bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of pain and catastrophizing on the long-term course of depression in the general population: the HUNT pain study
Authors: Glette Mari , Stiles Tore C. , Jensen Mark P. , Nilsen Tom Ivar Lund , Borchgrevink Petter C. , Landmark Tormod
Published: January 2021

Pain and depression are episodic conditions that might take a chronic course. They are clearly related, but information on how they influence each other in the process of chronification is limited. Pain catastrophizing is hypothesized to play a role in the development of depression and chronic pain, but few longitudinal studies have investigated their association over a longer term. In this study, a random cohort from the general population (n = 4764) answered questions about pain, catastrophizing, and depression at 5 assessments in yearly intervals. Linear mixed models showed that within persons, increases in pain intensity and catastrophizing were independently associated with increases in depressive symptoms {mean change = −1.12, 95% confidence interval (CI) [−1.32 to −0.91] and −1.29, 95% CI [−1.52 to −1.05], respectively}. In prospective analyses restricted to individuals without depression above cutoff at baseline, chronic pain increased the risk of endorsing depression over the following 4 years (odds ratio = 2.01, 95% CI [1.71-2.37]). Seven percent showed a chronic course of depression, as indicated by scores above cutoff on at least 3 of 5 assessments. The number of years lived with chronic pain was associated with a chronic course of depression, with odds ratios increasing from 1.55 (95% CI [0.87-2.91]) to 14.19 (95% CI [8.99-22.41]) when reporting chronic pain on 2 vs 5 assessments compared with none. The results suggest that when pain intensity or catastrophizing change, depressive symptoms change in the same direction. When pain and catastrophizing become chronic, they seem to be mutually reinforcing determinants for chronic depression.
Quantitative language features identify placebo responders in chronic back pain
Authors: Berger Sara E. , Branco Paulo , Vachon-Presseau Etienne , Abdullah Taha B. , Cecchi Guillermo , Apkarian A. Vania
Published: January 2021

Although placebo effect sizes in clinical trials of chronic pain treatments have been increasing, it remains unknown if characteristics of individuals' thoughts or previous experiences can reliably infer placebo pill responses. Research using language to investigate emotional and cognitive processes has recently gained momentum. Here, we quantified placebo responses in chronic back pain using more than 300 semantic and psycholinguistic features derived from patients' language. This speech content was collected in an exit interview as part of a clinical trial investigating placebo analgesia (62 patients, 42 treated; 20 not treated). Using a nested leave-one-out cross-validated approach, we distinguished placebo responders from nonresponders with 79% accuracy using language features alone; a subset of these features—semantic distances to identity and stigma and the number of achievement-related words—also explained 46% of the variance in placebo analgesia. Importantly, these language features were not due to generic treatment effects and were associated with patients' specific baseline psychological traits previously shown to be predictive of placebo including awareness and personality characteristics, explaining an additional 31% of the variance in placebo analgesia beyond that of personality. Initial interpretation of the features suggests that placebo responders differed in how they talked about negative emotions and the extent that they expressed awareness to various aspects of their experiences; differences were also seen in time spent talking about leisure activities. These results indicate that patients' language is sufficient to identify a placebo response and implie that specific speech features may be predictive of responders' previous treatment.
Difference of pain vulnerability in adult and juvenile rodents: the role of SIRT1-mediated ClC-3 trafficking in sensory neurons
Authors: Zhang Xiao-Long , Zhang Jin-Jun , Chen Zi-Hang , Yang Kai-Bin , Zhang Xi , Xiao Yi-Bin , Lei Yi , Cao Xian-Ying , Xie Man-Xiu
Published: January 2021

Adults are more likely to suffer from chronic pain than minors, and its underlying mechanism remains unclear. SIRT1 an important age-related protein with function of lifespan extension; whether SIRT1 plays a role in the different pain vulnerability of adult and juvenile remains unclear. Here, we found that the expression level of SIRT1 in dorsal root ganglia (DRG) was related to the pain vulnerability. After nerve injury, the expression of SIRT1 in DRG was decreased in adult rodents whereas increased in juvenile rodents. Differential manipulation of SIRT1 abolished the different pain vulnerability between adult and juvenile rodents. Furthermore, SIRT1 interacted with ClC-3 channel and mediated ClC-3 membrane trafficking and Cl− current in DRG neurons. Differential manipulation of ClC-3 also abolished the difference in pain vulnerability between adult and juvenile rodents. The different anti-inflammatory ability determined the different change trends of SIRT1 and ClC-3 trafficking contributed to the different pain vulnerability in adult and juvenile rodents. In addition, the serum SIRT1 level was negatively correlated with the pain score in patients with chronic pain. These findings revealed the mechanism of the difference in pain vulnerability between adult and juvenile rodents and provided evidence for age-specific treatment of chronic pain.
Prognostic factors for adolescent knee pain: an individual participant data meta-analysis of 1281 patients
Authors: Holden Sinead , Kasza Jessica , Winters Marinus , van Middelkoop Marienke ,   Adolescent Knee Health Group, Rathleff Michael Skovdal
Published: January 2021

Adolescent knee pain has a propensity for chronicity, impacting physical activity and health into adulthood. The aim of this study is to investigate prognostic factors in adolescents with knee pain using individual participant data (IPD) meta-analysis. Studies were identified through a systematic search and a collaborative group. We included IPD from prospective studies of adolescents (age 10-19 years) with nontraumatic knee pain (13 studies and 1516 adolescents with 1281 unique participants). Primary outcomes were pain intensity and function (Knee Injury and Osteoarthritis Outcome Score “Sport/Rec” subscale). Primary endpoint was 12 months. Risk of bias was appraised with Quality in Prognosis Studies tool. Harmonised IPD was analysed by multilevel modelling. Fifty-one percent reported knee pain after 12-months. Lower baseline pain frequency was associated with lower pain intensity at 12 months (“less than weekly”; 12 (95% confidence interval [CI] 7-17) and “monthly”; 15 (95% CI 9-22) points lower on a 100-point pain scale, compared with “almost daily pain”). Other factors most strongly associated with 1-year pain prognosis were lower quality of life (30, 95% CI 19-42 points per unit change in the EQ5D index score), female sex (8 points, 95% CI 4-12 higher compared with males), and bilateral pain (7, 95% CI 1-13 points higher pain). Similar factors were associated with function. Body mass index, pain sensitivity, and knee strength were not associated with prognosis of pain or function. Adolescent knee pain is associated with clinically relevant long-term pain and functional deficits. Self-reported characteristics may help identify those at risk of poor prognosis.
Nonlinear increase of pain in distance-based and area-based spatial summation
Authors: Adamczyk Wacław M. , Manthey Linn , Domeier Christin , Szikszay Tibor M. , Luedtke Kerstin
Published: January 2021

When nociceptive stimulation affects a larger body area, pain increases. This effect is called spatial summation of pain (SSp). The aim of this study was to describe SSp as a function of the size or distance of a stimulated area(s) and to test how this function is shaped by the intensity and SSp test paradigm. Thirty-one healthy volunteers participated in a within-subject experiment. Participants were exposed to area-based and distanced-based SSp. For area-based SSp, electrocutaneous noxious stimuli were applied by up to 5 electrodes (5 areas) forming a line-like pattern; for distance-based SSp, the same position and lengths of stimuli were used but only 2 electrodes were stimulated. Each paradigm was repeated using pain of low, moderate, and high intensity. It was found that the pattern of pain intensity followed a logarithmic (power) rather than a linear function. The dynamics of the pain increase were significantly different across pain intensities, with more summation occurring when pain was perceived as low. Results indicated that area-based SSp is more painful than distance-based SSp when low and moderate but not when high pain intensity is induced. Presented findings have important implications for all studies in which the spatial dimension of pain is measured. When the area or separation between nociceptive stimulation increases, pain does not increase linearly and the pattern of the pain increase is a result of the interaction between intensity and the number of nociceptive sites. A power function should be considered when predicting the size of a nociceptive source.
Chronic pain susceptibility is associated with anhedonic behavior and alterations in the accumbal ubiquitin-proteasome system
Authors: Guimarães Marco Rafael , Anjo Sandra Isabel , Cunha Ana Margarida , Esteves Madalena , Sousa Nuno , Almeida Armando , Manadas Bruno , Leite-Almeida Hugo
Published: January 2021

It remains unknown why on similar acute/subacute painful conditions, pain persists in some individuals while in others it resolves. Genetic factors, mood, and functional alterations, particularly involving the mesolimbic network, seem to be key. To explore potential susceptibility or resistance factors, we screened a large population of rats with a peripheral neuropathy and we isolated a small subset (<15%) that presented high thresholds (HTs) to mechanical allodynia (reduced pain manifestation). The phenotype was sustained over 12 weeks and was associated with higher hedonic behavior when compared with low-threshold (LT) subjects. The nucleus accumbens of HT and LT animals were isolated for proteomic analysis by Sequential Window Acquisition of All Theoretical Mass Spectra. Two hundred seventy-nine proteins displayed different expression between LT and HT animals or subjects. Among several protein families, the proteasome pathway repeatedly emerged in gene ontology enrichment and KEGG analyses. Several alpha and beta 20S proteasome subunits were increased in LT animals when compared with HT animals (eg, PSMα1, PSMα2, and PSMβ5). On the contrary, UBA6, an upstream ubiquitin-activating enzyme, was decreased in LT animals. Altogether these observations are consistent with an overactivation of the accumbal proteasome pathway in animals that manifest pain and depressive-like behaviors after a neuropathic injury. All the proteomic data are available through ProteomeXchange with identifier PXD022478.
Projections from the lateral parabrachial nucleus to the lateral and ventral lateral periaqueductal gray subregions mediate the itching sensation
Authors: Li Jia-Ni , Ren Jia-Hao , He Cheng-Bo , Zhao Wen-Jun , Li Hui , Dong Yu-Lin , Li Yun-Qing
Published: January 2021

Lateral and ventral lateral subregions of the periaqueductal gray (l/vlPAG) have been proved to be pivotal components in descending circuitry of itch processing, and their effects are related to the subclassification of neurons that were meditated. In this study, lateral parabrachial nucleus (LPB), one of the most crucial relay stations in the ascending pathway, was taken as the input nucleus to examine the modulatory effect of l/vlPAG neurons that received LPB projections. Anatomical tracing, chemogenetic, optogenetic, and local pharmacological approaches were used to investigate the participation of the LPB-l/vlPAG pathway in itch and pain sensation in mice. First, morphological evidence for projections from vesicular glutamate transporter-2-containing neurons in the LPB to l/vlPAG involved in itch transmission has been provided. Furthermore, chemogenetic and optogenetic activation of the LPB-l/vlPAG pathway resulted in both antipruritic effect and analgesic effect, whereas pharmacogenetic inhibition strengthened nociceptive perception without affecting spontaneous scratching behavior. Finally, in vivo pharmacology was combined with optogenetics which revealed that AMPA receptor-expressing neurons in l/vlPAG might play a more essential role in pathway modulation. These findings provide a novel insight about the connections between 2 prominent transmit nuclei, LPB and l/vlPAG, in both pruriceptive and nociceptive sensations and deepen the understanding of l/vlPAG modulatory roles in itch sensation by chosen LPB as source of ascending efferent projections.
Mechanical sensitization, increased axonal excitability, and spontaneous activity in C-nociceptors after ultraviolet B irradiation in pig skin
Authors: Werland Fiona , de Col Roberto , Hirth Michael , Turnquist Brian , Schmelz Martin , Obreja Otilia
Published: January 2021

Ultraviolet B (UVB) irradiation induces hyperalgesia in human and animal pain models. We investigated mechanical sensitization, increase in axonal excitability, and spontaneous activity in different C-nociceptor classes after UVB in pig skin. We focused on units with receptive fields covering both irradiated and nonirradiated skin allowing intraindividual comparisons. Thirty-five pigs were irradiated in a chessboard pattern, and extracellular single-fibre recordings were obtained 10 to 28 hours later (152 fibers). Units from the contralateral hind limb served as a control (n = 112). Irradiated and nonirradiated parts of the same innervation territory were compared in 36 neurons; low threshold C-touch fibers (n = 10) and sympathetic efferents (n = 2) were unchanged, but lower mechanical thresholds and higher discharge frequency at threshold were found in mechanosensitive nociceptors (n = 12). Half of them could be activated with nonnoxious brush stimuli in the sunburn. Four of 12 mechanoinsensitive nociceptors were found sensitized to mechanical stimulation in the irradiated part of the receptive field. Activity-dependent slowing of conduction was reduced in the irradiated and in the nonirradiated skin as compared with the control leg, whereas increased ability to follow high stimulation frequencies was restricted to the sunburn (108.5 ± 37 Hz UVB vs 6.3 ± 1 Hz control). Spontaneous activity was more frequent in the sunburn (72/152 vs 31/112). Mechanical sensitization of primary nociceptors and higher maximum after frequency are suggested to contribute to primary hyperalgesia, whereas the spontaneous activity of silent nociceptors might offer a mechanistic link contributing to ongoing pain and facilitated induction of spinal sensitization.
The Use of Methylphenidate for Cognitive Enhancement in Young Healthy Adults
Authors: Koren Gideon , Korn Liat
Published: January 2021

Objective

Methylphenidate (MP), a drug of choice for attention-deficit/hyperactivity disorder (ADHD), is a federally restricted substance CII in the United States because of abuse and dependence, and similar restrictions are practiced in Canada and around the world. This designation is given to drugs with medical value that present a high potential for abuse. In view of these severe restrictions, it is concerning to find out that a large group of healthy young adults, at least as large as the ADHD group of patients, take MP for cognitive enhancement, in an attempt to improve their academic achievements during studies and examinations. These young adults buy MP illegally and consume it without any medical supervision. The objective of the present debate piece is to present the ethical and clinical issues that need to be addressed in an attempt to solve this dilemma.

Methods

The issues presented here are systematically reviewed and discussed along the following lines: MP effectiveness in enhancing cognitive achievements in healthy people; “As these are normal healthy people, what is the duty of physicians to ‘treat’ them?”; potential benefits of cognitive enhancement to healthy people; the risks of MP; “How do these young people get their MP?”; and “What can be done?”

Results

Methylphenidate is widely used for cognitive enhancement without medical supervision. The effectiveness of MP for cognitive enhancement is well documented along a dose-response curve. Congruent with the results of the randomized trials, repeated studies based on interviews suggest that numerous young people report that cognitive enhancement helps them in improving their academic achievements, and hence also improve their feeling of well-being. Presently, most regulatory and medical organizations limit the use of MP to ADHD and narcolepsy. Yet, the American Academy of Neurology ruled that there is a moral, ethical, and legal basis to prescribe the drug for cognitive enhancement. The drug has known dose-dependent adverse effects that can have serious ramifications and may often lead to poor adherence. The relative risk of MP causing sudden death/arrhythmia is 1.46 (95% confidence interval, 1.03–2.07), and there are estimated 20 million college and university students in the United States in 2020. The rate of sudden death/arrhythmias in this age group ranges between 1 and 10 per 100,000. This translates to an excess of 146 deaths caused by MP every year in the United States considering postsecondary students only.

Discussion

We propose that an ethical-clinical debate should be followed by an action plan to ensure that the present reality of millions of young people taking unsupervised MP is not accepted as a force majeure that cannot be changed.
Clinical Implications of Horizontal Beating Nystagmus Induced by Dix-Hallpike Test in the Diagnosis of Horizontal Canal Benign Paroxysmal Positional Vertigo
Authors: Kong Tae Hoon , Song Mee Hyun , Shim Dae Bo
Published: January 2021

Objectives:

The purpose of this study was to identify the diverse patterns of nystagmus during the Dix-Hallpike test (DHT) and analyze their clinical significance in horizontal canal benign paroxysmal positional vertigo (HC-BPPV).

Study Design:

Retrospective medical records review.

Patients:

Two hundred ninety-five patients diagnosed with HC-BPPV.

Methods:

Various nystagmus patterns identified during the DHT in patients with HC-BPPV were analyzed. The correlation between the affected side of HC-BPPV and the direction of the horizontal beating nystagmus (HBN) during the DHT was also analyzed.

Results:

The nystagmus pattern during the DHT in 128 patients with geotropic HC-BPPV demonstrated, direction-changing positional nystagmus on both sides in 48 (37.5%) patients, HBN toward one side in 25 (19.6%) patients, and no nystagmus in 55 (42.9%) patients. In 144 patients with apogeotropic HC-BPPV, 54 (37.5%) patients presented with direction-changing positional nystagmus on both sides, 27 (18.8%) patients presented with HBN toward one side, and 63 (43.7%) patients did not show nystagmus during the DHT. The direction of HBN provoked by the DHT was significantly correlated with the affected side in each subtype of HC-BPPV (geotropic type, p = 0.049; apogeotropic type, p = 0.040; respectively).

Conclusion:

More than half of the patients with HC-BPPV (56.6%) showed HBN during the DHT. When HBN was present during the DHT, it may provide a clue for determining the subtype and affected side in diagnosis of HC-BPPV before performing the supine roll test.
Postural Sway Predicts Growth in Untreated Vestibular Schwannoma: A Retrospective Volumetric Study
Authors: Nilsen Kathrin Skorpa , Dhayalan Dhanushan , Lund-Johansen Morten , Goplen Frederik Kragerud
Published: January 2021

Background:

One in three vestibular schwannomas (VS) will grow within 3 years after diagnosis, but no reliable baseline parameter has been found to predict such growth.

Objective:

To determine if postural sway is associated with growth of untreated VS.

Methods:

Patients with newly diagnosed sporadic VS assigned to a wait-and-scan protocol were identified from a prospectively maintained database. Postural sway was measured by posturography at baseline and patients were classified as steady or unsteady. Observer-blinded volumetric tumor measurements were performed on the diagnostic MRI and a 3-year control MRI. Tumor growth quantified as relative growth (%) and volume-doubling time (VDT and VDT−1) were investigated as dependent variables against baseline parameters.

Results:

Out of 204 VS patients, 53 (26%) were classified as unsteady on the platform at baseline. Median tumor volume was 0.32 cm3 (range 0.02–4.79), and 51% demonstrated significant growth within 3 years. Unsteady patients had significantly faster-growing tumors, with a mean relative growth of 172.5% compared to 79.5% in steady patients (p < 0.006). Seventy-seven percent of unsteady patients had >20% volume increase, compared to 42% in steady patients (p < 0.001). Mean VDT−1 was 0.65 doublings per year for unsteady patients, and 0.22 for steady patients (p < 0.001). Multivariate regression analysis including demographic and clinical parameters showed an OR of 5.6 (95% CI 2.6, 11.8) for growth in unsteady patients.

Conclusions:

This is the first demonstrated association between a measurable parameter and future growth in untreated VS. Our findings may help clinicians identify patients with a higher risk for tumor growth and provide closer monitoring or early treatment.
Cerebrospinal Fluid Leak Following Translabyrinthine Vestibular Schwannoma Surgery—Is Mesh Cranioplasty Necessary for Prevention?
Authors: Selleck Anne Morgan , Hodge Sarah E. , Brown Kevin D.
Published: January 2021

Objective:

Evaluate the incidence of cerebrospinal fluid leak following vestibular schwannoma surgery for mesh cranioplasty closure versus periosteal closure in the translabyrinthine approach. Determine nonsurgical variables associated with higher rates of cerebrospinal fluid leak following vestibular schwannoma surgery.

Study Design:

Retrospective chart review.

Setting:

Tertiary academic referral center.

Patients:

One hundred thirty-two patients with adequate documentation who underwent sporadic vestibular schwannoma resection via a translabyrinthine approach between 2000 and 2019.

Intervention:

Translabyrinthine excision of vestibular schwannoma with mesh cranioplasty closure or watertight periosteal closure.

Main Outcome Measures:

Primary outcome measures included the incidence of postoperative cerebrospinal fluid leak, total length of hospital stay (including the initial hospital stay as well as hospital days during any readmission within 30 days), and total operative time.

Results:

Our overall cerebrospinal fluid leak rate was 9.1% with a leak rate of 12.8% in our translabyrinthine titanium mesh closure group and 0% in our translabyrinthine periosteal closure. There was no statistically significant effect of age, body mass index, or size of tumor on the incidence of cerebrospinal fluid leak. There was also no statistically significantly difference between the two groups on length of operative time or number of days spent in the intensive care unit.

Conclusion:

Mesh cranioplasty is not a prerequisite for achieving a low cerebrospinal fluid leak rate following translabyrinthine approach for vestibular schwannoma resection. In our series, a significantly lower cerebrospinal fluid leak rate was demonstrated with the periosteal closure.
Stereotactic Radiosurgery for Vestibular Schwannoma Outcomes in Patients With Perfect Word Recognition—A Retrospective Cohort Study
Authors: Fouad Ayman , Tran Emma D. , Feng Austin Y. , Alyono Jennifer C. , Ma Yifei , Blevins Nikolas H. , Jackler Robert K. , Santa Maria Peter L.
Published: January 2021

Objectives:

To investigate tumor control rate and hearing outcomes following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) cases with perfect (100%) word recognition score (WRS).

Study Design:

A retrospective cohort study.

Setting:

Tertiary referral center.

Patients:

Inclusion criteria were receiving primary SRS, a pretreatment WRS of 100%, and availability of both pre- and posttreatment audiometric data for evaluation.

Intervention:

SRS delivered by Cyberknife.

Main Outcome Measures:

Tumor growth rates and audiological outcomes after SRS.

Results:

The cohort consisted of 139 patients, with more than 1-year follow-up (mean 6.1 yrs). SRS tumor control rate was 87% for the whole cohort. Growth before SRS was documented in 24% (n = 34 of 139). The proportion of sporadic VS cases who maintained hearing (decline <10 dB of pure-tone audiometry or <20% of WRS) at 3 years was 50%, at 5 years was 45%, and at 10 years was 42%. In multivariate analysis, increased age was found to be predictive of increased hearing loss (p = 0.03), while the following factors were shown not to be significant: sex (p = 0.5), tumor size (p = 0.2), pre-SRS tumor growth (p = 0.5), and target volume (p = 0.42).

Conclusions:

Among patients with VS who had perfect WRS and underwent SRS, the overall tumor control rate was 87% comparable to observation. Hearing maintenance and preservation of “serviceable” hearing rates after 5 years in VS patients with perfect WRS treated by SRS is less than that when comparing to similar observation cohorts. Given this finding we do not advocate using SRS to preserve hearing, over observation, in tumors with perfect WRS.
Investigating Predictors of Increased Length of Stay After Resection of Vestibular Schwannoma Using Machine Learning
Authors: Dang Sabina , Manzoor Nauman F. , Chowdhury Naweed , Tittman Sarah M. , Yancey Kristen L. , Monsour Meredith A. , O’Malley Matthew R. , Rivas Alejandro , Haynes David S. , Bennett Marc L.
Published: January 2021

Objective:

To evaluate the predictors of prolonged length of stay (LOS) after vestibular schwannoma resection.

Study Design:

Retrospective chart review.

Setting:

Tertiary referral center.

Patients:

Patients who underwent vestibular schwannoma resection between 2008 and 2019.

Interventions:

Variables of interest included age, body mass index, comorbidities, symptoms, previous intervention, microsurgical approach, extent of resection, operative time, preoperative tumor volume, and postoperative complications. Predictive modeling was done through multivariable linear regression and random forest models with 80% of patients used for model training and the remaining 20% used for performance testing.

Main Outcome Measures:

LOS was evaluated as the number of days from surgery to discharge.

Results:

Four hundred one cases from 2008 to 2019 were included with a mean LOS of 3.0 (IQR = 3.0–4.0). Postoperatively, 14 (3.5%) of patients had LOS greater than two standard deviations from the mean (11 days). In a multivariate linear regression model (adjusted R2 = 0.22; p < 0.001), preoperative tumor volume (p < 0.001), coronary artery disease (p = 0.002), hypertension (p = 0.029), and any major complication (p < 0.001) were associated with increased LOS (by 0.12, 3.79, 0.87, and 3.20 days respectively). A machine learning analysis using a random forest identified several potential nonlinear relationships between LOS and preoperative tumor dimensions (length, volume) and operative time that were not captured on regression. The random forest model had lower prediction error compared to the regression model (RMSE 5.67 vs. 44.59).

Conclusions:

Tumor volume, coronary artery disease, hypertension, and major complications impact LOS. Machine learning methods may identify nonlinear relationships worthy of targeted clinical investigation and allow for more accurate patient counseling.
Performance With an Adhesive Bone Conduction Device in Active Transcutaneous Bone Conduction Implant Users
Authors: Dahm Valerie , Traxler Stefanie , Liepins Rudolfs , Auinger Alice B. , Sterrer Elisabeth , Kaider Alexandra , Riss Dominik , Arnoldner Christoph
Published: January 2021

Objectives:

The aim of this study was to evaluate the performance and limits of an adhesive bone conduction hearing aid in patients implanted with an active transcutaneous bone conduction implant. Therefore, hearing performance and subjective benefit of patients with mixed and conductive hearing loss were assessed with both bone conduction devices.

Study Design and Patients:

This cohort study was conducted at a tertiary care center. Fifteen subjects, who had been implanted with an active transcutaneous device previously, were included and used the adhesive hearing device for 3 weeks instead of the implant. Subjects underwent two sets of audiological tests as well as assessments of quality of life at the beginning and at the end of the testing period.

Results:

Audiological results showed a significantly greater improvement in regards to functional hearing gain and word recognition scores with the transcutaneous bone conduction device than the nonimplantable adhesive device. Regression analysis showed a trend toward greater improvement with the transcutaneous device compared with the adhesive device in patients with an increasing bone conduction threshold. Hearing-specific and general quality-of-life questionnaires revealed no significant difference between the two devices.

Conclusion:

Patients with mixed or conductive hearing loss experience hearing gain with both, the adhesive device and the active transcutaneous device. The adhesive device may be a valuable alternative to the active transcutaneous device, depending on the individual bone conduction threshold.
Evaluation of the efficiency and safety of botulinum toxin A injection on improving facial scars
Authors: Xu Dan , Zhang Da-Song , Hu Xue-Feng , Hu Meng-Yao
Published: January 2021

Background:

Botulinum toxin A injection is an established method of treatment. Clinical practitioners use it widely in their practice to prevent the occurrence of facial scars. However, the effectiveness and safeness of has not been comprehensively established. The objective of the current systematic review is to evaluate the efficacy and safety of using botulinum toxin A injection to improve facial scars.

Methods and analysis:

This systematic review involves browsing a number of electronic databases to search for related articles. The search will include databases in both English (PubMed, EMBASE, Web of Science, Spocus, and Cochrane Central Register of Controlled Trials) and Chinese (WanFang database, China Nation Knowledge Infrastructure, and VIP database), the periods of searching will be from inception till the 15th of September 2020. Completing the search in databases allows to consider randomized controlled studies that compares botulinum toxin A interventions to any comparison interventions in those who have facial scars. The review will be inclusive of papers in both languages, English and Chinese. The independent screening of studies for eligibility is conducted by 2 independent authors. Discussion was used to resolve discrepancies between the authors. The Cochrane Risk of Bias Tool V.2.0 is adopted for evaluating the methodological quality of each study. Data extraction was performed by 2 independent authors. For dichotomous outcomes, the were expressed as relative risk (RR) with 95% confidence intervals (CI). For continuous outcomes the results were expressed as the mean difference (MD) or standardized mean difference (SMD) with 95% CI. The statistical analysis of the present study is carried out in RevMan 5.3 software.

Results:

This study will output a comprehensive synthesis of existing evidence in relation to botulinum toxin A. Moreover, the results will also provide an interpretation of the effectiveness and safety of botulinum toxin A.

Conclusion:

The present review contributes to the existing body of knowledge by adding more evidence to evaluate if botulinum toxin A is effective and safe to be used as an intervention for improving facial scars.

OSF registration number:

DOI 10.17605/OSF.IO/94TXP (https://osf.io/94TXP/).
Xuan Fei Bai Du Fang for treating coronavirus disease 2019
Authors: Cui Yuying , Yao Jinming , Shao Guoliang , Liao Lin
Published: January 2021

Background:

Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease with a high fatality rate. Up to now, there are an estimated 26 million confirmed cases and 865,000 deaths around the world. But no effective way can control this disease. As the country that first discovered and treated the COVID-19, China has formed relatively mature prevention and treatment methods such as “3 prescriptions and 3 drugs.” Xuan Fei Bai Du Fang, as a member of “3 prescriptions and 3 drugs,” has very good clinical effects

Methods:

The PubMed, EMBASE, ClinicalTrials.gov, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for randomized controlled studies published to date. This study only screens clinical randomized controlled trials on QFBDF for COVID-19 to evaluate its efficacy and safety.

Import all literatures that meet the requirements into Endnote X9 software. The information was finally cross-checked by 2 reviewers. Papers selected for review were assessed for risk of bias according to the criteria. Quality assessment on design of study, risk of bias, indirectness and imprecision were assessed using the GRADE framework. Where sufficient studies were available, publication bias was assessed visually using funnel plots. Relative risks for primary and secondary outcomes were calculated on an intent-to-treat basis and pooled using random effects meta-analysis. the continuous is expressed by mean difference or standard mean difference, eventually the data is synthesized using a fixed effect model or a random effect model depending on whether or not heterogeneity exists. The heterogeneity of studies will be evaluated by Q-test and I
2 statistic with RevMan5.3.

Results:

The time from a positive diagnosis to a negative result of 2 consecutive nucleic acid tests (not on the same day), cure rate. The results of our research will be published in a peer-reviewed journal.

Conclusion:

The purpose of this systematic review is to provide new evidence for the effectiveness and safety of Xuan Fei Bai Du Fang in the treatment of COVID-19.

PROSPERO registration number:

CRD42020213950.
Slowly growing solitary neurofibroma of the thumb
Authors: Kim Kwang Seog , Lee Dong Gyu , Lee Do Hun , Hwang Jae Ha , Lee Sam Yong
Published: January 2021

Rationale:

Neurofibromas can develop as part of neurofibromatosis or as a solitary tumor. Although solitary neurofibromas generally grow slowly, they rarely grow for more than 10 years, and such tumors have not been described in the hand.

Patient concerns:

A 60-year-old woman presented with a mass on the dorsum of the proximal phalanx of the right thumb that had been enlarging since more than a decade.

Diagnoses:

Preoperative imaging revealed a moderately defined soft tissue mass, which measured 1.5 cm × 1.5 cm × 0.7 cm, with no bone and joint abnormalities on the right thumb. The final diagnosis of the tumor was solitary neurofibroma without evidence of neurofibromatosis.

Intervention:

En bloc resection of the tumor was performed through a longitudinal skin incision.

Outcomes:

After surgery, the patient had no complaints of pain but had a temporary tingling sensation. After 14 months of follow-up, no signs of recurrence of the tumor were observed and she was highly satisfied with the results of the surgery.

Lessons:

Solitary neurofibroma is quite rare, especially one in the hand. However, in dealing with soft tissue tumors of the hand, particularly those with neurologic symptoms, neurofibroma should be included in the differential diagnosis.
Efficacy and safety of radiofrequency ablation versus laparoscopic hepatectomy for small hepatocellular carcinoma
Authors: Zhu Fuping , Chang Qing , Duan Shigang , Leng Weiye
Published: January 2021

Background:

Hepatocellular carcinoma (HCC) is one of the most common type of malignant tumors in adults, and is the most common cause of death in people with cirrhosis. Both laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) are radical treatments for small HCC. However, there is no international standard for the treatment of small HCC, and it is still controversial to choose LH or RFA in treating small HCC. We try to carry out a randomized, controlled, prospective study to compare the the short-term and long-term effects and safety of LH versus RFA in the treatment of small HCC.

Methods:

This study is a single-center, evaluator-blinded, randomized, controlled clinical trial (RCT). The patients will be randomly divided into RFA group and LH group in a 1:1 ratio according to a computer-generated randomization list. Postoperative complications rates, Alpha fetoprotein (AFP), hospital stay, 1, 2, 3-year overall survival (OS) rates, disease-free survival (DFS) rates and all possible adverse events will be recorded. Statistical analyses will be performed with SPSS v22.0 software.

Conclusions:

The study will compare the the short-term and long-term effects and safety of LH versus RFA in the treatment of small HCC.

OSF Registration number:

doi: 10.17605/OSF.IO/HNX2T
Efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy
Authors: Mai Weihua , Wei Aisheng , Lin Xiaoxuan , Wang Funeng , Ye Jianhong , Chen Ping
Published: January 2021

Background:

Diabetic peripheral neuropathy is a common complication of diabetes and the main cause of disability. At present, there is no specific therapeutic regimen. Mecobalamin is often used as a neurotrophic drug, and its long-term effects are not satisfactory when used alone. Clinical practice indicates that traditional Chinese medicine injection with mecobalamin has a therapeutic advantage in treating diabetic peripheral neuropathy while it lacks evidence-based medicine. In this scheme, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy has been studied.

Methods:

Computers were used to search the English database (PubMed, the Cochrane Library, Embase, Web of Science), and Chinese database (CNKI, Wanfang, CBMDISC, VIP). Besides, manual searching was conducted to search for Baidu Scholar, CHICTR, Google Scholar. During the establishment of the database to November 2020, a randomized controlled trial on traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was conducted. There were 2 researchers independently conducting data extraction and quality evaluation of literature on the included studies, RevMan5.3 was performed for meta-analysis on the included literature.

Results:

In this study, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was evaluated by the total effective rate, motor nerve conduction velocity, sensory nerve conduction velocity, adverse reactions, and glucose metabolism level.

Conclusion:

This study can provide an evidence-based basis on the clinical applications of traditional Chinese medicine injection with mecobalamin in the treatment of diabetic peripheral neuropathy.

Ethics and dissemination:

The study does not involve patient privacy or rights and does not require approval from an ethics committee. The results may be published in peer-reviewed journals or disseminated at relevant conferences.

OSF Registration number:

DOI 10.17605/OSF.IO/KPW5E.
Renal cell carcinoma in children and adolescents
Authors: He Min , Cai Jiabin , Zhu Kun , Gu Weizhong , Li Minju , Xiong Jieni , Guan Zhonghai , Wang Jinhu , Shu Qiang
Published: January 2021

Renal cell carcinoma (RCC) is infrequent in the pediatric population. In addition, till date, only a few reports have summarized the characteristics of pediatric RCC and differences between pediatric and adult RCC. Therefore, the current study aimed to investigate the clinical characteristics of RCC in children and adolescents, and identify the differences between children and adolescent patients and adult patients through literature retrieval.

The data of 13 pediatric patients diagnosed with RCC at the Children's Hospital of Zhejiang University School of Medicine between 2005 and 2019 were retrospectively analyzed.

Three patients were aged <5 years, 2 were aged 6 to 10 years, and 8 were aged 11 to 18 years. Among the 13 patients, common clinical manifestations included abdominal pain in 5 patients, gross hematuria in 4, and an abdominal mass in 1, while the other 3 patients were incidentally detected after an abdominal contusion. The pathological types were microphthalmia family translocation RCC in 9 patients, clear-cell RCC in 2, papillary RCC in 1, and unclassified in 1. All the children underwent radical nephrectomy, including 2 patients with advanced disease who underwent preoperative transcatheter arterial chemoembolization. The mean follow-up time was 58.6 months. Two patients died after 4 and 17 months of follow-up, respectively.

In conclusion, microphthalmia family translocation renal cell carcinoma is the predominant type of pediatric RCC associated with advanced tumor stage. The early diagnosis and treatment of pediatric patients is important for improving prognosis. Nevertheless, future studies are urgently needed to determine the treatment for pediatric advanced RCC to increase the survival rate.
Clinical effectiveness of liraglutide on weight loss in South Koreans
Authors: Park Joon Seok , Kwon Jieun , Choi Hyung Jin , Lee Changhyun
Published: January 2021

Among Asian countries, South Korea was the first to approve liraglutide as a treatment for obesity. Thus, the clinical effectiveness of liraglutide has not been studied in Asian populations.

In this study, we retrospectively analyzed obese patients [body mass index (BMI) >27 kg/m2] who were treated with liraglutide between March 2018 and March 2019 in a single clinic. Weight, BMI, HbA1c, and clinical data were collected before liraglutide treatment. Changes in body weight and composition and their relationships with clinical variables were examined at re-prescription dates within 30, 60, 90, and 180 days.

A total of 169 subjects were studied. The average age was 41.5 years, and 42% of the subjects were male. The average weight was 85.2 kg, and the average BMI was 30.8 kg/m2. Weight reduction was significant (–5.5 ± 3.4 kg, 30 days: –3.2 ± 1.8 kg, 60 days: –4.5 ± 2.3 kg, 90 days: –6.3 ± 2.6 kg, 180 days: –7.8 ± 3.5 kg) during the follow-up period and increased with longer treatment time (P < .001). The percentages of subjects that showed ≥ 5% and ≥ 10% body weight reduction were 62.1% and 17.2%, respectively. In the body composition analysis, skeletal muscle weight loss was –3.56 ± 29.7%, which was significantly smaller than fat weight loss of –11.06 ± 10.4% (P = .03). Weight loss was not significantly related to age, sex, baseline BMI, baseline HbA1c, smoking status, alcohol consumption, coffee intake.

In conclusion, Liraglutide treatment led to meaningful weight loss in South Korean patients, and fat mass reduction was prominent during treatment. Furthermore, liraglutide showed greater clinical effectiveness with longer treatment time.
The minor C-allele of the rs2014355 variant in ACADS gene is associated with exercise-induced increase in HDL cholesterol levels in Taiwanese adults
Authors: Yang Tzi-Peng , Shih Fen-Fen , Hsu Ming-Yi , Tsai Meng-Hsiun , Nfor Oswald Ndi , Chen Pei-Hsing , Ho Chien-Chang , Lin Chuan-Chao , Liaw Yung-Po
Published: January 2021

We investigated the association between high-density lipoprotein cholesterol (HDL-C) and rs2014355 variant in the gene, short-chain acyl-coenzyme A dehydrogenase (ACADS) based on exercise habits.

Data collected between 2008 and 2015 for individuals aged 30 to 70 years were available in the Taiwan Biobank (TWB) database. Backward stepwise linear regression was used to evaluate the associations of rs2014355 and exercise with HDL-C levels.

We analyzed data of 5515 physically active and 4169 inactive biobank participants. The HDL-C concentrations were higher in the exercise compared to no exercise group (beta value, β = 1.79856; P < .0001). We observed that the test for interaction was significant for the ACADS rs2014355 variant and exercise (P for interaction =.0412). Multivariate analyses showed significant association between TC+CC genotype and HDL-C in the exercise (β = 1.09785; P value = .0146) compared to the no-exercise group (β = −0.03754, P = .9154).

In summary, the association between HDL-C and exercise differed significantly with respect to ACADS rs2014355 genotypes. Compared to the TT genotype, the TC+CC genotype together with exercise was associated with higher levels of HDL-C.
The efficacy of bosentan combined with vardenafil in the treatment of postoperative pulmonary hypertension in children with congenital heart disease
Authors: Gao Chao , Liu Junting , Zhang Runhan , Zhao Manting , Wu Yongli
Published: January 2021

Background:

Congenital heart disease in children with pulmonary hypertension is a common and serious complication, which has a direct impact on the surgical effect and prognosis of children. Bosentan and vardenafil are commonly used drugs for the treatment of postoperative pulmonary hypertension in children with congenital heart disease, and there are few clinical studies on their combined use. Therefore, the purpose of this randomized controlled trial is to evaluate the effectiveness and safety of the combined use of 2 drugs in the treatment of postoperative pulmonary hypertension in children with congenital heart disease.

Methods:

This is a prospective randomized controlled trial to study the effectiveness and safety of bosentan combined with vardenafil in the treatment of postoperative pulmonary hypertension in children with congenital heart disease. Approved by the clinical research ethics committee of our hospital. The patients were randomly divided into 1 of 2 treatment regimens:

Patients, doctors, nurses, and data collection assistants were blinded to group allocation. Observation indicators include: oxyhemoglobin saturation (SpO2), 6-min Walking Test Distance (6 MWTD), systolic pulmonary artery pressure, mean pulmonary artery pressure, Borg score, NYHAFC score, etc. Data were analyzed using the statistical software package SPSS version 25.0 (Chicago, IL).

Discussion:

This study will evaluate the effectiveness and safety of bosentan combined with vardenafil in the treatment of pulmonary hypertension after congenital heart disease in children. The results of this experiment will provide a clinical basis for the use of bosentan combined with vardenafil to treat pulmonary hypertension after congenital heart disease in children.

Ethics and dissemination:

Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.

OSF Registration number:

DOI 10.17605/OSF.IO/962BT.