Rejected

Hydroxyurea reduces pain crises, acute chest syndrome and blood transfusions in sickle cell disease (SCD), but potential detrimental effects on fertility and birth outcomes impede its use. Data on the effects of hydroxyurea taken for SCD during conception and pregnancy are scarce. The Sickle Cell Disease Implementation Consortium collected self-reported pregnancy history, corresponding hydroxyurea use, and pregnancy outcomes in women with SCD in the clinical setting. Among 1285 women 18-45 years of age, 737 (57.4%) reported 1788 pregnancies (1079 live births, 394 miscarriages, 40 stillbirths, 207 abortions, 48 current pregnancies, and 20 missing outcomes) of which 241 (15.9%) live births, miscarriages or stillbirths were conceived while on hydroxyurea. In univariate analyses, pregnancy number more than three, severe sickle genotype, history of stillbirth or miscarriage, and chronic kidney disease at enrollment were covariates significantly associated with a pregnancy ending in miscarriage or stillbirth. After adjustment for covariates and additional SCD severity markers in multivariate analyses, hydroxyurea use during conception and pregnancy, but not during conception only, was associated with an increase in the odds ratio (OR) of miscarriage or stillbirth (OR 2.21, 95% confidence interval [CI] 1.40-3.47). In analyses of live birth outcomes, hydroxyurea use during conception and pregnancy was associated with birth weight <5.5 pounds in full-term infants (OR 2.98, 95% CI 1.09-7.38) but not with prematurity or serious medical problems at birth. These findings suggest that hydroxyurea use may be safe up to the time of conception, but that clinicians should continue to advise caution regarding use during pregnancy. This article is protected by copyright. All rights reserved.

Low-value pharmaceutical care exists in general practice. However, the extent among Dutch GPs remains unknown.

Randomized clinical trial.

BACKGROUND Spontaneous bacterial peritonitis is a common infection in hospitalized patients with ascites, particularly in patients with cirrhosis. Spontaneous bacterial peritonitis is often associated with acute kidney injury. The causative agents of spontaneous bacterial peritonitis are usually gram-negative bacteria, but lately, the prevalence of spontaneous bacterial peritonitis caused by gram-positive bacteria is rising. CASE REPORT In this report, we present the case of a 77-year-old woman with a history of cardiorenal syndrome with ascites and chronic kidney disease who was admitted with diarrhea, fever, and abdominal pain. Ascitic fluid paracentesis revealed spontaneous bacterial peritonitis due to Listeria monocytogenes. During hospitalization, her ascites gradually enlarged and her kidney function deteriorated. The deterioration of kidney function was at least partially attributed to sepsis caused by spontaneous bacterial peritonitis. In addition to proper antibiotic therapy with ampicillin and daily hemodialysis sessions, large-volume paracentesis and albumin infusions were instituted. After 5 days, she showed a fast improvement, the ascites subsided, and her renal function returned to baseline. CONCLUSIONS Spontaneous bacterial peritonitis caused by Listeria monocytogenes is associated with a poor outcome. Acute kidney injury in patients with spontaneous bacterial peritonitis is common and related with a poor outcome. Data about the role of large-volume paracentesis and albumin replacement in patients with spontaneous bacterial peritonitis are still ambiguous. In the literature, all patients with spontaneous bacterial peritonitis due to Listeria monocytogenes who underwent large-volume paracentesis survived.

This paper proposes the design of combination opioid-adrenergic tethered compounds to enhance efficacy and specificity, lower dosage, increase duration of activity, decrease side effects, and reduce risk of developing tolerance and/or addiction. Combinations of adrenergic and opioid drugs are sometimes used to improve analgesia, decrease opioid doses required to achieve analgesia, and to prolong the duration of analgesia. Recent mechanistic research suggests that these enhanced functions result from an allosteric adrenergic binding site on opioid receptors and, conversely, an allosteric opioid binding site on adrenergic receptors. Dual occupancy of the receptors maintains the receptors in their high affinity, most active states; drops the concentration of ligand required for full activity; and prevents downregulation and internalization of the receptors, thus inhibiting tolerance to the drugs. Activation of both opioid and adrenergic receptors also enhances heterodimerization of the receptors, additionally improving each drug's efficacy. Tethering adrenergic drugs to opioids could produce new drug candidates with highly desirable features. Constraints-such as the locations of the opioid binding sites on adrenergic receptors and adrenergic binding sites on opioid receptors, length of tethers that must govern the design of such novel compounds, and types of tethers-are described and examples of possible structures provided.

The primary aim of the study was to use the duration until the first postoperative analgesic requirement after two different block techniques to compare the analgesic effect. The secondary aims were to compare the two methods for postoperative Children's Hospital Eastern Ontario Pain Scale (CHEOPS) scores, complications, and parental satisfaction level.

This study assessed subjective symptoms associated with exposure to static magnetic fields (SMFs) and radiofrequency (RF) energy, and perceived safety risk of scanners among magnetic resonance (MR) staff working in the 1.5 and 3 T MRI units. A questionnaire survey was completed by 77 clinical imaging staff working in two hospitals (A and B) in the Mangaung metropolitan region. 50 participants working with the MR scanners were regarded as exposed group and 27 participants from CT scan and X-ray departments were classified as control group. The study comprised 57% females and 43% male participants with an average MRI experience of 5.4 years. Using logistic regression, tinnitus was significantly different between various job titles (< .034) and it was reported more often (OR 8:00; CI 1.51, 15.17) by those who worked on a 3 T scanner. Increased years of MRI experience was a significant predictor of headache (< .05), and reporting of nausea was significantly different between various job titles (p < .01). There was an increased risks of reporting vertigo often among female participants (OR: 4.43; CI 0.91, 21.47), those with 5-15 years of MRI experience (OR: 2.09; CI 0.47, 9.34), and those with a light to moderate workload (OR: 2.70; CI 0.49, 14.86). Using linear regression, presence in zone IV during image acquisitioning was the only significant predictor for the sensation of glowing (p < .000). Movement of head/ upper body in the scanner bore was a significant predictor of nausea (< .026), vertigo (< .014), instability when standing (< .014), and a metallic taste (< .031). There was no correlation between reporting of symptoms and perceived risk of scanners. However, shift duration (r = 0.576), movement of head/upper body in the scanner bore (r = 0.424), and strength of the scanners (r = 0.299) were significantly correlated with perceived risk of scanners. MRI safety training and a comprehensive occupational health and safety program are necessary.

Mucosal immunity plays an important role in the control of viral respiratory infections like SARS-CoV-2. While systemic immune responses against the SARS-2-CoV-2 have been studied in children, there is no information on mucosal antibody response, especially in the lower respiratory tract of children coronavirus disease 2019 (COVID-19) and post-infectious multisystem inflammatory syndrome in children (MIS-C) against emerging SARS-CoV-2 variants. Therefore, we evaluated neutralizing antibody responses in paired plasma and endotracheal aspirates of pediatric severe, acute COVID-19 or MIS-C patients against SARS-CoV-2 WA1/2020, as well as against variants of concern (VOCs). Neutralizing antibody responses against the SARS-CoV-2 WA1/2020 strain in pediatric plasma were 2-fold or 35-fold higher compared with the matched endotracheal aspirate in COVID-19 or MIS-C patients, respectively. In contrast to plasma, neutralizing antibody responses against the VOCs and variants of interest (VOIs) in endotracheal aspirates were lower, with only one endotracheal aspirate demonstrating neutralizing titers against the Iota, Kappa, Beta, Gamma, and Omicron variants. In conclusion, our findings suggest that children and adolescents with severe COVID-19 or MIS-C have weak mucosal neutralizing antibodies in the trachea against circulating SARS-CoV-2 Omicron and other VOCs, which may have implications for recovery and for re-infection with emerging SARS-CoV-2 variants.

The aim of this study was to determine the efficacy and safety of intensive versus standard nonsedating antihistamines (NSAs) for chronic spontaneous urticaria (CSU) patients.

Pembrolizumab is approved for patients with metastatic urothelial carcinoma (UC) who progressed under platinum therapy. The aim of this study was to assess the efficacy and safety of pembrolizumab in a cohort of real-life UC patients.