Rotavirus gastroenteritis hospitalizations in provinces with different vaccination coverage rates in Spain, 2013-2018.

BACKGROUND: Rotavirus (RV) vaccines are available in Spain since 2006 but are not included in the National Immunization Program. RV vaccination has reached an intermediate vaccination coverage rate (VCR) but with substantial differences between provinces. The aim of this study was to assess the ratio of RV gastroenteritis (RVGE) admissions to all-cause hospitalizations in children under 5 years of age in areas with different VCR. METHODS: Observational, multicenter, cross-sectional, medical record-based study. All children admitted to the study hospitals with a RVGE confirmed diagnosis during a 5-year period were selected. The annual ratio of RVGE to the total number of all-cause hospitalizations in children < 5 years of age were calculated. The proportion of RVGE hospitalizations were compared in areas with low (< 30%), intermediate (31-59%) and high (> 60%) VCR. RESULTS: From June 2013 to May 2018, data from 1731 RVGE hospitalizations (16.47% of which were nosocomial) were collected from the 12 study hospitals. RVGE hospital admissions accounted for 2.82% (95 CI 2.72-3.00) and 43.84% (95% CI 40.53-47.21) of all-cause and Acute Gastroenteritis (AGE) hospitalizations in children under 5 years of age, respectively. The likelihood of hospitalization due to RVGE was 56% (IC95%, 51-61%) and 27% (IC95%, 18-35%) lower in areas with high and intermediate VCR, respectively, compared to the low VCR areas. CONCLUSIONS: RVGE hospitalization ratios are highly dependent on the RV VCR. Increasing VCR in areas with intermediate and low coverage rates would significantly reduce the severe burden of RVGE that requires hospital management in Spain. Clinical trial registration Not applicable.

Chronic hepatitis C and chronic kidney disease: Advances, limitations and unchartered territories.

Over the past few years, treatment options for chronic hepatitis C virus (HCV) infection have evolved dramatically. The current approved interferon-free direct-acting antiviral (DAA) regimens have been shown to be safe and effective with sustained virologic response (SVR) rates of >90% in most patients. Unique issues yet remain such as the challenges in patients with impaired renal function or decompensated cirrhosis. Patients with stages 4-5 chronic kidney disease (CKD) have a higher prevalence of HCV infection compared with the general population. Chronic HCV in those on dialysis and in kidney transplant recipients is associated with higher morbidity and mortality than uninfected patients. The HCV-infected population is also at risk of developing extrahepatic manifestations associated with altered immune system function and chronic inflammation with cryoglobulinaemic vasculitis being the most common of these manifestations. Therefore, patients with CKD stages 4-5 have to be considered priority patients for HCV therapy. New antiviral therapies have the potential to improve outcomes in this vulnerable patient population, including those on haemodialysis. Recently published studies conducted in kidney transplant recipients have demonstrated successful outcomes. It is thus essential that we carefully select the most appropriate DAA regimen and the best time for treatment in the context of kidney transplantation or cryoglobulinaemic vasculitis. While sofosbuvir, the only approved nucleotide NS5B inhibitor, has been the backbone of most pangenotypic therapeutic regimens, it has a limitation in those with advanced kidney disease. The currently approved regimens for those with stage 4/5 CKD, while effective, have challenges in that they apply to genotype 1/4 and may require RBV for genotype 1a. Globally, genotype 3 is a common infection, and thus, this group with CKD presents a huge unmet need for effective therapies. As therapy of HCV in renal transplant recipients has been highly successful, it provides an opportunity to expand the use of HCV-infected organs in solid organ transplantation.

Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir.

Registration studies show entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B, but relapse rates after treatment discontinuation have not been well established. Relapse rates and predictors of relapse were evaluated in naïve HBeAg-positive and HBeAg-negative patients treated with ETV. Treatment duration was defined according to international guidelines. Virological relapse was defined as reappearance in serum of hepatitis B virus (HBV) DNA to >2000 IU/mL after discontinuation of treatment. A hundred and sixty-nine consecutive patients were treated for a median 181 weeks. 61% were HBeAg positive, 23% had cirrhosis, and mean HBV DNA level was 6.88 ± 1.74 log10 IU/mL. Ninety-two per cent became HBV DNA negative; 71% of HBeAg+ve patients became HBeAg negative and 68% anti-HBe positive; 14% became HBsAg negative and 13% anti-HBs positive. At the end of the study, 36 patients discontinued treatment: one due to breakthrough associated with resistant variants and 35 (20%) due to sustained virological response; 33 of these patients developed HBeAg seroconversion and 18 HBsAg seroconversion. Median off-treatment time was 69 weeks. Nine patients (26%), all HBeAg positive at baseline, developed virological relapse after a median 48 weeks off-treatment, 3 of them showed HBeAg reversion and 4 lost anti-HBe. No patient with HBsAg seroconversion relapsed. HBeAg clearance after week 48 of treatment was associated with an increase risk of relapse. After ETV discontinuation, HBsAg seroconversion was maintained in 100% of the patients, HBeAg seroconversion maintained in 90%, and virological relapse rate was 24%.

Effectiveness of entecavir in chronic hepatitis B NUC-naive patients in routine clinical practice.

INTRODUCTION: Registration studies showed entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B virus (HBV), but its effectiveness in routine clinical practice is unknown. MATERIALS AND METHODS: Sixty-nine HBeAg positive and negative NUC naïve chronic HBV patients were treated with ETV for 110 weeks. 63% were HBeAg positive, 16% were cirrhotics, mean HBV-DNA was 7.09 log IU/ml and mean ALT was 157 IU/ml. RESULTS: Sixty-one (88%) patients achieved undetectable DNA, with 46%, 77% and 100% virological response rates at week 24, 48 and 96 of treatment, respectively. Thirty-seven (84%) patients in the HBeAg-positive population achieved undetectable DNA, with 67% and 100% virological response rates at week 48 and 96 of treatment, respectively. Twenty-four (96%) patients in the HBeAg-negative population achieved undetectable DNA, with 91% and 100% virological response rates at week 48 and 96 of treatment, respectively. Twenty-three (53%) patients cleared HBeAg and 19 (44%) patients seroconverted to antiHBe positive status; seven (10%) patients cleared hepatitis B surface antigen and five (7%) patients developed antiHBs. At the end of the study, 10 patients successfully stopped therapy: nine HBeAg positive (four developed antiHBs positive) and one HBeAg negative. None of the patients had primary non-response. ETV resistance was not tested. None of the patients developed hepatocellular carcinoma, underwent liver transplantation or died because of liver-related events. No serious adverse events were reported. CONCLUSION: The ETV monotherapy showed high virological response rates, a favourable safety profile for NUC-naive HBeAg-positive and negative patients treated in routine clinical practice.

How to integrate stereotactic body radiation therapy and hypofractionation in the management of stage III lung cancer in the age of immunotherapy.

The constant advances in the field of lung cancer immunotherapy have recently reached the treatment of locally advanced disease with the approval of durvalumab after concurrent chemoradiation. However, radiation therapy continues to be key for controlling the disease at this stage. Over the years, different strategies have been employed to try to optimize outcomes using radiotherapy, with cardiac and pulmonary toxicity as the main limitation on its success. The interest in the use of hypofractionation and stereotactic body radiation therapy for stage III non-small cell lung cancer has increased as knowledge regarding these kinds of treatments has been enhanced. Hypofractionation is a relatively frequent treatment, although the level of evidence that supports it is limited. For its part, stereotactic body radiation therapy has been particularly studied as a boost after chemoradiation, with encouraging results. In both cases, study of how to integrate these tools with chemotherapy and particularly with immunotherapy is essential, as they may have an immunomodulatory role.

Characteristics of Liver Transplantation in Argentina: A Multicenter Study.

INTRODUCTION: There is a lack of information regarding outcomes after liver transplant in Latin America. OBJECTIVES: This study sought to describe outcomes after liver transplant in adult patients from Argentina. METHODS: We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. RESULTS: A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. CONCLUSIONS: We believe the information contained in this article might be of value for reviewing current practices and developing local policies.

The underlying structure of the subtelomeric region detected by microphotometrical scanning and chromosome graphic image analysis.

Previous research showed that the microphotometrical scanning of T-banded subtelomeric regions reveals the presence of specific patterns of the Giemsa stain density distributions as detected in chromosomes of normal human lymphocytes and CHO cells. Analyses with this method of the T-banded subtelomeric segments of CHO endoreduplicated chromosomes confirmed that these density patterns replicate in a similar way in sister chromosomes. Besides, the specific removal of portions of the subtelomeric segments appearing as tiny holes located where these density patterns are found suggested that both phenomena are related. The possible connection of these findings to the molecular structure of the subtelomeric region is briefly discussed.

Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: The role of silymarin in the treatment of liver cirrhosis is controversial. AIM: Clinical outcome,biochemical profile and the antiperoxidative effects of silymarin MZ-80 during 6 months treatment were investigated in patients with alcoholic liver cirrhosis. METHODS: Sixty consecutive patients with alcoholic liver cirrhosis were randomized to receive either silymarin MZ-80 (S) (150 mg t.i.d. per day) or placebo (P) for periods of 6 months. Erythrocyte total glutathione (GSH) content, platelet malondialdehyde (MDA) and serum amino-terminal propeptide of procollagen Type III (PIIINP) were determined at baseline and at the end of treatment. RESULTS: Forty-nine patients completed the study (24 S and 25 P). The 2 groups were well-matched for demographic as well as baseline clinical and laboratory parameters. Silymarin increased total GSH at 6 months (4.5 +/- 3.4 to 5.8 +/- 4.0 micromol/g Hb) whereas, in the placebo group, GSH remained unchanged (4.1 +/- 3.9 to 4.4 +/- 4.1 micromol/gHb) (p < 0.001), and platelet-derived non-induced MDA decreased by 33% (p < 0.015). A parallel decrease in PIIINP values was seen with silymarin (1.82 1.03 to 1.36 +/- 0.5 U/ml, p < 0.033) but not with placebo (1.31 +/- 0.4 to 1.27 +/- 0.6 U/ml). There were no concurrent changes on laboratory indices of the pathology. CONCLUSIONS: Silymarin is well-tolerated and produces a small increase in glutathione and a decrease in lipid peroxidation in peripheral blood cells in patients with alcoholic liver cirrhosis. Despite these effects no changes in routine liver tests were observed during the course of therapy.

Interactions of cephradine and cefaclor with the intestinal absorption of D-galactose.

Oral cephalosporins are frequently prescribed beta-lactam antibiotics. Although it has been well established that cephalosporins compete with dipeptides for absorption in the intestine, using the same transport mechanism, little is known about the action of the drugs on the absorption of other nutrients. In this work the effect of cephradine and cefaclor on the absorption of D-galactose has been studied. Intestinal sugar uptake was measured in-vitro in pieces of intestine (50 mg) and brush-border membrane vesicles, and in-vivo in intestinal loops. Galactose uptake was inhibited by cephalosporins in a dose-related, time-dependent manner. In-vivo the inhibition appeared when the antibiotics were on the luminal side of the enterocyte and when they reached the gut from the basolateral side. Only the active transport of the sugar was modified; passive transfer did not change in the presence of cephalosporins. In brush-border membrane vesicles, cephradine and cefaclor did not alter sugar uptake in either sodium or potassium gradients. Both antibiotics non-competitively inhibited basolateral Na+,K(+)-ATPase activity. These findings show that cephradine and cefaclor inhibit the active-transport component of galactose absorption because they reduce the activity of the basolateral Na+,K(+)-ATPase.

[Drug selection in hospitals. A model of reference in self-management of resources]. / Selección de medicamentos en el hospital. Un modelo de autogestión de prestaciones referencial.

The practice of medicine today must balance the optimal use of new pharmaceutical agents with the need for cost containment. Hospital policy regarding therapeutics and its historical perspective are discussed. Various aspects of the operations of Pharmacy and Therapeutics Committees are presented. The potential benefits of a formulary system are therapeutic, economic and educational and it could lead to a uniformity of drug usage throughout a district. The role of Clinical Pharmacology to provide advice to both Institution and physicians in how therapeutic practice may be optimized is also stressed.

Use of liver grafts from anti-hepatitis B core-positive donors: a multicenter study in Argentina.

Liver transplantation success is limited by the availability of donors. To overcome this limitation, anti-core-positive donors are increasingly being accepted, but underutilization of this resource still occurs. We performed the current study to determine the prevalence of anti-core-positive donors in our region and to describe the management of these donors and their recipients. Between January 2005 and July 2011, the national transplant database included 2,262 registered liver donors among whom 106 (4.7%) were anti-core-positive including 59 (56%) discarded and 47 (44%) implanted organs. A median of 14.5 offers (range 4-60) were rejected before harvesting and implanting the accepted grafts. The only difference between the implanted and the discarded grafts was found for the alanine aminotransferase level, which was higher among the discarded ones (50 ± 59 UI/L vs 25 ± 16, P < .05). Among 40 recipients included in the study, 5 (12.5%) did not receive any prophylaxis; 18 (45%) a nucleos(t)ide analog 11 (25.5%), heptitis B immunoglobulin and nucleos(t)ide analogs and 6 (15%) pretransplant hepatitis B vaccination. Over a mean follow-up of 871 ± 585 days, 4 de novo hepatitis B cases were identified at 545, 720, 748, and 1,080 days posttransplantation. None of these patients had received any prophylaxis. In all cases entecavir successfully controlled viral replication. We believe that better utilization of these donors and careful management of their recipients represent safe strategies to expand the liver donor pool in Argentina.

Effects of spermine on water absorption, polyethylene glycol 4000 permeability and collagenase activity in rat descending colon in vivo.

1. The effects of spermine in the concentration range 0-10 mmol/l on (a) the fluid absorption, (b) the polyethylene glycol permeability, (c) the release of collagenase activity activity into the lumen and (d) the histological appearance of rat descending colon were examined. 2. Spermine (5 mmol/l) decreased fluid absorption from 48.83 +/- 2.98 (n = 7) to 23.98 +/- 2.32 (n = 6) microliters h-1 cm-2 (P < 0.01); polyethylene glycol 4000 permeability was increased from 0.030 +/- 0.001 (n = 7) to 0.047 +/- 0.003 (n = 6) cm/h (P < 0.01) and luminal collagenase activity increased from a negligible control value to 250 +/- 39 (n = 6) units/ml (P < 0.001). Spermine also caused oedema formation within the mucosal interstitial fluid, without inducing an overt breakdown of the mucosa at the luminal surface. 3. Polyamine-free dialysed seminal plasma had no effect on polyethylene glycol 4000 permeability, although it still caused a significant decrease in colonic fluid absorption from 48.83 +/- 2.98 (n = 7) (control) to 31.41 +/- 2.08 (n = 5) microliters h-1 cm-2 (P < 0.01). 4. Low-molecular-mass heparin (600 units/ml) prevented the spermine (5 mmol/l)- and whole-semen-induced increase in colonic polyethylene glycol 4000 permeability and reduced the effect of semen on fluid absorption by 63% (P < 0.001) and that of spermine by 56% (P < 0.01). 5. The Zn2+ chelator and collagenase inhibitor o-phenanthroline reduced the effect of spermine on fluid absorption and polyethylene glycol 4000 permeability by 100% (P < 0.001) and on interstitial oedema formation. o-Phenanthroline also reduced the effects of whole semen on fluid absorption (by 70%, P < 0.01) and on polyethylene glycol 4000 permeability by 95%, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Exposure of rat colonic mucosa to human semen in vivo induces mucosal cytolysis, abolishes fluid absorption and raises paracellular permeability.

1. The effects of human semen on rat descending colon fluid absorption, permeability to 3H-labelled polyethylene glycol 4000 and the histological appearance of the mucosa were examined. Also, the semen was fractioned by centrifugation into plasma and sperm fractions and the effects of these fractions on rat colonic function were examined. The effects of trypsin and bacterial collagenase, mimetics of acrosin and seminal collagenase activity, were examined in order to investigate which component of human semen alters colonic permeability. 2. Contact between human semen and rat descending colonic mucosa for 3 h decreased fluid absorption from 52.0 +/- 2.9 microliters h-1 cm-2 (control) to 10.7 +/- 3.4 microliters h-1 cm-2 (P less than or equal to 0.001), increased the permeability to polyethylene glycol 4000 from 0.099 +/- 0.006 cm/h (control) to 0.31 +/- 0.04 cm/h (P less than or equal to 0.001) and caused cytolysis of the surface mucosa. 3. Spermatozoa inside the colonic lumen were destroyed within 1 h with release of acrosomal contents; this raised the activity of the acrosomal proteolytic enzyme acrosin by 40-fold (P less than or equal to 0.005) and of seminal plasma metalloproteinase (collagenase) by about twofold (mean activity 1623 +/- 240 units/ml of luminal fluid). 4. The changes in colonic permeability induced by seminal plasma were similar to those induced by similar activities of clostridial collagenase. 5. We conclude that seminal collagenase is present in sufficient amounts to cause acute damage to the colonic mucosa, and that this could be a factor in facilitating viral transmission across the colonic wall.

Effects on fluid and Na+ flux of varying luminal hydraulic resistance in rat colon in vivo.

1. A new method of measuring fluid and ionic movements and the dehydrating power of the colon in vivo is described. A range of agarose gel cylinders, with calibrated hydraulic conductivities (Lp), were inserted into the lumen of the descending colon of anaesthetized rats. Fluxes of fluid, Na+ and K+ out of the gels were measured over a period of 60-110 min. 2. Fluid absorption by the colon from 2.5% agarose gels was not slower than from solution without gel. Fluid absorption was inhibited by 66% when the agarose concentration was raised to 10%. In contrast 2.5% agarose gels caused a 73% (P < 0.001) reduction in water flow from rat ileum. 3. Increasing gel concentration to 10% or above caused the absorbate from the gels to become hypertonic (P < 0.001). 4. The measured suction pressure applied by the colonic hypertonic absorbate to the gels increased from 44 +/- 2.3 cmH2O (n = 23) with 2.5% agarose gels to 6713 +/- 960 cmH2O (n = 13) with 15% (P < 0.001). 5. Deoxycholate (2 mM) produced a decrease in fluid and Na+ absorption and reduced the suction pressure and power exerted by the colon.

Effects of cefroxadine on L-leucine absorption in rat jejunum.

The effect of cefroxadine, an aminocephalosporin (beta lactam antibiotic) on rat intestinal L-leucine transport has been studied. Cefroxadine inhibited the L-leucine uptake by the intestinal mucosa in a dose-dependent fashion. In vivo studies showed that cefroxadine reduced L-leucine absorption. This effect was irreversible. Only the active transport component of the absorption was inhibited. Oxygen consumption of the mucosa was reduced by cefroxadine which inhibited the activity of the basolateral (Na(+)-K+) ATPase also.

Effect of cefatrizine and cephaloglycine on L-leucine absorption in rat jejunum.

1. The oral cephalosporins: cefatrizine and cephaloglycine inhibit the L-leucine absorption in vivo on rat jejunum. 2. This inhibition is dose and time dependent and the effect is irreversible. 3. These antibiotics have a systemic effect on L-leucine absorption. 4. The inhibition of these antibiotics affect only leucine transport, without affecting the diffusion. 5. Cefatrizine and cephaloglycine inhibit the basolateral (Na(+)-K+) ATPase activity in rat jejunum.

The association of tobacco and alcohol consumption with the use of health care services in Spain.

BACKGROUND: Information on the impact of tobacco and alcohol consumption on the use of health services is scant and partially inconsistent. This paper examines the relationship between tobacco and alcohol consumption and the use of health care services in Spain. METHODS: Data were drawn from the 1993 Spanish National Health Survey, covering a random 21,120-person representative sample of Spain's noninstitutionalized population ages 16 years and older. Information was obtained through home-based interviews. RESULTS: Compared with never smokers, male smokers of more than 20 cigarettes/day tend to be hospitalized more frequently (odds ratio (OR) 1.31; 95% confidence limits (CL) 0.89-1.93) and make greater use of hospital emergencies (OR 1.51; 95%CL 1.13-2.01; P < 0.01). Among female smokers of more than 20 cigarettes/day, hospitalizations (OR 1.62; 95%CL 0.80-3.26) and medical visits (OR 1. 35; 95%CL 0.79-2.30) are also higher than among never smokers, although the associations do not reach statistical significance. Compared with never smokers, ex-smokers of both sexes make greater use of health care services (P < 0.01 for most services). There is a negative dose-response relationship (P < 0.001) between alcohol consumption and utilization of hospital and ambulatory services, for both sexes. Results are reasonably consistent across all age groups and are observed after adjustment for the principal confounding factors. We have found no evidence of a tobacco-alcohol interaction with the use of health care services. CONCLUSIONS: Smokers and ex-smokers make greater use of health care services. Control of smoking might reduce the use of such services and the ensuing human and economic costs. However, as alcohol consumption increases, the use of health care services decreases. This finding should not be used to promote even the moderate consumption of alcoholic drinks.

Variations in blood levels of aminoglycosides related to in vitro anticoagulant usage.

Aminoglycosides (AMG) remain an important therapeutic modality for the treatment of gram-negative infections. Adequate AMG levels have been associated with a lower risk of toxicity. Because AMG levels cannot be predicted with confidence, drug concentrations need to be measured. The authors studied the effect of different anticoagulants on AMG concentrations, which were determined by enzyme immunoanalysis. Blood samples from patients treated with AMG were obtained, and were immediately distributed in five tubes containing EDTA, sodium-citrate, or heparin at concentrations of 5 and 50 U/ml; one serum aliquot was kept as a control. All AMG determinations were performed by the enzyme multiplied immunoassay technique with Cobas-Mira equipment. The average coefficient of variations was < 3%. All samples were run the same day. Analysis of variance for repeated measures was used. Twenty-four patients (21 male and 6 female) with a mean age of 50 years (95% confidence interval = 43 to 58) and mean serum creatinine concentrations of 0.87 to 0.29 +/- Standard Deviation received 89% gentamicin and 11% tobramycin. Peak levels of AMG obtained from plasma collected with sodium citrate or heparin were significantly lower (p < 0.001) than in serum or plasma collected with EDTA. The higher the level of AMG in serum, the greater the discrepancies between drug concentrations measured with different anticoagulants. The anticoagulant used was of critical importance in determining AMG blood levels, which were underestimated when citrate or heparin were present.