Category: Nevin Manimala

Trials. 2022 Jul 27;23(1):601. doi: 10.1186/s13063-022-06516-1.

ABSTRACT

BACKGROUND: To assess the quality of reporting of RCT protocols approved by UK research ethics committees before and after the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline.

METHODS: We had access to RCT study protocols that received ethical approval in the UK in 2012 (n=103) and 2016 (n=108). From those, we assessed the adherence to the 33 SPIRIT items (i.e. a total of 64 components of the 33 SPIRIT items). We descriptively analysed the adherence to SPIRIT guidelines as proportion of adequately reported items (median and interquartile range [IQR]) and stratified the results by year of approval and sponsor.

RESULTS: The proportion of reported SPIRIT items increased from a median of 64.9% (IQR, 57.6-69.2%) in 2012 to a median of 72.5% (IQR, 65.3-78.3%) in 2016. Industry-sponsored RCTs reported more SPIRIT items in 2012 (median 67.4%; IQR, 64.1-69.4%) compared to non-industry-sponsored trials (median 59.8%; IQR, 46.5-67.7%). This gap between industry- and non-industry-sponsored trials increased in 2016 (industry-sponsored: median 75.6%; IQR, 71.2-79.0% vs non-industry-sponsored: median 65.3%; IQR, 51.6-76.3%).

CONCLUSIONS: The adherence to SPIRIT guidelines has improved in the UK from 2012 to 2016 but remains on a modest level, especially for non-industry-sponsored RCTs.

PMID:35897110 | DOI:10.1186/s13063-022-06516-1

BMC Ophthalmol. 2022 Jul 27;22(1):323. doi: 10.1186/s12886-022-02548-y.

ABSTRACT

PURPOSE: To compare the visual outcomes of digital and slit-beam manual marking for toric intraocular lenses (IOL) in cataract surgery.

SETTING: Single-center, Beijing Tongren Hospital, China.

DESIGN: Retrospective study.

METHODS: All patients with cataracts and regular corneal astigmatism greater than 0.75 diopters (D) underwent cataract surgery and astigmatism correction between June 2019 and June 2020. To mark the target axis of the toric IOL and the location of the incision, intraoperative digital marking was used by Callisto eye image-guided system in one group, while preoperative manual slit-beam marking was used in the other group. Uncorrected and best-corrected spectacle visual acuity, refraction, toric IOL axis, total higher order aberrations, coma, spherical aberration, and trefoil were evaluated at 1, 4, and 12 weeks postoperatively.

RESULTS: Seventy-two eyes of 58 patients were included. At 3 months after surgery, the mean residual refractive cylinder was 0.42 ± 0.45D in the digital group and 0.39 ± 0.40D in the manual group (P = 0.844). There were no significant differences between groups in spherical equivalent refraction, uncorrected and best-corrected spectacle visual acuity, or the parameters of vector analysis. All toric IOL alignment errors were within 10° of the intended axis, and among them, about 42% of eyes in the digital group and 61% of eyes in the manual group had a rotation of 0-2° (P = 0.038). Trefoil in the manual group decreased postoperatively compared with the digital group (P = 0.012). Other aberration analyses did not reveal any statistical differences between groups.

CONCLUSIONS: Accurate slit-beam manual marking and digital image-guided marking are equally effective for toric IOL alignment.

PMID:35897093 | DOI:10.1186/s12886-022-02548-y

BMC Public Health. 2022 Jul 27;22(1):1432. doi: 10.1186/s12889-022-13826-1.

ABSTRACT

BACKGROUND: Evidence on the association between the presence of fast-food outlets and Body Mass Index (BMI) is inconsistent. Furthermore, mechanisms underlying the fast-food outlet presence-BMI association are understudied. We investigated the association between the number of fast-food outlets being present and objectively measured BMI. Moreover, we investigated to what extent this association was moderated by neighbourhood socio-economic status (NSES) and healthy food outlets. Additionally, we investigated mediation by frequency of fast-food consumption and amount of fat intake.

METHODS: In this cross-sectional study, we used baseline data of adults in Lifelines (N = 149,617). Geo-coded residential addresses were linked to fast-food and healthy food outlet locations. We computed the number of fast-food and healthy food outlets within 1 kilometre (km) of participants’ residential addresses (each categorised into null, one, or at least two). Participants underwent objective BMI measurements. We linked data to Statistics Netherlands to compute NSES. Frequency of fast-food consumption and amount of fat intake were measured through questionnaires in Lifelines. Multivariable multilevel linear regression analyses were performed to investigate associations between fast-food outlet presence and BMI, adjusting for individual and environmental potential confounders. When exposure-moderator interactions had p-value < 0.10 or improved model fit (∆AIC ≥ 2), we conducted stratified analyses. We used causal mediation methods to assess mediation.

RESULTS: Participants with one fast-food outlet within 1 km had a higher BMI than participants with no fast-food outlet within 1 km (B = 0.11, 95% CI: 0.01, 0.21). Effect sizes for at least two fast-food outlets were larger in low NSES areas (B = 0.29, 95% CI: 0.01, 0.57), and especially in low NSES areas where at least two healthy food outlets within 1 km were available (B = 0.75, 95% CI: 0.19, 1.31). Amount of fat intake, but not frequency of fast-food consumption, explained this association for 3.1%.

CONCLUSIONS: Participants living in low SES neighbourhoods with at least two fast-food outlets within 1 km of their residential address had a higher BMI than their peers with no fast-food outlets within 1 km. Among these participants, healthy food outlets did not buffer the potentially unhealthy impact of fast-food outlets. Amount of fat intake partly explained this association. This study highlights neighbourhood socio-economic inequalities regarding fast-food outlets and BMI.

PMID:35897088 | DOI:10.1186/s12889-022-13826-1

Pilot Feasibility Stud. 2022 Jul 27;8(1):158. doi: 10.1186/s40814-022-01113-0.

ABSTRACT

BACKGROUND: Persistent pain in adolescence adversely affects everyday life and is an important public health problem. The primary aim was to determine the feasibility of an 8-week app-based self-management intervention to reduce pain and improve health-related quality of life in a community-based population of adolescents with persistent pain. A secondary aim was to explore differences in health outcomes between the intervention and control groups.

METHODS: A sample of 73 adolescents aged 16-19 years with persistent pain from a community-based population were randomized into 2 groups. The intervention group received the Norwegian culturally adapted version of the iCanCope with Pain^TM app, which includes symptom tracking, goal setting, self-management strategies, and social support. The attention control group received a symptom tracking app. Feasibility was assessed as attrition rates and level of engagement (interactions with the app). The secondary outcomes included pain intensity, health-related quality of life, self-efficacy, pain self-efficacy, perceived social support from friends, anxiety and depression, and patient global impression. Statistical analyses were conducted using SPSS.

RESULTS: Demographic and baseline outcome variables did not differ between the 2 groups. No differences were found between the participants completing the study and those who withdrew. Twenty-eight adolescents completed the intervention as planned (62% attrition). Both groups had a low level of app engagement. Intention-to-treat analysis (n = 19 + 14) showed no significant differences in outcomes between groups. However, the large effect size (Cohen’s d = .9) for depression suggested a lower depression score in the intervention group.

CONCLUSIONS: High treatment attrition and low engagement indicate the need for changes in trial design in a full-scale randomized controlled trial to improve participant retention.

TRIAL REGISTRATION: The iCanCope with Pain Norway trial was retrospectively registered in Clinical Trials.gov (ID: NCT03551977 ). Registered 6 June 2018.

PMID:35897086 | DOI:10.1186/s40814-022-01113-0

Alzheimers Res Ther. 2022 Jul 27;14(1):105. doi: 10.1186/s13195-022-01048-x.

ABSTRACT

BACKGROUND: The ability of ¹⁸F-PI-2620 PET to measure the spatial distribution of tau pathology in Alzheimer’s disease (AD) has been demonstrated in previous studies. The objective of this work was to evaluate tau deposition using ¹⁸F-PI-2620 PET in beta-amyloid positive subjects with a diagnosis of mild cognitive impairment (MCI) or mild AD dementia and characterize it with respect to amyloid deposition, cerebrospinal fluid (CSF) assessment, hippocampal volume, and cognition.

METHODS: Subjects with a diagnosis of MCI due to AD or mild AD dementia and a visually amyloid-positive ¹⁸F-florbetaben PET scan (n=74, 76 ± 7 years, 38 females) underwent a baseline ¹⁸F-PI-2620 PET, T1-weighted magnetic resonance imaging (MRI), CSF assessment (Aβ42/Aβ40 ratio, p-tau, t-tau) (n=22) and several cognitive tests. A 1-year follow-up ¹⁸F-PI-2620 PET scans and cognitive assessments were done in 15 subjects.

RESULTS: Percentage of visually tau-positive scans increased with amyloid-beta deposition measured in ¹⁸F-florbetaben Centiloids (CL) (7.7% (<36 CL), 80% (>83 CL)). ¹⁸F-PI-2620 standardized uptake value ratio (SUVR) was correlated with increased ¹⁸F-florbetaben CL in several regions of interest. Elevated ¹⁸F-PI-2620 SUVR (fusiform gyrus) was associated to high CSF p-tau and t-tau (p=0.0006 and p=0.01, respectively). Low hippocampal volume was associated with increased tau load at baseline (p=0.006 (mesial temporal); p=0.01 (fusiform gyrus)). Significant increases in tau SUVR were observed after 12 months, particularly in the mesial temporal cortex, fusiform gyrus, and inferior temporal cortex (p=0.04, p=0.047, p=0.02, respectively). However, no statistically significant increase in amyloid-beta load was measured over the observation time. The MMSE (Recall score), ADAS-Cog14 (Word recognition score), and CBB (One-card learning score) showed the strongest association with tau deposition at baseline.

CONCLUSIONS: The findings support the hypothesis that ¹⁸F-PI-2620 PET imaging of neuropathologic tau deposits may reflect underlying neurodegeneration in AD with significant correlations with hippocampal volume, CSF biomarkers, and amyloid-beta load. Furthermore, quantifiable increases in ¹⁸F-PI-2620 SUVR over a 12-month period in regions with early tau deposition are consistent with the hypothesis that cortical tau is associated with cognitive impairment. This study supports the utility of ¹⁸F-PI-2620 PET to assess tau deposits in an early AD population. Quantifiable tau load and its corresponding increase in early AD cases could be a relevant target engagement marker in clinical trials of anti-amyloid and anti-tau agents.

TRIAL REGISTRATION: Data used in this manuscript belong to a tau PET imaging sub-study of the elenbecestat MissionAD Phase 3 program registered in ClinicalTrials.gov ( NCT02956486 ; NCT03036280 ).

PMID:35897078 | DOI:10.1186/s13195-022-01048-x

Crit Care. 2022 Jul 27;26(1):228. doi: 10.1186/s13054-022-04079-w.

ABSTRACT

BACKGROUND: While the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as ‘mild’, ‘moderate’ or ‘severe’ based on this fails to capture enormous heterogeneity in pathophysiology and treatment response. We hypothesized that data-driven characterization of TBI could identify distinct endotypes and give mechanistic insights.

METHODS: We developed an unsupervised statistical clustering model based on a mixture of probabilistic graphs for presentation (< 24 h) demographic, clinical, physiological, laboratory and imaging data to identify subgroups of TBI patients admitted to the intensive care unit in the CENTER-TBI dataset (N = 1,728). A cluster similarity index was used for robust determination of optimal cluster number. Mutual information was used to quantify feature importance and for cluster interpretation.

RESULTS: Six stable endotypes were identified with distinct GCS and composite systemic metabolic stress profiles, distinguished by GCS, blood lactate, oxygen saturation, serum creatinine, glucose, base excess, pH, arterial partial pressure of carbon dioxide, and body temperature. Notably, a cluster with ‘moderate’ TBI (by traditional classification) and deranged metabolic profile, had a worse outcome than a cluster with ‘severe’ GCS and a normal metabolic profile. Addition of cluster labels significantly improved the prognostic precision of the IMPACT (International Mission for Prognosis and Analysis of Clinical trials in TBI) extended model, for prediction of both unfavourable outcome and mortality (both p < 0.001).

CONCLUSIONS: Six stable and clinically distinct TBI endotypes were identified by probabilistic unsupervised clustering. In addition to presenting neurology, a profile of biochemical derangement was found to be an important distinguishing feature that was both biologically plausible and associated with outcome. Our work motivates refining current TBI classifications with factors describing metabolic stress. Such data-driven clusters suggest TBI endotypes that merit investigation to identify bespoke treatment strategies to improve care. Trial registration The core study was registered with ClinicalTrials.gov, number NCT02210221 , registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).

PMID:35897070 | DOI:10.1186/s13054-022-04079-w

Ital J Pediatr. 2022 Jul 27;48(1):127. doi: 10.1186/s13052-022-01317-3.

ABSTRACT

According to the latest version of the Diagnostic and Statistical Manual of Mental Disorders, somatic symptom and related disorders (SSRDs) are defined as psychopathological manifestations characterized by physical signs not attributable to organic pathology. Their incidence has grown dramatically over the past few decades, and treatment is challenging. Besides other interventions on the child and the family, physiotherapy is considered an integral part of the treatment, although there is no evidence for its efficacy.The study aimed to review the available proof on the effectiveness of physiotherapy in children and adolescents with SSRDs. A systematic literature search was conducted on MEDLINE/PubMed, CINAHL, Cochrane Library, PsycINFO, and PEDro, including 1999 to 2021. The methodological quality of the publications was assessed by applying the guidelines proposed by the Equator network, according to the different study designs. The scientific bibliography on the subject was minimal and had poor methodological quality. The choice of outcome indicators and the scales to measure them varied from study to study and were not standardized, making comparison and meta-analysis challenging.Conclusion: According to the available evidence, it is impossible to answer the review question regarding the effectiveness of physiotherapy in children and adolescents with SSRDs. It is necessary to improve the methodological quality of the studies. Definition of standard rehabilitation treatments, identification of appropriate result indicators, and adoption of standardized evaluation scales are needed.

PMID:35897067 | DOI:10.1186/s13052-022-01317-3

BMC Endocr Disord. 2022 Jul 27;22(1):193. doi: 10.1186/s12902-022-01107-2.

ABSTRACT

BACKGROUND: In our previous published study, we demonstrated that a qualitatively assessed elevation in deltoid muscle echogenicity on ultrasound was both sensitive for and a strong predictor of a type 2 diabetes (T2DM) diagnosis. This study aims to evaluate if a sonographic quantitative assessment of the deltoid muscle can be used to detect T2DM.

METHODS: Deltoid muscle ultrasound images from 124 patients were stored: 31 obese T2DM, 31 non-obese T2DM, 31 obese non-T2DM and 31 non-obese non-T2DM. Images were independently reviewed by 3 musculoskeletal radiologists, blinded to the patient’s category. Each measured the grayscale pixel intensity of the deltoid muscle and humeral cortex to calculate a muscle/bone ratio for each patient. Following a 3-week delay, the 3 radiologists independently repeated measurements on a randomly selected 40 subjects. Ratios, age, gender, race, body mass index, insulin usage and hemoglobin A_1c were analyzed. The difference among the 4 groups was compared using analysis of variance or chi-square tests. Both univariate and multivariate linear mixed models were performed. Multivariate mixed-effects regression models were used, adjusting for demographic and clinical variables. Post hoc comparisons were done with Bonferroni adjustments to identify any differences between groups. The sample size achieved 90% power. Sensitivity and specificity were calculated based on set threshold ratios. Both intra- and inter-radiologist variability or agreement were assessed.

RESULTS: A statistically significant difference in muscle/bone ratios between the groups was identified with the average ratios as follows: obese T2DM, 0.54 (P < 0.001); non-obese T2DM, 0.48 (P < 0.001); obese non-T2DM, 0.42 (P = 0.03); and non-obese non-T2DM, 0.35. There was excellent inter-observer agreement (intraclass correlation coefficient 0.87) and excellent intra-observer agreements (intraclass correlation coefficient 0.92, 0.95 and 0.94). Using threshold ratios, the sensitivity for detecting T2DM was 80% (95% CI 67% to 88%) with a specificity of 63% (95% CI 50% to 75%).

CONCLUSIONS: The sonographic quantitative assessment of the deltoid muscle by ultrasound is sensitive and accurate for the detection of T2DM. Following further studies, this process could translate into a dedicated, simple and noninvasive screening method to detect T2DM with the prospects of identifying even a fraction of the undiagnosed persons worldwide. This could prove especially beneficial in screening of underserved and underrepresented communities.

PMID:35897066 | DOI:10.1186/s12902-022-01107-2

Arthroplasty. 2022 Jul 27;4(1):34. doi: 10.1186/s42836-022-00129-4.

ABSTRACT

BACKGROUND: Recent studies show an increase in the prevalence of iron deficiency anemia (IDA) worldwide and a concomitant rise in the number of revision total knee arthroplasty (RTKA). The literature evaluating the association between IDA and perioperative outcomes following RTKA are limited. Therefore, the purpose of this study was to determine whether IDA patients undergoing RTKA have higher rates of (1) in-hospital lengths of stay (LOS), (2) complications; and (3) costs.

METHODS: Using International Classification of Disease, Ninth Revision (ICD-9) and Current Procedural Terminology (CPT), a retrospective query was performed from January 1^st, 2005 to March 31^st, 2014. The inclusion criteria consisted of those patients who have IDA undergoing RTKA. Study group patients were 1:5 ratio matched to a comparison cohort by age, sex, and various comorbidities: coronary artery disease, chronic obstructive pulmonary disease, diabetes mellitus, hyperlipidemia, hypertension, obesity, and tobacco use, yielding a total of 106,534 patients within the study (n = 17,784) and control (n = 88,750) cohorts. Outcomes assessed included: in-hospital LOS, costs of care, and medical complications. Multivariate Logistic regression analyses were used to calculate the odds-ratios (OR) and respective 95% confidence intervals (95%CI). Welch’s t-tests were used to compare in-hospital LOS and costs of care. Following Bonferroni-correction, a P-value less than 0.001 was considered statistically significant.

RESULTS: IDA patients undergoing RTKA were found to have significantly higher in-hospital LOS (4-days vs. 3-days, P < 0.0001). Additionally, IDA patients were found to have significantly higher odds (OR) of medical complications (OR: 5.29, P < 0.0001) such as: pneumonia (OR: 6.86, P < 0.0001), respiratory failures (OR: 5.95, P < 0.0001), myocardial infarctions (OR: 4.31, P < 0.0001) and other complications. Furthermore, IDA patients incurred significantly higher day of surgery ($16,976.01 vs. $14,515.81, P < 0.0001) and 90-day costs ($22,548.71 vs. $16,819.15, P < 0.0001).

CONCLUSION: The study demonstrated IDA patients undergoing RTKA have higher rates of in-hospital LOS, costs of care, and medical complications. Orthopedic surgeons and other healthcare professionals can use this information to adequately educate these patients of the potential complications following their procedure.

PMID:35897041 | DOI:10.1186/s42836-022-00129-4

World J Surg Oncol. 2022 Jul 28;20(1):242. doi: 10.1186/s12957-022-02695-y.

ABSTRACT

BACKGROUND: This study aimed to investigate the predictive values of serum biomarkers including absolute eosinophil count (AEC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) with respect to immune-related adverse events (irAEs) during anti-PD-1/PD-L1 inhibitor treatment in patients with advanced malignant tumors.

METHODS: We retrospectively analyzed 95 patients with advanced cancer who were treated with anti-PD-1/PD-L1 inhibitors from January 1, 2017, to May 1, 2020, in our cancer center. We then analyzed associations between irAEs and anti-PD-1/PD-L1 inhibitor responses and evaluated the predictive values of serum biomarkers with respect to the risk of irAEs.

RESULTS: The incidence of irAEs was 55.8%. There were no statistically significant differences between the irAEs and no-irAEs groups in an objective response rate (ORR) or disease control rate (DCR). However, landmark analysis showed that the irAEs group had better survival after 120 days following the initiation of anti-PD-1/PD-L1 inhibitor treatment, compared with the no-irAEs group. The incidences of irAEs were greater in the high-AEC and low-NLR groups than in the low-AEC and high-NLR groups. Univariate logistic analysis showed that low NLR, ECOG performance status (0-1), and high AEC were risk factors for irAEs. Multivariate logistic analysis showed that high AEC and good ECOG performance status were independent predictors for irAEs.

CONCLUSIONS: irAEs may be associated with a survival benefit. Baseline AEC is a strong predictor of irAEs in patients undergoing treatment with anti-PD-1/PD-L1 inhibitors.

PMID:35897018 | DOI:10.1186/s12957-022-02695-y