Vitamin D Supply of Multivitamins Commercialized Online by Amazon in Western and Southern Europe: A Labeling Analysis.

Multivitamins are commonly used by the general population, often without medical prescription. The purpose of this report is to inform on the daily vitamin D supply provided by multivitamins containing vitamin D that are commercialized online by Amazon in Western and Southern Europe. We surveyed multivitamins aimed at adults using the following marketplaces: amazon.es®, amazon.de®, amazon.it®, and amazon.fr®. We identified 199 vitamin D3-containing multivitamins sold by Amazon marketplaces: 77 from amazon.es®, 73 from amazon.de®, 33 from amazon.it®, and 16 from amazon.fr®. No multivitamin contained vitamin D2. The daily vitamin D3 supply ranged from 16 to 2000 IU: it was less than 400 IU daily in 108 (54%), 400−800 IU daily in 53 (27%), and more than 800 IU daily in the remaining 38 (19%) products. The vitamin D3 supply of products sold by amazon.it® was on average higher (p < 0.05) than that of products sold by amazon.de®, amazon.fr®, and amazon.es®. In conclusion, the vitamin D supply of multivitamins sold by Amazon may be insufficient, marginally sufficient, or adequate for subjects at high risk of hypovitaminosis D such as subjects 65 years or more of age, pregnant (or lactating) women, or patients on drug treatment or with an underlying disease, where a vitamin D supplementation is advocated.

Kidney tubular injury induced by valproic acid: systematic literature review.

BACKGROUND: Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury. METHODS: We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered. RESULTS: For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-ß-glucosaminidase, was often noted. CONCLUSIONS: Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. A higher resolution version of the Graphical abstract is available as Supplementary information.

Seasonal variability of the vitamin D effect on physical fitness in adolescents.

Studies investigating the relationship between vitamin D and physical fitness in youth have provided inconsistent findings. Recent evidence indicates that the expression of receptors and vitamin D-modulated genes in young subjects has a seasonal profile. Therefore, we investigated the role of vitamin D on physical fitness across seasons in a total of 977 male adolescents. Anthropometrics, lifestyle, dietary habits, biochemical profiles and physical fitness were studied. Multiple linear regression models, including pairwise interaction terms involving total 25-OH-vitamin D, were fitted. The interacting effect of season and total 25-OH-vitamin D had a significant influence on physical fitness performance (spring and total 25-OH-vitamin D: ß 0.19, SE 0.07, p = 0.007; summer and total 25-OH-vitamin D: ß 0.10, SE 0.06, p = 0.11; autumn and total 25-OH-vitamin D: ß 0.18, SE 0.07, p = 0.01), whereas the main effect of total 25-OH-vitamin D alone was not significant (p = 0.30). Body fat percentage, recreational physical activity level, time spent per day gaming/TV-watching, smoking, and hemoglobin levels were also related to the physical fitness performance score. Future studies should further explore the role of seasonal-dependent effects of vitamin D on health.

Trimethoprim-associated electrolyte and acid-base abnormalities.

INTRODUCTION: The antimicrobial trimethoprim is structurally related to potassium-sparing diuretics and may consequently lead to derangements in electrolyte and acid-base balance. Since no report so far analyzed the literature documenting individual cases with electrolyte and acid-base derangements induced by trimethoprim, a systematic review was carried out. EVIDENCE ACQUISITION: We retained 53 reports documenting 68 cases (42 males and 26 females 23 to 96 years of age) of electrolyte or acid-base derangements occurring on trimethoprim for about 5 days. EVIDENCE SYNTHESIS: One hundred five electrolyte imbalances were detected in the 68 patients: hyperkalemia (>5.0 mmol/L) in 62 (91%), hyponatremia (<135 mmol/L) in 29 (43%) and metabolic acidosis (pH<7.38 and bicarbonate <19 mmol/L) in 14 (21%) cases. Following possible predisposing factors for electrolyte and acid-base abnormalities were found in 54 (79%) patients: high-dose trimethoprim, comedication with drugs that have been associated with electrolyte and acid-base derangements, preexisting kidney disease, age ≥80 years and diabetes mellitus. CONCLUSIONS: High-dose trimethoprim, comedicated with drugs that have been associated with electrolyte and acid-base derangements, poor kidney function, age ≥80 years and diabetes mellitus predispose to trimethoprim-associated electrolyte and acid-base abnormalities. Clinicians must recognize patients at risk, possibly avoid drug combinations that may worsen the problem and monitor the laboratory values.

Dietary Chloride Deficiency Syndrome: Pathophysiology, History, and Systematic Literature Review.

Metabolic alkalosis may develop as a consequence of urinary chloride (and sodium) wasting, excessive loss of salt in the sweat, or intestinal chloride wasting, among other causes. There is also a likely underrecognized association between poor salt intake and the mentioned electrolyte and acid-base abnormality. In patients with excessive loss of salt in the sweat or poor salt intake, the maintenance of metabolic alkalosis is crucially modulated by the chloride-bicarbonate exchanger pendrin located on the renal tubular membrane of type B intercalated cells. In the late 1970s, recommendations were made to decrease the salt content of foods as part of an effort to minimize the tendency towards systemic hypertension. Hence, the baby food industry decided to remove added salt from formula milk. Some weeks later, approximately 200 infants (fed exclusively with formula milks with a chloride content of only 2-4 mmol/L), were admitted with failure to thrive, constipation, food refusal, muscular weakness, and delayed psychomotor development. The laboratory work-up disclosed metabolic alkalosis, hypokalemia, hypochloremia, and a reduced urinary chloride excretion. In all cases, both the clinical and the laboratory features remitted in ≤7 days when the infants were fed on formula milk with a normal chloride content. Since 1982, 13 further publications reported additional cases of dietary chloride depletion. It is therefore concluded that the dietary intake of chloride, which was previously considered a "mendicant" ion, plays a crucial role in acid-base and salt balance.

Maintenance Fluid Therapy with Saline, Dextrose-Supplemented Saline or Lactated Ringer in Childhood: Short-Term Metabolic Effects.

Maintenance with isotonic fluids is recommended in children with gastroenteritis and failure of oral rehydration therapy. However, little is known on the short-term effects of the commonly prescribed intravenous solutions on metabolic balance in children. The aim of this study is to report on our experience with normal saline, dextrose-supplemented saline and lactated Ringer solution. METHODS: A retrospective analysis from the charts of all previously apparently healthy children with acute gastroenteritis, mild to moderate dehydration and failure of oral rehydration, evaluated between January 2016 and December 2019 at our institution, was performed. Subjects prescribed the above-mentioned maintenance intravenous fluids and with blood testing immediately before starting fluid therapy and 4-6 h later, were eligible. The changes in bicarbonate, ionized sodium, potassium, chloride, anion gap and glucose were investigated. Kruskal-Wallis test with the post-hoc Dunn's comparison and the Fisher exact test were applied. RESULTS: A total of 134 out of 732 children affected by acute gastroenteritis were included (56 patients were prescribed normal saline, 48 dextrose-supplemented normal saline and 30 lactated Ringer solution). The effect of the three solutions on sodium and potassium was similar. As compared to non-supplemented normal saline (+0.4 (-1.9 - +2.2) mmol/L), dextrose-supplemented normal saline (+1.5 (+0.1 - +4.2) mmol/L) and lactated Ringer (+2.6 (+0.4 - +4.1) mmol/L) solution had a positive effect on plasma bicarbonate. Finally, the influence of dextrose-supplemented saline on blood glucose was different (+1.1 (+0.3 - +2.2) mmol/L) compared to that observed in cases hydrated with non-supplemented saline (-0.4 (-1.2 - +0.3) mmol/L) or lactated Ringer solution (-0.4 (-1.2 - +0.1) mmol/L). CONCLUSIONS: This study points out that maintenance intravenous therapies using normal saline, dextrose-supplemented saline or lactated Ringer solution have different effects on metabolic balance. A personalized fluid therapy that takes into account the clinical and biochemical variables is advised.

Vitamin D Status Among Male Late Adolescents Living in Southern Switzerland: Role of Body Composition and Lifestyle.

BACKGROUND: Poor vitamin D status is a worldwide health problem. Yet, knowledge about vitamin D status among adolescents in Southern Europe is limited. This study investigated concentrations and modulating factors of vitamin D in a healthy population of male late adolescents living in Southern Switzerland. METHODS: All apparently healthy subjects attending for the medical evaluation before the compulsory military service in Southern Switzerland during 2014-2016 were eligible. Dark-skin subjects, subjects on vitamin D supplementation or managed with diseases or drugs involved in vitamin D metabolism were excluded. Anthropometric measurements (body height, weight, fat percentage, mid-upper arm and waist circumference) and blood sampling for total 25-hydroxy-vitamin D, total cholesterol and ferritin concentrations testing, were collected. Participants filled in a structured questionnaire addressing their lifestyle. Characteristics of the subjects with adequate (≥50 nmol/L-≤250 nmol/L) and insufficient (<50 nmol/L) vitamin D values were compared by Kruskal-Wallis test or χ2 test. Odds ratios for 25-hydroxy-vitamin D insufficiency were calculated by univariate and AIC-selected multiple logistic regression models. RESULTS: A total of 1045 subjects volunteered to participate in the study. Insufficient concentrations of vitamin D were detected in 184 (17%). The season of measurement was the most significant factor associated with vitamin D levels and approximately 40% of subjects presented insufficient vitamin D concentrations in winter. After model selection, body fat percentage, frequency and site of recreational physical activity, and the seasonality were significantly associated with the risk of vitamin D insufficiency. CONCLUSIONS: Among healthy male late adolescents in Southern Switzerland, about one every fourth subject presents a poor vitamin D status in non-summer seasons. Body fat percentage, frequent and outdoor recreational physical activity are modulating factors of vitamin D status in this population.

Magnesium in cystic fibrosis--Systematic review of the literature.

BACKGROUND: The metabolism of sodium, potassium, and chloride and the acid-base balance are sometimes altered in cystic fibrosis. Textbooks and reviews only marginally address the homeostasis of magnesium in cystic fibrosis. METHODS: We performed a search of the Medical Subject Headings terms (cystic fibrosis OR mucoviscidosis) AND (magnesium OR hypomagnes[a]emia) in the US National Library of Medicine and Excerpta Medica databases. RESULTS: We identified 25 reports dealing with magnesium and cystic fibrosis. The results of the review may be summarized as follows. First, hypomagnesemia affects more than half of the cystic fibrosis patients with advanced disease; second, magnesemia, which is normally age-independent, relevantly decreases with age in cystic fibrosis; third, aminoglycoside antimicrobials frequently induce both acute and chronic renal magnesium-wasting; fourth, sweat magnesium concentration was normal in cystic fibrosis patients; fifth, limited data suggest the existence of an impaired intestinal magnesium balance. Finally, stimulating observations suggest that magnesium supplements might achieve an improvement in respiratory muscle strength and mucolytic activity of both recombinant and endogenous deoxyribonuclease. CONCLUSIONS: The first comprehensive review of the literature confirms that, despite being one of the most prevalent minerals in the body, the importance of magnesium in cystic fibrosis is largely overlooked. In these patients, hypomagnesemia should be sought once a year. Furthermore, the potential of supplementation with this cation deserves more attention.

Symptomatic management of fever by Swiss board-certified pediatricians: results from a cross-sectional, Web-based survey.

BACKGROUND: Symptomatic management is often all that is recommended in children with fever. To date, only 2 nationwide surveys of pediatricians regarding their attitudes toward fever have been published. OBJECTIVE: The aim of this study was to describe the management of children with fever by pediatricians in Switzerland. METHODS: For this survey, an initial close-ended questionnaire was tested and subsequently corrected. Between June 2010 and March 2011, an invitation was sent via electronic mail containing a link to the final version of the questionnaire. The survey was not commercially sponsored. RESULTS: The questionnaire was sent to 900 pediatricians, of whom 322 (36%) responded. A total of 96% of respondents identified ≥38.5°C as the rectal temperature threshold for fever treatment, and 64% indicated that they prescribe antipyretics for the treatment of general discomfort. A total of 95% of respondents indicated that they prescribe paracetamol (acetaminophen) as the first choice of antipyretic drug, and 91% indicated that they often prescribe ibuprofen as well. An alternating regimen of 2 drugs and physical antipyresis were indicated as common practice by 77% and 65% of pediatricians, respectively. Homeopathic remedies are rarely prescribed (<10% of respondents). The most commonly prescribed routes of administration in children aged 18 months, 5 years, and 10 years were rectal (78%), oral (87%), and oral (99%), respectively. Ninety-two percent of respondents indicated that they believe that an exaggerated fear of fever is common among parents, but 81% stated that they do not lower the temperature threshold for initiating pharmacologic treatment exclusively to calm parents. Most respondents (95%) indicated a belief that it is possible to educate families about the fear of fever. CONCLUSIONS: Based on the findings from the present survey, antipyretics are often prescribed to treat the general discomfort that accompanies fever. Nonetheless, a gap exists between available evidence and clinical practice. Guidelines should take this fact into account.

Preference for formulations containing calcium and vitamin D(3) in childhood: a randomized-sequence, open-label trial.

BACKGROUND: Children who experience adverse reactions to cow's milk or who have diseases predisposing them to low bone mass are often prescribed a supplementation of calcium and vitamin D(3), but adherence can be poor. Age-specific preferences for different formulations may exist and at least partially explain poor compliance. OBJECTIVE: The aim of this study was to compare the preference of Swiss children at risk for low bone mass for either a single-serving sachet or a suspension containing calcium and vitamin D(3). METHODS: Two different commercial formulations containing calcium and vitamin D(3), either as a lemon-flavored single-serving sachet or as a banana-flavored commercial suspension, were tested for preference by means of a 5-point facial hedonic scale in children aged 4 to 7 and 8 to 11 years. A concealed random allocation procedure was used. The investigator asking about preference was blinded to the sequence. RESULTS: A total of 40 Swiss children (13 boys and 7 girls aged 4-7 years; 11 boys and 9 girls aged 811 years) were assessed in this study. Low bone mass risks included adverse reactions to cow's milk (n = 25); cerebral palsy (4), juvenile idiopathic arthritis (4), cystic fibrosis (3), inflammatory bowel diseases (2), anorexia nervosa (1), and osteogenesis imperfecta (1). Two children (10%) aged 4 to 7 years were not able to express their preference. Twelve of the remaining 18 children (67%) aged 4 to 7 years preferred the suspension, 5 (28%) did not express a clear preference, and 1 (5%) preferred the sachet (P < 0.002). In children aged 8 to 11 years, 15 (75%) preferred the sachet, 4 (20%) did not express a clear preference, and 1 (5%) preferred the suspension (P < 0.001). The results were not significantly different between boys and girls or between children initially presented the suspension and those initially presented the sachet. CONCLUSIONS: In this small study, significantly more Swiss children aged 4 to 7 years who were prescribed a supplementation of calcium and vitamin D(3) preferred a banana-flavored suspension compared with those who preferred a lemon-flavored single-serving sachet. However, significantly more children aged 8 to 11 years prescribed the same supplementation preferred the single-serving sachet compared with the suspension.

Long-term follow-up of patients with Bartter syndrome type I and II.

BACKGROUND: Little information is available on a long-term follow-up in Bartter syndrome type I and II. METHODS: Clinical presentation, treatment and long-term follow-up (5.0-21, median 11 years) were evaluated in 15 Italian patients with homozygous (n = 7) or compound heterozygous (n = 8) mutations in the SLC12A1 (n = 10) or KCNJ1 (n = 5) genes. RESULTS: Thirteen new mutations were identified. The 15 children were born pre-term with a normal for gestational age body weight. Medical treatment at the last follow-up control included supplementation with potassium in 13, non-steroidal anti-inflammatory agents in 12 and gastroprotective drugs in five patients. At last follow-up, body weight and height were within normal ranges in the patients. Glomerular filtration rate was <90 mL/min/1.73 m(2) in four patients (one of them with a pathologically increased urinary protein excretion). In three patients, abdominal ultrasound detected gallstones. The group of patients with antenatal Bartter syndrome had a lower renin ratio (P < 0.05) and a higher standard deviation score (SDS) for height (P < 0.05) than a previously studied group of patients with classical Bartter syndrome. CONCLUSIONS: Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10 years. Gallstones might represent a new complication of antenatal Bartter syndrome.

Patients with biallelic mutations in the chloride channel gene CLCNKB: long-term management and outcome.

BACKGROUND: Little information on the management and long-term follow-up of patients with biallelic mutations in the chloride channel gene CLCNKB is available. METHODS: Long-term follow-up was evaluated from 5.0 to 24 years (median, 14 years) after diagnosis in 13 patients with homozygous (n = 10) or compound heterozygous (n = 3) mutations. RESULTS: Medical treatment at last follow-up control included supplementation with potassium in 12 patients and sodium in 2 patients and medical treatment with indomethacin in 9 patients. At the end of follow-up, body height was 2.0 standard deviation score or less in 6 patients; 2 of these patients had growth hormone deficiency. Body weight (