The minimal important difference in orthodontic treatment duration: a survey across adult patients.

BACKGROUND: The minimal important difference (MID) is defined as the smallest difference that the patient perceives as important. Furthermore, the smallest worthwhile effect (SWE) is the important change measured with the benefit-harm trade-off method. The aim of this study was to evaluate the MID in orthodontic treatment duration to inform the decision regarding seeking procedures to accelerate orthodontic tooth movement and reduce treatment duration. METHODS: We constructed a survey eliciting views of the MID from adult participants from four countries undergoing orthodontic treatment. Ten questions addressed reduction in the treatment duration for both durations 12 and 24 months, and four questions were related to the reduction in treatment duration that the patients would require to undergo surgical or non-surgical adjunctive procedures. We applied a univariable random effects logistic regression model to examine the association between the participants' characteristics and the MID. Then, we fitted a multivariable logistic random effects regression including significant predictors. RESULTS: Four hundred and fifty adults, with a median age of 21 (interquartile range: 19-24), undergoing orthodontic treatment participated in the survey. Of the respondents, 60% considered 15 days as a trivial reduction from 12 months duration of therapy and 70% considered 15 days a trivial reduction from 24 months. Of the respondents, 48% considered the period of 2 months a moderate reduction from 12 months, and 60% considered 2 months a moderate reduction from 24 months. From these results, we inferred that patients considered reductions of approximately 1 month as the MID in the treatment duration for both 12 and 24 months. However, SWE was considerably more than the MID for most of the participants to decide undergoing surgical adjunctive procedures to reduce the time of therapy. The participants required smaller SWE to undergo non-surgical procedures compared to surgical procedures. CONCLUSION: The MID in the treatment duration is one month for both treatment durations 12 and 24 months. Patients require a greater SWE than the MID to undergo adjunctive procedures to shorten the duration, particularly for surgical procedures.

Timing matters: An analysis of the relationship between red cell transfusion timing and hospitalization outcomes in sickle cell crisis patients using the National Inpatient Sample database.

Vaso-occlusive pain crisis is a debilitating complication of sickle cell disease (SCD) and it is the most common cause of hospitalization among these individuals. We studied the inpatient outcomes among patients admitted with sickle cell crisis based on the timing of red blood cell transfusion. In this retrospective study, we used the United States National Inpatient Sample (NIS) data for the year 2019, to identify adult patients hospitalized with the principal diagnosis of sickle cell crisis who received simple red blood cell transfusion during their hospitalization. Patients were divided into two groups. Those who received simple red cell transfusion within 24 hours of admission were classified as early transfusion. After adjusting for confounders, the mean adjusted length of stay for patients with early transfusion was significantly lower than those who received a late blood transfusion by 3.51 days (p-value < 0.001) along with a decrease in mean adjusted hospitalization charges and cost, by 25,487 and 4,505 United States Dollar (USD) respectively. The early red cell transfusion was also associated with a decrease in inpatient mortality, demonstrated by an adjusted odds ratio (aOR) of 0.19 (p-value 0.036), and a reduction in in-hospital sepsis, with an aOR of 0.28 (p-value < 0.001), however, no statistically significant difference was found between the two groups regarding acute respiratory failure requiring intubation, vasopressors requirement, acute kidney injury requiring dialysis and intensive care unit (ICU) admission. We recommend timely triage and reassessment to identify sickle cell crisis patients requiring blood transfusion. This intervention can notably affect the inpatient length of stay, resource utilization, and hospitalization outcomes.

Pakistan's First Child & Adolescent Psychiatry Inpatient Unit: Characteristics of admitted patients and response to treatment over a 7-year period.

BACKGROUND & OBJECTIVE: Child & adolescent mental health needs to be considered as an integral component of overall health, however significant gaps exist in service provision especially inpatient services in Pakistan. The paper presents the characteristics of admitted youths and response to treatment in Pakistan's first dedicated child & adolescent psychiatry inpatient unit in Lahore over a period of first seven years. The aim of this study was to better understand the various characteristics of children and youth admitted to this inpatient unit and response to treatment over a seven years' period since the inception of the unit. METHODS: Inpatient medical records of children & adolescents admitted to dedicated Child & Adolescent Inpatient Unit at King Edward Medical University, Lahore were reviewed. Data was extracted regarding referral patterns, sociodemographic factors and diagnosis for the first seven years, from 2012 to 2019. Patients' scores on Strengths and Difficulties Questionnaire and Clinical Global Impressions Scales administered during intake were also reviewed. RESULTS: Six hundred and thirty-four (634) patients, 56% (355) being females were admitted to the unit during seven years with mean age of 12.3 ± 2.3. Mean duration of admission was 15.60 ± 6.3 days. Most predominant ICD-10 Axis-I psychiatric diagnosis were neurotic, stress related and somatoform disorders (262); mood disorders (78); schizophrenia, schizotypal & delusional disorders (77) and behavioral and emotional disorders with onset usually occurring in childhood and adolescence (44). One hundred and fifty-nine (25%) children had comorbid diagnosis of intellectual disability on Axis-III. Strengths and difficulties questionnaire scores were in abnormal range for significant proportion (>50 %) of patients. CGI mean scores showed marked improvement at discharge. CONCLUSION: Neurotic, stress related and somatoform disorders are the most common diagnosis in youth needing inpatient treatment in Pakistani setup. Study results indicate that there is a clear need for specialized inpatient child and adolescent services such as ours in low- & middle-income countries.

Psychological burden of quarantine in children and adolescents: A rapid systematic review and proposed solutions.

As COVID-19 grips the world, many people are quarantined or isolated resulting in adverse consequences for the mental health of youth. This rapid review takes into account the impact of quarantine on mental health of children and adolescents, and proposes measures to improve psychological outcomes of isolation. Three electronic databases including PubMed, Scopus, and ISI Web of Science were searched. Two independent reviewers performed title and abstract screening followed by full-text screening. This review article included 10 studies. The seven studies before onset of COVID 19 about psychological impact of quarantine in children have reported isolation, social exclusion stigma and fear among the children. The most common diagnoses were acute stress disorder, adjustment disorder, grief, and post-traumatic stress disorder. Three studies during the COVID-19 pandemic reported restlessness, irritability, anxiety, clinginess and inattention with increased screen time in children during quarantine. These adverse consequences can be tackled through carefully formulated multilevel interventions.

Spot and Cumulative Urine Samples Are Suitable Replacements for 24-Hour Urine Collections for Objective Measures of Dietary Exposure in Adults Using Metabolite Biomarkers.

BACKGROUND: Measurement of multiple food intake exposure biomarkers in urine may offer an objective method for monitoring diet. The potential of spot and cumulative urine samples that have reduced burden on participants as replacements for 24-h urine collections has not been evaluated. OBJECTIVE: The aim of this study was to determine the utility of spot and cumulative urine samples for classifying the metabolic profiles of people according to dietary intake when compared with 24-h urine collections in a controlled dietary intervention study. METHODS: Nineteen healthy individuals (10 male, 9 female, aged 21-65 y, BMI 20-35 kg/m2) each consumed 4 distinctly different diets, each for 1 wk. Spot urine samples were collected ∼2 h post meals on 3 intervention days/wk. Cumulative urine samples were collected daily over 3 separate temporal periods. A 24-h urine collection was created by combining the 3 cumulative urine samples. Urine samples were analyzed with metabolite fingerprinting by both high-resolution flow infusion electrospray mass spectrometry (FIE-HRMS) and proton nuclear magnetic resonance spectroscopy (1H-NMR). Concentrations of dietary intake biomarkers were measured with liquid chromatography triple quadrupole mass spectrometry and by integration of 1H-NMR data. RESULTS: Cross-validation modeling with 1H-NMR and FIE-HRMS data demonstrated the power of spot and cumulative urine samples in predicting dietary patterns in 24-h urine collections. Particularly, there was no significant loss of information when post-dinner (PD) spot or overnight cumulative samples were substituted for 24-h urine collections (classification accuracies of 0.891 and 0.938, respectively). Quantitative analysis of urine samples also demonstrated the relation between PD spot samples and 24-h urines for dietary exposure biomarkers. CONCLUSIONS: We conclude that PD spot urine samples are suitable replacements for 24-h urine collections. Alternatively, cumulative samples collected overnight predict similarly to 24-h urine samples and have a lower collection burden for participants.

Diversity and association of phenotypic and metabolomic traits in the close model grasses Brachypodium distachyon, B. stacei and B. hybridum.

Background and Aims: Morphological traits in combination with metabolite fingerprinting were used to investigate inter- and intraspecies diversity within the model annual grasses Brachypodium distachyon, Brachypodium stacei and Brachypodium hybridum . Methods: Phenotypic variation of 15 morphological characters and 2219 nominal mass ( m / z ) signals generated using flow infusion electrospray ionization-mass spectrometry (FIE-MS) were evaluated in individuals from a total of 174 wild populations and six inbred lines, and 12 lines, of the three species, respectively. Basic statistics and multivariate principal component analysis and discriminant analysis were used to differentiate inter- and intraspecific variability of the two types of variable, and their association was assayed with the rcorr function. Key Results: Basic statistics and analysis of variance detected eight phenotypic characters [(stomata) leaf guard cell length, pollen grain length, (plant) height, second leaf width, inflorescence length, number of spikelets per inflorescence, lemma length, awn length] and 434 tentatively annotated metabolite signals that significantly discriminated the three species. Three phenotypic traits (pollen grain length, spikelet length, number of flowers per inflorescence) might be genetically fixed. The three species showed different metabolomic profiles. Discriminant analysis significantly discriminated the three taxa with both morphometric and metabolome traits and the intraspecific phenotypic diversity within B. distachyon and B. stacei . The populations of B. hybridum were considerably less differentiated. Conclusions: Highly explanatory metabolite signals together with morphological characters revealed concordant patterns of differentiation of the three taxa. Intraspecific phenotypic diversity was observed between northern and southern Iberian populations of B. distachyon and between eastern Mediterranean/south-western Asian and western Mediterranean populations of B. stacei . Significant association was found for pollen grain length and lemma length and ten and six metabolomic signals, respectively. These results would guide the selection of new germplasm lines of the three model grasses in ongoing genome-wide association studies.

Racial and ethnic disparities in heart transplantation for end-stage heart failure: An analysis of the national inpatient sample (NIS) database.

PURPOSE: This study aims to examine disparities among heart transplant recipients in the United States, utilizing the latest data from the National Inpatient Sample (NIS). METHODS: We conducted a retrospective cohort analysis of NIS discharge data (2017-2020), focusing on adult end-stage heart failure (ESHF) patients, identified using the ICD-10 CM code I50.84. Our analysis included four racial groups: White, Black, Hispanic, and Asian. We employed univariable and multivariate regression analyses to determine the unadjusted and adjusted odds of heart transplantation across these racial groups, using Stata version 14.2 for statistical calculations. RESULTS: Of 110,015 ESHF patients, 3,695 received heart transplants. Predominantly, recipients were male with a Charlson comorbidity index ≥3 and covered by private insurance. Transplants mainly occurred in large, teaching hospitals. Despite minor differences in age and median household income among races, baseline patient and hospital characteristics showed no significant variations. Compared to Whites, Blacks had a significantly lower transplant rate (AOR: 0.6; 95  % CI: 0.46-0.77; p < 0.001), while Hispanics and Asians showed no significant disparities. Mean ages varied slightly across groups (p = 0.0047), yet inpatient length of stay and hospitalization costs did not significantly differ. CONCLUSION: Our findings highlight a significant disparity in heart transplant rates between Black and White ESHF patients in the U.S., with Black patients less likely to receive transplants compared to their White counterparts.

Independent predictors of mortality and 5-year trends in mortality and resource utilization in hospitalized patients with diffuse large B cell lymphoma.

Background: This retrospective study analyzed factors influencing all-cause inpatient mortality in 80,930 adult patients (2016-2020) with diffuse large B cell lymphoma using the National Inpatient Sample database. Methods: Utilizing ICD-10 codes, patients were identified, and statistical analysis was conducted using STATA. Fisher's exact and Student's t tests compared proportions and variables, multivariate logistic regression examined mortality predictors, and a 5-year longitudinal analysis identified mortality and resource utilization trends. Results: The inpatient mortality rate was found to be 6.56% with a mean age of 67.99 years. Several hospital- and patient-level factors including specific comorbidities such as congestive heart failure, atrial fibrillation, acute kidney injury, chronic obstructive pulmonary disease, liver failure, pancytopenia, tumor lysis syndrome, and severe protein-calorie malnutrition were independently associated with inpatient mortality. Hospitalization costs showed an increasing trend, impacting the overall population and survivors. Conclusion: These insights may refine risk assessment, treatment selection, and interventions.

Double Trouble: COVID-19 Infection Exacerbates Sickle Cell Crisis Outcomes in Hospitalized Patients-Insights from National Inpatient Sample 2020.

Background: This study investigated the impact of COVID-19 on patients with sickle cell crisis (SCC) using National Inpatient Sample (NIS) data for the year 2020. Methods: A retrospective cohort analysis was conducted utilizing International Classification of Diseases (ICD-10) codes to identify adults who were admitted with a principal diagnosis of sickle cell crisis. The primary outcomes examined were inpatient mortality, while the secondary outcomes assessed included morbidity, hospital length of stay, and resource utilization. Analyses were conducted with STATA. Multivariate logistic and linear regression analyses were used to adjust for confounding variables. Results: Of 66,415 adult patients with a primary SCC diagnosis, 875 were identified with a secondary diagnosis of COVID-19 infection. Unadjusted mortality rate was higher for SCC patients with COVID-19 (2.28%) compared to those without (0.33%), with an adjusted odds ratio (aOR) of 8.49 (p = 0.001). They also showed increased odds of developing acute respiratory failure (aOR = 2.37, p = 0.003) and acute kidney injury requiring dialysis (aOR = 8.66, p = 0.034). Additionally, these patients had longer hospital stays by an adjusted mean of 3.30 days (p < 0.001) and incurred higher hospitalization charges by an adjusted mean of USD 35,578 (p = 0.005). Conclusions: The SCC patients with COVID-19 presented higher mortality rates, increased morbidity indicators, longer hospital stays, and substantial economic burdens.

Autoimmune diabetes from pembrolizumab: A case report and review of literature.

BACKGROUND: Immunotherapy, specifically the use of checkpoint inhibitors such as pembrolizumab, has become an important tool in personalized cancer therapy. These inhibitors target proteins on T-cells that regulate the immune response against tumor cells. Pembrolizumab, which targets the programmed cell death 1 receptor on T-cells, has been approved for the treatment of metastatic melanoma and non-small cell lung cancer. However, it can also lead to immune-related side effects, including pneumonitis, colitis, thyroid abnormalities, and rare cases of type 1 diabetes. CASE SUMMARY: The case presented involves an adult patient in 30s with breast cancer who developed hyperglycemia after receiving pembrolizumab treatment. The patient was diagnosed with diabetic ketoacidosis and further investigations were performed to evaluate for new-onset type 1 diabetes. The patient had a history of hypothyroidism and a family history of breast cancer. Treatment for diabetic ketoacidosis was initiated, and the patient was discharged for close follow-up with an endocrinologist. CONCLUSION: This literature review highlights the occurrence of diabetic ketoacidosis and new-onset type 1 diabetes in patients receiving pembrolizumab treatment for different types of cancer. Overall, the article emphasizes the therapeutic benefits of immunotherapy in cancer treatment, particularly pembrolizumab, while also highlighting the potential side effect of immune-related diabetes that can occur in a small percentage of patients. Here we present a case where pembrolizumab lead to development of diabetes after a few cycles highlighting one of the rare yet a serious toxicity of the drug.

Metabolomic analysis reveals a common pattern of metabolic re-programming during invasion of three host plant species by Magnaporthe grisea.

The mechanisms by which biotrophic and hemi-biotrophic fungal pathogens simultaneously subdue plant defences and sequester host nutrients are poorly understood. Using metabolite fingerprinting, we show that Magnaporthe grisea, the causal agent of rice blast disease, dynamically re-programmes host metabolism during plant colonization. Identical patterns of metabolic change occurred during M. grisea infections in barley, rice and Brachypodium distachyon. Targeted metabolite profiling by GC-MS confirmed the modulation of a conserved set of metabolites. In pre-symptomatic tissues, malate and polyamines accumulated, rather than being utilized to generate defensive reactive oxygen species, and the levels of metabolites associated with amelioration of redox stress in various cellular compartments increased dramatically. The activity of NADP-malic enzyme and generation of reactive oxygen species were localized to pathogen penetration sites, and both appeared to be suppressed in compatible interactions. Early diversion of the shikimate pathway to produce quinate was observed, as well as accumulation of non-polymerized lignin precursors. These data are consistent with modulation of defensive phenylpropanoid metabolism by M. grisea and the inability of susceptible hosts to mount a hypersensitive reaction or produce lignified papillae (both involving reactive oxygen species) to restrict pathogen invasion. Rapid proliferation of M. grisea hyphae in plant tissue after 3 days was associated with accelerated nutrient acquisition and utilization by the pathogen. Conversion of photoassimilate into mannitol and glycerol for carbon sequestration and osmolyte production appear to drive hyphal growth. Taken together, our results suggest that fungal pathogens deploy a common metabolic re-programming strategy in diverse host species to suppress plant defence and colonize plant tissue.

A Standardized Strategy for Simultaneous Quantification of Urine Metabolites to Validate Development of a Biomarker Panel Allowing Comprehensive Assessment of Dietary Exposure.

SCOPE: Metabolites derived from individual foods found in human biofluids after consumption could provide objective measures of dietary intake. For comprehensive dietary assessment, quantification methods would need to manage the structurally diverse mixture of target metabolites present at wide concentration ranges. METHODS AND RESULTS: A strategy for selection of candidate dietary exposure biomarkers is developed. An analytical method for 62 food biomarkers is validated by extensive analysis of chromatographic and ionization behavior characteristics using triple quadrupole mass spectrometry. Urine samples from two food intervention studies are used: a controlled, inpatient study (n = 19) and a free-living study where individuals (n = 15) are provided with food as a series of menu plans. As proof-of-principle, it is demonstrated that the biomarker panel could discriminate between menu plans by detecting distinctive changes in the concentration in urine of targeted metabolites. Quantitative relationships between four biomarker concentrations in urine and dietary intake are shown. CONCLUSION: Design concepts for an analytical strategy are demonstrated, allowing simultaneous quantification of a comprehensive panel of chemically-diverse biomarkers of a wide range of commonly-consumed foods. It is proposed that integration of self-reported dietary recording tools with biomarker approaches will provide more robust assessment of dietary exposure.

Metabolite signal identification in accurate mass metabolomics data with MZedDB, an interactive m/z annotation tool utilising predicted ionisation behaviour 'rules'.

BACKGROUND: Metabolomics experiments using Mass Spectrometry (MS) technology measure the mass to charge ratio (m/z) and intensity of ionised molecules in crude extracts of complex biological samples to generate high dimensional metabolite 'fingerprint' or metabolite 'profile' data. High resolution MS instruments perform routinely with a mass accuracy of < 5 ppm (parts per million) thus providing potentially a direct method for signal putative annotation using databases containing metabolite mass information. Most database interfaces support only simple queries with the default assumption that molecules either gain or lose a single proton when ionised. In reality the annotation process is confounded by the fact that many ionisation products will be not only molecular isotopes but also salt/solvent adducts and neutral loss fragments of original metabolites. This report describes an annotation strategy that will allow searching based on all potential ionisation products predicted to form during electrospray ionisation (ESI). RESULTS: Metabolite 'structures' harvested from publicly accessible databases were converted into a common format to generate a comprehensive archive in MZedDB. 'Rules' were derived from chemical information that allowed MZedDB to generate a list of adducts and neutral loss fragments putatively able to form for each structure and calculate, on the fly, the exact molecular weight of every potential ionisation product to provide targets for annotation searches based on accurate mass. We demonstrate that data matrices representing populations of ionisation products generated from different biological matrices contain a large proportion (sometimes > 50%) of molecular isotopes, salt adducts and neutral loss fragments. Correlation analysis of ESI-MS data features confirmed the predicted relationships of m/z signals. An integrated isotope enumerator in MZedDB allowed verification of exact isotopic pattern distributions to corroborate experimental data. CONCLUSION: We conclude that although ultra-high accurate mass instruments provide major insight into the chemical diversity of biological extracts, the facile annotation of a large proportion of signals is not possible by simple, automated query of current databases using computed molecular formulae. Parameterising MZedDB to take into account predicted ionisation behaviour and the biological source of any sample improves greatly both the frequency and accuracy of potential annotation 'hits' in ESI-MS data.

Developing a Food Exposure and Urine Sampling Strategy for Dietary Exposure Biomarker Validation in Free-Living Individuals.

SCOPE: Dietary choices modulate the risk of chronic diseases and improving diet is a central component of public health strategies. Food-derived metabolites present in urine could provide objective biomarkers of dietary exposure. To assist biomarker validation, this work aims to develop a food intervention strategy mimicking a typical annual diet over a short period of time and assesses urine sampling protocols potentially suitable for future deployment of biomarker technology in free-living populations. METHODS AND RESULTS: Six different menu plans comprehensively represent a typical UK annual diet that is split into two dietary experimental periods. Free-living adult participants (n = 15 and n = 36, respectively) are provided with all their food, as a series of menu plans, over a period of three consecutive days. Multiple spot urine samples are collected and stored at home. CONCLUSION: A successful food exposure strategy is established following a conventional UK eating pattern, which is suitable for biomarker validation in free-living individuals. The urine sampling procedure is acceptable for volunteers and delivered samples suitable for biomarker quantification. The study design provides scope for validation of existing biomarker candidates and potentially for discovery of new biomarker leads, and should help inform the future deployment of biomarker technology for habitual dietary exposure measurement.

Failure rates of miniscrews inserted in the maxillary tuberosity.

INTRODUCTION: Anchorage conservation in orthodontics has always been a challenge. OBJECTIVE: The aim of this current study was to find out the failure rate of miniscrews inserted in the maxillary tuberosity (MT) region. METHODS: This pilot study consisted of 40 patients (23 female, 17 male; mean age = 20.1±8.9 years) that had received 60 MT miniscrews for orthodontic treatment. Clinical notes and pictures were used to find out the primary outcome of miniscrew failure. Independent failure factors were also investigated. Logistic regression analysis was done for predictor's relation with MT miniscrews failure. RESULTS: There was no significant correlation in failure rate according to various predictor variables, except for miniscrews installed by lesser experienced operators, which showed significantly more failure. The odds ratio for miniscrew failure placed by inexperienced operators was 4.16. CONCLUSION: A 26.3% failure rate of mini-implants inserted in the MT region was observed.

Failure rates of miniscrews inserted in the maxillary tuberosity

ABSTRACT Introduction: Anchorage conservation in orthodontics has always been a challenge. Objective: The aim of this current study was to find out the failure rate of miniscrews inserted in the maxillary tuberosity (MT) region. Methods: This pilot study consisted of 40 patients (23 female, 17 male; mean age = 20.1±8.9 years) that had received 60 MT miniscrews for orthodontic treatment. Clinical notes and pictures were used to find out the primary outcome of miniscrew failure. Independent failure factors were also investigated. Logistic regression analysis was done for predictor's relation with MT miniscrews failure. Results: There was no significant correlation in failure rate according to various predictor variables, except for miniscrews installed by lesser experienced operators, which showed significantly more failure. The odds ratio for miniscrew failure placed by inexperienced operators was 4.16. Conclusion: A 26.3% failure rate of mini-implants inserted in the MT region was observed.

RESUMO Introdução: a manutenção da ancoragem sempre foi um desafio na Ortodontia. Objetivo: o objetivo do presente estudo foi descobrir a taxa de falhas dos mini-implantes instalados na região da tuberosidade maxilar (TM). Métodos: o presente estudo piloto avaliou 40 pacientes (23 mulheres, 17 homens; idade média = 20,1 ± 8,9 anos) que receberam 60 mini-implantes na TM durante o tratamento ortodôntico. Anotações clínicas e fotografias foram usadas para investigar o principal motivo para a falha do mini-implante. Fatores de insucesso independentes também foram investigados. Uma análise de regressão logística foi realizada para medir o impacto de cada fator preditivo sobre a falha na instalação dos mini-implantes na TM. Resultados: as diferentes variáveis preditivas não demonstraram correlação significativa com a taxa de falhas, com exceção da instalação dos mini-implantes realizada por operadores inexperientes, que mostrou quantidade significativamente maior de falhas. A razão de chances para a falha dos mini-implantes instalados por operadores inexperientes foi de 4,16. Conclusão: observou-se uma taxa de falhas de 26,3% para os mini-implantes instalados na região da TM.