scholarly journals HOspitalised Pneumonia Extended (HOPE) Study to reduce the long-term effects of childhood pneumonia: protocol for a multicentre, double-blind, parallel, superiority randomised controlled trial

BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e026411
Author(s):  
Anne B Chang ◽  
Siew Moy Fong ◽  
Tsin Wen Yeo ◽  
Robert S Ware ◽  
Gabrielle B McCallum ◽  
...  
Keyword(s):  
Research Ethics ◽  
Randomised Trial ◽  
Long Term Effects ◽  
Double Blind ◽  
Childhood Pneumonia ◽  
Department Of Health ◽  
Increased Risk ◽  
Amoxicillin Clavulanate ◽  
Randomised Controlled

IntroductionEarly childhood pneumonia is a common problem globally with long-term complications that include bronchiectasis and chronic obstructive pulmonary disease. It is biologically plausible that these long-term effects may be minimised in young children at increased risk of such sequelae if any residual lower airway infection and inflammation in their developing lungs can be treated successfully by longer antibiotic courses. In contrast, shortened antibiotic treatments are being promoted because of concerns over inducing antimicrobial resistance. Nevertheless, the optimal treatment duration remains unknown. Outcomes from randomised controlled trials (RCTs) on paediatric pneumonia have focused on short-term (usually <2 weeks) results. Indeed, no long-term RCT-generated outcome data are available currently. We hypothesise that a longer antibiotic course, compared with the standard treatment course, reduces the risk of chronic respiratory symptoms/signs or bronchiectasis 24 months after the original pneumonia episode.Methods and analysisThis multicentre, parallel, double-blind, placebo-controlled randomised trial involving seven hospitals in six cities from three different countries commenced in May 2016. Three-hundred-and-fourteen eligible Australian Indigenous, New Zealand Māori/Pacific and Malaysian children (aged 0.25 to 5 years) hospitalised for community-acquired, chest X-ray (CXR)-proven pneumonia are being recruited. Following intravenous antibiotics and 3 days of amoxicillin-clavulanate, they are randomised (stratified by site and age group, allocation-concealed) to receive either: (i) amoxicillin-clavulanate (80 mg/kg/day (maximum 980 mg of amoxicillin) in two-divided doses or (ii) placebo (equal volume and dosing frequency) for 8 days. Clinical data, nasopharyngeal swab, bloods and CXR are collected. The primary outcome is the proportion of children without chronic respiratory symptom/signs of bronchiectasis at 24 months. The main secondary outcomes are ‘clinical cure’ at 4 weeks, time-to-next respiratory-related hospitalisation and antibiotic resistance of nasopharyngeal respiratory bacteria.Ethics and disseminationThe Human Research Ethics Committees of all the recruiting institutions (Darwin: Northern Territory Department of Health and Menzies School of Health Research; Auckland: Starship Children’s and KidsFirst Hospitals; East Malaysia: Likas Hospital and Sarawak General Hospital; Kuala Lumpur: University of Malaya Research Ethics Committee; and Klang: Malaysian Department of Health) have approved the research protocol version 7 (13 August 2018). The RCT and other results will be submitted for publication.Trial registrationACTRN12616000046404.

Statistical analysis plan for the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure trial

2020 ◽  
Vol 22 (1) ◽  
pp. 63-71
Author(s):  
Rameela Chandrasekhar ◽  
◽  
Christopher G Hughes ◽  
Brenda T Pun ◽  
Onur M Orun ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Randomised Trial ◽  
Randomised Clinical Trial ◽  
Statistical Analysis Plan ◽  
Brain Dysfunction ◽  
Neurological Dysfunction ◽  
Long Term Effects ◽  
Double Blind ◽  
Mechanically Ventilated

BACKGROUND: The best sedative medication to reduce delirium, mortality and long term brain dysfunction in mechanically ventilated septic patients is unclear. This multicentre, double-blind, randomised trial investigates the short term and long term effects of dexmedetomidine versus propofol for sedation in mechanically ventilated severely septic patients. OBJECTIVES: To describe the statistical analysis plan for this randomised clinical trial comprehensively and place it in the public domain before unblinding. METHODS: To ensure that analyses are not selectively reported, we developed a comprehensive statistical analysis plan before unblinding. This trial has an enrolment target of 420 severely septic and mechanically ventilated adult patients, randomly assigned to dexmedetomidine or propofol in a 1:1 ratio. Enrolment was completed in January 2019, and the study was estimated to be completed in September 2019. The primary endpoint is days alive without delirium or coma during first 14 study days. Secondary outcomes include 28-day ventilator-free days, 90-day all-cause mortality and cognitive function at 180 days. Time frames all begin on the day of randomisation. All analyses will be conducted on an intention-to-treat basis. CONCLUSION: This study will compare the effects of two sedatives in mechanically ventilated severely septic patients. In keeping with the guidance on statistical principles for clinical trials, we have developed a comprehensive statistical analysis plan by which we will adhere, as this will avoid bias and support transparency and reproducibility. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01739933).

scholarly journals Long-term effects of a modified, low-protein infant formula on growth and body composition: Follow-up of a randomized, double-blind, equivalence trial

2021 ◽  
Author(s):  
Stefanie M.P. Kouwenhoven ◽  
Nadja Antl ◽  
Martijn J.J. Finken ◽  
Jos W.R. Twisk ◽  
Eline M. van der Beek ◽  
...  
Keyword(s):  
Body Composition ◽  
Infant Formula ◽  
Long Term Effects ◽  
Double Blind ◽  
Equivalence Trial ◽  
Low Protein

scholarly journals Impacts of treatments on recurrence and 28-year survival of ischemic stroke patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ting-Ann Wang ◽  
Tzy-Haw Wu ◽  
Shin-Liang Pan ◽  
Hsiu-Hsi Chen ◽  
Sherry Yueh-Hsia Chiu
Keyword(s):  
Ischemic Stroke ◽  
Cerebrovascular Disease ◽  
Cox Regression ◽  
Controlled Trial ◽  
Stroke Recurrence ◽  
Long Term Effects ◽  
Stroke Patients ◽  
Double Blind ◽  
Term Survival

AbstractAspirin and nicametate are well-established therapies for preventing recurrence and mortality from stroke in patients diagnosed as ischemic stroke. However, their respective effects on the recurrence, making allowance for the duration of recurrence and death without the occurrence of recurrence, and long-term survival have not been well elucidated. We aimed to evaluate long-term effect of two kinds of treatment on cerebrovascular death among ischemic stroke patients with or without the recurrence of stroke. Data used in this study were derived from the cohort based on a multicenter randomized double-blind controlled trial during 1992 to 1995 with the enrollment of a total of 466 patients with first-time non-cardioembolic ischemic stroke who were randomly allocated to receive aspirin (n = 222) or nicametate (n = 244). The trial cohort was followed up over time to ascertain the date of recurrence within trial period and death until Sep of 2019. The time-dependent Cox regression model was used to estimate the long-term effects of two treatments on death from cerebrovascular disease with and without recurrence. A total of 49 patients experienced stroke recurrence and 89 cerebrovascular deaths was confirmed. Patients treated with nicametate were more likely, but non statistically significantly, to have recurrence (aHR: 1.73, 95% CI 0.96–3.13) as compared with those treated by aspirin. Nicametate reduced the risk of cerebrovascular death about 37% (aHR: 0.63, 95% CI 0.41–0.97) compared with aspirin. The aspirin group had a lower recurrence rate than the nicametate group even with recurrence after 1–2 years of follow-up of first stroke but the latter had significantly reduced death from cerebrovascular disease for nicametate group, which requires more research to verify.

Repair of Protruding Bilateral Cleft Lip and Palate With Staged Premaxilla Setback Osteotomy, Cheiloplasty, and Palatoplasty in Trisomy 17p Patient: A Review of Syndromic Clinical Characteristic

2021 ◽  
pp. 105566562110698
Author(s):  
Kristaninta Bangun ◽  
Jessica Halim ◽  
Vika Tania
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Surgical Techniques ◽  
Chromosome 17 ◽  
Long Term Effects ◽  
Surgical Strategies ◽  
Increased Risk ◽  
The Cost

Chromosome 17 duplication is correlated with an increased risk of developmental delay, birth defects, and intellectual disability. Here, we reported a female patient with trisomy 17 on the whole short arm with bilateral complete cleft lip and palate (BCLP). This study will review the surgical strategies to reconstruct the protruding premaxillary segment, cleft lip, and palate in trisomy 17p patient. The patient had heterozygous pathogenic duplication of chromosomal region chr17:526-18777088 on almost the entire short arm of chromosome 17. Beside the commonly found features of trisomy 17p, the patient also presented with BCLP with a prominent premaxillary portion. Premaxillary setback surgery was first performed concomitantly with cheiloplasty. The ostectomy was performed posterior to the vomero-premaxillary suture (VPS). The premaxilla was firmly adhered to the lateral segment and the viability of philtral flap was not compromised. Two-flap palatoplasty with modified intravelar veloplasty (IVV) was performed 4 months after. Successful positioning of the premaxilla segment, satisfactory lip aesthetics, and vital palatal flap was obtained from premaxillary setback, primary cheiloplasty, and subsequent palatoplasty in our trisomy 17p patient presenting with BLCP. Postoperative premaxillary stability and patency of the philtral and palatal flap were achieved. Longer follow-up is needed to evaluate the long-term effects of our surgical techniques on inhibition of midfacial growth. However, the benefits that the patient received from the surgery in improving feeding capacity and facial appearance early in life outweigh the cost of possible maxillary retrusion.

Second-Generation Consequences of Small-for-Dates Birth

PEDIATRICS ◽  
1989 ◽  
Vol 84 (2) ◽  
pp. 343-347
Author(s):  
Mark A. Klebanoff ◽  
Olav Meirik ◽  
Heinz W. Berendes
Keyword(s):  
Confidence Interval ◽  
Birth Outcomes ◽  
Odds Ratio ◽  
Intrauterine Growth Retardation ◽  
Long Term Effects ◽  
Intrauterine Growth ◽  
Increased Risk ◽  
Reported Study ◽  
Increase In Risk

This is the first reported study of birth outcomes of a group of women whose own birth weights and gestational ages had been previously recorded. Births occurring from 1972 to 1983 among 1154 Swedish women, born from 1955 to 1965, were studied. Women who were themselves small for gestational age (SGA) at birth were at increased risk of giving birth to a SGA infant (odds ratio = 2.21, 95% confidence interval = 1.41, 3.48). Women who had been SGA had an even greater increase in risk of giving birth to a preterm infant (odds ratio = 2.96, 95% confidence interval = 1.47, 5.94). Women who were preterm at birth were not at increased risk of giving birth to either preterm (odds ratio = 0.65, 95% confidence interval = 0.15, 2.74) or SGA (odds ratio 1.21, 95% confidence interval = 0.62, 2.38) infants. It is concluded that the long-term effects of intrauterine growth retardation may extend to the next generation; women who had been SGA should be considered at increased risk to give birth to both growth-retarded and preterm infants.

scholarly journals Maternal Overnutrition Induces Long-Term Cognitive Deficits across Several Generations

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 7 ◽  
Author(s):  
Gitalee Sarker ◽  
Daria Peleg-Raibstein
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Deficits ◽  
Maternal Obesity ◽  
Cognitive Impairments ◽  
Long Term Effects ◽  
Ample Evidence ◽  
Increased Risk ◽  
Maternal Overnutrition

Ample evidence from epidemiological studies has linked maternal obesity with metabolic disorders such as obesity, cardiovascular disease, and diabetes in the next generation. Recently, it was also shown that maternal obesity has long-term effects on the progeny’s central nervous system. However, very little is known regarding how maternal overnutrition may affect, in particular, the cognitive abilities of the offspring. We reported that first-generation offspring exposed to a maternal high-fat diet (MHFD) displayed age-dependent cognitive deficits. These deficits were associated with attenuations of amino acid levels in the medial prefrontal cortex and the hippocampus regions of MHFD offspring. Here, we tested the hypothesis that MHFD in mice may induce long-term cognitive impairments and neurochemical dysfunctions in the second and third generations. We found that MHFD led to cognitive disabilities and an altered response to a noncompetitive receptor antagonist of the N-Methyl-D-aspartic acid (NMDA) receptor in adult MHFD offspring in both second and third generations in a sex-specific manner. Our results suggest that maternal overnutrition leads to an increased risk of developing obesity in subsequent generations as well as to cognitive impairments, affecting learning and memory processes in adulthood. Furthermore, MHFD exposure may facilitate pathological brain aging which is not a consequence of obesity. Our findings shed light on the long-term effects of maternal overnutrition on the development of the central nervous system and the underlying mechanisms which these traits relate to disease predisposition.

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