Tag: nevin manimala

J Med Internet Res. 2022 Dec 1;24(12):e41527. doi: 10.2196/41527.

ABSTRACT

BACKGROUND: There is no recognized gold standard method for estimating the number of individuals with substance use disorders (SUDs) seeking help within a given geographical area. This presents a challenge to policy makers in the effective deployment of resources for the treatment of SUDs. Internet search queries related to help seeking for SUDs using Google Trends may represent a low-cost, real-time, and data-driven infoveillance tool to address this shortfall in information.

OBJECTIVE: This paper assesses the feasibility of using search query data related to help seeking for SUDs as an indicator of unmet treatment needs, demand for treatment, and predictor of the health harms related to unmet treatment needs. We explore a continuum of hypotheses to account for different outcomes that might be expected to occur depending on the demand for treatment relative to the system capacity and the timing of help seeking in relation to trajectories of substance use and behavior change.

METHODS: We used negative binomial regression models to examine temporal trends in the annual SUD help-seeking internet search queries from Google Trends by US state for cocaine, methamphetamine, opioids, cannabis, and alcohol from 2010 to 2020. To validate the value of these data for surveillance purposes, we then used negative binomial regression models to investigate the relationship between SUD help-seeking searches and state-level outcomes across the continuum of care (including lack of care). We started by looking at associations with self-reported treatment need using data from the National Survey on Drug Use and Health, a national survey of the US general population. Next, we explored associations with treatment admission rates from the Treatment Episode Data Set, a national data system on SUD treatment facilities. Finally, we studied associations with state-level rates of people experiencing and dying from an opioid overdose, using data from the Agency for Healthcare Research and Quality and the CDC WONDER database.

RESULTS: Statistically significant differences in help-seeking searches were observed over time between 2010 and 2020 (based on P<.05 for the corresponding Wald tests). We were able to identify outlier states for each drug over time (eg, West Virginia for both opioids and methamphetamine), indicating significantly higher help-seeking behaviors compared to national trends. Results from our validation analyses across different outcomes showed positive, statistically significant associations for the models relating to treatment need for alcohol use, treatment admissions for opioid and methamphetamine use, emergency department visits related to opioid use, and opioid overdose mortality data (based on regression coefficients having P≤.05).

CONCLUSIONS: This study demonstrates the clear potential for using internet search queries from Google Trends as an infoveillance tool to predict the demand for substance use treatment spatially and temporally, especially for opioid use disorders.

PMID:36454620 | DOI:10.2196/41527

JAMA Netw Open. 2022 Dec 1;5(12):e2244486. doi: 10.1001/jamanetworkopen.2022.44486.

ABSTRACT

IMPORTANCE: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use.

OBJECTIVE: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form-Cognitive Function 8a scale, for which population-normed T scores were reported.

EXPOSURES: SARS-CoV-2 status (positive or negative test result) at enrollment.

MAIN OUTCOMES AND MEASURES: Mean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis.

RESULTS: Among 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19-positive group and 147 of 275 participants (53.5%) in the COVID-19-negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19-positive group vs the COVID-19-negative group only for social participation (β = 3.32; 95% CI, 1.84-4.80; P < .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19-positive group were concentrated among participants aged 18 to 34 years (eg, social participation: β = 3.90; 95% CI, 1.75-6.05; P < .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: β = 4.16; 95% CI, 2.12-6.20; P < .001).

CONCLUSIONS AND RELEVANCE: In this study, participants in both the COVID-19-positive and COVID-19-negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19.

PMID:36454572 | DOI:10.1001/jamanetworkopen.2022.44486

JAMA Netw Open. 2022 Dec 1;5(12):e2244505. doi: 10.1001/jamanetworkopen.2022.44505.

ABSTRACT

IMPORTANCE: SARS-CoV-2, which causes COVID-19, poses considerable morbidity and mortality risks. Studies using data collected during routine clinical practice can supplement randomized clinical trials to provide needed evidence, especially during a global pandemic, and can yield markedly larger sample sizes to assess outcomes for important patient subgroups.

OBJECTIVE: To evaluate the association of remdesivir treatment with inpatient mortality among patients with COVID-19 outside of the clinical trial setting.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study in US hospitals using health insurance claims data linked to hospital chargemaster data from December 1, 2018, to May 3, 2021, was conducted among 24 856 adults hospitalized between May 1, 2020, and May 3, 2021, with newly diagnosed COVID-19 who received remdesivir and 24 856 propensity score-matched control patients.

EXPOSURE: Remdesivir treatment.

MAIN OUTCOMES AND MEASURES: All-cause inpatient mortality within 28 days of the start of remdesivir treatment for the remdesivir-exposed group or the matched index date for the control group.

RESULTS: A total of 24 856 remdesivir-exposed patients (12 596 men [50.7%]; mean [SD] age, 66.8 [15.4] years) and 24 856 propensity score-matched control patients (12 621 men [50.8%]; mean [SD] age, 66.8 [15.4] years) were included in the study. Median follow-up was 6 days (IQR, 4-11 days) in the remdesivir group and 5 days (IQR, 2-10 days) in the control group. There were 3557 mortality events (14.3%) in the remdesivir group and 3775 mortality events (15.2%) in the control group. The 28-day mortality rate was 0.5 per person-month in the remdesivir group and 0.6 per person-month in the control group. Remdesivir treatment was associated with a statistically significant 17% reduction in inpatient mortality among patients hospitalized with COVID-19 compared with propensity score-matched control patients (hazard ratio, 0.83 [95% CI, 0.79-0.87]).

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study using health insurance claims and hospital chargemaster data, remdesivir treatment was associated with a significantly reduced inpatient mortality overall among patients hospitalized with COVID-19. Results of this analysis using data collected during routine clinical practice and state-of-the-art methods complement results from randomized clinical trials. Future areas of research include assessing the association of remdesivir treatment with inpatient mortality during the circulation of different variants and relative to time from symptom onset.

PMID:36454570 | DOI:10.1001/jamanetworkopen.2022.44505

Pathology. 2022 Oct 13:S0031-3025(22)00270-7. doi: 10.1016/j.pathol.2022.08.004. Online ahead of print.

ABSTRACT

Primary appendiceal adenocarcinoma (APCA), goblet cell adenocarcinoma (GCA), and low/high-grade appendiceal mucinous neoplasms (LAMN/HAMN) are distinct entities with overlapping clinical presentation and histomorphology, leading to diagnostic challenges. We retrospectively reviewed our archived cases between 2010 and 2018 for diagnosis reappraisal and comparative analysis using updated terminology and modern parameters. A total of 87 cases (22 APCA, 40 GCA, and 25 LAMN pT≥3) were included. The entire cohort had 49 women and 38 men with a median age of 59.9 (range 26-88) years. There were no statistically significant differences in age and sex among the three groups. Clinically, patients with GCA were more likely to present with acute appendicitis (65%) and more likely to have appendectomy as initial surgery (68%). Both APCA and GCA were more likely to involve the proximal appendix while LAMN was more likely to involve the distal appendix (p<0.05). All APCAs were associated with mucosal precursor lesions, most commonly tubular, tubulovillous, or villous adenoma, flat LAMN/HAMN-pTis mucinous epithelium, or mixed, which correlated with distinct histomorphology, tumour differentiation, and stage. Although polypoid precursor lesions were rare in GCA, a significant proportion of GCA showed crypt atypia associated with neoplastic cells. Immunohistochemically, APCA had more frequent β-catenin nuclear positivity and loss of SATB2 expression (p<0.05). KRAS mutation was more common in APCA than in GCA (8/11 vs 1/7, p<0.01). We further validated the three-tiered grading system (G1, G2, G3) in GCA, which correlated well with tumour stage and patient survival. APCA had worse progression-free and disease-specific survivals than GCA and LAMN (pT≥3) with the latter being relatively indolent even when perforated with peritoneal spread. Our study is the first comprehensive comparison between all three appendiceal neoplasms. We also describe a spectrum of previously under-recognised crypt atypia in GCA, which should trigger a diligent search for GCA if present.

PMID:36454563 | DOI:10.1016/j.pathol.2022.08.004

JAMA Otolaryngol Head Neck Surg. 2022 Dec 1. doi: 10.1001/jamaoto.2022.3781. Online ahead of print.

ABSTRACT

IMPORTANCE: Tall cell morphology (TCM) is a rare and aggressive variant of papillary thyroid carcinoma (PTC) that has been associated with poor outcomes; however, the risk factors for worse survival are not well characterized.

OBJECTIVE: To identify prognostic factors associated with cancer recurrence and death in patients with PTC-TCM.

DESIGN, SETTING, AND PARTICIPANTS: All patients treated for PTC-TCM at a single tertiary-level academic health care institution from January 1, 1997, through July 31, 2018, were included. Tall cell variant (TCV) was defined as PTC with TCM of 30% or more; and tall cell features (TCF) was defined as PTC with TCM of less than 30%. Patients with other coexisting histologic findings and/or nonsurgical management were excluded. Clinicopathologic features associated with worse outcomes were identified using Kaplan-Meier and Cox proportional-hazards model. Data were analyzed from March 1, 2018, to August 15, 2018.

MAIN OUTCOMES AND MEASURES: Locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and overall survival (OS) after surgery.

RESULTS: A total of 365 patients (median [range] age, 51.8 [15.9-91.6] years; 242 [66.3%] female) with PTC-TCM (TCV, 32%; TCF, 68%) were evaluable. Total thyroidectomy was performed in 336 (92%) patients; 19 (5.2%) received radiotherapy; and 15 (4.1%) received radioactive iodine. Clinical features were pT3 or T4, 65%; node-positive, 53%; and positive surgical margins, 24%. LRRFS at 1-, 3-, 5-, and 10-year was 95%, 87%, 82%, and 73%, respectively. On multivariable analysis, male sex and age were not independent predictors of inferior 5-year LRRFS, whereas positive surgical margins (HR, 3.5; 95% CI, 2.0-6.3), positive lymph nodes (HR, 2.8; 95% CI, 1.4-5.8), and primary tumor size of 3 cm or more (HR, 3.3; 95% CI, 1.4-7.8) were strongly associated with worse LRRFS. Age 55 years or older (HR, 3.2; 95% CI, 1.5-7.0), male sex (HR 4.5; 95% CI, 2.1-10.0), positive surgical margins (HR, 2.7; 95% CI, 1.2-6.0), nodal positivity (HR, 3.1; 95% CI, 1.3-7.7), tumor diameter of 1.5 cm or more (HR, 20.6; 95% CI, 2.8-152.1), and TCV vs TCF (HR, 3.1; 95% CI, 1.5-6.7) were associated with worse DRFS. Male sex (HR, 3.1; 95% 1.4-6.8) and tumor diameter of 1.5 cm or more (HR, 2.8; 95% CI, 1.0-7.4) were associated with worse OS. A findings-based nomogram was constructed to predict 10-year LRRFS (C index, 0.8).

CONCLUSIONS AND RELEVANCE: This retrospective cohort study found that in patients with PTC-TCM, positive surgical margins, node positive disease, and tumor size of 3 cm or more were risk factors for worse LRRFS. Intensified locoregional therapy, including adjuvant radiation, may be considered for treating these patients.

PMID:36454559 | DOI:10.1001/jamaoto.2022.3781

JAMA Ophthalmol. 2022 Dec 1. doi: 10.1001/jamaophthalmol.2022.4942. Online ahead of print.

ABSTRACT

IMPORTANCE: The association of proliferative diabetic retinopathy (PDR) interventions of panretinal photocoagulation (PRP) and intravitreal injections (IVIs) with tractional retinal detachment (TRD) is unclear.

OBJECTIVES: To determine whether different treatment types or a 6-month or longer period of loss to follow-up (LTFU) is associated with TRD.

DESIGN, SETTING, AND PARTICIPANTS: This nested case-control study included data from January 1, 2000, to June 30, 2021, of patients with PDR. Those who progressed to TRD were matched to non-TRD controls up to a 5:1 ratio. Exclusion criteria included 2 or fewer years in the plan, history of nondiabetic retinopathy, vitreous hemorrhage, previous RD, or any other surgically indicated diagnosis. Patient data were obtained from a deidentified commercial and Medicare Advantage medical claims database. Statistical analysis was performed from January to May 2022.

EXPOSURES: Primary exposures of interest were prior treatment (PRP, IVI, both) and any period of 6 months or longer in which the patient received no eye care.

MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) of IVI only compared with PRP and 6-month or longer LTFU on development of TRD.

RESULTS: After application of inclusion and exclusion criteria, a total of 214 patients (mean [SD] age, 55.6 [12.4] years; 115 female [53.7%]) with PDR and TRD were matched to 978 controls (mean [SD] age, 65.6 [11.3] years; 507 female [51.8%]) with only PDR. Among patients with TRD, 69 (32.2%) were treated with laser only, 17 (7.9%) were treated with injection only, 39 (18.2%) were treated with both, and 89 (41.6%) had no prior treatment. Among patients in the PDR-only group, 207 (21.2%) received laser only, 83 (8.5%) received injection only, 57 (5.8%) received both, and 631 (64.5%) received no treatment. After adjusted analysis, no difference in odds of TRD for patients who received injection only compared with patients who received laser only was found (adjusted OR [aOR], 0.56; 95% CI, 0.27-1.14). Patients who received both treatments had higher odds of TRD compared with those who received laser only (aOR, 2.33; 95% CI, 1.21-4.48), and patients who had no treatment had lower odds of TRD (aOR, 0.46; 95% CI, 0.29-0.71; P < .001 for treatment category). Similarly, no difference was seen in the odds of TRD between those with LTFU for 6 months or longer and those without LTFU (aOR, 0.72; 95% CI, 0.49-1.07; P = .11).

CONCLUSIONS AND RELEVANCE: Results of this case-control analysis suggest that there is no increased risk of TRD associated with IVI-only treatment or with 6-month or longer periods of LTFU, which supports the findings of other investigations. Nonetheless, LTFU rates continue to remain high in patients with PDR, which can contribute to substantial vision loss regardless of treatment regimen.

PMID:36454552 | DOI:10.1001/jamaophthalmol.2022.4942

Protein Sci. 2022 Dec 1:e4523. doi: 10.1002/pro.4523. Online ahead of print.

ABSTRACT

Understanding protein-protein interactions (PPIs) is fundamental to infer how different molecular systems work. A major component to model molecular recognition is the Buried Surface Area (BSA), i.e., the area that becomes inaccessible to solvent upon complex formation. Till date many attempts tried to connect BSA to molecular recognition principles, and in particular, to the underlying binding affinity. However, the most popular approach to calculate BSA is to use a single (or in some cases few) bound structures, consequently neglecting a wealth of structural information of the interacting proteins derived from ensembles corresponding to their unbound and bound states. Moreover, the most popular method inherently assumes the component proteins to bind as rigid entities. To address the above shortcomings, we developed a Monte Carlo method-based Interface Residue Assessment Algorithm (IRAA), to calculate a combined distribution of BSA for a given complex. Further, we apply our algorithm to human ACE2 and SARS-CoV-2 Spike protein complex, a system of prime importance. Results show a much broader distribution of BSA compared to that obtained from only the bound structure or structures and extended residue members of the interface with implications to the underlying biomolecular recognition. We derive that specific interface residues of ACE2 and of S-protein are consistently highly flexible, whereas other residues systematically show minor conformational variations. In effect, IRAA facilitates use of all available structural data for any biomolecular complex of interest, extracting quantitative parameters with statistical significance, thereby providing a deeper biophysical understanding of the molecular system under investigation. This article is protected by copyright. All rights reserved.

PMID:36454539 | DOI:10.1002/pro.4523

Ir J Med Sci. 2022 Dec 1. doi: 10.1007/s11845-022-03239-9. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate urodynamic examination results and treatment methods of neurogenic lower urinary tract dysfunction (NLUTD) in patients with traumatic thoracic spinal cord injury (SCI).

METHODS: Ninety-one patients with traumatic thoracic SCI were included in the study. The urodynamic analyses of the patients were conducted retrospectively using their laboratory outcomes. The patients were divided into subgroups according to the sensory innervation of the bladder (T1-10/T11-12), the preservation of sensory functions in the sacral segment (complete lesion/incomplete lesion), and the duration of injury (< 6 months/ ≥ 6 months) and evaluations in subgroups were carried out.

RESULTS: A total of 91 patients (69 males, 22 females) were included in the study. When comparing between the subgroups, the sense of bladder fullness was preserved more in the T11-T12 group with a statistically significant difference (p < 0.001). While storage disorder, the rate of indwelling catheter use during hospitalization, bacterial growth of 10⁵ CFU/ml in the urine culture, and anticholinergic drug recommendation after urodynamic examination were higher in the complete lesion group, the rate of spontaneous/catheter-free voiding, the number of patients in which sense of bladder fullness was preserved-partially preserved, and alpha-blocker drug recommendation after urodynamic examination was higher in the incomplete lesion group, with a statistically significant difference in all parameters (all p values < 0.05).

CONCLUSION: Our results demonstrate that there are differences in neurogenic lower urinary tract dysfunction features in subgroups of traumatic thoracic SCI patients. Regular urinary system evaluation and necessary changes in treatment should be carried out in this patient group.

PMID:36454536 | DOI:10.1007/s11845-022-03239-9

Indian J Pediatr. 2022 Dec 1. doi: 10.1007/s12098-022-04350-6. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe prevalence of various imaging findings in chronic granulomatous disease (CGD) patients; and find imaging biomarkers for differentiating chest infections caused by different micro-organisms.

METHODS: A retrospective study was conducted on 15 patients (49 scans) with proven CGD. Scans which had a correlative microbiological diagnosis for organisms were included in the analysis. The scans were reviewed by 3 radiologists on a predefined proforma, under the lung parenchymal, airway, pleural, mediastinal, and extrathoracic abnormalities. Analysis of various imaging parameters on a semiquantitative scale was performed, followed by a correlation of each imaging findings with causative organisms.

RESULT: The mean age of presentation was nearly 7 y, with a male preponderance. Definitive proof of causative organisms was obtained in 22 scans. Bacterial infection was found in 7, fungal in 12, tubercular in 2, and viral in 1 scan. Most prevalent thoracic imaging manifestations included lymphadenopathy (commonest), consolidation, nodules, air trapping, and bronchiectasis. Fungal infections showed necrotic conglomerate lymphadenopathy, cavitating nodules, and multilobar consolidation more frequently than bacterial infections (though not statistically significant). Abscesses and lymphadenopathy were the most common extrathoracic manifestations.

CONCLUSION: In patients with CGD, multifocal or multilobar consolidation, mass-like consolidation, cavitating nodules, and conglomerate necrotic lymphadenopathy should alert the radiologist to a possible fungal cause.

PMID:36454508 | DOI:10.1007/s12098-022-04350-6

Forensic Toxicol. 2022 Jul;40(2):357-365. doi: 10.1007/s11419-022-00627-9. Epub 2022 May 10.

ABSTRACT

PURPOSE: Prevalence measures of sociological interest concerning cocaine presence on banknotes are fraught with (i) the extreme variability of its concentration (seven orders of magnitude); (ii) the high number of banknotes needed for the statistical significance. Banknote dust from counting machines from a large and representative number of banknotes in circulation in a specific area represents the most eligible sample to ascertain cocaine circulation. No chromatographic method is available in this respect. This study aims at developing the first analytical methodology for the determination of cocaine in banknote dust samples.

METHODS: This novel and straightforward approach consists of a simple methanol extraction followed by analytical determinations via ultra-high performance liquid chromatography coupled to Orbitrap high-resolution mass spectrometry.

RESULTS: Satisfactory analytical performance was obtained with a coefficient of determination of 0.996; maximum within-run and between-run precisions were, respectively, 1.85% and 5.20%. Limits of detection and quantification were, respectively, 3 and 9 ng/mL with an overall process efficiency of 93.2%. The method developed was successfully applied to 9 banknote dust samples from local banknote counter machines. The found concentrations ranged from 2.18E + 02 to 2.31E + 03 μg of cocaine per gram of banknote dust and varied only one order of magnitude, much less than cocaine concentration on banknotes.

CONCLUSIONS: To have an idea of cocaine circulation in a geographical area, the sampling of banknote dust, compared to banknotes, consists of tremendous advantages in terms of statistical significance, higher cocaine concentrations, and lower variability: this is crucial from the sociological point of view.

PMID:36454419 | DOI:10.1007/s11419-022-00627-9