes of death (20.0%), and diseases of the respiratory system (16.3%). Autopsies were performed on 4.9%, largely judicial. The parameters studied showed large differences in the analyses depending on the place of death. Discussion: This study again shows considerable quality deficiencies in the issuance of death certificates. Despite the dual approach of the Munich health authority (control, training), the quality of death certificates could not be sustainably improved in recent years. Types and causes of death showed partly considerable differences depending on the place of death and the doctor who issued the certificate. The deficits identified in the information provided under the heading "Causes of death" are also likely to have a negative impact on the cause of death statistics.

[COVID-19-associated deaths]. / COVID-19-assoziierte Sterbefälle: Erste Daten aus Münchner Todesbescheinigungen.

INTRODUCTION: In December 2019, the new infectious coronavirus disease 2019 (COVID-19) first appeared in China. So far, no systematic evaluation of death certificates of COVID-19-associated deaths has been presented. METHODS: The death certificates of all deaths in Munich during the period from 1 March to 31 July 2020 were analyzed. The previously defined inclusion criteria were the indication of corona, COVID-19 and SARS-CoV­2 in the death certificates. The variables were entered anonymously according to a developed key. The collected data were evaluated descriptively. RESULTS: In the period under investigation, a total of 5840 people died in the Munich City area. Of these deaths 332 (5.7%) were COVID-19-associated. In 281 deaths (84.6%) there was a definite COVID-19 and in 51 deaths (15.4%) the suspicion of this disease. The most frequent causes of death were acute respiratory distress syndrome or respiratory insufficiency (59.1%), multiple organ failure (21.4%) and sepsis (10%). An average of 1.8 pre-existing illnesses were reported in the death certificates. Most frequently mentioned were diseases of the circulatory system (54.8%), the nervous system (22.8%) and metabolic diseases (18.9%). The average age at death was 79 years and the most frequent place of death was a hospital (85%). An autopsy was attempted by the doctors who issued the death certificates for 18.1% of the collective, most frequently in the case of unexplained or unnatural causes of death and young age of the deceased. Clinical pathological autopsies were performed on 11% of the collective and judicial autopsies on 1%. DISCUSSION: This study is the first evaluation of death certificates with respect to the novel infectious COVID-19. Number and essential characteristics of COVID-19-associated deaths in Munich during the so-called first wave could be mapped. The interest of physicians in autopsies was rather low despite the appearance of a new infectious disease.

Hematology and serum biochemistry of feline immunodeficiency virus-infected and feline leukemia virus-infected cats.

BACKGROUND: Hematological and biochemical values in cats naturally infected by feline immunodeficiency virus (FIV) or feline leukemia virus (FeLV) are not completely documented. OBJECTIVE: Report differences in laboratory values between FIV- or FeLV-infected and noninfected and between FIV- and FeLV-infected cats. ANIMALS: Three thousand seven hundred and eighty client-owned cats tested for FIV and FeLV. METHODS: Retrospective study. Evaluation of clinicopathologic changes in cats with defined FIV and FeLV status and for which laboratory data were available. RESULTS: FIV-infected cats were more likely to be neutropenic (odds ratio [OR]=3.6, 95% confidence interval [95% CI] 2.1-6.2, P < .0001) and had lower serum activities of aspartate aminotransferase and glutamate dehydrogenase than control cats; serum total protein (8.1 +/- 1.1 versus 7.6 +/- 1.3 g/dL, P < .001) and gamma-globulin concentrations (2.2 +/- 1.1 versus 1.7 +/- 1.3 g/dL, P < .001) were higher than in uninfected cats. Compared with controls, FeLV-infected cats had a higher risk of anemia (OR = 3.8, 95% CI 2.4-6.0, P < .0001), thrombocytopenia (OR = 5.0, 95% CI 3.0-8.4, P < .0001), neutropenia (OR = 3.6, 95% CI 2.1-6.1, P < .0001), lymphocytosis (OR = 2.8, 95% CI 1.6-4.8, P= .0002), and lower erythrocyte counts (6.13 +/- 2.95 x 10(3) versus 8.72 +/- 2.18 x 10(3)/microL, P < .001), thrombocyte counts (253.591 +/- 171.841 x 10(3) versus 333.506 +/- 156.033 x 10(3)/microL, P < .001), hematocrit (28.72 +/- 12.86 versus 37.67 +/- 8.90%, P < .001), hemoglobin and creatinine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Hematologic abnormalities are common in FeLV-infected but not in FIV-infected cats. Clinicopathologic abnormalities are less frequent in FIV-infected cats and might reflect an unspecific immunologic response.

Streptococcus pneumoniae serotype 4 outbreak in a home for the aged: report and review of recent outbreaks.

OBJECTIVE: To describe a pneumonia outbreak caused by Streptococcus pneumoniae among residents of a home for the aged and to review contemporary pneumococcal outbreaks. DESIGN: Epidemiological investigation. METHODS: S pneumoniae isolates were serotyped and analyzed by pulsed-field gel electrophoresis. Paired sera were tested for antibodies to pneumococcal surface adhesin A protein (PsaA, a 37-kDa cell-wall protein). Pneumococcal outbreaks reported in the last decade in English were reviewed. RESULTS: Pneumonia developed in 18 of 200 residents. In 11 (61%), a pneumococcal etiology was demonstrated. S pneumoniae, serotype 4, was isolated from the blood cultures of 3 patients; all isolates were indistinguishable by pulsed-field gel electrophoresis. Pneumococcal involvement was established in 2 by sputum culture and latex agglutination of parapneumonic fluid and in 6 others by a twofold rise in optical density of serum antibody reactive to PsaA. Pneumococcal immunization had not previously been received by any patient; mortality was 22%. No additional cases were noted following administration of pneumococcal vaccine and antibiotic prophylaxis with penicillin or erythromycin. Twenty-six outbreaks of invasive pneumococcal disease since 1990 were reviewed. Twelve occurred in the United States, and serotypes 23F, 14, and 4 accounted for 8 (67%) of 12 outbreaks. All confirmed serotypes in US outbreaks are included in the 23-valent vaccine. More than one half of pneumococcal outbreaks worldwide involved elderly persons in hospitals or long-term-care facilities. CONCLUSIONS: A pneumococcal pneumonia outbreak occurred among unvaccinated residents of a residential facility for the aged. Institutionalized elderly persons are at risk of outbreaks of pneumococcal disease and should be vaccinated.

Shoulder girdle abscess due to Streptococcus agalactiae complicating esophageal dilation.

Bacteremia can result very unusually in significant complications after esophageal dilation. Procedure-related mucosal trauma may be a determinant, whereas pathogenic bacteria primarily originate from the patient's oropharyngeal flora. We describe an unusual case of Streptococcus agalactiae bacteremia and shoulder girdle abscess complicating esophageal bougienage. Consideration of specific risk factors and use of scrupulous procedural technique are warranted and will likely reduce pyogenic sequelae.

Listeria monocytogenes osteomyelitis.

Listeria monocytogenes is usually an opportunistic pathogen causing either meningitis or bacteremia in adults. Focal infection outside the central nervous system occurs infrequently. We describe two cases of osteomyelitis caused by L monocytogenes. Certain characteristics of L monocytogenes may make cure difficult, particularly in a deep-seated focus such as bone, and may warrant special consideration when planning therapy.

A review of percutaneous drainage in splenic abscess.

The availability of ultrasonography and computerized tomography has significantly improved diagnostic capability in the evaluation of splenic abscess. In addition, recent evidence has shown that percutaneous drainage of splenic abscess is a safe and efficacious approach to therapy and is indicated especially when patients are seriously ill, postoperative or when the risks of general anesthesia, surgical drainage or splenectomy are substantial. Adequacy of response to percutaneous drainage correlates positively with the presence of unilocular collections that have a discrete wall without internal septations. In contrast, multiloculated or complex pyogenic splenic abscesses should usually be treated using operative intervention. Discussion of important features of this illness, as well as a comprehensive review of reported instances and guidelines related to percutaneous drainage of splenic abscess, are presented herein. A team approach, which uses the experience of imaging and surgical personnel, is invaluable in therapy when a splenic abscess is encountered.

Primary subcutaneous abscess due to Streptococcus pneumoniae.

A primary subcutaneous abscess and associated bacteremia due to Streptococcus pneumoniae, type 9V, occurred in a healthy 23-year-old man. Penicillin therapy and surgical drainage were curative.

El equipo de la salud frente a la desnutricion. Prevencion, diagnostico y rehabilitacion segun nuevos criterios integrales. / Health team in face of malnutrition. Prevention, diagnosis and rehabilitation according comprehensive new criteria

Se propone considerar la desnutricion infantil en nuestro medio, como una enfermedad evitable, recuperable y de registro obligatorio. La prevencion apunta basicamente a mejorar las condiciones de vida, control de crecimiento y desarrollo y educacion para la salud. El tratamiento persigue dos objetivos simultaneos y complementarios: en el nino, recuperacion de su peso y desarrollo integral; en la familia, rehabilitacion de su capacidad y aptitud para la crianza en salud.Se describen metodos de evaluacion de riesgo y de gravedad, normatizando las conductas del equipo de salud, en los distintos grados y formas de presentacion. El criterio adoptado ha resultado en esta experiencia la unica forma viable y conducente para lograr resultados positivos en el aspecto medico asistencial del complejo problema social que constituye la desnutricion infantil

El equipo de la salud frente a la desnutricion. Prevencion, diagnostico y rehabilitacion segun nuevos criterios integrales. / Health team in face of malnutrition. Prevention, diagnosis and rehabilitation according comprehensive new criteria

Se propone considerar la desnutricion infantil en nuestro medio, como una enfermedad evitable, recuperable y de registro obligatorio. La prevencion apunta basicamente a mejorar las condiciones de vida, control de crecimiento y desarrollo y educacion para la salud. El tratamiento persigue dos objetivos simultaneos y complementarios: en el nino, recuperacion de su peso y desarrollo integral; en la familia, rehabilitacion de su capacidad y aptitud para la crianza en salud.Se describen metodos de evaluacion de riesgo y de gravedad, normatizando las conductas del equipo de salud, en los distintos grados y formas de presentacion. El criterio adoptado ha resultado en esta experiencia la unica forma viable y conducente para lograr resultados positivos en el aspecto medico asistencial del complejo problema social que constituye la desnutricion infantil