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BP medication timing: Bedtime or daytime, the effect is the sameFor adults with hypertension being treated in the primar...
27/06/2025

BP medication timing: Bedtime or daytime, the effect is the same

For adults with hypertension being treated in the primary care setting, taking their blood pressure (BP)-lowering medications at bedtime is safe but confers no additional cardiovascular protection as opposed to taking them in the morning, according to the results of the BedMed trial.

Bedtime administration of BP-lowering meds did not result in reduced incidence of the composite primary outcome of all-cause death or hospitalization/emergency department (ED) visit for stroke, acute coronary syndrome, or heart failure over a median follow-up of 4.6 years when compared with morning administration (2.3 vs 2.4 per 100 patient-years, respectively; adjusted hazard ratio, 0.96, 95 percent confidence interval [CI], 0.77–1.19; p=0.70). [JAMA 2025;doi:10.1001/jama.2025.4390]

The same was true for all individual components of the primary outcome and for all predefined subgroups, including s*x, age, frailty status, polypharmacy, comorbidities, and antihypertensive medication class, among others.

Likewise, results for the safety outcomes did not differ between the bedtime and morning dosing groups. These included the incidence of nonvertebral and hip fractures, falls, new glaucoma diagnosis, and cognitive decline at 18 months, among others.

BP levels are not different

Twenty-four-hour ambulatory blood pressure monitoring data collected over a median of 9.6 months into the trial showed no significant differences in mean daytime systolic BP (133.8 vs 136.2 mm Hg; p=0.15) and mean daytime diastolic BP (75.2 vs 75.6 mm Hg; p=0.72) between the bedtime and morning dosing groups.

Meanwhile, overnight mean systolic BP was significantly lower with bedtime vs morning dosing (116.5 vs 123.9 mm Hg; difference, −7.4 mm Hg, 95 percent CI, −11.2 to −3.7; p

--Metabolites, metabolomics pathways linked to high-sodium diet.A US study has found metabolites and metabolomics pathwa...
08/08/2024

--Metabolites, metabolomics pathways linked to high-sodium diet.
A US study has found metabolites and metabolomics pathways that are connected to a high-sodium diet, which include metabolites associated with biotin, propanoate, lysine, and branched-chain amino acids (BCAA) pathways.

“The metabolomics signature for a higher sodium low-potassium diet is associated with multiple components of elevated cardio metabolic risk,” the authors said.

This study explored the association of habitual sodium and potassium intakes, measured by two to four 24-h urine samples with plasma metabolites (quantified using liquid chromatography-tandem mass spectrometry) and metabolomic pathways in a total of 1,028 healthy older adults from the Women’s and Men’s Lifestyle Validation Studies.

The primary exposures included energy-adjusted 24-h urinary sodium excretion, potassium excretion, and sodium-to-potassium ratio, calculated based on energy expenditure derived from the doubly labelled water method. The authors examined the partial association of the metabolomics scores, obtained from elastic net regressions, with cardio metabolic biomarkers.

Higher sodium excretion correlated with 38 metabolites, such as higher piperine, phosphatidylethanolamine, and C5:1 carnitine among others. On the other hand, pathway analysis revealed the association of higher sodium excretion with enhanced biotin and propanoate metabolism, as well as enhanced degradation of lysine and BCAAs.

Notably, quinic acid and proline-betaine were some of the metabolites related to higher potassium and lower sodium-to-potassium ratio.

After adjusting for confounders, the metabolomics score for sodium-to-potassium ratio showed a positive association with fasting insulin (Spearman’s rank correlation coefficient ρ=0.27), C-peptide (ρ=0.30), and triglyceride (ρ=0.46) and a negative association with adiponectin (ρ=‒0.40) and high-density lipoprotein cholesterol (ρ=‒0.42).

“High-sodium and low-potassium intakes are associated with a higher risk of hypertension and cardiovascular disease,” the authors said.

Am J Clin Nutr 2024;120:153-161.



Limited ambulation, poor nutrition predict fractures in children with neurologic conditionStephen PadillaFragility fract...
11/09/2023

Limited ambulation, poor nutrition predict fractures in children with neurologic condition
Stephen Padilla

Fragility fractures occur in a few children with long-term neurologic condition (LTNC)

and are associated with limited ambulation, feeding difficulties, and poor

nutritional status, according to a

Singapore study.

Recommendations have been made to

improve bone health in children with LTNC,

which include promoting weight-bearing

activities, looking out for underweight

children, avoiding vitamin D deficiency,

and ensuring adequate calcium intake.

"In addition to preventive measures and

mitigating risk factors, using dual X-ray

absorptiometry (DEXA) scan for assessment of bone mass in high-risk patients and treatment with bisphosphonates are the ways forward to optimize bone health in children with LTNC," the researchers said. [Singap Med J

2023;64:550-556]

A retrospective review was conducted in

patients with LTNC on follow-up in a

paediatric neurology clinic and those who

presented with fracture to a paediatric orthopaedic clinic to search for fragility fractures. The researchers then gathered data on patients' demographics, medical history, intervention, biochemical bone

markers, and fracture history.

Fragility rate

In total, 136 patients with LTNC were

included, of whom 65 percent were

dependent on mobility (Gross Motor Function Classification System [GMFCS] V), 60 percent were underweight, and 60 percent were fed via gastrostomy or nasogastric tube, or were on oral pureed diet. In addition, 60 percent of children

were treated with anticonvulsants.

The local prevalence of fragility fractures

was 3 percent. Such fractures were

associated with low-impact activities such

as transfer and dressing. Of the patients,

7.4 percent had undergone measurements

of vitamin D levels and 33 percent of

calcium levels.

The finding on fracture rate is similar to

the 4 percent found in systematic review of

five studies on children with cerebral palsy

and 3.6 percent in schools for physically

disabled children, including those with

cerebral palsy, traumatic brain injury, encephalitis, myopathy, and chromosomal

anomalies, in Japan. [Dev Med Child Neurol

2009;51:773-778; Environ Health Prev Med

2010;15:135-140]

"In our study, the risk factors for

poor bone health included high GMFCS

level, lack of regular weight-bearing

exercises, being underweight, feeding

difficulty, and use of anticonvulsant and

steroid," the researchers said. "The study

also showed that only a minority of children had regular calcium and vitamin D monitoring and supplementation."

Recommendations

Given the prevalent problem of poor bone

health and the lack of guidelines on bone

health monitoring in children with LTNC, the following recommendations were made by the researchers: promote weight- bearing activities, avoid vitamin D deficiency, and ensure adequate calcium intake.

However, excessive dietary calcium intake

could exacerbate constipation and

increase the risk of urolithiasis in

nonambulant children with LTNC. [J Spinal

Cord Med 2012;35:9-21]

"Therefore, we suggest that calcium replacement should be considered only if there is poor dietary intake of calcium," the researchers said. "We also

recommend bone health monitoring and

management for children who are

assumed to have osteoporosis if they have

any history of fragility fracture or bone

pain. [J Clin Densitom 2014;17:281-294]

Acute sinusitis in kids: Bacterial testing may curb antibiotic useJairia Dela Cruz Acute sinusitis in kids: Bacterial te...
08/09/2023

Acute sinusitis in kids: Bacterial testing may curb antibiotic use
Jairia Dela Cruz

Acute sinusitis in kids: Bacterial testing may curb antibiotic use
Antibiotics do little in the absence of bacterial pathogens in the nasopharynx of children with acute sinusitis, according to a study, suggesting that testing for specific bacteria on presentation may help prevent unnecessary antibiotic use.

In a cohort of 510 children (2 to 11 years of age) with acute sinusitis who were randomly assigned to receive treatment with amoxicillin (90 mg/kg/d) plus clavulanate (6.4 mg/kg/d; n=254) or placebo alone (n=256) for 10 days, antibiotic treatment did not reduce the symptom burden for those without S pneumoniae, H influenzae, or M catarrhalis in their nasopharynx at the index diagnosis, reported lead study author Dr Nader Shaikh of University of Pittsburgh School of Medicine, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, US.

Amoxicillin plus clavulanate was only slightly better than placebo at reducing the symptoms of sinusitis in children who tested negative for the pathogens. The difference in the Pediatric Rhinosinusitis Symptom Scale (PRSS) scores between the two treatment arms was only –0.88 points (95 percent confidence interval [CI], −1.63 to −0.12). [JAMA 2023;330:349-358]

In contrast, antibiotics were associated with a better symptom resolution than placebo for children who tested positive for the pathogens, with the between-group difference in PRSS scores being –1.95 points (95 percent CI, −2.40 to −1.51).

“This finding is biologically plausible because pathogens that cause sinusitis originate in the nasopharynx,” Shaikh pointed out. “If no pathogens are present in the nasopharynx, the probability of bacterial sinusitis is very low. Placebo-controlled studies in adults have reported similar findings.” [Pediatr Infect Dis J 2013;32:805-809; Pediatr Infect Dis J 2006;25:1032-1036; Eur J Clin Microbiol Infect Dis 2001;20:445-451; Lancet 1996;347:1507-1510]

Nasal discharge colour matters little

According to Shaikh, many parents and doctors believe that the colour of nasal discharge may serve as an indicator of infection, such that having yellow or green mucous means that a child has a bacterial infection.

In fact, European and Canadian sinusitis guidelines recommend the use of purulent nasal discharge to select which children for antimicrobial treatment. Furthermore, a 2007 survey in the US showed that 86 percent of paediatricians considered the presence of coloured nasal discharge as “very important” or “moderately important” in their decision to diagnose acute sinusitis. [Otolaryngol Head Neck Surg 2011;40:S99-S193; Rhinology 2020;58:1-464; Pediatrics 2009;123:e193-e198]

However, the present data showed that antibiotics were not more beneficial to children with green or yellow nasal discharge relative to those with clear-coloured nasal discharge. The differences in PRSS score between antibiotics and placebo were –1.62 points (95 percent CI, −2.09 to −1.16) in the subgroup of kids with coloured nasal discharge and –1.70 points (95 percent CI, −2.38 to −1.03) in the subgroup of those with clear-coloured nasal discharge.

What it boils down to is that the colour of mucous is not relevant for bacterial infection and, therefore, should not influence therapeutic decisions, Shaikh stressed.

“If kids with green or yellow discharge benefitted more from antibiotics than those with clear-coloured discharge, we would know that colour is relevant for bacterial infection,” he said. “But we found no difference, which means that colour should not be used to guide medical decisions.”

A new way to manage acute sinusitis

In current practice, many clinicians prescribe immediate antibiotics for acute sinusitis in children, despite the American Academy of Pediatrics guideline recommendation that clinicians consider observation as a treatment option. Shaikh found this practice of blanket antibiotic prescription problematic. [Pediatrics 2013;132:e262-e280; JAMA Netw Open 2022;5:e2214153; Pediatrics 2023;151:151]

“Five million kids in the US get prescribed antibiotics for sinusitis each year. Our study suggests that only half of these kids see an improvement in symptoms with antibiotic use, so by identifying who they are, we could greatly reduce unnecessary antibiotic use,” he said.

In the study cohort, if antibiotic use was limited to kids with bacteria in their nasopharyngeal secretions at the time of diagnosis, antibiotic use would drop by 28 percent. Interestingly, previous studies have shown that while M catarrhalis is a frequent colonizer of the nasopharynx, it infrequently causes infection. Indeed, the exploratory analysis confirmed that most of the treatment benefit observed with antibiotics was due to the presence of H influenzae and S pneumoniae. [Eur J Clin Microbiol Infect Dis 2022;41:37-44; J Infect 2017;75:26-34; PLoS One 2016;11:e0150949]

Thus, if only H influenzae and S pneumoniae were considered as pathogens and antibiotics were given only to kids whose nasal swab specimen tested positive for such pathogens, antibiotic use would decrease by 53 percent. These findings remained consistent regardless of whether pathogens were identified by culture or by molecular testing.

Shaikh and colleagues are positive that the testing of children with suspected sinusitis for bacterial pathogens would represent a paradigm shift.

“Sinusitis is one of the most common diseases we see in children, but it’s difficult to diagnose because it’s based on the duration of symptoms: If the child has a runny nose or congestion for more than 10 days, we suspect sinusitis,” Shaikh said. “For an ear infection, we can look inside the ear; for pneumonia, we listen to the lungs. But for sinusitis, we have nothing to go on from a physical exam. That was very unsatisfying to me.”

Jumping through hoops

Then again, there are barriers that stand in the way of a potential paradigm shift in the management of acute sinusitis in children, Shaikh acknowledged.

For the most part, obtaining results of bacterial testing can take time, he noted. For bacterial culture testing, the results are usually ready in 2 to 3 days. However, a reasonably accurate rapid antigen test for S pneumoniae (90 percent sensitivity, 95 percent specificity) is commercially available and can be performed at the point of care. Similar bedside tests for H influenzae and M catarrhalis could be developed. Alternatively, testing for pathogens could be completed in a matter of hours using commercially available multiplex polymerase chain reaction tests. [J Clin Microbiol 2002;40:4748-4749; Eur J Clin Microbiol Infect Dis 2012;31:703-706]

Bacterial testing also requires nasopharyngeal swab collection, which might be viewed as invasive by some families. According to Shaikh, this method of specimen collection represents another potential barrier to bacterial testing. But the COVID-19 pandemic has resulted in routine collection of nasopharyngeal swab samples, so such concerns may be lower than before the pandemic.

Finally, the cost of care would increase due to the need for bacterial testing, and this can make it difficult for some families to afford the care that their children need.

Watchful waiting without antibiotics

In the absence of testing, observation is also a reasonable treatment option, according to Shaikh.

The findings from the current study showed that while children in the placebo group had less favourable symptom outcomes than those in the antibiotic group overall, the placebo group had lower rates of clinically significant diarrhoea (11.4 percent vs 4.7 percent). Additionally, children who received placebo never experienced a serious adverse event and rarely developed acute otitis media, with 50 percent achieving symptom resolution by day 9.

“[W]atchful waiting without antibiotics, depends on the willingness of the child’s family to accept the increased burden of symptoms in their child (who has already been unwell for at least 6 days) and to embrace daily monitoring for worsening symptoms,” Shaikh said.

Shaikh concluded by emphasizing the need for parents and healthcare providers to work together to make informed decisions about the best course of treatment for acute sinusitis in children.
Credit to CIMS.

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