Tag: pubmed

Thyroid. 2023 Sep 12. doi: 10.1089/thy.2023.0317. Online ahead of print.

ABSTRACT

BACKGROUND: Hypothyroidism is common, and in iodine-sufficient areas is primarily caused by autoimmune destruction of the thyroid gland. Observational studies have consistently shown an inverse association between serum 25-hydroxyvitamin D concentration and autoimmune diseases; however, there is a lack of evidence from randomized controlled trials to support a benefit of vitamin D supplementation, particularly for autoimmune thyroid diseases. We therefore aimed to assess the effect of vitamin D supplementation on the incidence of hypothyroidism.

METHODS: We analyzed data from the D-Health Trial (N=21,315), a randomized, double-blind, placebo-controlled trial of 60,000 international units per month of supplemental vitamin D3 among Australians aged 60 years and over. Hypothyroidism, a tertiary outcome of the D-Health Trial, was defined by treatment with levothyroxine, ascertained via linkage with the Australian Pharmaceutical Benefits Scheme. The outcome was time to first prescription of levothyroxine. We began follow-up at 12 months after randomization; people who had died or who had been dispensed levothyroxine during the first year were excluded. Flexible parametric survival models were used to assess the effect of vitamin D supplementation on hypothyroidism, overall and within strata defined by age, sex, body mass index, and predicted baseline vitamin D status.

RESULTS: We included 17,851 participants in the main analysis (vitamin D=8939; placebo=8912). During a median follow up of 4.1 years (IQR 4.1-4.1) 293 participants developed hypothyroidism (vitamin D=138 [1.5%]; placebo=155 [1.7%]). Vitamin D supplementation did not significantly reduce the incidence of hypothyroidism (overall hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.71-1.12). There was some suggestion of an effect in females (overall HR 0.78; 95% CI 0.58-1.06) but not in males (overall HR 1.06; 95% CI 0.74-1.50; p interaction 0.20).

CONCLUSIONS: Vitamin D supplementation did not reduce the incidence of hypothyroidism overall; however, the possible beneficial effect observed in females warrants further investigation.

CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763.

PMID:37698908 | DOI:10.1089/thy.2023.0317

Int Endod J. 2023 Sep 12. doi: 10.1111/iej.13975. Online ahead of print.

ABSTRACT

AIM: Fat mass and obesity-associated (FTO) protein, the first discovered N6-methyladenine (m6A) demethylase, played positive roles in bone formation. In this study, the aim was to investigate the function and potential mechanism of Fto in dentine formation.

METHODOLOGY: In vivo model, postnatal 12-day (PN12), 4-week-old (4 wk), 6-week-old (6 wk) healthy male C57BL/6J were randomly divided into Fto knockout (Fto^-/- ) mice and wild-type (WT) littermates according to their genotypes, with 3-5 mice in each group. The mandibles of Fto^-/- mice and WT control littermates were isolated for analysis by micro-computed tomography (micro-CT), 3-dimensional reconstruction and Haematoxylin-eosin (HE) staining. In vitro, mouse dental papilla cells (mDPCs) and human dental stem pulp cells (hDPSCs) were cultured with odontogenetic medium to evaluate differentiation capacity; expression levels of odontoblastic related genes were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). The inclusion levels of Runt-related transcription factor 2 (RUNX2) exon 5 in mDPCs and hDPSCs were detected by semiquantitative real-time polymerase chain reaction (RT-PCR). The RNA binding motif protein 4 (RBM4) m6A site was verified through m6A methylated RNA immunoprecipitation (MeRIP) and the stability of RBM4 mRNA influenced by FTO knockdown was measured by mRNA stability assay. Differences with p values < .05 were regarded as statistically significant.

RESULTS: We discovered that Fto^-/- mice showed significant dentine formation defects characterized by widened pulp cavity, enlarged pulp-tooth volume ratio, thinned dentine and pre-dentine layer of root (p < .05). Fto^-/- mDPCs and FTO-silencing hDPSCs not only exhibited insufficient mineralization ability and decreased expression levels of odontoblastic mineralization related genes (p < .05), but showed significantly reduced Runx2 exon 5 inclusion level (p < .05). FTO knockdown increased the m6A level of RBM4 and destabilized the mRNA of RBM4, thus contributing to the reduced RBM4 expression level. Moreover, Rbm4 overexpression in Fto^-/- mDPCs can partly restore Runx2 exon 5 inclusion level and the differentiation ability disrupted by Fto knockout.

CONCLUSION: Thus, within the limitations of this study, the data suggest that FTO promotes odontoblastic differentiation during dentine formation by stabilizing RBM4 mRNA to promote RUNX2 exon 5 inclusion.

PMID:37698901 | DOI:10.1111/iej.13975

JMIR Serious Games. 2023 Sep 12;11:e42067. doi: 10.2196/42067.

ABSTRACT

BACKGROUND: Many studies have started integrating virtual reality (VR) into neurorehabilitation for children with cerebral palsy (CP). The results of the effects of VR on motor skill learning, including the short- to long-term results of relevant studies, must be pooled in a generic framework.

OBJECTIVE: This systematic review and meta-analysis aimed to investigate the short- to long-term effects of therapies including VR on motor skill learning in children with CP.

METHODS: Two examiners followed the inclusion and exclusion criteria of the “Participant, Intervention, Control, and Outcome” framework. Randomized controlled trials (RCTs) and non-RCTs were considered if they compared VR-included interventions with control groups on motor functions and daily life activities in children with CP. PubMed, ScienceDirect, Embase, and IEEE Xplore databases were searched. The modified Downs and Black assessment was used to assess the methodological quality of the included studies. Meta-analyses and subgroup analyses for RCTs were conducted whenever possible.

RESULTS: A total of 7 RCTs, 2 non-RCTs, and 258 children with CP were included. The priority focus of 78% (7/9) of the studies was upper limb functions. There was a significant short-term effect of adding VR to conventional therapies on upper limb functions when compared with conventional therapies (P=.04; standardized mean difference [SMD]=0.39, 95% CI 0.01-0.76). The overall medium- to long-term effects showed a trend toward favoring the VR group, although the difference was not statistically significant (P=.06; SMD=0.37, 95% CI -0.02 to 0.77). For balance (P=.06; SMD=1.04, 95% CI -0.04 to 2.12), gross motor functions (P=.30; SMD=2.85, 95% CI -2.57 to 8.28), and daily life activities outcomes (P=.21; SMD=0.29, 95% CI -0.16 to 0.74), the overall effect in the short term also showed a trend toward favoring the VR group, but these results were not statistically significant.

CONCLUSIONS: VR seems to have additional benefits for motor skill learning in children with CP. Studies with follow-up outcomes of VR training focusing on balance and gross motor functions in patients with CP were quite limited. Future research on balance and gross motor function outcomes should target particularly long-term results of therapies including VR on motor skill learning.

TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021227734; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021227734.

PMID:37698895 | DOI:10.2196/42067

JAMA Netw Open. 2023 Sep 5;6(9):e2333360. doi: 10.1001/jamanetworkopen.2023.33360.

NO ABSTRACT

PMID:37698865 | DOI:10.1001/jamanetworkopen.2023.33360

JAMA Netw Open. 2023 Sep 5;6(9):e2332715. doi: 10.1001/jamanetworkopen.2023.32715.

ABSTRACT

IMPORTANCE: Variability in intervention participation within care management programs can complicate standard analysis strategies.

OBJECTIVE: To evaluate whether care management was associated with reduced hospital readmissions among individuals with higher participation probabilities.

DESIGN, SETTING, AND PARTICIPANTS: A total of 800 hospitalized patients aged 18 years and older were randomized as part of the Health Care Hotspotting randomized clinical trial, which was conducted in Camden, New Jersey, from June 2014 to September 2017. Data were collected through October 2018. In this new analysis performed between April 6, 2022, and April 23, 2023, the distillation method was applied to account for variable intervention participation. A gradient-boosting machine learning model produced predicted probabilities of engaged participation using baseline covariates only. Predicted probabilities were used to trim both intervention and control populations in an equivalent manner, and intervention effects were reevaluated within study population subsets that were increasingly concentrated with patients having higher participation probabilities. Patients had 2 or more hospitalizations in the 6-month preenrollment period and documented evidence of chronic illness and social complexity.

INTERVENTION: Multidisciplinary teams provided services to patients in the intervention arm for a mean 120 days after hospital discharge. Patients in the control group received usual postdischarge care.

MAIN OUTCOMES AND MEASURES: Hospital readmission rates and counts 30, 90, and 180 days postdischarge.

RESULTS: Of 800 eligible patients, 782 had complete discharge information and were included in this analysis (mean [SD] age, 56.6 [12.7] years; 395 [50.5%] female). In the intent-to-treat analysis, the unadjusted 180-day readmission rate for treatment and control groups was 60.1% vs 61.7% (adjusted odds ratio, 0.95; 95% CI, 0.71-1.28; P = .73) and the mean (SD) number of 180-day readmissions was 1.45 (1.89) vs 1.48 (1.94) (adjusted incidence rate ratio, 0.99, 95% CI, 0.88-1.12; P = .86). Among the population with the highest participation probabilities, the mean (SD) 180-day readmission count was 1.22 (1.74) vs 1.57 (1.74) and the incidence rate ratio attained statistical significance (adjusted incidence rate ratio, 0.74; 95% CI, 0.56-0.99; P = .045). Adjusted odds ratios and adjusted incidence rate ratios for 30- and 90-day outcomes reached statistical significance after population distillation.

CONCLUSIONS AND RELEVANCE: This secondary analysis of a randomized clinical trial found that care management was associated with reduced readmissions among patients with higher participation probabilities, suggesting that program operation could be improved by addressing barriers to participation and refining inclusion criteria to identify patients most likely to benefit.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02090426.

PMID:37698862 | DOI:10.1001/jamanetworkopen.2023.32715

JAMA Netw Open. 2023 Sep 5;6(9):e2333182. doi: 10.1001/jamanetworkopen.2023.33182.

ABSTRACT

IMPORTANCE: Alcohol biomarkers can improve detection of heavy alcohol use in clinical care, yet cutoffs for phosphatidylethanol (PEth), a blood biomarker, have not been established.

OBJECTIVE: To determine the optimal cutoff for PEth for heavy alcohol consumption in a study of middle-age and older adults.

DESIGN, SETTING, AND PARTICIPANTS: This was a 4-week diagnostic study of adults with paroxysmal atrial fibrillation (AF) and current alcohol consumption, recruited from general cardiology and cardiac electrophysiology outpatient clinics from September 2014 to September 2019. Data were analyzed from October 2021 to March 2022.

MAIN OUTCOMES AND MEASURES: The main aim was to determine the optimal PEth cutoff for heavy alcohol consumption, using the Secure Continuous Remote Alcohol Monitor (SCRAM) to measure transdermal alcohol. Area under the curve (AUC) for PEth-detected compared with SCRAM-detected heavy alcohol consumption in any week over the prior 4 weeks (ie, ≥3 [women] and ≥4 [men] episodes) or any estimated breath alcohol of 0.08% or greater in any week, and the PEth cutoff was calculated using the Youden J statistic. Similar analyses were conducted comparing PEth with individual drinks reported by pressing an event monitor, retrospective self-report via the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and using 2-week look-backs.

RESULTS: In this diagnostic study of 64 patients with both PEth and SCRAM measures over 4 weeks (54 [84.4%] men; mean age, 65.5 [95% CI, 62.6-68.5] years; 51 [79.7%] White), 31 (48.4%) had any SCRAM-detected heavy alcohol consumption over the 4 weeks, and the median (IQR) PEth at 4 weeks was 23 ng/mL (<limit of quantification to 60 ng/mL). The AUC for PEth vs any SCRAM-detected heavy alcohol consumption was 0.83 (95% CI, 0.72-0.93). The optimal PEth cutoff was 18.5 ng/mL (AUC, 0.83; 95% CI, 0.72-0.93), with sensitivity of 83.9% (95% CI, 66.3%-94.5%) and specificity of 72.7% (95% CI, 54.5%-86.7%). The PEth test characteristics by individual drink reporting using the event monitors and by the AUDIT-C, and by these measures and by SCRAM collected for 2-week intervals, were similar to those compared with the 4-week SCRAM.

CONCLUSIONS AND RELEVANCE: In a predominately middle-age and older White male population, PEth compared well with SCRAM. A PEth cutoff of 18.5 ng/mL (or rounded to 20 ng/mL, a recommended PEth cutoff for significant alcohol consumption) can be used in clinical care to detect heavy alcohol consumption in middle-age and older men.

PMID:37698861 | DOI:10.1001/jamanetworkopen.2023.33182

JAMA Netw Open. 2023 Sep 5;6(9):e2333347. doi: 10.1001/jamanetworkopen.2023.33347.

ABSTRACT

IMPORTANCE: Cardiovascular toxic effects derived from high exposures to individual organochlorine compounds are well documented. However, there is no evidence on low but continuous exposure to combined organochlorine compounds in the general population.

OBJECTIVE: To evaluate the association of combined exposure to several organochlorine compounds, including organochlorine pesticides and polychlorinated biphenyls, with incident cardiovascular disease (CVD) in the general population.

DESIGN, SETTING, AND PARTICIPANTS: This prospective nested case-control study included data from 2 cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-Year-Olds (60YO), with matched case-control pairs based on age, sex, and sample date. Baseline blood sampling occurred from November 2003 to September 2009 (SMC-C) and from August 1997 to March 1999 (60YO), with follow-up through December 2017 (SMC-C) and December 2014 (60YO). Participants with myocardial infarction or ischemic stroke were matched with controls for composite CVD evaluation. Data were analyzed from September 2020 to May 2023.

EXPOSURES: A total of 25 organochlorine compounds were measured in blood at baseline by gas chromatography-triple quadrupole mass spectrometry. For 7 compounds, more than 75% of the samples were lower than the limit of detection and not included.

MAIN OUTCOMES AND MEASURES: Incident cases of primary myocardial infarction and ischemic stroke were ascertained via linkage to the National Patient Register (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I21 and I63). The quantile-based g-computation method was used to estimate the association between the combined exposure to several organochlorine compounds and composite CVD.

RESULTS: Of 1528 included participants, 1024 (67.0%) were female, and the mean (SD) age was 72 (7.0) years in the SMC-C and 61 (0.1) years in the 60YO. The odds ratio of composite CVD was 1.71 (95% CI, 1.11-2.64) per 1-quartile increment of total organochlorine compounds mixture. Organochlorinated pesticides were the largest contributors, and β-hexachlorocyclohexane and transnonachlor had the highest impact. Most of the outcome was not explained by disturbances in the main cardiometabolic risk factors, ie, high body mass index, hypertension, lipid alteration, or diabetes.

CONCLUSIONS AND RELEVANCE: In this prospective nested case-control study, participants with higher exposures to organochlorines had an increased probability of experiencing a cardiovascular event, the major cause of death worldwide. Measures may be required to reduce these exposures.

PMID:37698859 | DOI:10.1001/jamanetworkopen.2023.33347

Updates Surg. 2023 Sep 12. doi: 10.1007/s13304-023-01642-0. Online ahead of print.

ABSTRACT

This study aims to assess the feasibility of the Overlap anastomosis technique in minimally invasive Ivor-Lewis esophagectomy. An accompanying video presentation elucidates our surgical procedures. A retrospective review of 46 patients diagnosed with middle and lower esophageal cancer was conducted. These patients underwent minimally invasive Ivor-Lewis esophagectomy with Overlap anastomosis between January 2019 and December 2020. A consistent team of surgeons performed all procedures. The initial phase involved laparoscopic stomach mobilization, intra-abdominal lymphadenectomies, and preparation of the tubular stomach. Subsequently, with the patient in the left decubitus position, thoracoscopy was used to dissect the esophagus, excise the diseased segment, and conduct mediastinal lymph node dissection. The final stage encompassed the intrathoracic gastroesophageal anastomosis using the Overlap method. All surgeries were completed without converting to an open approach, achieving complete resection. There were no operative fatalities, with an average surgery duration of 259.4 min. Average statistics included intraoperative blood loss of 92.3 ml, 16.2 lymph nodes dissected, and a postoperative hospital stay of 10.3 days. Postoperative complications comprised three instances of hoarseness due to recurrent laryngeal nerve palsy, two cases of aspiration pneumonia, one occurrence of chylothorax, and one gastric emptying disorder. Anastomotic technique-related complications were minimal, with only one patient experiencing an anastomotic leak that resolved spontaneously and two patients facing anastomotic stenosis, which was subsequently alleviated. Our findings posit that the Overlap anastomosis method is safe and efficient for minimally invasive Ivor-Lewis esophagectomy, marked by a notably low rate of anastomosis-related complications. Further evaluation of its long-term implications remains necessary.

PMID:37698809 | DOI:10.1007/s13304-023-01642-0

Ir J Med Sci. 2023 Sep 12. doi: 10.1007/s11845-023-03507-2. Online ahead of print.

ABSTRACT

BACKGROUND: Smoking continues to cause harm on a huge scale in Ireland. Doctors can help this harm through providing safe, effective and clinically sound stop smoking care, but the needs of Irish doctors in this area are largely uncharted.

AIMS: We assessed the knowledge, attitudes and practices of Irish doctors regarding stop smoking care and electronic cigarettes.

METHODS: An Internet-based cross-sectional survey was administered to members of the Royal College of Physicians in Ireland and the Irish College of General Practitioners. Descriptive statistics for key parameters were derived and factors associated with more consistent practice of brief intervention, a key component of stop smoking care, were analysed using chi-square testing.

RESULTS: There were 250 responses (58.7% female, 53.0% aged under 45 years, 55.1% graduated in medicine before 2000 and 57.2% worked in general practice). Most (84.9%) reported often or always asking about patient’s smoking behaviour, and most (86.1%) reported often or always advising patients to stop. However, providing or arranging effective stop smoking care was weak and less consistently practised, and while most (91.4%) saw it as a responsibility, few doctors (28.5%) agreed they were sufficiently trained in this area of clinical care. Confidence in the knowledge of e-cigarettes was poor.

CONCLUSIONS: While there is a strong reservoir support and areas of good reported practice in stop smoking care among doctors in Ireland, the development of their knowledge and skills in arranging effective care should be supported if doctors are to fulfil their huge potential role in tackling the harm caused by smoking.

PMID:37698805 | DOI:10.1007/s11845-023-03507-2

Int J Implant Dent. 2023 Sep 12;9(1):28. doi: 10.1186/s40729-023-00489-9.

ABSTRACT

OBJECTIVES: The aim of the ITI Consensus Workshop on zygomatic implants was to provide Consensus Statements and Clinical Recommendations for the use of zygomatic implants.

MATERIALS AND METHODS: Three systematic reviews and one narrative review were written to address focused questions on (1) the indications for the use of zygomatic implants; (2) the survival rates and complications associated with surgery in zygomatic implant placement; (3) long-term survival rates of zygomatic implants and (4) the biomechanical principles involved when zygoma implants are placed under functional loads. Based on the reviews, three working groups then developed Consensus Statements and Clinical Recommendations. These were discussed in a plenary and finalized in Delphi rounds.

RESULTS: A total of 21 Consensus Statements were developed from the systematic reviews. Additionally, the group developed 17 Clinical Recommendations based on the Consensus Statements and the combined expertise of the participants.

CONCLUSIONS: Zygomatic implants are mainly indicated in cases with maxillary bone atrophy or deficiency. Long-term mean zygomatic implant survival was 96.2% [95% CI 93.8; 97.7] over a mean follow-up of 75.4 months (6.3 years) with a follow-up range of 36-141.6 months (3-11.8 years). Immediate loading showed a statistically significant increase in survival over delayed loading. Sinusitis presented with a total prevalence of 14.2% [95% CI 8.8; 22.0] over a mean 65.4 months follow-up, representing the most common complication which may lead to zygomatic implant loss. The international experts suggested clinical recommendations regarding planning, surgery, restoration, outcomes, and the patient’s perspective.

PMID:37698775 | DOI:10.1186/s40729-023-00489-9