Nevin Manimala

Pharmacoepidemiol Drug Saf. 2023 Aug 23. doi: 10.1002/pds.5681. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) are common and a leading cause of injury. However, information on ADR risks of individual medicines is often limited. The aim of this hypothesis-generating study was to assess the relative importance of ADR-related and emergency hospital admission for large group of medication classes.

METHODS: This study was a propensity-matched case-control study in English primary care. Data sources were Clinical Practice Research Databank and Aurum with longitudinal, anonymized, patient level electronic health records (EHRs) from English general practices linked to hospital records. Cases aged 65-100 with ADR-related or emergency hospital admission were matched to up to six controls by age, sex, morbidity and propensity scores for hospital admission risk. Medication groups with systemic administration as listed in the British National Formulary (used by prescribers for medication advice). Prescribing in the 84 days before the index date was assessed. Only medication groups with 50+ cases exposed were analysed. The outcomes of interest were ADR-related and emergency hospital admissions. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CI).

RESULTS: The overall population included 121 546 cases with an ADR-related and 849 769 cases with emergency hospital admission. The percentage of hospitalizations with an ADR-related code for admission diagnosis was 1.83% and 6.58% with an ADR-related code at any time during hospitalization. A total of 137 medication groups was included in the main ADR analyses. Of these, 13 (9.5%) had statistically non-significant adjusted ORs, 58 (42.3%) statistically significant ORs between 1.0 and 1.5, 37 (27.0%) between 1.5-2.0, 18 (13.1%) between 2.0-3.0 and 11 (8.0%) 3.0 or higher. Several classes of antibiotics (including penicillins) were among medicines with largest ORs. Evaluating the 14 medications most often associated with ADRs, a strong association was found between the number of these medicines and the risk of ADR-related hospital admission (adjusted OR of 7.53 (95% CI 7.15-7.93) for those exposed to 6+ of these medicines).

CONCLUSIONS AND RELEVANCE: There is a need for a regular systematic assessment of the harm-benefit ratio of medicines, harvesting the information in large healthcare databases and combining it with causality assessment of individual case histories.

PMID:37609702 | DOI:10.1002/pds.5681

J Orthop Res. 2023 Aug 23. doi: 10.1002/jor.25665. Online ahead of print.

ABSTRACT

The aim of the current study is to compare the clinical outcomes of cast immobilization (CI) versus surgical treatment after 1 year for distal radius fractures (DRFs) in the elderly population. The cohort included patients aged 70-89 who suffered an acute, closed, and displaced DRF and who were treated conservatively or surgically at our clinic between August 2018 and January 2022. Those who had pathological fractures, open fractures, concomitant ulna fractures (except ulna styloid fractures), were not between the ages of 70 and 89, or refused to participate were excluded from the study. The study gathered data on patient demographics, initial radiological measurements, clinical measurements after 1 year, treatment models employed, and rates of complications. Of the total number of patients (276), CI was used on 77.2% (213), whereas the other 25 had volar-locked plates (VLP), 25 received external fixators with percutaneous pinning (EFPP), and 13 had isolated percutaneous pinning (IPP). 19 of 276 individuals had complications, with Complex Regional Pain Syndrome and Carpal Tunnel Syndrome being the most often documented. EFPP resulted in significantly higher Disability of the Arm, Shoulder, and Hand (DASH) score values than VLP and IPP at the 1st postoperative year (p < 0.05). No statistically significant difference was found between the DASH score and ROM values at the 1st postoperative year for patients who received CI versus those who underwent surgery (p > 0.05). In the first postoperative year, CI still retains its validity and performs similarly to surgery for DRFs in older individuals. VLPP and IPP methods outperformed EFPP surgeries.

PMID:37609694 | DOI:10.1002/jor.25665

Thorac Cancer. 2023 Aug 23. doi: 10.1111/1759-7714.15080. Online ahead of print.

ABSTRACT

BACKGROUND: This study evaluated the efficacy and safety of the combination chemotherapy of docetaxel plus S-1 in patients with previously treated non-small cell lung cancer (NSCLC) compared to docetaxel alone.

METHODS: Patients with previously treated NSCLC were randomly assigned to docetaxel alone (arm A) or a combination of docetaxel and S-1 (arm B) for a maximum of four cycles. The primary endpoint was overall survival (OS).

RESULTS: The study was terminated early because of poor accrual. The number of patients evaluated were 74 and 77 in arm A and arm B, respectively. The median OS was 9.8 months (95% confidence interval [CI]: 6.8-15.2) and 12.3 months (95% CI: 9.2-14.5) in arms A and B, respectively. In arms A and B, the median progression-free survival was 3.5 months (95% CI: 2.7-4.0) and 4.1 months (95% CI: 3.2-4.7), respectively. No statistically significant difference was observed in OS (hazard ratio [HR]: 0.984, 95% CI: 0.682-1.419, p = 0.4569) or progression-free survival (HR: 0.823, 95% CI: 0.528-1.282, p = 0.0953). The major toxicity was myelosuppression. The incidence of grade 3 or more neutropenia was higher in arm A than in arm B (44.6% vs. 35.1%). However, the incidence of grade 3 or more febrile neutropenia and infection with neutropenia (12.2% vs. 22.1%) was more frequently observed in arm B.

CONCLUSIONS: The prematurely terminated study did not show the benefit of two cytotoxic agents over single-agent therapy for previously treated NSCLC patients.

PMID:37609677 | DOI:10.1111/1759-7714.15080

Front Neurol. 2023 Aug 7;14:1201932. doi: 10.3389/fneur.2023.1201932. eCollection 2023.

ABSTRACT

INTRODUCTION: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder that is potentially reversible and clinically characterized by a specific triad of symptoms, including gait disturbance, cognitive disorders, and urinary incontinence. In INPH assessment, the most commonly used test is the Timed Up and Go test (TUG), but a more comprehensive assessment would be necessary. The first aim of the present study is to verify the sensitivity of a protocol with both clinical and instrumental outcome measures for gait and balance in recognizing INPH patients. The second aim is to verify the most important spatio-temporal parameters in INPH assessment and their possible correlations with clinical outcome measures.

METHODS: Between January 2019 and June 2022, we evaluated 70 INPH subjects. We assessed balance performances with the Berg Balance Scale (BBS), Short Physical Performance Battery (SPPB), and TUG, both single (ST) and dual task (DT). We also performed an instrumental gait assessment with the GAITRite electronic walkway system, asking the patients to walk on the carpet for one minute at normal speed, fast speed, and while performing a dual task. We compared the results with those of 20 age-matched healthy subjects (HS).

RESULTS: INPH patients obtained statistically significant lower scores at the BBS, SPPB, and TUG DT but not at the TUG ST, likely because the DT involves cognitive factors altered in these subjects. Concerning instrumental gait evaluation, we found significant differences between HS and INPH patients in almost all spatio-temporal parameters except cadence, which is considered a relevant factor in INPH guidelines. We also found significant correlations between balance outcome measures and gait parameters.

DISCUSSION: Our results confirm the usefulness of BBS and suggest improving the assessment with SPPB. Although the TUG ST is the most commonly used test in the literature to evaluate INPH performances, it does not identify INPH; the TUG DT, instead, might be more useful. The GAITRite system is recognized as a quick and reliable tool to assess walking abilities and spatio-temporal parameters in INPH patients, and the most useful parameters are stride length, stride width, speed, and the percentage of double support. Both clinical and instrumental evaluation may be useful in recognizing subjects at risk for falls.

PMID:37609661 | PMC:PMC10441237 | DOI:10.3389/fneur.2023.1201932

Front Neurol. 2023 Aug 4;14:1213491. doi: 10.3389/fneur.2023.1213491. eCollection 2023.

ABSTRACT

OBJECTIVE: Swallowing examination is crucial in patients with dysphagia. We aimed to compare qualitative and quantitative videofluoroscopic swallowing study (VFSS) results to provide reference for standardizing quantitative parameters.

MATERIALS AND METHODS: In total, 117 patients with dysphagia were included, 38 with Parkinson’s disease and 39 and 40 in convalescence following cerebral hemorrhage and infarction. VFSS was both qualitatively and quantitatively analyzed.

RESULTS: A significant difference of Oral transit time was found between the oral motor function grades (p < 0.001), also was swallowing reaction times found between swallowing reaction duration grades (p < 0.001), and soft palate lift duration between the soft palate lift grades (p < 0.001). Superior hyoid bone movement (p < 0.001), anterior hyoid bone movement (p < 0.001), hyoid pause time (p < 0.001), and hyoid movement duration (p = 0.032) had significant differences between the hyoid laryngeal complex movement grades, as did the pharyngeal cavity transit time among the cricopharyngeal muscle opening duration grades (p < 0.001). The laryngeal vestibule closure duration differed among the glottic closure grades (p < 0.001). No statistically significant difference in upper esophageal sphincter opening diameter (p = 0.682) or duration (p = 0.682) among the cyclopharyngeal muscle opening duration grades. The pharyngeal area at rest did not significantly differ among the different vallecular residue (p = 0.202) and pyriform sinus residue (p = 0.116) grades.

CONCLUSION: Several quantitative parameters can reflect the swallowing assessment process well. Further optimization of quantitative parameters is recommended.

PMID:37609654 | PMC:PMC10441781 | DOI:10.3389/fneur.2023.1213491

Clin Ophthalmol. 2023 Aug 17;17:2423-2428. doi: 10.2147/OPTH.S407538. eCollection 2023.

ABSTRACT

PURPOSE: To compare the prediction accuracy of the Argos biometer using standard keratometry to the prediction accuracy of the IOLMaster 700 biometer using Total Keratometry.

METHODS: This was a randomized, prospective, single surgeon study of 80 right eyes of 80 patients that had preoperative biometry with both the Argos and IOLMaster 700 devices, followed by cataract surgery and intraocular lens (IOL) implantation. Prediction errors (directional and absolute) for each device were determined from the 1 month postoperative manifest refraction.

RESULTS: The directional prediction error was 0.07 ± 0.32 D for the Argos and 0.08 ± 0.34 D for the IOLMaster 700. The mean of the difference in prediction error (directional) was 0.02 D, which was not statistically significant (p > 0.05). The absolute prediction error was 0.21 ± 0.25 D for the Argos and 0.25 ± 0.24 D for the IOLMaster 700. The mean of the difference in absolute prediction error was 0.04 D, which was statistically significant (p < 0.004) but not clinically significant. The percentage of eyes with absolute prediction error ≤ 0.5 D was 91% (73 eyes) for the Argos and 88% (70 eyes) for the IOLMaster 700. This difference was not statistically significant.

CONCLUSION: The prediction accuracies were similar between the Argos and IOLMaster 700 in eyes with normal axial length. There was a significant difference in mean absolute prediction error between devices; however, this was not clinically meaningful.

PMID:37609646 | PMC:PMC10441632 | DOI:10.2147/OPTH.S407538

iScience. 2023 Jul 4;26(8):107269. doi: 10.1016/j.isci.2023.107269. eCollection 2023 Aug 18.

ABSTRACT

We present DoSurvive, a user-friendly survival analysis web tool and a cancer prognostic biomarker centered database. DoSurvive is the first database that allows users to perform multivariant survival analysis for cancers with customized gene/patient list. DoSurvive offers three survival analysis methods, Log rank test, Cox regression and accelerated failure time model (AFT), for users to analyze five types of quantitative features (mRNA, miRNA, lncRNA, protein and methylation of CpG islands) with four survival types, i.e. overall survival, disease-specific survival, disease-free interval, and progression-free interval, in 33 cancer types. Notably, the implemented AFT model provides an alternative method for genes/features which failed the proportional hazard assumption in Cox regression. With the unprecedented number of survival models implemented and high flexibility in analysis, DoSurvive is a unique platform for the identification of clinically relevant targets for cancer researcher and practitioners. DoSurvive is freely available at http://dosurvive.lab.nycu.edu.tw/.

PMID:37609633 | PMC:PMC10440714 | DOI:10.1016/j.isci.2023.107269

J Pept Sci. 2023 Aug 22:e3537. doi: 10.1002/psc.3537. Online ahead of print.

ABSTRACT

The aim of this research was to select the fragments that make up the outer layer of the collagen IV (COL4A6) protein and to assess their potential usefulness for regenerative medicine. It was expected that because protein-protein interactions take place via contact between external domains, the set of peptides forming the outer sphere of collagen IV will determine its interaction with other proteins. Cellulose-immobilized protein fragment libraries treated with polyclonal anti-collagen IV antibodies were used to select the peptides forming the outer sphere of collagen IV. In the first test, 33 peptides that strongly interacted with the polyclonal anti-collagen IV antibodies were selected from a library of non-overlapping fragments of collagen IV. The selected fragments of collagen IV (cleaved from the cellulose matrix) were tested for their cytotoxicity, their effects on cell viability and proliferation, and their impact on the formation of reactive oxygen species (ROS). The studies used RAW 264.7 mouse macrophage cells and Hs 680.Tr human fibroblasts. PrestoBlue, ToxiLight™, and ToxiLight 100% Lysis Control assays were conducted. The viability of fibroblasts cultured with the addition of increasing concentrations of the peptide mix did not show statistically significant differences from the control. Fragments 161-170, 221-230, 721-730, 1331-1340, 1521-1530, and 1661-1670 of COL4A6 were examined for cytotoxicity against BJ normal human foreskin fibroblasts. None of the collagen fragments were found to be cytotoxic. Further research is underway on the potential uses of collagen IV fragments in regenerative medicine.

PMID:37607826 | DOI:10.1002/psc.3537

J Psychiatry Neurosci. 2023 Aug 22;48(4):E285-E294. doi: 10.1503/jpn.230016. Print 2023 Jul-Aug.

ABSTRACT

BACKGROUND: It has been suggested that the dorsolateral prefrontal cortex (DLPFC), especially the left DLPFC, has an important role in the pathophysiology and the treatment of major depressive disorder (MDD); furthermore, the contributory and antidepressant role of γ-aminobutyric acid (GABA) is increasingly recognized. Given that most female patients with MDD are of reproductive age, we sought to assess in vivo baseline GABA levels in the left DLPFC among unmedicated females of reproductive age with depression.

METHODS: We compared healthy females and females with MDD. Both groups were of reproductive age. We confirmed absence of current or past psychiatric diagnosis among healthy controls or a current diagnosis of MDD via a structured interview. We measured GABA+ (including homocarnosine and macromolecules), referenced to creatine and phosphocreatine, via magnetic resonance spectroscopy using a 3 Tesla magnet.

RESULTS: We included 20 healthy controls and 13 participants with MDD. All participants were unmedicated at the time of the study. All females were scanned during the early follicular phase of the menstrual cycle. Levels of GABA+ in the left DLPFC were significantly lower among participants with MDD (median 0.08) than healthy controls (median 0.10; U = 66.0, p = 0.02, r = 0.41).

LIMITATIONS: When we adjusted for fit error as a covariate, we lost statistical significance for left DLPFC GABA+. However, when we adjusted for signal-to-noise ratio, statistical significance was maintained.

CONCLUSION: Our results suggest that GABA+ levels in the left DLPFC may vary by depression status and should be examined as a possible treatment target.

PMID:37607825 | DOI:10.1503/jpn.230016

BMJ Open. 2023 Aug 22;13(8):e071321. doi: 10.1136/bmjopen-2022-071321.

ABSTRACT

OBJECTIVE: To construct a machine-learning (ML) model for health systems with organised falls prevention programmes to identify older adults at risk for fall-related admissions.

DESIGN: This prognostic study used population-level administrative health data to develop an ML prediction model.

SETTING: This study took place in Alberta, Canada during 2018-2019.

PARTICIPANTS: Albertans aged 65 and older with at least one prior admission. Those with palliative conditions or emigrated out of Alberta were excluded.

EXPOSURE: Unit of analysis was the individual person.

MAIN OUTCOMES/MEASURES: We identified fall-related admissions. A CatBoost model was developed on 2018 data to predict risk of fall-related emergency department visits or hospitalisations. Temporal validation was done using 2019 data to evaluate model performance. We reported discrimination, calibration and other relevant metrics measured at the end of 2019 on both ranked predictions and predicted probability thresholds. A cost-savings simulation was performed using 2019 data.

RESULTS: Final number of study participants was 224 445. The validation set had 203 584 participants with 19 389 fall-related events (9.5% pretest probability) and an ML model c-statistic of 0.70. The highest ranked predictions had post-test probabilities ranging from 40% to 50%. Net benefit analysis presented mixed results with some net benefit using the ML model in the 6%-30% range. The top 50 percentile of predicted risks represented nearly $C60 million in health system costs related to falls. Intervening on the top 25 or 50 percentiles of predicted risk could realise substantial (up to $C16 million) savings.

CONCLUSION: ML prediction models based on population-level administrative data can assist health systems with fall prevention programmes identify older adults at risk of fall-related admissions and reduce costs. ML predictions based on ranked predictions or probability thresholds could guide subsequent interventions to mitigate fall risks. Increased access to diverse forms of data could improve ML performance and further reduce costs.

PMID:37607796 | DOI:10.1136/bmjopen-2022-071321