The sport movement must protect children and young athletes from all forms of abuse. However, research points to a disconnect between policy and implementation of policy against sexual abuse. No ...studies have investigated measures against sexual abuse in Swedish sport. The purpose of this study was to explore measures against sexual abuse in the 10 largest sports federations (SFs) for child and youth sport in Sweden. The study draws on interviews with representatives (
= 18) of the SFs and on a review of SFs' website content regarding sexual abuse and safe sport. Results show that the SFs have taken few or no measures against sexual abuse. Measures for safe sports vary in existence, development, and organization between the SFs, and many SFs are in the early stages of safe sport measures and practice. Although the SF representatives emphasize that sexual abuse is unacceptable, a conflict between making it visible or invisible emerges and creates a gap between policy and practice. Reproducing a culture of silence around sexual abuse in sports seems advantageously for SFs. Social and organizational factors that can debilitate safe sport measures and facilitate sexual abuse in sport are discussed.
Adenovirus type 37 (Ad37) is a leading cause of epidemic keratoconjunctivitis (EKC), a severe and highly contagious ocular disease. Whereas most other adenoviruses infect cells by engaging CD46 or ...the coxsackie and adenovirus receptor (CAR), Ad37 binds previously unknown sialic acid-containing cell surface molecules. By glycan array screening, we show here that the receptor-recognizing knob domain of the Ad37 fiber protein specifically binds a branched hexasaccharide that is present in the GD1a ganglioside and that features two terminal sialic acids. Soluble GD1a glycan and GD1a-binding antibodies efficiently prevented Ad37 virions from binding and infecting corneal cells. Unexpectedly, the receptor is constituted by one or more glycoproteins containing the GD1a glycan motif rather than the ganglioside itself, as shown by binding, infection and flow cytometry experiments. Molecular modeling, nuclear magnetic resonance and X-ray crystallography reveal that the two terminal sialic acids dock into two of three previously established sialic acid-binding sites in the trimeric Ad37 knob. Surface plasmon resonance analysis shows that the knob-GD1a glycan interaction has high affinity. Our findings therefore form a basis for the design and development of sialic acid-containing antiviral drugs for topical treatment of EKC.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To describe operating room nurses' experiences of well leg compartment syndrome and how they work perioperative to prevent it during the lithotomy position.
The study had a qualitative design.
Focus ...group interviews were performed with 10 operating room (OR) nurses. The interviews were semi-structured and analysed by qualitative content analysis. The study complied with the Consolidated Criteria for Reporting Qualitative Research (COREQ).
The main theme showed that the OR nurses shoulder duty and responsibility, independently and in the team, but they need more structural support and knowledge. The themes showed that they follow routines whenever possible and take responsibility for positioning; however, they have to balance between flexibility and strict routines. Although they also develop and participate in teamwork, they still need further knowledge.
The severe complication of well leg compartment syndrome (WLCS) can occur when the patient is in the lithotomy position. Maintaining the same routines and paying attention to the WHO's surgical safety checklist were described as actions that could prevent well leg compartment syndrome.
No patient or public contribution. We have interviewed nurses but without financial support since the study was performed and supervised within a master programme.
Hyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. ...Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption. This randomized, double-blind, placebo-controlled trial assessed the effects of tenapanor on serum phosphate concentration in patients with hyperphosphatemia receiving hemodialysis. After a 1- to 3-week washout of phosphate binders, we randomly assigned 162 eligible patients (serum phosphate =6.0 to <10.0 mg/dl and a 1.5-mg/dl increase from before washout) to one of six tenapanor regimens (3 or 30 mg once daily or 1, 3, 10, or 30 mg twice daily) or placebo for 4 weeks. The primary efficacy end point was change in serum phosphate concentration from baseline (randomization) to end of treatment. In total, 115 patients (71%) completed the study. Mean serum phosphate concentrations at baseline (after washout) were 7.32-7.92 mg/dl for tenapanor groups and 7.87 mg/dl for the placebo group. Tenapanor provided dose-dependent reductions in serum phosphate level from baseline (least squares mean change: tenapanor =0.47-1.98 mg/dl; placebo =0.54 mg/dl;
=0.01). Diarrhea was the most common adverse event (tenapanor =18%-68%; placebo =12%) and frequent at the highest tenapanor doses. In conclusion, tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis. Additional studies are required to clarify the optimal dosing of tenapanor in patients with CKD-related hyperphosphatemia.
Background
Tenapanor (RDX5791, AZD1722), a small molecule with minimal systemic availability, is an inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3). Tenapanor acts locally in the gut to ...reduce absorption of sodium and phosphate. It is being developed for the treatment of patients with hyperphosphatemia in CKD requiring dialysis and patients with constipation-predominant irritable bowel syndrome. We report the safety, pharmacodynamics, and pharmacokinetics of tenapanor in Japanese volunteers.
Methods
In this phase 1, double-blind study (NCT02176252), healthy Japanese adults (aged 20–45 years) received single-dose tenapanor 180 mg (
n
= 6), repeated-dose tenapanor 15, 30, 60, or 90 mg twice daily (
n
= 12 each) for 7 days, or placebo (
n
= 14). All participants received a standardized diet.
Results
Single and repeated doses of tenapanor resulted in higher mean stool sodium content vs. placebo (single dose, 41.9 mmol/day; repeated dose, range of means 21.3–32.2 mmol/day; placebo, 4.1 mmol/day) accompanied by lower urinary sodium content (single dose, 110 mmol/day; repeated dose, 101–112 mmol/day; placebo, 143 mmol/day). Additionally, stool phosphorus content was increased (single dose, 31.0 mmol/day; repeated dose, 17.6–24.8 mmol/day; placebo, 16.8 mmol/day) and urinary phosphorus content decreased (single dose, 18.7 mmol/day; repeated dose, 15.3–19.4 mmol/day; placebo, 25.5 mmol/day). Tenapanor had minimal systemic exposure, provided a softer stool consistency, and was well tolerated.
Conclusions
Tenapanor treatment reduced absorption of intestinal sodium and phosphate from the gut in Japanese adults. Tenapanor had minimal systemic exposure and was well tolerated. Further research into the clinical benefits of tenapanor is warranted.
The Parechovirus genus of the Picornaviridae family contains two species, Human parechovirus (HPeV) and Ljungan virus (LV). The HPeVs (including the former echoviruses 22 and 23, now HPeV type 1 ...(HPeV1) and HPeV2, respectively) cause a wide spectrum of disease, including aseptic meningitis, gastroenteritis, encephalitis, acute respiratory illness, and neonatal sepsis-like disease. The LVs were isolated from bank voles in Sweden during a search for an infectious agent linked to fatal myocarditis cases in humans. Because of the decline in use of cell culture and neutralization to investigate enterovirus-like disease, very few laboratories currently have the capability to test for parechoviruses. We have developed a real-time reverse transcription-PCR (RT-PCR) assay for detection of all known members of the genus PARECHOVIRUS: The assay targets the conserved regions in the 5' nontranslated region (5'NTR) of the parechovirus genome and can detect both HPeVs and LVs, unlike other published parechovirus 5' NTR assays, which only detect known HPeVs or only LVs. HPeV and LV can be differentiated by sequencing the 5'NTR real-time RT-PCR amplicon, when needed. The assay is approximately 100 times more sensitive than cell culture and may be used to test original clinical specimens. The availability of a broad-specificity PCR method should facilitate the detection of new human parechoviruses, as well as new parechoviruses in other mammalian species, and provide an opportunity to investigate the role of these viruses in human and animal disease.
Vandetanib is a selective inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) signalling, indicated for ...the treatment of medullary thyroid cancer. We investigated potential drug-drug interactions between vandetanib and metformin organic cation transporter 2 (OCT2) substrate; NCT01551615; digoxin P-glycoprotein (P-gp) substrate; NCT01561781; midazolam cytochrome P450 (CYP) 3A4 substrate; NCT01544140; omeprazole (proton pump inhibitor) or ranitidine (histamine H2-receptor antagonist; both NCT01539655).
Four open-label, phase I studies were conducted in healthy volunteers: n = 14 (metformin), n = 14 (digoxin), n = 17 (midazolam), n = 16 (omeprazole), n = 18 (ranitidine). Three of these comprised the following regimens: metformin 1000 mg ± vandetanib 800 mg, midazolam 7.5 mg ± vandetanib 800 mg, or digoxin 0.25 mg ± vandetanib 300 mg. The randomized study comprised vandetanib 300 mg alone and then either (i) omeprazole 40 mg (days 1-4), and omeprazole + vandetanib (day 5); or (ii) ranitidine 150 mg (day 1), and ranitidine + vandetanib (day 2). The primary objective assessed metformin, digoxin, midazolam and vandetanib pharmacokinetics.
Vandetanib + metformin increased metformin area under the plasma concentration-time curve from zero to infinity (AUC0-∞) and maximum observed plasma concentration (Cmax) by 74 and 50 %, respectively, and decreased the geometric mean metformin renal clearance (CLR) by 52 % versus metformin alone. Vandetanib + digoxin increased digoxin area under the concentration-time curve from zero to the last quantifiable concentration (AUC0-last) and Cmax by 23 and 29 %, respectively, versus digoxin alone, with only a 9 % decrease in CLR. Vandetanib had no effect on midazolam exposure. Vandetanib exposure was unchanged during co-administration with omeprazole/ranitidine. Treatment combinations were generally well tolerated.
Patients receiving vandetanib with metformin/digoxin may require additional monitoring of metformin/digoxin, with dose adjustments where necessary. Vandetanib with CYP3A4 substrates or omeprazole/ranitidine is unlikely to result in clinically relevant drug-drug interactions.
Interdialytic weight gain in patients on hemodialysis is associated with adverse cardiovascular outcomes and increased mortality. The degree of interdialytic weight gain is influenced by sodium ...intake. We evaluated the effects of tenapanor (AZD1722 and RDX5791), a minimally systemically available inhibitor of the sodium/hydrogen exchanger isoform 3, on interdialytic weight gain in patients with CKD stage 5D treated with hemodialysis.
This phase 2, randomized, double-blind study (NCT01764854; conducted January to September of 2013) enrolled adults on maintenance hemodialysis with interdialytic weight gain ≥3.0% of postdialysis weight and ≥2 kg. Patients were randomly assigned (1:1) to receive tenapanor or placebo. The primary end point was change in mean interdialytic weight gain (percentage of baseline postdialysis weight) from baseline (mean across a 2-week run-in period) to week 4. In a subgroup of inpatients, 24-hour stool sodium and stool weight were assessed for 1 week.
Sixteen patients received 1 week of inpatient treatment (tenapanor, eight; placebo, eight), and 72 patients received 4 weeks of treatment in an outpatient setting (tenapanor, 37; placebo, 35; completers: tenapanor, 31; placebo, 33). In the outpatient cohort, no significant effect on interdialytic weight gain was detected; least squares mean changes in relative interdialytic weight gain from baseline to week 4 were tenapanor, -0.26% (95% confidence interval, -0.57% to 0.06%) and placebo, -0.23% (95% confidence interval, -0.54% to 0.07%; P=0.46). During week 1 (inpatient cohort only), compared with placebo, tenapanor treatment resulted in higher stool sodium content (mean ±SD: tenapanor, 36.6 ±21.8 mmol/d; placebo, 2.8 ±2.7 mmol/d; P<0.001) and higher stool weight (tenapanor, 172.5 ±68.1 g/d; placebo, 86.3 ±30.0 g/d; P<0.01). A similar safety profile was observed across treatment groups with the exception of diarrhea, which occurred more frequently with tenapanor treatment.
Tenapanor treatment increased stool sodium and weight over placebo in patients undergoing hemodialysis. However, over 4 weeks of treatment, there was no difference in interdialytic weight gain between patients treated with tenapanor and those receiving placebo.
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