SEOM clinical practice guideline: management and prevention of febrile neutropenia in adults with solid tumors (2018).

Febrile neutropenia (FN) is a common dose-limiting toxicity of chemotherapy, with a profound impact on the evolution of patients with cancer, due to the potential development of serious complications, mortality, delays, and decrease in treatment intensity. This article seeks to present an updated clinical guideline, with recommendations regarding the diagnosis, prevention, and treatment of febrile neutropenia in adults with solid tumors. The aspects covered include how to properly approach the risk of microbial resistances, epidemiological aspects, considerations about the initial empirical approach adapted to the risk, special situations, and prevention of complications. A decision-making algorithm is included for use in the emergency department based on a new, validated tool, the Clinical Index of Stable Febrile Neutropenia, which can be used in patients with solid tumors who appear stable in the initial phase of neutropenic infections, and can help detect those at high risk for complications in whom early discharge must be avoided.

The prognostic impact of additional intrathoracic findings in patients with cancer-related pulmonary embolism.

AIM: To assess the prevalence and prognostic significance of additional intrathoracic findings (AIFs) in patients with cancer and pulmonary embolism (PE). AIFs were considered alterations other than the characteristic ones intrinsic to PE or changes in cardiovascular morphology. METHODS: Subjects have been taken from a Spanish national multidisciplinary and multicenter study of PE and cancer who were treated between 2004 and 2015. The endpoint was the appearance of serious complications or death within 15 days. RESULTS: The registry contains 1024 eligible patients; 41% diagnosed by computed tomography pulmonary angiography versus 59% by non-angiographic CT. Serious complications occurred within 15 days in 18.9%, [95% confidence interval (CI), 16.6-21.4%] and 9.5% (95% CI 7.9-11.5%) died. At least one AIF was seen in 72.6%. The most common AIFs were as follows: pulmonary nodules (30.9%), pleural effusion (30.2%), tumor progression (28.3%), atelectasis (19.0%), pulmonary infarct (15.2%), emphysema (13.4%), pulmonary lymphangitic carcinomatosis (4.5%), and pneumonia (6.1%). Patients with AIF exhibited a higher complication rate at 15 days: 21.9% versus 13.0%, odds ratio (OR) 1.8 (95% CI 1.2-2.8), P = 0.03, and 15-day mortality: 15.0% versus 7.3%, OR 1.9 (95% CI 1.1-3.2), P = 0.020. Patients with pneumonia, pneumothorax, pulmonary edema, pulmonary nodules, tumor progression, pulmonary fibrosis, and pleural effusion showed an excess of adverse events. CONCLUSIONS: Additional intrathoracic findings are highly prevalent and significantly impact prognosis in patients with PE and cancer, making them germane to the classification of this population.

Predicting serious complications in patients with cancer and pulmonary embolism using decision tree modelling: the EPIPHANY Index.

BACKGROUND: Our objective was to develop a prognostic stratification tool that enables patients with cancer and pulmonary embolism (PE), whether incidental or symptomatic, to be classified according to the risk of serious complications within 15 days. METHODS: The sample comprised cases from a national registry of pulmonary thromboembolism in patients with cancer (1075 patients from 14 Spanish centres). Diagnosis was incidental in 53.5% of the events in this registry. The Exhaustive CHAID analysis was applied with 10-fold cross-validation to predict development of serious complications following PE diagnosis. RESULTS: About 208 patients (19.3%, 95% confidence interval (CI), 17.1-21.8%) developed a serious complication after PE diagnosis. The 15-day mortality rate was 10.1%, (95% CI, 8.4-12.1%). The decision tree detected six explanatory covariates: Hestia-like clinical decision rule (any risk criterion present vs none), Eastern Cooperative Group performance scale (ECOG-PS; <2 vs ⩾2), O2 saturation (<90 vs ⩾90%), presence of PE-specific symptoms, tumour response (progression, unknown, or not evaluated vs others), and primary tumour resection. Three risk classes were created (low, intermediate, and high risk). The risk of serious complications within 15 days increases according to the group: 1.6, 9.4, 30.6%; P<0.0001. Fifteen-day mortality rates also rise progressively in low-, intermediate-, and high-risk patients: 0.3, 6.1, and 17.1%; P<0.0001. The cross-validated risk estimate is 0.191 (s.e.=0.012). The optimism-corrected area under the receiver operating characteristic curve is 0.779 (95% CI, 0.717-0.840). CONCLUSIONS: We have developed and internally validated a prognostic index to predict serious complications with the potential to impact decision-making in patients with cancer and PE.

Performance of the clinical index of stable febrile neutropenia (CISNE) in different types of infections and tumors.

PURPOSE: The clinical index of stable febrile neutropenia (CISNE) can contribute to patient safety without increasing the complexity of decision-making. However, febrile neutropenia (FN) is a diverse syndrome. The aim of this analysis is to assess the performance of CISNE according to the type of tumor and infection and to characterize these patients. METHODS: We prospectively recruited 1383 FN episodes in situations of apparent clinical stability. Bonferroni-adjusted z tests of proportions were used to assess the association between the infections suspected at the time of onset and the type of tumor with the risk of serious complications and mortality. The performance of CISNE was appraised in each category using the Breslow-Day test for homogeneity of odds ratios and Forest Plots. RESULTS: 171 patients had a serious complication (12.3 %, 95 % confidence interval 10.7-14.2 %). The most common initial assumptive diagnoses were: fever without focus (34.5 %), upper respiratory infection (14.9 %), enteritis (12.7 %), stomatitis (11.8 %), and acute bronchitis (10.7 %). Lung and breast were the most common tumors, accounting for approximately 56 % of the series. The distribution of complications, mortality, and bacteremia varies for each of these categories. However, Breslow-Day tests indicate homogeneity of the odds ratio of the dichotomized CISNE score to predict complications in all infection and tumor subtypes. CONCLUSION: Despite FN's clinical and microbiological heterogeneity, the CISNE score was seen to be consistent and robust in spite of these variations. Hence, it appears to be a safe tool in seemingly stable FN.

On the necessity of new decision-making methods for cancer-associated, symptomatic, pulmonary embolism.

BACKGROUND: Acute symptomatic pulmonary embolism (PE) varies in its clinical manifestations in patients with cancer and entails specific issues. The objective is to assess the performance of five scores (PESI, sPESI, GPS, POMPE, and RIETE) and a clinical decision rule to predict 30-day mortality. METHODS: This is an ambispective, observational, multicenter study that collected episodes of PE in patients with cancer from 13 Spanish centers. The main criterion for comparing scales was the c-indices and 95% confidence intervals (CIs) of the models for predicting 30-day mortality. RESULTS: 585 patients with acute symptomatic PE were recruited. The 30-day mortality rate was 21.3 (95% CI; 18.2-24.8%). The specific scales (POMPE-C and RIETE) were equally effective in discriminating prognosis (c-index of 0.775 and 0.757, respectively). None of these best performing scales was superior to the ECOG-PS with a c-index of 0.724. The remaining scores (PESI, sPESI, and GPS) performed worse, with c-indexes of 0.719, 0.705, and 0.722, respectively. The dichotomic "clinical decision rule" for ambulatory therapy was at least equally reliable in defining a low risk group: in the absence of all exclusion criteria, 30-day mortality was 2%, compared to 5% and 4% in the POMPE-C and RIETE low-risk categories, respectively. CONCLUSION: The accuracy of the five scales examined was not high enough to rely on to predict 30-day mortality and none of them contribute significantly to qualitative clinical judgment.

Central adiposity in children born small and large for gestational age.

OBJECTIVE: To evaluate body composition differences between children that were born small (SGA) or large for gestational age (LGA) compared with their counterparts born adequate for gestational age (AGA). METHODS: Body composition was assessed in 124 healthy Caucasian children (50% girls) aged 6-10, classified according to their birth weight for gestational age as AGA, SGA and LGA. Fat mass (FM), percentage of FM, lean mass (LM), bone mineral content (BMC) and bone mineral density were measured by dual-energy X-ray absorptiometry (DXA) in the whole body and at different body regions. RESULTS: LM (adjusted for age and sex) and total BMC (adjusted for age, sex and weight) were both significantly higher in LGA children and lower in SGA when compared with those born AGA. After adjustments for height, LM and BMC differences between groups were not significant. In SGA children, truncal (P<0.05) and abdominal fatness (P<0.01) were higher when compared with both AGA and LGA children, after adjustments for age, sex and height. There were no differences in the percentage of total and central FM between children born LGA and AGA. CONCLUSIONS: During childhood, children born SGA had higher central adiposity regardless of their body size. Children born LGA seem to have a higher body size but with harmonic body composition and adequate body fat distribution. Small size for gestational age at birth could programme excess abdominal fat deposition in children, which is a major factor for the clustering of cardiovascular disease risk factors defining the metabolic syndrome.

[Use of psychoactive drugs in a health and welfare centre]. / Utilización de psicofármacos en un centro sociosanitario.

OBJECTIVE: To analyse the use of psychoactive drugs in a health and welfare centre and compare this use with current guidelines. METHOD: A cross-sectional study of the drug treatment regime of hospitalised patients in a health and welfare centre was carried out. Information was obtained from prescriptions and the clinical histories of patients in the centre. The following variables were assessed: demographic data, treatment with psychoactive drugs, date of commencing treatment, dosage, drug combinations, indication and total number of drugs analysed. The results were compared with the literature and current prescription guidelines. RESULTS: 45 of the 70 patients analysed were taking psychoactive drugs: 51.1% were being treated with neuroleptic drugs, 42.2% with antidepressants, and 6.7% with anxiolytic agents. 62% were women. The overall mean age was 80.3 years old. The average number of psychoactive drugs administered to each patient was 1.6 and the average number of total drugs prescribed was 10.5. The most frequently administered psychoactive drugs were risperidone, lorazepam and citalopram. The most frequent association was neuroleptic drugs with benzodiazepine. The indication and dosage prescribed were appropriate according to the data sheet, although some inappropriate prescription practices were observed. CONCLUSIONS: The results of the study would recommend controlling the duration of treatment with benzodiazepine, confirming the diagnosis of states of depression and correctly monitoring the associations between psychoactive drugs.

Minimal incision in parotidectomy.

Conservative parotidectomy has been for years an effective and well-established technique. Recently, aesthetic considerations have been reviewed. A minimal pre- and retroauricular incision is proposed that does not extend to the hair-bearing skin. This reduces the length of the scar and the extent of the dissection improving aesthetic results. This is a retrospective study of 32 parotidectomies performed through this incision because of benign parotid diseases and diagnosed by fine needle aspiration cytology. The minimal incision is mainly indicated in small and medium-sized tumours located in the superficial lobe of the parotid gland. Neither operating time nor the morbidity associated with parotidectomy is increased with this safe and effective technique for the treatment of benign parotid masses.

[Follow-up of the use of metformin among the high risk population]. / Seguimiento de la utilización de metformina en la población de riesgo.

OBJECTIVE: To perform a follow-up of the use of metformin in order to ensure the appropriate prescription of the drug among the population with the highest risk of adverse reactions. METHOD: A prospective follow-up was conducted of the use of metformin during a four-month period. In the patients recruited for the study, the following data were recorded: age, sex, weight and height, cause of hospitalization, pharmacotherapeutic profile, origin of the prescription (prior to hospitalization or during the hospital stay), glycemia, renal function, side effects and cause of the discontinuation of the treatment, if appropriate. RESULTS: The mean number of patients hospitalized each day during the study period was 352 (standard deviation +/- 36,8), the mean age was 73 years (33-102) and the total number of patients studied was 135, with 46% of males.Since prescription of metformin is contraindicated in patients with creatinine values > 0.132 mMol/L, renal function was monitored. Based on the data of 20 patients, six pharmaceutical interventions were performed in order to recommend the discontinuation of the treatment, which was accepted in 83% of the cases. Side effects and glycemia were also recorded. CONCLUSIONS: During the follow-up period, we did not observe any severe side effects such as associated lactic acidosis, although in some cases metformin was prescribed to patients in which it was not recommended. However, the follow-up of patients is important, since we have observed side effects (diarrhea) that require reduction of the dose of metformin.

[Congenital absence of the inferior vena cava as a risk factor for pulmonar thromboembolism]. / Agenesia de vena cava inferior como factor de riesgo de tromboembolismo pulmonar.

The absence of the inferior vena cava is a rare congenital anomaly. Currently its diagnosis is based on non-invasive imaging techniques (computerised axial tomagraphy and nuclear magnetic resonance). In most cases, it constitutes a casual finding upon practising these image tests unrelated to this congenital anomaly. In the symptomatic patients, the complaints associated are secondary to venous insufficiency and/or deep vein thrombosis. Recently the congenital absence of inferior vena cava has been described as a risk factor of deep vein thrombosis in young patients. We present a case of congenital absence of inferior vena cava that was admitted in our hospital because of pulmonary thromboembolism.

Intestinal pseudo-obstruction in systemic lupus erythematosus.

In order to document intestinal pseudo-obstruction (IPO) as a recently recognized manifestation of systemic lupus erythematosus (SLE), we report the case or a woman with SLE who presented with IPO and we review 21 other previously reported cases from an English literature search. In 41% of the cases, IPO was the initial manifestation of their underlying lupus. The clinical and laboratory features were not significantly different from those reported in large series of patients with SLE, except for an apparent association with an urinary tract involvement (ureterohydronephrosis and interstitial cystitis). The pathogenic mechanism of this complication is not fully understood, but seems to be heterogeneous. IPO responded readily to high dose steroid therapy in all patients, but in some cases this complication evolved regardless of the underlying disease activity. A high level of awareness of this complication is needed to avoid unnecessary surgical intervention.

[Monitoring antidepressant use in acute hospital]. / Seguimiento de la utilización de antidepresivos en un hospital de agudos.

OBJECTIVE: To carry out a prospective study on the current use of antidepressants (ADs) in an acute hospital, in order to determine the prescription sources, therapeutic indications, safety and monitoring of these drugs and their use at patient discharge. METHOD AND RESULTS: To this end the therapeutic drug profiles of non-psychiatric inpatients treated with tri-cyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs) were prospectively reviewed. The following was collected from the patientsâ medical record: reason for admittance, AD indication, prescription source (primary care or in-hospital), modifications of antidepressant treatment during stay, drug-related adverse events (DRAEs), interactions with other drugs, and whether patients were still on antidepressants upon discharge. The mean numer of daily inpatients was 382.6, of which 4.4% received ADs (11-25). Females were 67.5% and males were 32.5%, with a mean age of 67 years (37-92). The total number of patients studied was 126. Prescribed SSRIs represented 73% of cases (92), whereas tricyclic antidepressants represented 27% (34). Prescription originated in primary care for 79.4% of cases (29% tricyclics, 71% SSRIs) and within hospital for 20.6% of cases (tricyclics 11, SSRIs 15), p = 0.02. AD indications were endogenous depression in 72.2%, reactive depression in 7.1%, neuropathic pain in 7.1%, cancer-related pain in 2.4%, and indications not specified in medical records in 11.1%. Treatment was ongoing at patient discharge in 97.5% of cases. CONCLUSIONS: AD prescription source was most commonly primary care. Prescription of ADs for unauthorised indications was seen: management of dementia in the elderly and shyness, support treatment for fibromyalgia, and migraine prophylaxis. In virtually all inpatients on ADs prescriptions were maintained without modification during stay. In the follow-up of patients on ADs, no clinically significant interactions leading to treatment changes were seen.

Survival evaluation of treatment modality in squamous cell carcinoma of the oral cavity and oropharynx.

The treatment of squamous cell carcinoma of the mouth and oropharynx continues to change. In this primary report, we compared the results obtained by combined surgery and radiation therapy, or either modality alone. Other methods such as brachytherapy, or hyperfractionated radiotherapy, were not included in our protocols. A statistical analysis of the 3- and 5-year survival rates in relation to location and size of the primary tumour, stage at initial presentation, treatment modality and recurrence, was carried out in 88 patients with squamous cell carcinoma of the oral cavity or oropharynx. The overall survival rate was 73.8% at 3 years and 66.3% at 5 years. Size of tumour and stage at presentation were significant when P value was adjusted by site. Survival was significantly associated with type of treatment (combined approach obtained superior results), location of primary tumour, and recurrence. The type of neck dissection did not show any effect. Therapeutic modality used, stage, and location of primary tumour significantly influenced survival. A more selective combined initial treatment according to site and stage (distribution) is recommended.

The Aegean Sea oil spill on the Galician Coast (NW Spain). III:The assessment of long-term sublethal effects on mussels.

Several biomarkers of exposure to organic pollutants, namely the cytochrome P450 system, glutathione S-transferases, superoxide dismutase, DT-diaphorase and lipid peroxidation, were measured on mussels collected in five locations along the Galician Coast (NW Spain), 6, 9 and 12 months after the Aegean Sea oil spill. Among the studied biomarkers, a significant induction of the cytochrome P450 content and lipid peroxidation, determined as tissue concentration of malondialdehyde equivalents, was detected in mussels collected near the wreck point 6 months after the spillage. Thereafter, no significant differences between reference and polluted sites were detected. Nevertheless, the data suggest the existence of oxidative stress in mussel populations during the September-December samplings. A significant elevation of superoxide dismutase activity was detected in September-9 months after the accident-and this elevation was particularly evident in those stations located closest to the wreck point. Lipid peroxidation increased throughout the year and despite the existence of a strong seasonal effect, the whole data set was correlated with total PAH body burden (R= 0.56).

Correlation between objective automatic and auscultatory mercury manometer blood pressure measurements.

The automatic blood pressure (BP) measurement device (A) developed for the World Health Organization (WHO) Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study was compared in Spain with the standard auscultatory-mercury manometer (M) in 440 randomly selected subjects, 50-54 years old (50% men and 50% women). BPs were recorded simultaneously in the same arm. Systolic BP (SBP), analyzed in 1,440 readings, was 127.5 +/- 18.9 mm Hg by A system and 127.6 +/- 18.6 mm Hg by M system (NS). Diastolic BP (DBP) was 71.3 +/- 11.7 mm Hg by A and 79.3 +/- 11 mm Hg by M (p less than 0.001). We confirmed good correlations in SBP and DBP measured by both methods (r = 0.95 and r = 0.88, respectively; both p less than 0.001). Nearly complete consistency was noted between SBP readings by both methods but not between DBP readings; the readings by M were significantly higher than those by A. Since A's consistency with SBP and DBP readings obtained by the intra-arterial method (the most commonly used method) previously had been proven to be satisfactory, DBP obtained by clinical practice is possibly overestimated in adults.

Relationship between urinary amino acids and diets in Spanish Cardiovascular Diseases and Alimentary Comparison Study.

A randomized, cross-sectional study was carried out to examine dietary pattern and urinary amino acids excretion in two Spanish free-living populations. A total of 288 adults (50-54 years old; 50% men and 50% women), randomly selected from the census, took part in the study; of these, 146 were living in an urban district of Madrid and 142 in a rural area. Dietary intakes by 7-day recall questionnaires, smoking habits, and alcohol intake were examined in each participant, and 24-h urine was collected in aliquot cups designed for the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. All amino acid excretions averaged higher in men than in women in both areas, and higher in the urban than in the rural population. Main dietary differences between urban and rural populations were higher consumption of fish in urban than in rural populations and higher consumption of bread in rural than in urban populations. Urinary taurine excretion as well as 3-methylhistidine or histidine were significantly associated with fish and meat consumptions, respectively, estimated by 7-day dietary recall questionnaires.