MSMpred: interactive modelling and prediction of individual evolution via multistate models.

BACKGROUND: Modelling the course of a disease regarding severe events and identifying prognostic factors is of great clinical relevance. Multistate models (MSM) can be used to describe diseases or processes that change over time using different states and the transitions between them. Specifically, they are useful to analyse a disease with an increasing degree of severity, that may precede death. The complexity of these models changes depending on the number of states and transitions taken into account. Due to that, a web tool has been developed making easier to work with those models. RESULTS: MSMpred is a web tool created with the shiny R package that has two main features: 1) to allow to fit a MSM from specific data; 2) to predict the clinical evolution for a given subject. To fit the model, the data to be analysed must be upload in a prespecified format. Then, the user has to define the states and transitions as well as the covariates (e.g., age or gender) involved in each transition. From this information, the app returns histograms or barplots, as appropriate, to represent the distributions of the selected covariates and boxplots to show the patient' length of stay (for uncensored data) in each state. To make predictions, the values of selected covariates from a new subject at baseline has to be provided. From these inputs, the app provides some indicators of the subject's evolution such as the probability of 30-day death or the most likely state at a fixed time. Furthermore, visual representations (e.g., the stacked transition probabilities plot) are given to make predictions more understandable. CONCLUSIONS: MSMpred is an intuitive and visual app that eases the work of biostatisticians and facilitates to the medical personnel the interpretation of MSMs.

SARS-Cov-2 incubation period according to vaccination status during the fifth COVID-19 wave in a tertiary-care center in Spain: a cohort study.

BACKGROUND: The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period. METHODS: We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The distribution of the incubation period was estimated using the generalized odds-rate class of regression models. RESULTS: From 406 surveyed patients, 242 provided adequate information to be included in the analysis. The median incubation period was 2.8 days (95%CI: 2.5-3.1) and no differences between vaccinated and unvaccinated patients were found. Sex and age are neither shown not to be significantly related to the COVID-19 incubation time. CONCLUSIONS: Knowing the incubation period is crucial for controlling the spread of an infectious disease: decisions on the duration of the quarantine or on the periods of active monitoring of people who have been at high risk of exposure depend on the length of the incubation period. Furthermore, its probability distribution is a key element for predicting the prevalence and the incidence of the disease.

In vitro assessment of PEEK and titanium implant abutments: Screw loosening and microleakage evaluations under dynamic mechanical testing.

STATEMENT OF PROBLEM: Polyetheretherketone (PEEK) has been advocated to replace metal components in dentistry. Although PEEK is a high-performance polymer with a white color, adequate biological response, and resistance to fracture, data to support PEEK as an alternative material for implant abutments are lacking. PURPOSE: The purpose of this in vitro study was to assess the mechanical and functional properties of PEEK implant abutments as a nonmetallic alternative to titanium abutments, which presents esthetic limitations and greater difficulty to customize clinically. MATERIAL AND METHODS: Implant abutments manufactured by using PEEK (n=24) or titanium grade 5 (n=24) were attached to MIS Implants type M4 3.75×16 mm with an internal screw tightened to 25 Ncm. Screw loosening and microleakage was assessed by submersion in a 2% methylene blue solution for 48 hours at 37 °C. Both groups were compared with and without applying dynamic loading; fatigue testing was performed following the International Organization for Standardization (ISO) 14801:2016 standard. All specimens were observed under a stereomicroscope at ×8 magnification. Statistically significant differences among the PEEK and titanium implant abutments were tested with 2-factor ANOVA and the chi-square analysis for nonpaired and paired data, respectively (α=.05). RESULTS: The implant abutments made of titanium were better in all mechanical tests. The torque loss of titanium abutments was approximately 10%, while PEEK showed a significantly higher (P<.05) torque loss of up to 50%. Moreover, 91.6% of the titanium abutments did not present microleakage, while there was no specimen of PEEK abutments without microleakage, once subjected to dynamic loading (P<.05). CONCLUSIONS: Titanium implant abutments (Ti6Al4V) were better in all tests performed. However, PEEK abutments may be suitable for long-term interim restorations, especially in the anterior area, in patients without parafunction.

Multi-organ involvement and intratubular calcium phosphate deposition in the kidney biopsy: what should we investigate?

BACKGROUND: Anorexia nervosa is frequently associated with alcohol use disorder. Both of them may adversely affect almost every body system, leading to worse clinical outcomes and high mortality risk. Nonetheless, there is little evidence interrelating anorexia nervosa, alcohol use disorder, and kidney failure. CASE: We report a case of a 30-year-old male with multi-organ involvement at admission, including pancytopenia, electrolyte alterations, impaired liver function, and renal failure. The kidney biopsy revealed calcium phosphate crystalline nephropathy and IgA nephropathy. The bone marrow biopsy and aspiration showed a hypocellular bone marrow and a focal spindle cell infiltrate with atypical vascular proliferation. Nonspecific liver disease was revealed by ultrasound. Further investigation was performed, uncovering a possible masked diagnosis of anorexia nervosa and alcohol use disorder. With the restoration of adequate nutrition and the withdrawal of possible external triggers, a partial recovery was achieved. CONCLUSIONS: Anorexia nervosa and alcohol use disorder may promote tissue injury, including kidney failure, specifically calcium phosphate crystalline nephropathy and IgA nephropathy. This multi-organ involvement may lose its reversibility if anorexia nervosa and alcohol use disorder remain persistent. An early diagnosis and a successful multidisciplinary approach may prevent life-threatening complications. LEVEL OF EVIDENCE: Level V, case report.

Acute tubulointerstitial nephritis induced by the tyrosine kinase inhibitor vandetanib.

Few cases of immunoallergic tubulointerstitial nephritis associated with tyrosine kinase inhibitors have been described. We describe the first report case associated with vandetanib, a tyrosine kinase inhibitor indicated for the treatment of aggressive and symptomatic medullary thyroid cancer (CMT) in patients with locally advanced or metastatic non-resectable disease.

Using the geometric average hazard ratio in sample size calculation for time-to-event data with composite endpoints.

BACKGROUND: Sample size calculation is a key point in the design of a randomized controlled trial. With time-to-event outcomes, it's often based on the logrank test. We provide a sample size calculation method for a composite endpoint (CE) based on the geometric average hazard ratio (gAHR) in case the proportional hazards assumption can be assumed to hold for the components, but not for the CE. METHODS: The required number of events, sample size and power formulae are based on the non-centrality parameter of the logrank test under the alternative hypothesis which is a function of the gAHR. We use the web platform, CompARE, for the sample size computations. A simulation study evaluates the empirical power of the logrank test for the CE based on the sample size in terms of the gAHR. We consider different values of the component hazard ratios, the probabilities of observing the events in the control group and the degrees of association between the components. We illustrate the sample size computations using two published randomized controlled trials. Their primary CEs are, respectively, progression-free survival (time to progression of disease or death) and the composite of bacteriologically confirmed treatment failure or Staphylococcus aureus related death by 12 weeks. RESULTS: For a target power of 0.80, the simulation study provided mean (± SE) empirical powers equal to 0.799 (±0.004) and 0.798 (±0.004) in the exponential and non-exponential settings, respectively. The power was attained in more than 95% of the simulated scenarios and was always above 0.78, regardless of compliance with the proportional-hazard assumption. CONCLUSIONS: The geometric average hazard ratio as an effect measure for a composite endpoint has a meaningful interpretation in the case of non-proportional hazards. Furthermore it is the natural effect measure when using the logrank test to compare the hazard rates of two groups and should be used instead of the standard hazard ratio.

Managing a Pregnancy in the Presence of the Rare Blood Group Antibody PP1Pk.

Pregnant women with p phenotype, who lack antigens P, P1, and Pk, spontaneously form anti-PP1Pk antibodies whose primary target is the placenta. The risk of miscarriage in these women is 50%-70% and reaches 87% in the second trimester. The therapies aim to reduce the titer of antibodies early in pregnancy. They also have risk of hemolytic transfusion reaction, with very few compatible red blood cell donors in the world. In this study, we present a case of successful pregnancy managed with autologous blood donations and plasmapheresis.

Revision of Apocharips Fergusson (Hymenoptera: Figitidae: Charipinae) with description of three new species from Colombia.

The genus Apocharips is here revised. Three previously described species are considered as valid: Apocharips angelicae Pujade-Villar & Evenhuis, 2002, A. hansoni Menke, 1993, and A. trapezoidea (Hartig, 1841). Apocharips eleaphila (Silvestri, 1915) and A. peraperta (Silvestri, 1915) are synonymyzed with A. trapezoidea. Three new species are here described: Apocharips colombiana Ferrer-Suay & Pujade-Villar n. sp., Apocharips tamanii Paretas-Martinez & Pujade-Villar n. sp. and Apocharips tropicale Ferrer-Suay & Paretas-Martinez n. sp. A key to the six species included in Apocharips is given.

Dental anxiety, cardiovascular changes and patient preconceptions toward implants and root canal treatments: An observational study.

Background: There is little information about dental anxiety and the patient's vital signs during dental procedures. This study evaluates and compare patient anxiety levels and cardiovascular changes before and during root canal treatment (RCT) and single-tooth implant procedures. Material and Methods: Preoperative data and pre-treatment considerations were recorded. HR and SpO2 were monitored during treatment procedures at five points. Data were analyzed accordingly using Mann Whitney or X2 tests. 80 patients met the inclusion criteria. Results: Anxiety and fear scores were strongly correlated (p< 0.001). Both treatments resulted in low levels of dental anxiety and fear. Patients with a prior dental bad experience presented higher anxiety scores in the implant treatment group (p< 0.05). Implant treatment was considered a more time-consuming and more painful procedure than root canal treatment (p< 0.05). No significant relation was found between the level of anxiety with HR and SpO2. Conclusions: No significant relation was found between the level of dental anxiety with HR and SpO2. Single-implant treatment was pre-considered to be a more time-consuming and more painful procedure when compared with a RCT. HR was higher at the initial stages and decreased as both procedures finished. Key words:Dental anxiety, endodontics, dental implants, oximetry, heart rate.

Screening for Prognostic microRNAs Associated with Treatment Failure in Diffuse Large B Cell Lymphoma.

Diffuse large B cell lymphoma (DLBCL) treatment with R-CHOP regimen produces 5-year progression-free survival and overall survival of around 60-70%. Our objective was to discover prognostic biomarkers allowing early detection of the remaining 30-40% with poor long-term outcome. For this purpose, we applied a novel strategy: from a cohort of DLBCL patients, treated with standard therapy, a discovery group of 12 patients with poor prognosis (advanced stage III-IV, R-IPI > 2) was formed, consisting of six chemoresistant (refractory/early relapse < 12 months) and six chemosensitive (complete remission > 3 years) subjects. By using microarray assays, the most differentially expressed miRNAs were defined as an initial set of prognostic miRNA candidates. Their expression was then analyzed in a validation cohort of 68 patients and the three miRNAs with the most significant impact on event-free and overall survival were selected. In the DLBCL cell line U-2932 the transfection with miR-1244 and miR-193b-5p, but not miR-1231, blocked the effect of CHOP on cell viability. A subsequent gene set enrichment analysis in patients revealed the implication of the first two miRNAs in cell cycle control and chemoresistance-related pathways, whereas the last one was involved in immunological processes. In conclusion, this novel strategy identified three promising prognostic markers for DLBCL patients at high risk of failure with standard therapy.

Host nutrition-based approach for biotechnological production of the antifungal cyclic lipopeptide jagaricin.

In today's, society multi-resistant pathogens have become an emerging threat, which makes the search for novel anti-infectives more urgent than ever. A promising class of substances are cyclic lipopeptides like the antifungal jagaricin. Jagaricin is formed by the bacterial mushroom pathogen Janthinobacterium agaricidamnosum. It has shown antifungal activity against human pathogenic fungi like Candida albicans and Aspergillus fumigatus. In addition, jagaricin is nearly non-toxic for plants, which makes it a promising agent for agricultural applications. Cyclic lipopeptides formed by microorganisms originate from their secondary metabolism. This makes it very challenging to determine the inducing factor for product formation, especially for unknown microbial systems like J. agaricidamnosum. In the presented study, a biotechnological process for jagaricin formation was developed, investigating impact factors like the medium, oxygen availability, and phosphate. For this reason, experiments were conducted on microtiter plate, shake flask, and stirred tank bioreactor level. Ultimately, a final maximum jagaricin concentration of 251 mg L-1 (15.5 mgJagaricin∙gCDW-1) could be achieved, which is an increase of approximately 458 % in comparison to previous results in standard glucose medium. This concentration allows the production of significantly higher amounts of jagaricin and enables further experiments to investigate the potential of this substance.

General Anxiety in Dental Staff and Hemodynamic Changes over Endodontists' Workday during the Coronavirus Disease 2019 Pandemic: A Prospective Longitudinal Study.

INTRODUCTION: The aim of this study was to assess general anxiety levels in endodontists and dental assistants related to different conditions during the pandemic and lockdown and to evaluate hemodynamic changes in endodontists' heart rate (HR), blood pressure, and blood oxygenation during their workday. METHODS: Anxiety levels in endodontists and dental assistants were recorded weekly during the state of alarm declared because of the coronavirus disease 2019 pandemic. Hemodynamic parameters were monitored using a sphygmomanometer for HR and blood pressure and a pulse oximeter for oxygen saturation. Measurements were taken before and after each root canal treatment as well as on arrival at the clinic and at the end of the working day. Rest data, recorded every Saturday, served as a control. Data analysis was performed using chi-square, paired t, Mann-Whitney, and analysis of variance tests (P < .05). RESULTS: General anxiety decreased over the weeks, with significant differences between weeks 1 and 4 (P < .05). Endodontists perceived higher anxiety levels of anxiety during anesthesia inoculation and dental assistants during the dental unit's disinfection and equipment material (P < .05). There was a significant increase in the cardiovascular response in all endodontists in the clinic registrations compared with rest data (P < .05). Values were higher in the strict confinement period and significant for HR when arriving at the clinic (P < .05). CONCLUSIONS: Levels of general anxiety were higher during the first weeks. The chief perceived factors related to anxiety in endodontists and dental assistants were the risk of contagion and protection measures. Higher HR and blood pressure levels were registered during the workday, especially when arriving at the clinic.

Dental Anxiety, Fear, and Root Canal Treatment Monitoring of Heart Rate and Oxygen Saturation in Patients Treated during the Coronavirus Disease 2019 Pandemic: An Observational Clinical Study.

INTRODUCTION: The present study aimed to evaluate anxiety in patients and to monitor their heart rate (HR) and blood oxygenation (SpO2) before, during, and after a root canal treatment (RCT) during the state of alarm in 2 different periods of strict and partial confinement. METHODS: The patients who required a primary RCT were selected. Demographic, preoperative, and postoperative variables were registered, including perceived dental anxiety, fear, HR, and SpO2. Spearman correlation, chi-square, Mann-Whitney, and Kruskal-Wallis tests were used for frequency distribution and variable interaction, and Wilcoxon and Mann-Whitney tests were used to compare HR and SpO2 between groups and different treatment points. RESULTS: Ninety-six patients were included. The median Modified Dental Anxiety Scale scores were 8 (interquartile range [IQR], 6-9.25) and 6 (IQR, 5.5-8) in patients treated during the strict and partial confinement periods. The median fear scores were 2 (IQR, 0-5) and 3 (IQR, 1-5), respectively. Having a previous dental bad experience resulted in higher dental anxiety and fear (P < .05). HR was increased in patients with higher MDAS and fear scores and in those treated during the strict confinement (P < .05). In treatment time points T6 (x-ray taking), and T7 (post-treatment), HR decreased compared with the other evaluated treatment time points (P < .05). No clinical differences were found regarding SpO2. CONCLUSIONS: Self-perception on dental anxiety and fear was similar to other studies in a nonpandemic context. Patients with higher levels of dental anxiety and those treated in the strict confinement period presented an elevated HR. However, it can be stated that RCT performed by endodontists does not result in a significant alteration in patients.

Minerval induces apoptosis in Jurkat and other cancer cells.

Minerval is an oleic acid synthetic analogue that impairs lung cancer (A549) cell proliferation upon modulation of the plasma membrane lipid structure and subsequent regulation of protein kinase C localization and activity. However, this mechanism does not fully explain the regression of tumours induced by this drug in animal models of cancer. Here we show that Minerval also induced apoptosis in Jurkat T-lymphoblastic leukaemia and other cancer cells. Minerval inhibited proliferation of Jurkat cells, concomitant with a decrease of cyclin D3 and cdk2 (cyclin-dependent kinase2). In addition, the changes that induced on Jurkat cell membrane organization caused clustering (capping) of the death receptor Fas (CD95), caspase-8 activation and initiation of the extrinsic apoptosis pathway, which finally resulted in programmed cell death. The present results suggest that the intrinsic pathway (associated with caspase-9 function) was activated downstream by caspase-8. In a xenograft model of human leukaemia, Minerval also inhibited tumour progression and induced tumour cell death. Studies carried out in a wide variety of cancer cell types demonstrated that apoptosis was the main molecular mechanism triggered by Minerval. This is the first report on the pro-apoptotic activity of Minerval, and in part explains the effectiveness of this non-toxic anticancer drug and its wide spectrum against different types of cancer.

[Perception of the risk to adquire a sexually transmitted disease in a young population]. / Percepción del riesgo de contraer una enfermedad de transmisión sexual en población joven.

OBJECTIVE: To find out the perception of the risk of adquire a sexually transmitted disease (STD) in young people (15-21 years), and their attitudes and behaviour to adopt protective measures in sexual relationships. DESIGN: Socioconstructive qualitative study performed between the years 2006 and 2008 SETTING: Two Primary Care Centres in the city of Girona. PARTICIPANTS: A total of 34 young people selected from lists provided by doctors and key informers. METHODS: Theoretical sample from different designed profiles. The data was obtained and saturated by performing 5 group interviews. A thematic content analysis of the narrative data was made of the categorical subject. RESULTS: They had partial knowledge on AIDS and very little on other STD. The risk of pregnancy has the most influence on adopting protective measures. Despite easy access and knowledge of condoms, in some cases they are not used either in stable relationships or in sporadic ones, with different reasons for having this risk behaviour. They have limited contact with the health services, and when they do it is mainly to ask for emergency contraception. CONCLUSIONS: Health strategies should be directed towards adolescents, taking into account what they need from the health services as regards sexual health, in a different context from the health centre. Information should be focused on combating erroneous beliefs, such as AIDS is a disease of "others" and not "ours", and address these actions, not only to improve knowledge and attitudes but also changes in behaviour.

Genetic Variants Associated with Chronic Kidney Disease in a Spanish Population.

Chronic kidney disease (CKD) patients have many affected physiological pathways. Variations in the genes regulating these pathways might affect the incidence and predisposition to this disease. A total of 722 Spanish adults, including 548 patients and 174 controls, were genotyped to better understand the effects of genetic risk loci on the susceptibility to CKD. We analyzed 38 single nucleotide polymorphisms (SNPs) in candidate genes associated with the inflammatory response (interleukins IL-1A, IL-4, IL-6, IL-10, TNF-α, ICAM-1), fibrogenesis (TGFB1), homocysteine synthesis (MTHFR), DNA repair (OGG1, MUTYH, XRCC1, ERCC2, ERCC4), renin-angiotensin-aldosterone system (CYP11B2, AGT), phase-II metabolism (GSTP1, GSTO1, GSTO2), antioxidant capacity (SOD1, SOD2, CAT, GPX1, GPX3, GPX4), and some other genes previously reported to be associated with CKD (GLO1, SLC7A9, SHROOM3, UMOD, VEGFA, MGP, KL). The results showed associations of GPX1, GSTO1, GSTO2, UMOD, and MGP with CKD. Additionally, associations with CKD related pathologies, such as hypertension (GPX4, CYP11B2, ERCC4), cardiovascular disease, diabetes and cancer predisposition (ERCC2) were also observed. Different genes showed association with biochemical parameters characteristic for CKD, such as creatinine (GPX1, GSTO1, GSTO2, KL, MGP), glomerular filtration rate (GPX1, GSTO1, KL, ICAM-1, MGP), hemoglobin (ERCC2, SHROOM3), resistance index erythropoietin (SOD2, VEGFA, MTHFR, KL), albumin (SOD1, GSTO2, ERCC2, SOD2), phosphorus (IL-4, ERCC4 SOD1, GPX4, GPX1), parathyroid hormone (IL-1A, IL-6, SHROOM3, UMOD, ICAM-1), C-reactive protein (SOD2, TGFB1,GSTP1, XRCC1), and ferritin (SOD2, GSTP1, SLC7A9, GPX4). To our knowledge, this is the second comprehensive study carried out in Spanish patients linking genetic polymorphisms and CKD.

Consensus document for ultrasound training in the specialty of Nephrology. / Documento de consenso para la formación en ecografía en la especialidad de Nefrología.

Ultrasound is an essential tool in the management of the nephrological patient allowing the diagnosis, monitoring and performance of kidney intervention. However, the usefulness of ultrasound in the hands of the nephrologist is not limited exclusively to the ultrasound study of the kidney. By ultrasound, the nephrologist can also optimize the management of arteriovenous fistula for hemodialysis, measure cardiovascular risk (mean intimate thickness), implant central catheters for ultrasound-guided HD, as well as the patient's volemia using basic cardiac ultrasound, ultrasound of the cava inferior vein and lungs. From the Working Group on Interventional Nephrology (GNDI) of the Spanish Society of Nephrology (SEN) we have prepared this consensus document that summarizes the main applications of ultrasound to Nephrology, including the necessary basic technical requirements, the framework normative and the level of training of nephrologists in this area. The objective of this work is to promote the inclusion of ultrasound, both diagnostic and interventional, in the usual clinical practice of the nephrologist and in the Nephrology Services portfolio with the final objective of offering diligent, efficient and comprehensive management to the nephrological patient.

GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study.

OBJECTIVES: The prognosis of old or immunocompromised patients with refractory or relapsing diffuse large-cell lymphoma (DLCL) is very poor as the current standard of salvage therapy with autologous stem cell transplantation (ASCT) is not feasible for most of them. New active regimens with an acceptable toxicity profile are needed. We aim to report the results of a phase II trial of the GEMOX-R regimen in DLCL. METHODS: A total of 32 patients received GEMOX-R regimen in 2-wk intervals if feasible or every 3 wk for a planned six to eight courses. RESULTS: Median age of the population was 69 yr. Forty-one percent of the patients were primary refractory and 59% after relapsing. At GEMOX-R, 75% of patients had a stage III-IV and an adjusted International Prognostic Index > 1 was observed in 69%. The response rate was 43% with 34% complete response. Neutropenia and thrombopenia grade III-IV were observed in 43% of the patients and neurotoxicity grade III-IV in 7% of cases. Median follow-up for alive patients was 13 months and the median survival was 9.1 months. At 12 months, the overall survival and progression-free survival were 41% and 29%, respectively. CONCLUSIONS: GEMOX-R is a new salvage regimen for DLCL with high activity and relatively safe toxicity profile, which can be offered to elderly patients not candidates of ASCT consolidation. The high efficacy of the regimen in this unfavorable population and also in immunocompromised situations warrant further investigation of this regimen in all salvage situations of this type of lymphomas.

Effect of effervescent paracetamol on blood pressure: a crossover randomized clinical trial.

OBJECTIVE: To evaluate the effect of effervescent paracetamol on office and ambulatory blood pressure (BP) compared with noneffervescent paracetamol in hypertensive patients. DESIGN: This was a multicenter open crossover randomized clinical trial. SETTING: Primary care centers in Catalonia and the Basque Country. PARTICIPANTS: Inclusion criteria were office BP 150/95 mmHg or less and daytime ambulatory BP 140/90 mmHg or less, stable pharmacologic or nonpharmacologic antihypertensive treatment, and concomitant chronic osteoarticular pain. INTERVENTIONS: Baseline randomized assignment to 3-week periods of effervescent paracetamol (1 g three times a day) first and noneffervescent paracetamol later, or inversely, during a 7-week study period. At the start and end of each treatment period, 24-h ambulatory BP monitoring was performed. MAIN OUTCOME MEASURES: Differences in 24-h SBP between baseline and end of both treatment periods. The main analyses were performed according to the intention-to-treat principle. RESULTS: In intention-to-treat analysis, 46 patients were analyzed, 21 were treated with paracetamol effervescent and noneffervescent later, and 25 followed the opposite sequence. The difference in 24-h SBP between the two treatments was 3.99 mmHg (95% confidence interval 1.35-6.63; P = 0.004), higher in the effervescent paracetamol treatment period. Similarly, the per-protocol analysis showed a difference in 24-h SBP between the two groups of 5.04 mmHg (95% confidence interval 1.80-8.28; P = 0.004), higher in the effervescent paracetamol treatment period. Self-reported pain levels did not differ between groups and did not vary by treatment period. No serious adverse events were reported in either study arm. CONCLUSION: Effervescent paracetamol tablets are responsible for a significant daytime and overall increase in ambulatory 24-h SBP. TRIAL REGISTRATION: NCT: 02514538 EudraCT: 2010-023485-53.

Long-term hematological reconstitution and clinical evaluation of autologous peripheral blood stem cell transplantation after cryopreservation of cells with 5% and 10% dimethylsulfoxide at -80 degrees C in a mechanical freezer.

We report the long-term evaluation over 12 years of a simplified technique for stem-cell cryopreservation at -80 degrees C without rate-controlled freezing and with 5% (n=251) or 10% (n=47) DMSO as the sole cryoprotectant. Platelet recovery was greater in the 5% DMSO group while long-term hematological recovery did not differ. Factors influencing a faster hematological recovery were infusion of more than 2.7x10(6)/Kg of CD34+ cells, 10% DMSO cryopreservation and G-CSF. We confirm that the procedure is feasible with reduction in infusion-related toxicity from 60% using 5% DMSO. Differences in hematological reconstitution were not clinically significant if a minimum of 1.5x10(6)/Kg CD34+-cells were infused.