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Nevin Manimala Statistics

Oncological and functional outcomes of transoral surgery compared with non-surgical management in small-volume oropharyngeal cancer: a systematic review protocol

JBI Evid Synth. 2023 May 29. doi: 10.11124/JBIES-22-00349. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this systematic review is to investigate oncological and functional outcomes following primary transoral surgery compared with non-surgical management in patients with small-volume (T1-2, N0-2) oropharyngeal cancer.

INTRODUCTION: The incidence of oropharyngeal cancer is rising. Transoral surgery was introduced to provide a minimally invasive treatment option for patients with small-volume oropharyngeal cancer and to avoid the morbidity that results from open surgery and the potential acute and late toxicities of chemoradiotherapy.

INCLUSION CRITERIA: The review will include all studies on adult patients with small-volume oropharyngeal cancer managed by transoral surgery or non-surgical management with radiotherapy and/or chemotherapy. All patients must have undergone treatment with curative intent. Participants who underwent palliative treatment will be excluded.

METHODS: This review will follow the JBI methodology for systematic reviews of effectiveness. Eligible study designs will include randomized controlled trials, quasi-experimental studies, and prospective or retrospective cohort studies. Databases to be searched will include PubMed, Embase, CINAHL, Cochrane CENTRAL, and multiple trial registries from 1972. Titles and abstracts will be reviewed, and full-text articles will be retrieved if they meet the inclusion criteria. All eligible studies will be critically appraised by 2 independent reviewers using the appropriate JBI tools for experimental and observational designs. Where possible, outcome data from studies will be pooled with statistical meta-analysis to compare both oncological and functional outcomes between the two groups. All time to event to data will be converted to a common metric for oncological outcomes. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach will be followed to assess the certainty of findings.

SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 352509.

PMID:37246954 | DOI:10.11124/JBIES-22-00349

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Long Time Scale Ensemble Methods in Molecular Dynamics: Ligand-Protein Interactions and Allostery in SARS-CoV-2 Targets

J Chem Theory Comput. 2023 May 29. doi: 10.1021/acs.jctc.3c00020. Online ahead of print.

ABSTRACT

We subject a series of five protein-ligand systems which contain important SARS-CoV-2 targets, 3-chymotrypsin-like protease (3CLPro), papain-like protease, and adenosine ribose phosphatase, to long time scale and adaptive sampling molecular dynamics simulations. By performing ensembles of ten or twelve 10 μs simulations for each system, we accurately and reproducibly determine ligand binding sites, both crystallographically resolved and otherwise, thereby discovering binding sites that can be exploited for drug discovery. We also report robust, ensemble-based observation of conformational changes that occur at the main binding site of 3CLPro due to the presence of another ligand at an allosteric binding site explaining the underlying cascade of events responsible for its inhibitory effect. Using our simulations, we have discovered a novel allosteric mechanism of inhibition for a ligand known to bind only at the substrate binding site. Due to the chaotic nature of molecular dynamics trajectories, regardless of their temporal duration individual trajectories do not allow for accurate or reproducible elucidation of macroscopic expectation values. Unprecedentedly at this time scale, we compare the statistical distribution of protein-ligand contact frequencies for these ten/twelve 10 μs trajectories and find that over 90% of trajectories have significantly different contact frequency distributions. Furthermore, using a direct binding free energy calculation protocol, we determine the ligand binding free energies for each of the identified sites using long time scale simulations. The free energies differ by 0.77 to 7.26 kcal/mol across individual trajectories depending on the binding site and the system. We show that, although this is the standard way such quantities are currently reported at long time scale, individual simulations do not yield reliable free energies. Ensembles of independent trajectories are necessary to overcome the aleatoric uncertainty in order to obtain statistically meaningful and reproducible results. Finally, we compare the application of different free energy methods to these systems and discuss their advantages and disadvantages. Our findings here are generally applicable to all molecular dynamics based applications and not confined to the free energy methods used in this study.

PMID:37246943 | DOI:10.1021/acs.jctc.3c00020

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Early-Life and Family Risk Factors for Tic Disorder Persistence into Adulthood

Mov Disord. 2023 May 29. doi: 10.1002/mds.29454. Online ahead of print.

ABSTRACT

BACKGROUND: Many children with tic disorders outgrow their tics, but little is known about the proportion of individuals who will continue to require specialist services in adulthood and which variables are associated with tic persistence.

OBJECTIVES: The aims were to estimate the proportion of individuals first diagnosed with tic disorders in childhood who continued to receive tic disorder diagnoses after age 18 years and to identify risk factors for persistence.

METHODS: In this Swedish nationwide cohort study including 3761 individuals diagnosed with tic disorders in childhood, we calculated the proportion of individuals whose diagnoses persisted into adulthood. Minimally adjusted logistic regression models examined the associations between sociodemographic, clinical, and family variables and tic disorder persistence. A multivariable model was then fitted, including only variables that were statistically significant in the minimally adjusted models.

RESULTS: Seven hundred and fifty-four (20%) children with tic disorders received a diagnosis of a chronic tic disorder in adulthood. Psychiatric comorbidity in childhood (particularly attention-deficit hyperactivity disorder, obsessive-compulsive disorder, pervasive developmental disorders, and anxiety disorders) and psychiatric disorders in first-degree relatives (particularly tic and anxiety disorders) were the strongest risk factors for persistence. We did not observe statistically significant associations with socioeconomic variables, perinatal complications, comorbid autoimmune diseases, or family history of autoimmune diseases. All statistically significant variables combined explained approximately 10% of the variance in tic disorder persistence (P < 0.0001).

CONCLUSIONS: Childhood psychiatric comorbidities and family history of psychiatric disorders were the strongest risk factors associated with tic disorder persistence into adulthood. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:37246931 | DOI:10.1002/mds.29454

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The effect of sleep positional therapy on nocturnal gastroesophageal reflux measured by esophageal pH-impedance monitoring

Neurogastroenterol Motil. 2023 May 29:e14614. doi: 10.1111/nmo.14614. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: The aim of the study was to evaluate the effect of an electronic positional therapy wearable device on nocturnal gastroesophageal reflux measured by pH-impedance reflux monitoring.

METHODS: We performed a single-center, prospective, interventional study in 30 patients with nocturnal reflux symptoms and a nocturnal esophageal acid exposure time (AET) ≥1.5% measured off acid-suppressive medication by ambulatory pH-impedance reflux monitoring. Patients were treated with an electronic positional therapy wearable device for 2 weeks. The device vibrates in the right lateral decubitus position so it conditions patients to avoid that sleep position. After 2 weeks treatment, the pH-impedance study was repeated. Primary outcome was the change in nocturnal AET. Secondary outcomes include change in number of reflux episodes and reflux symptoms.

RESULTS: Complete data were available for 27 patients (13 females, mean age 49.8 years). The median nocturnal AET decreased from 6.0% (IQR, 2.3-15.3) to 3.1% (0.1-10.8) after 2 weeks of treatment (p = 0.079). The number of reflux episodes was significantly reduced after 2 weeks of treatment (baseline: 8.0 (3.0-12.3) vs. end: 3.0 (1.0-8.0); p = 0.041). Treatment led to a statistically significant decrease in time spent in right lateral decubitus position (baseline: mean 36.9% ± 15.2% vs. end: 2.7% ± 8.2%; p = <0.001) and an increase in the left lateral decubitus position (baseline 29.2% ± 14.8% vs. end: 63.3% ± 21.9%; p = <0.001). Symptom improvement was reported by 70.4% of the patients.

CONCLUSIONS: Sleep positional therapy using an electronic wearable device promotes sleeping in the left lateral decubitus position and improves reflux parameters measured by pH-impedance reflux monitoring.

PMID:37246930 | DOI:10.1111/nmo.14614

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Functional outcome of an ‘all-inside’ technique in female anterior cruciate ligament reconstruction at long-term follow-up: A gender-sensitive analysis

Womens Health (Lond). 2023 Jan-Dec;19:17455057231175810. doi: 10.1177/17455057231175810.

ABSTRACT

BACKGROUND: As the awareness towards gender-specific therapies continues to increase among all fields of medicine, so does the need for gender-sensitive evaluations of established surgical techniques. With a higher likelihood of anterior cruciate ligament injury in women, a critical assessment of the functional outcome of anterior cruciate ligament reconstruction regarding patient sex is indispensable. Almost all pre-existing literature on this subject is based on anterior cruciate ligament reconstructions carried out before 2008, when ‘all-inside’ techniques did not exist. This implicates the need to investigate this technique towards its differences in outcome between male and female patients.

OBJECTIVES: The purpose of this study was to determine whether there is a difference concerning the functional outcome of an ‘all-inside’ technique for anterior cruciate ligament reconstruction in female patients when compared to a cohort of male patients matched for body mass index and age.

DESIGN: Retrospective analysis.

METHODS: All female patients who underwent anterior cruciate ligament reconstruction using an all-inside technique between 2011 and 2012 were examined for inclusion. Functional outcome parameters investigated included the Lysholm Knee Score, International Knee Documentation Committee score, Visual Analogue Scale score and the Tegner Activity Scale. All parameters were documented before surgery and at 3-, 6-, 12- and >24 months follow-up. At 24-month follow-up, anterior-posterior knee laxity was tested using the KT-2000 arthrometer device. For comparison, an equivalent group of male patients who underwent the same procedure was matched.

RESULTS: 27 female patients were matched with 27 male patients. The average age was 29 years, and a mean follow-up of 90 months could be achieved with 27 of patients reaching a follow-up of > 10 years. The evaluated scores showed no significant difference between female and male patients. Women presented with poorer functional outcome at 3- as well as 6-month follow-ups compared to men, without reaching statistical significance. After 12 months, no further differences could be found.

CONCLUSION: This study proved that an all-inside technique for anterior cruciate ligament reconstruction is able to produce the same functional outcome in female as in male patients at long-term follow-up. The results on short-term outcome indicate the need for further research towards gender-specific differences after anterior cruciate ligament reconstruction, their potential causes and potential of improvement.

LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID:37246602 | DOI:10.1177/17455057231175810

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Painful Temporomandibular disorders in Confucian-heritage cultures: Their inter-relationship with bodily pain, psychological well-being, and distress

J Oral Rehabil. 2023 May 29. doi: 10.1111/joor.13522. Online ahead of print.

ABSTRACT

OBJECTIVES: This study investigated the inter-relationship of painful Temporomandibular disorders (TMDs) with bodily pain, psychological well-being, and distress in young people from a Confucian-heritage culture (CHC).

METHODS: Adolescents/young adults were recruited from a local polytechnic in Singapore. While the presence/severity of painful TMDs and bodily pain were established with the DC/TMD TMD Pain Screener (TPS) and Maciel’s Pain Inventory, psychological well-being and distress were evaluated with the Scales of Psychological Well-being-18 (SPWB-18) and Patient Health Questionnaire-4 (PHQ-4). Statistical explorations were conducted using Chi-square/Mann-Whitney U tests, Spearman’s correlation, and logistic regression analyses (α = 0.05).

RESULTS: Among the 225 participants (mean age 20.1 ± 3.9 years) examined, 11.6% had painful TMDs and 68.9% experienced multi-site bodily pain. Though painful TMDs were accompanied by a higher occurrence of multi-site bodily pain, the overall/discrete number of bodily pain sites did not differ substantially between the “no TMD pain” (NT) and “with TMD pain” (WT) groups. Besides ear pain, differences in overall/discrete bodily pain scores were also insignificant. However, significant differences in environmental mastery, overall psychological distress, depression, and anxiety subscale scores were discerned between the NT and WT groups. Psychological well-being and distress were moderately and negatively correlated (rs = -0.56). Multivariate analysis indicated that ear pain and psychological distress increased the prospect of painful TMDs CONCLUSIONS: The prevalence of multi-site bodily pain was high in young people from CHCs irrespective of the presence of painful TMDs. Enhancing environmental mastery and relieving depression/anxiety may help manage TMD pain.

PMID:37246585 | DOI:10.1111/joor.13522

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White matter microstructure changes in adults with major depressive disorder: evidence from diffusion magnetic resonance imaging

BJPsych Open. 2023 May 29;9(3):e101. doi: 10.1192/bjo.2023.30.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) is a serious psychiatric disorder marked by low mood and anhedonia. Understanding the neural mechanism of MDD is essential for the treatment of depression. White matter fibres, connecting different computational units in the brain, have an important effect on brain function; however, the mechanism of white matter fibre abnormality in MDD is still unclear.

AIMS: Our study expected to find white matter abnormalities associated with the frontal lobe and hippocampus in individuals with MDD.

METHOD: Using diffusion tensor imaging data and tract-based spatial statistics, we investigated the microstructural differences in white matter fibre tracts between 30 adults with MDD compared with 31 healthy controls, and calculated the association between MDD-related microstructural changes and illness duration.

RESULTS: It was found that patients with MDD showed reduced fractional anisotropy in the genu and body of the corpus callosum, right corona radiata and part of the thalamic radiations, suggesting lower fibrous myelination levels in these regions; the decreased fractional anisotropy in these regions was associated with longer illness duration.

CONCLUSIONS: Our results suggest that MDD may be associated with microstructural damage of key fibre tracts, which could provide insights into the understanding and treatment of MDD.

PMID:37246576 | DOI:10.1192/bjo.2023.30

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How do public health nurses in Norwegian school health services support siblings of children with complex care needs?

Scand J Caring Sci. 2023 May 29. doi: 10.1111/scs.13184. Online ahead of print.

ABSTRACT

AIMS: There is a paucity of data regarding the care and support provided by Norwegian school health services to siblings of children with complex care needs. Public health nurses are an integral part of these universal services, which focus on health promotion and disease prevention in primary and secondary schools. This study aimed to explore health promotion interventions by public health nurses for siblings in Norwegian schools and to identify regional differences.

METHODS: An online national questionnaire was distributed to Norwegian public health nurses and leaders of public health nursing services (N = 487). The questions were related to how the nurses support siblings of children with complex care needs. The quantitative data were analysed using descriptive statistics. An inductive thematic analysis of free-text comments was conducted.

ETHICAL APPROVAL: The study was approved by the Norwegian Centre for Research Data.

RESULTS: The majority of public health nursing leaders (67%) reported that the services in their municipality had no system to identify siblings or to provide them with routine care. However, 26% of public health nurses reported that routine support was provided to siblings. Regional differences were identified.

STUDY LIMITATIONS: This study included responses from 487 PHNs from all four health regions in Norway. The study design is limited and gives a brief outline of the current situation. Further data are needed to provide in-depth knowledge.

CONCLUSIONS: This survey provides important knowledge for health authorities and professionals working with siblings, about inadequate support and regional differences in care provided to siblings by school health services.

PMID:37246570 | DOI:10.1111/scs.13184

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Rotator Cuff Injuries in the Pediatric Population: A Retrospective Review of Patient Characteristics and Treatment at a Single Center

Sports Health. 2023 May 29:19417381231174021. doi: 10.1177/19417381231174021. Online ahead of print.

ABSTRACT

BACKGROUND: As youth participation in contact and overhead sports has increased in recent decades, so has the occurrence of injuries of the shoulder. Rotator cuff injury (RCI) is an infrequent shoulder pathology in pediatric patients and its description in the literature has been scarce. A greater understanding of RCI characteristics and treatment outcomes in children and adolescents would improve our understanding of this pathology and help to better guide clinical decision-making.

HYPOTHESIS: To identify pediatric patients with magnetic resonance imaging-confirmed RCI treated at a single center to summarize injury characteristics, treatment, and outcomes. It was hypothesized that injuries would occur predominantly in overhead throwing athletes and would demonstrate good outcomes among both operatively and nonoperatively treated patients.

STUDY DESIGN: Cross-sectional study.

LEVEL OF EVIDENCE: Level 4.

METHODS: A retrospective review of pediatric patients (<18 years old) diagnosed with and treated for an RCI between January 1, 2011 and January 31, 2021. Patient demographics, injury mechanism and type, treatment, and outcomes were collected. Descriptive statistics were performed. Bivariate testing was used to compare operatively and nonoperatively treated cohorts.

RESULTS: A total of 52 pediatric patients treated for a rotator cuff avulsion, partial tear, or complete tear were identified. Mean age was 15 years and 67% of patients were male. Injuries were related most commonly to participation in throwing sports. Operative management occurred in 23% of patients, while 77% were managed nonoperatively. Treatment cohorts differed based on tear type, with all complete tears being managed operatively (P < 0.01). Associated shoulder pathology was common, with the most frequent finding being anterior shoulder instability pathology. Return to play was longer for operatively managed patients (7.1 vs 4.5 months; P < 0.01).

CONCLUSION: The present study expands the limited data available regarding RCIs in pediatric patients. Most injuries are associated with sports and involve the supraspinatus tendon. RCIs were associated with good outcomes and low rates of reinjury in patients managed both nonoperative and operatively. RCI should be considered in throwing athletes with shoulder pain, even in skeletally immature patients.

CLINICAL RELEVANCE: This retrospective study fills the hole in the literature by detailing the patterns associated with RCI characteristics and treatment outcomes. In contrast to studies of adult RCIs, our results suggest that outcomes are good regardless of treatment type.

PMID:37246566 | DOI:10.1177/19417381231174021

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Effect of different production methods on quality parameters of Hatay Künefe cheese

J Dairy Res. 2023 May 29:1-5. doi: 10.1017/S0022029923000298. Online ahead of print.

ABSTRACT

We investigated four different production methods of Künefe cheese, emphasizing their industrial importance. The four methods used fresh Künefe cheese (FKC), salted Künefe cheese (SKC), Boru type Künefe cheese (BKC) and culture-added processed Künefe cheese (CPKC), all used in the production of Künefe, a syrupy dessert unique to the Middle East. FKC was produced as a result of curd formation from raw milk with rennet and then the fermentation of curd. SKC was manufactured using the salting method in addition to FKC production. BKC was obtained using the dry cooking process with emulsifying salts applied to cheese curd. CPKC was produced by applying heat treatment to raw milk and using starter culture before adding rennet that was different to Boru-type Künefe cheese. The composition, color, meltability, texture and sensory properties of the Künefe cheeses were examined. As a result of statistical analysis, it was determined that the effect of different production methods on the composition, meltability, texture (except springiness and cohesiveness) and sensory properties was significant in all cheeses (P < 0.05). CKPC was the most appropriate cheese in various properties.

PMID:37246551 | DOI:10.1017/S0022029923000298