Impaired Efficacy Research Articles

Effects of cholinesterase inhibition on attention and working memory in Lewy body dementias.

Cholinesterase inhibitors are frequently used to treat cognitive symptoms in Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies). However, the selectivity of their effects remains unclear. In a novel rivastigmine withdrawal design, Parkinson's disease dementia and dementia with Lewy bodies patients were tested twice: once when taking rivastigmine as usual and once when they had missed one dose. In each session, they performed a suite of tasks (sustained attention, simple short-term recall, distractor resistance and manipulating the focus of attention) that allowed us to investigate the cognitive mechanisms through which rivastigmine affects attentional control. Consistent with previous literature, rivastigmine withdrawal significantly impaired attentional efficacy (quicker response latencies without a change in accuracy). However, it had no effects on cognitive control as assessed by the ability to withhold a response (inhibitory control). Worse short-term memory performance was also observed when patients were OFF rivastigmine, but these effects were delay and load independent, likely due to impaired visual attention. In contrast to previous studies that have examined the effects of dopamine withdrawal, cognitively complex tasks requiring control over the contents of working memory (ignoring, updating or shifting the focus of attention) were not significantly impaired by rivastigmine withdrawal. Cumulatively, these data support that the conclusion that cholinesterase inhibition has relatively specific and circumscribed-rather than global-effects on attention that may also affect performance on simple short-term memory tasks, but not when cognitive control over working memory is required. The results also indicate that the withdrawal of a single dose of rivastigmine is sufficient to reveal these impairments, demonstrating that cholinergic withdrawal can be an informative clinical as well as an investigative tool.

The relationship of sinus opacification, olfaction and dupilumab efficacy in patients with CRSwNP.

Loss of sense of smell is one of the most burdensome symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP) but its relationship to sinus disease on imaging is unclear. Dupilumab improves sense of smell and radiographic severity of sinus disease in patients with CRSwNP. We investigated the relationship of sinus opacification severity and loci to olfactory impairment and dupilumab efficacy in patients with CRSwNP from the SINUS-24/SINUS-52 (NCT02912468/NCT02898454) studies. Sinus opacification was evaluated using the Lund-Mackay computed tomography (LMK-CT) score and sense of smell using patient-reported loss of smell (LoS) score, University of Pennsylvania Smell Identification Test (UPSIT) score and the 22-item Sino-Nasal Outcome Test (SNOT-22) smell/taste item. At baseline, 95% of patients (688/724) had impaired sense of smell and opacification was extensive across all sinuses. Greater olfactory impairment was associated with greater opacification, especially in the ethmoid, sphenoid and frontal sinuses. At Week 24, reductions in LMK-CT total score and ethmoid and sphenoid sinus scores with dupilumab were weakly correlated with improvements in sense of smell assessed by LoS, UPSIT and SNOT-22 smell/taste item. More dupilumab than placebo patients achieved clinically meaningful improvement in LMK-CT total score at Week 24 and Week 52. Radiographic disease severity on imaging was associated with smell outcomes in this cohort. Opacification of the ethmoid, sphenoid and frontal sinuses was associated with severe smell loss. These data suggest that dupilumab effects on smell may be partly mediated through reduced sinus inflammation.

Decreased miR-17-92 Cluster Correlates with Senescent Features, Disrupted Oxidative Homeostasis, and Impaired Therapeutic Efficacy of Mesenchymal Stem Cells.

Aging and replicative cellular senescence are associated with the reduced therapeutic potential of mesenchymal stem cells (MSCs) on a variety of diseases. This study aimed to determine the mechanism in MSC senescence and further explore a modification strategy to reverse senescence-associated cell dysfunction in order to improve the therapeutic efficacy of MSCs on acute liver failure (ALF). We found that the adipose tissue-derived MSCs from old mice (oAMSCs) exhibited senescence phenotypes and showed reduced therapeutic efficacy in lipopolysaccharide and D-galactosamine-induced ALF, as shown by the increased hepatic necrosis, liver histology activity index scores, serum liver function indicator levels and inflammatory cytokine levels. The expression of miR-17-92 cluster members, especially miR-17 and miR-20a, was obviously decreased in oAMSCs and replicatively senescent AMSCs, and was consistent with the decreased oncogene c-Myc level during AMSC senescence and may mediate c-Myc stemness addiction. Further experiments revealed that c-Myc-regulated miR-17-92 expression contributed to increased p21 expression and redox system dysregulation during AMSC senescence. Furthermore, modification of AMSCs with the two key miRNAs in the miR-17-92 cluster mentioned above reversed the senescence features of oAMSCs and restored the therapeutic effect of senescent AMSCs on ALF. In conclusion, the cellular miR-17-92 cluster level is correlated with AMSC senescence and can be used both as an index for evaluating and as a modification target for improving the therapeutic potential of AMSCs.

Halting vaccine-derived poliovirus circulation: the novel type 2 oral vaccine might not be enough

Halting vaccine-derived poliovirus circulation: the novel type 2 oral vaccine might not be enough

A real-life pilot study of the clinical application of pharmacogenomics testing on saliva in epilepsy.

Response to antiseizure medications (ASMs) can be influenced by several gene polymorphisms, causing either lower efficacy or higher occurrence of adverse drug reactions (ADRs). We investigated the clinical utility of salivary pharmacogenomic testing on epilepsy patients. A commercialized pharmacogenomic salivary test was performed in a cohort of epileptic patients. Genetic variants on five genes (i.e., CYP1A2, CYP2C9, CYP2C19, EPHX1, and ABCB1) involved in common ASMs metabolism were selected. Twenty-one individuals (median age [Q1 -Q3 ]: 15 [6.5-28] years) were enrolled. Six patients harboring the homozygous *1F allele in CYP1A2 could have reduced chance of response to stiripentol due to fast metabolism. CYP2C9 had reduced activity in 10 patients (alleles *2 and *3), potentially affecting phenytoin (PHT), phenobarbital (PB), primidone, lacosamide (LCM), and valproic acid metabolism. Seven patients, carrying the *2 allele of CYP2C19, had an increased risk of ADRs with clobazam (CLB), PB, PHT, LCM, brivaracetam; while one individual with the *17 allele in heterozygosity reported a CLB fast metabolism. Six patients showed a CC polymorphism of EPHX1 associated with the impaired efficacy of carbamazepine. ABCB1 polymorphisms related to drug-resistance (3435 CC) or drug-sensitive phenotype (CT or TT) were found in 6 out of 7 patients. Pharmacogenomic testing on saliva proved easy and safe in clinical practice to convey information for the management of epileptic patients, especially those resistant to treatment or sensitive to severe ADRs.

Review of point-of-care platforms for diabetes: (2) medications and devices

Diabetes mellitus is a chronic heterogeneous metabolic disease characterized primarily by hyperglycemia due to impaired insulin secretion or impaired insulin efficacy. In recent years, a number of novel point-of-care platforms have been developed for sustained and controlled drug delivery. These platforms allow the patients to ingest insulin via transbuccal, nasal, inhalation, transdermal or subcutaneous routes, thereby effectively releasing insulin molecules the need for inconvenient and frequent needle injections. There are several issues needed to be addressed in developing such as platform: How many routes of administration are available for a point-of-care medication platform? What device components and configurations are available? What is the status of their application? This review will highlight our early attempts to address these questions. It is expected this review could provide a comprehensive overview of the medication platforms for diabetes, as well as open new avenues for developing the next-generation drug delivery devices for patients with diabetes.

Retropubic slings are more efficient than transobturator at 10-year follow-up: a Swedish register-based study

Introduction and hypothesisLong-term performance of mid-urethral slings (MUS) and potential differences between the retropubic and the transobturator technique for insertion are scarcely studied. This study aims to evaluate the efficacy and safety 10 years after surgery and compare the two main surgical techniques used.MethodsWomen who underwent surgery with a MUS between 2006 and 2010 were identified using the Swedish National Quality Register of Gynecological Surgery and were invited 10 years after the operation to answer questionnaires regarding urinary incontinence and its impact on quality-of-life parameters (UDI-6, IIQ-7) and impression of improvement, as well as questions regarding possible sling-related complications and reoperation.ResultsThe subjective cure rate reported by 2421 participating women was 63.3%. Improvement was reported by 79.2% of the participants. Women in the retropubic group reported higher cure rates, lower urgency urinary incontinence rates and lower UDI-6 scores. No difference was shown between the two methods regarding complications, reoperation due to complications or IIQ-7 scores. Persisting sling-related symptoms were reported by 17.7% of the participants, most commonly urinary retention. Mesh exposure was reported by 2.0%, reoperation because of the tape by 5.6% and repeated operation for incontinence by 6.9%, significantly more in the transobturator group (9.1% vs. 5.6%). Preoperative urinary retention was a strong predictor for impaired efficacy and safety at 10 years.ConclusionsMid-urethral slings demonstrate good results for the treatment of stress urinary incontinence and tolerable complication profiles in a 10-year perspective. The retropubic approach displays higher efficacy than the transobturator, with no difference regarding safety.

A revamped MIC-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk

BackgroundThe purpose of this study was to investigate the effect of our revamped MIE-McKeown operation on postoperative gastrointestinal function recovery.MethodsThis revamped MIE-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk and with the tubular stomach buried throughout esophageal bed and azygos arch, has been implemented from July 2020 to July 2021 by the same medical team of Gaozhou People's Hospital thoracic surgery for 13 times. Preoperative clinical data, main intraoperative indicators and postoperative complications were observed.ResultsAll patients had esophageal malignant tumors at the level of middle and lower thoracic non-azygous venous arch, with preoperative clinical stage CT1-2N0M0 stage i-ii. V-vst test was performed on the 7th postoperative day, and 10 patients were found to have no loss of safety/efficacy. There were 2 cases with impaired efficacy and no impaired safety, 1 case with impaired safety. There were 1 cases of pulmonary infection, 1 cases of anastomotic fistula combined with pleural and gastric fistula, 2 cases of hoarseness, 2 cases of arrhythmia, 10 cases of swallowing function were grade i, 2 cases of swallowing function were grade iii, 1 case of swallowing function was grade iv in watian drinking water test one month after operation.ConclusionsMerit of this revamped MIE-McKeown operation is well preserving the integrity of azygos arch of vagus nerve and bronchial artery, and it is technically safe and feasible. No postoperative mechanical obstruction of thoracostomach, huge thoracostomach and gastrointestinal dysfunction occurs.

The Efficacy and Safety of a Low-Dose Tranexamic Acid Bolus-Only Protocol Compared with the Moderate-Dose Protocol in Valvular Heart Surgery.

In 873 propensity score-matched pairs of patients undergoing valvular heart surgery, we compared a "moderate dose" of tranexamic acid (TXA) protocol (group 1; median TXA dose: 24 mg/kg body weight) with a 1.5-g "bolus-only" protocol (group 2; median TXA dose: 19 mg/kg body weight). The number of transfused patients was higher in group 2 than in group 1 (74.5 vs 66.0%, p < 0.001), as was the number of transfused red blood cell concentrates (p = 0.001). The risks of re-exploration and convulsive seizures were similar between groups (p > 0.50). Data indicate an impaired efficacy following the "bolus-only" protocol, without a significant safety improvement.

Dose adjustments of antimicrobials in patients with renal impairment

Caution should be exercised when prescribing medication in patients with renal impairment, owing to the risk of drug accumulation, poorly tolerated adverse effects and impaired efficacy​[1]​. These effects can generally be mitigated by adjusting the dose or increasing the dosing interval. This is the second article in a two-part series outlining the importance of antimicrobial […]

Immature Platelet Fraction Predicts Adverse Events in Patients With Acute Coronary Syndrome: the ISAR-REACT 5 Reticulated Platelet Substudy.

Immature or reticulated platelets are associated with impaired efficacy of antiplatelet drugs and adverse events in cardiovascular patients. Their role as a predictive biomarker in patients with acute coronary syndrome treated with potent P2Y12 receptor inhibitors is not fully understood. We aimed to prospectively evaluate reticulated platelets as a predictor of the primary end point of the ISAR-REACT 5 trial consisting of death, myocardial infarction, or stroke at 1 year in patients with acute coronary syndrome randomized to prasugrel or ticagrelor. Immature platelet fraction (IPF) was assessed within 48 hours after randomization. Patients were divided based on the IPF median values: the IPFhigh group included patients with IPF>median and the IPFlow group included patients with IPF≤median. Platelet aggregation was assessed using the Multiplate Analyzer and was correlated to IPF. Five hundred seventy-seven patients were included in the study. IPF values in % (median [interquartile range]) within the first 48 hours did not differ between the two study groups: 3.6 (2.5-5.2)% in the prasugrel group and 3.6 (2.5-5.4)% in the ticagrelor group (P=0.882). The incidence of the primary end point was significantly higher in the IPFhigh (IPF>3.6%) group compared with the IPFlow (IPF≤3.6%) group: 13.0% versus 7.2% (HRadj, 1.74 [1.02-3.00]; P=0.044), independently from the assigned drug (Pint=0.159). No significant association between IPF and BARC 3 to 5 bleeding was observed. ADP-induced platelet aggregation correlated significantly with IPF in patients treated with prasugrel (r=0.22; P=0.005) while no correlation was detected in patients treated with ticagrelor (r=0.09; P=0.257). Independently from drug treatment, IPF was associated with the primary end point and therefore is a promising biomarker for the prediction of adverse cardiovascular events in patients with acute coronary syndrome treated with prasugrel or ticagrelor. https://www. gov; Unique identifier: NCT01944800.

GPC2 antibody–drug conjugate reprograms the neuroblastoma immune milieu to enhance macrophage-driven therapies

BackgroundAntibody–drug conjugates (ADCs) that deliver cytotoxic drugs to tumor cells have emerged as an effective and safe anticancer therapy. ADCs may induce immunogenic cell death (ICD) to promote additional endogenous...

HUC-MSCs Attenuate Acute Graft-Versus-Host Disease through Chi3l1 Repression of Th17 Differentiation.

Mesenchymal stem cells (MSCs) have already demonstrated definitive evidence of their clinical benefits in acute graft-versus-host disease (aGvHD) and other inflammatory diseases. However, the comprehensive mechanism of MSCs' immunomodulation properties has not been elucidated. To reveal their potential immunosuppressive molecules, we used RNA sequencing to analyze gene expression in different tissue-derived MSCs, including human bone marrow, umbilical cord, amniotic membrane, and placenta, and found that chitinase-3-like protein 1 (Chi3l1) was highly expressed in human umbilical cord mesenchymal stem cells (hUC-MSCs). We found that hUC-MSCs treated with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) exhibited increased expression of Chi3l1 and concurrently repressed T-helper 17 cell (Th17) differentiation through inhibition of signal transducer and activator of transcription 3 (STAT3) activation. Furthermore, Chi3l1 knockdown hUC-MSCs exhibited impaired therapeutic efficacy in aGvHD mice with an increased inflammatory response by promoting Th17 cell differentiation, including an increase in IL-17A in the spleen, intestine, and serum. Collectively, these results reveal a new immunosuppressive molecule, Chi3l1, in hUC-MSCs in the treatment of aGvHD that regulates Th17 differentiation and inhibits STAT3 activation. These novel insights into the mechanisms of hUC-MSC immunoregulation may lead to the consistent production of hUC-MSCs with strong immunosuppressive functions and thus improved clinical utility.

Kinetics of the reduction of Creutzfeldt–Jakob disease prion seeding activity by steam sterilization support the use of validated 134°C programmes

Prions are renowned for their distinct resistance to chemical or physical inactivation, including steam sterilization. Impaired efficacy of inactivation poses a risk to patients for iatrogenic transmission of Creutzfeldt-Jakob disease (CJD) via contaminated surgical instruments. Most established prion inactivation methods were validated against scrapie agents, although those were found to be generally less thermostable than human prions. Thus, knowledge gaps regarding steam-sterilization kinetics of CJD prions should be filled and current guidelines reviewed accordingly. Prion inactivation through widely recommended steam sterilization at 134°C was assessed for several holding times by analysing the residual prion seeding activity using protein misfolding cyclic amplification (PMCA). Scrapie 263K was found to be the least thermoresistant prion strain showing no seeding activity after 1.5min at 134°C, while variant CJD was the most stable one demonstrating some seeding activity even after 18min of steam sterilization. Sporadic CJD subtype VV2 exhibited residual seeding activity after 3min, but no detectable activity after 5min at 134°C. Validated steam sterilization for 5min at 134°C as previously recommended for the routine reprocessing of surgical instruments in contact with high-risk tissues is able to substantially reduce the seeding activity of CJD agents, provided that no fixating chemical disinfection has been performed prior to sterilization and that thorough cleaning has reduced the protein load on the surface to less than 100μg per instrument.

Molecular Determinants of Sulfadoxine-Pyrimethamine Resistance in Plasmodium falciparum Isolates from Central Africa between 2016 and 2021: Wide Geographic Spread of Highly Mutated Pfdhfr and Pfdhps Alleles.

ABSTRACTSulfadoxine-pyrimethamine (SP) resistance impairs the efficacy of antimalarial drugs. Monitoring molecular markers in exported malaria infections provides an efficient way to trace the emergence of drug resistance in countries where malaria is endemic. Molecular markers in Pfdhfr and Pfdhps of 237 Plasmodium falciparum infections imported from central Africa between 2016 and 2021 were detected. The spatial and temporal distributions of Pfdhfr and Pfdhps mutations were analyzed. A high prevalence of Pfdhfr single-nucleotide polymorphisms (SNPs) (~92.34% to 99.10%) and a high frequency of the triple mutation haplotype I51R59N108 were observed. Cameroon, Equatorial Guinea, and Gabon showed a higher frequency (~96.61% to 100.00%) of I51R59N108 than other countries (~71.11% to 88.10%). The prevalence of C59R and I51R59N108 increased while that of other SNPs or haplotypes did not fluctuate greatly from 2016 to 2021. Large proportions of Pfdhps SNPs (A437G and K540E) were demonstrated. The SNP distribution of Pfdhps differed between countries, with S436A dominating in northern countries and A437G dominating in others. The proportions of I431V, A437G, and the triple mutant haplotype declined between 2016 and 2021, whereas the prevalence of the single mutant haplotype rose from 61.60% to 73.68%. Combinations of Pfdhfr-Pfdhps alleles conferring partial resistance, full resistance, and superresistance to SP, as defined in the text, were detected in 63.64%, 8.64%, and 0.91% of the samples, respectively. The octuple Pfdhfr-Pfdhps allele (I51R59N108-V431A436G437K540G581S613) was seen in 5.00% of the samples. We demonstrated the wide geographic spread and increasing trends in highly SP-resistant Pfdhfr genes and varying spatial patterns of Pfdhps mutants across countries in central Africa. The high prevalences of partially resistant, fully resistant, and superresistant Pfdhfr-Pfdhps combinations observed here indicated impaired SP efficacy. Increased molecular surveillance is required to monitor the changing status of the Pfdhfr and Pfdhps genes.IMPORTANCE Monitoring drug resistance is important for malaria control because its early detection enables timely action to prevent its spread and mitigate its impact. The wide geographic spread and the increasing trend of highly resistant Pfdhfr genes between 2016 and 2021 found in our study are worrisome and emphasize the urgency to monitor their updated status in central Africa. This study also illustrated the wide spread of the novel mutant Pfdhps I431V as well as the high prevalence of “partially resistant,” “fully resistant,” and “superresistant” Pfdhfr-Pfdhps combinations, indicating the urgent concern for SP efficacy in central Africa. These findings are alarming in central African countries where malaria is endemic, where SP was is widely used for the intermittent preventive treatment of malaria in pregnancy (IPTp) and the intermittent preventive treatment of malaria in infants below 5 years of age (IPTi), and urge enhanced molecular surveillance and responses to the threat of drug resistance.

The sensitivity and specificity of the modified volume-viscosity swallow test for dysphagia screening among neurological patients.

Oropharyngeal dysphagia (OD) is a highly prevalent condition after stroke and other neurological diseases. The volume-viscosity swallow test (V-VST) is a screening tool for OD. Considering that the recommendations of volume and thickeners in the original V-VST limited the popularization and application of the test in the Chinese population, we provide the modified V-VST to detect OD among neurological patients. In addition, the accuracy of the modified V-VST to screen OD needs to be verified. We included 101 patients with neurological diseases. OD was evaluated by a modified V-VST and a videofluoroscopy swallowing study (VFSS) using 3 volumes (i.e., 3, 5, and 10 ml) and 4 viscosities (i.e., water, mildly thick, moderately thick, and extremely thick). In this study, to compare with the original V-VST results, a volume of 20 ml was also included. The discriminating ability of modified V-VST in detecting OD was assessed by the sensitivity and specificity values of clinical signs of impaired efficiency (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallowing (cough, voice changes, and oxygen desaturation ≥3%) in comparison to the results of VFSS. The modified V-VST showed 96.6% sensitivity and 83.3% specificity for OD, 85.2% sensitivity and 70% specificity for impaired safety, and 90.9% sensitivity and 76.9% specificity for impaired efficacy. Our study suggests that the modified V-VST offers a high discriminating ability in detecting OD among neurological patients.

Gains and Losses Affect Learning Differentially at Low and High Attentional Load.

Prospective gains and losses influence cognitive processing, but it is unresolved how they modulate flexible learning in changing environments. The prospect of gains might enhance flexible learning through prioritized processing of reward-predicting stimuli, but it is unclear how far this learning benefit extends when task demands increase. Similarly, experiencing losses might facilitate learning when they trigger attentional reorienting away from loss-inducing stimuli, but losses may also impair learning by increasing motivational costs or when negative outcomes are overgeneralized. To clarify these divergent views, we tested how varying magnitudes of gains and losses affect the flexible learning of feature values in environments that varied attentional load by increasing the number of interfering object features. With this task design, we found that larger prospective gains improved learning efficacy and learning speed, but only when attentional load was low. In contrast, expecting losses impaired learning efficacy, and this impairment was larger at higher attentional load. These findings functionally dissociate the contributions of gains and losses on flexible learning, suggesting they operate via separate control mechanisms. One mechanism is triggered by experiencing loss and reduces the ability to reduce distractor interference, impairs assigning credit to specific loss-inducing features, and decreases efficient exploration during learning. The second mechanism is triggered by experiencing gains, which enhances prioritizing reward-predicting stimulus features as long as the interference of distracting features is limited. Taken together, these results support a rational theory of cognitive control during learning, suggesting that experiencing losses and experiencing distractor interference impose costs for learning.

Suitability of Methods to Determine Resistance to Biocidal Active Substances and Disinfectants—A Systematic Review

Biocide resistance is an increasing concern. However, it is currently unknown if an elevated MIC value for an isolate correlates with a lower log10 reduction in suspension tests or carrier tests. The aim of this review was therefore to evaluate if isolates with a suspected tolerance to a biocidal active substance reveal an elevated MIC value and an impaired efficacy in suspension tests and carrier tests. A Medline search was done on 6 July 2022 using the following terms: “resistance biocidal MIC suspension” (16 hits), “resistance biocidal MIC carrier” (22 hits), “resistance biocidal suspension carrier” (41 hits), “tolerance biocidal MIC suspension” (1 hit), “tolerance biocidal MIC carrier” (4 hits) and “tolerance biocidal suspension carrier” (3 hits). Studies were included when a tolerance or resistance to the biocidal active substance or disinfectant was suspected and at least two of the three endpoints were evaluated in parallel in comparison to the control isolates. In three out of five studies, the elevated MIC values did not correlate with an impaired bactericidal efficacy against the biocide-tolerant isolates. In three out of five studies, an impaired activity in the suspension tests was described that correlated with an impaired efficacy in the carrier tests (peracetic acid-tolerant K. pneumoniae and glutaraldehyde-tolerant M. chelonae; the two other studies did not allow a comparison. Overall, the results from the suspension tests and tests under practical conditions allowed to determine a clinically relevant resistance.

Identifying and addressing pill aversion in adults without physiological-related dysphagia: A narrative review.

Solid oral dosage forms (SODFs) (often called pills by patients) are the default formulation to treat medical ailments. Beneficial therapeutic outcomes rely on patients taking them as directed. Up to 40% of the population experience difficulties swallowing SODFs, resulting in reduced adherence and impaired therapeutic efficacy. Often associated with children, this also presents in adults with dysphagia, and without any organic dysphagia (non-physiological-related or functional dysphagia). This review aims to identify and appraise current interventions used to screen for and overcome pill aversion in adults with functional dysphagia. A comprehensive search of the literature was conducted. Articles reporting pill aversion in adults aged ≥18 years with no underlying cause, history of, or existing dysphagia were included. Study quality was determined using the STROBE tool for observational studies. A narrative synthesis of the findings was prepared. We identified 18 relevant cohort studies, which demonstrate that pill aversion is a global problem. Perceived ease of and/or SODF swallowability appears to be influenced by female gender, younger age, co-morbidities (e.g., depression), and physical SODF properties. Patients often modify their medicines rather than raise this issue with their healthcare team. Screening for pill aversion is haphazard but controlled postural adjustments, coating SODFs and behavioural interventions appear to be successful solutions. SODF swallowing difficulties are a barrier to effective medication use. Healthcare professionals must recognise that pill aversion is a problem requiring identification through effective screening and resolution by training interventions, appropriate formulation selection or specialist referral.

Recovery pattern analysis of swallowing function in patients undergoing total glossectomy and hemiglossectomy

ObjectivesTo investigate the recovery process of swallowing function and ascertain swallowing pattern in patients undergoing total glossectomy (TG). Materials and methodsA cohort study was conducted in consecutive patients with tongue squamous cell carcinoma who received TG/hemiglossectomy (HG) from May 2017 to December 2019. Exposure factors included tongue resection range (HG and TG) and postoperative radiotherapy (PRT and non-PRT). The swallowing functions were evaluated by M.D. Anderson dysphagia inventory (MDADI), water swallow test (WST), and tongue pressure (TP) at pretreatment, 1, 4, 7, 12, 18 and 24 months postoperatively. Videofluoroscopy swallowing study (VFSS) was applied to analyze swallowing pattern of TG patients. ResultsA total of 67 patients were enrolled, of which 17 underwent TG and 50 underwent HG. Both MDADI and TP of the TG and PRT group were lower than those of the HG and non-PRT group. TG patients had no evident improvement in MDADI and TP after surgery. There was a higher risk of swallowing unsafety with abnormal WST outcome in TG (P < 0.001, OR = 106.52) than that in HG. VFSS analysis identified prolonged oral and pharyngeal transit time, disorganized swallowing sequence, abnormal hyoid bone movement, and frequent invalid swallows in patients with TG. A shortened OTT (<5066.50 ms) and a larger pharyngeal constriction ratio (PCR > 0.31) were associated with increased risks of penetration and aspiration. ConclusionPostoperative swallowing pattern is a characteristic of severely impaired safety and efficacy in patients with TG. Impaired OTT and PCR are variables that should be examined when determining the need for rehabilitation treatment.