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Heller Omar opublikował 5 miesięcy, 1 tydzień temu
We examined UPSIT scores in relation to aMCI risk and HAND status, and continuous memory scores considering adjustments for demographics and relevant clinical or HIV disease characteristics.
Fifty-seven participants were classified with HAND (70%) and 35 participants were classified as high aMCI risk (43%). UPSIT scores were lower (worse) in the high versus low aMCI risk group [F (1,76) = 10.04, P = 0.002], but did not differ by HAND status [F (1,76) = 0.62, P = 0.43]. UPSIT scores positively correlated with all memory outcomes (Ps < 0.05).
Olfactory assessments may help in detecting early aMCI/Alzheimer’s disease among PWH and allow for appropriate and early disease intervention.
Olfactory assessments may help in detecting early aMCI/Alzheimer’s disease among PWH and allow for appropriate and early disease intervention.
We evaluated whether identification of undiagnosed HIV-infected people who inject drugs (PWID) via respondent-driven sampling (RDS) can be enhanced through a precision RDS (pRDS) approach.
First, using prior RDS data from PWID in India, we built a prediction algorithm for recruiting undiagnosed HIV-infected PWID. pRDS was tested in Morinda, Punjab where participants were randomly assigned to standard or pRDS. In the standard RDS approach, all participants received two recruitment coupons. For pRDS, the algorithm determined an individual’s probability of recruiting an undiagnosed PWID, and individuals received either two (low probability) or five (high probability) coupons. Efficiency in identifying undiagnosed HIV-infected PWID for the RDS approaches was evaluated in two ways the number needed to recruit (NNR) and identification rate/week.
Predictors of recruiting undiagnosed PWID included HIV/HCV infection, network size, syringe services utilization, and injection environment. 1631 PWID were recruited in Morinda. From the standard RDS approach, 615 were recruited, including 39 undiagnosed; from pRDS, 1012 were recruited, including 77 undiagnosed. In pRDS, those with higher predicted probability were more likely to recruit others with HIV/HCV co-infection, undiagnosed and viremic HIV, and who utilized services. pRDS had a significantly higher identification rate of undiagnosed PWID (1.5/week) compared with the standard (0.8/week). The NNR for pRDS (13.1) was not significantly lower than the standard approach (15.8).
pRDS identified twice as many undiagnosed and viremic PWID significantly faster than the standard approach. Leveraging RDS or similar network-based strategies should be considered alongside other strategies to ensure meeting UNAIDS targets.
pRDS identified twice as many undiagnosed and viremic PWID significantly faster than the standard approach. Leveraging RDS or similar network-based strategies should be considered alongside other strategies to ensure meeting UNAIDS targets.
The aim of this study was to evaluate safety and pharmacokinetics of maraviroc administered with standard antiretroviral prophylaxis to HIV-1 exposed infants and to determine the appropriate dose of maraviroc during the first 6 weeks of life.
A phase I, multicentre, open-label study enrolling two sequential cohorts.
IMPAACT 2007 participants enrolled by day 3 of life and were stratified by exposure to maternal efavirenz. Cohort 1 participants received two single 8 mg/kg maraviroc doses 1 week apart with pharmacokinetic sampling after each dose. Cohort 2 participants received 8 mg/kg maraviroc twice daily through 6 weeks of life with pharmacokinetic sampling at weeks 1 and 4. Maraviroc exposure target was Cavg at least 75 ng/ml. Laboratory and clinical evaluations assessed safety.
Fifteen Cohort 1 and 32 Cohort 2 HIV-exposed neonates were enrolled (median gestational age 39 weeks, 51% male). All 13 evaluable Cohort 1 infants met the pharmacokinetic target. Median exposure for the 25 evaluable Cohort 2 well tolerated during the first 6 weeks of life.
People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease.
This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population.
A double-blind multicentre, randomised, placebo-controlled trial was performed.
Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10-15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid–intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov NCT01813357).
Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011].
In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.
In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.
To measure mortality incidence rates and incidence rate ratios (IRR) in adolescents and youth living with perinatally acquired HIV (YPHIV) compared with those living with nonperinatally acquired HIV (YNPHIV), by region, by sex, and during the ages of 10-14, 15-19, and 20-24 years in IeDEA.
All those with a confirmed HIV diagnosis, antiretroviral therapy (ART)-naive at enrollment, and who have post-ART follow-up while aged 10-24 years between 2004 and 2016 were included. We estimated post-ART mortality incidence rates and 95% confidence intervals (95% CI) per 100 person-years for YPHIV (enrolled into care <10 years of age) and YNPHIV (enrolled ≥10 years and <25 years). We estimate mortality IRRs in a negative binomial regression model, adjusted for sex, region time-varying age, CD4+ cell count at ART initiation (<350 cells/μl, ≥350 cells/μl, unknown), and time on ART (<12 and ≥12 months).
Overall, 104 846 adolescents and youth were included 21 340 (20%) YPHIV (50% women) and 83 506 YNPHIV (80% women). Overall mortality incidence ratios were higher among YNPHIV (incidence ratio 2.3/100 person-years; 95% CI 2.2-2.4) compared with YPHIV (incidence ratio 0.7/100 person-years; 95% CI 0.7-0.8). Among adolescents aged 10-19 years, mortality was lower among YPHIV compared with YNPHIV (all IRRs <1, ranging from 0.26, 95% CI 0.13-0.49 in 10-14-year-old boys in the Asia-Pacific to 0.51, 95% CI 0.30-0.87 in 15-19-year-old boys in West Africa).
We report substantial amount of deaths occurring during adolescence. Mortality was significantly higher among YNPHIV compared to YPHIV. Specific interventions including HIV testing and early engagement in care are urgently needed to improve survival among YNPHIV.
We report substantial amount of deaths occurring during adolescence. Mortality was significantly higher among YNPHIV compared to YPHIV. Specific interventions including HIV testing and early engagement in care are urgently needed to improve survival among YNPHIV.
Tinnitus, phantom sound perception, arises from aberrant brain activity within auditory cortex. In tinnitus animal models, auditory cortex neurons show increased spontaneous firing and neural synchrony. In humans, similar hyperactivation in auditory cortex has been displayed with functional near-infrared spectroscopy (fNIRS). Resting-state functional connectivity (RSFC) or increased connectivity between brain regions has also been shown in tinnitus using fNIRS. However, current fNIRS technology utilizes infrared (IR)-sources and IR-detectors placed on the scalp that restricts (~3 cm depth IR penetration) signal capture to outer cerebral cortex due to skin and skull bone. To overcome this limitation, in this proof of concept study, we adapted fNIRS probes to fit in the external auditory canal (EAC) to physically place IR-probes deeper within the skull thereby extracting neural signals from deeper auditory cortex.
Twenty adults with tinnitus and 20 nontinnitus controls listened to periods of silence and broadband noise before and after 5 min of silence to calculate RSFC. Concurrent scalp probes over auditory cortex and an adapted probe placed in the right EAC were utilized.
For standard probes, left and right auditory cortex in tinnitus showed increased RSFC to each other and to other nonauditory cortices. Interestingly, adapted fNIRS probes showed trends toward increased RSFC.
While many areas for the adapted probes did not reach significance, these data using a highly innovative and newly created probe adapting fNIRS technology to the EAC substantiates our previously published data in human tinnitus and concurrently validates this technology as a useful and expanded brain imaging modality.
While many areas for the adapted probes did not reach significance, these data using a highly innovative and newly created probe adapting fNIRS technology to the EAC substantiates our previously published data in human tinnitus and concurrently validates this technology as a useful and expanded brain imaging modality.Minocycline and doxycycline, two semisynthetic second-generation tetracyclines, are reported to provide neuroprotection against brain injury and glutamate-induced neurotoxicity in neuronal cultures. Doxycycline has been postulated as the potential ideal candidate for further therapeutic development as it has fewer adverse effects than minocycline. In this study, we determined whether minocycline and doxycycline could similarly protect neurons against excitotoxic insults. We treated cultured rat cortical neurons and cerebellar granule neurons (CGN) with excitotoxic concentrations of NMDA or glutamate in the presence or absence of minocycline or doxycycline. Intracellular Ca concentration ([Ca]i) was also measured using a Fluorescent Light Imaging Plate Reader (FLIPR; Molecular Devices) with the calcium sensitive dye Fluo-3 AM. We found that minocycline and tetracycline markedly protected neurons against NMDA- and glutamate-induced neuronal death. In contrast, the structurally related tetracycline, doxycycline, was ineffective at concentrations up to 100 μM. Furthermore, minocycline, but not doxycycline, also significantly attenuated NMDA- or glutamate-induced [Ca]i in both cortical neurons and CGN. Our results suggest that minocycline but not doxycycline is able to directly block NMDA- or glutamate-induced excitotoxicity in neurons most likely by inhibiting NMDA- and glutamate-induced [Ca]i. This finding may contribute to our understanding of the molecular mechanisms underlying doxycycline- and minocycline-induced neuroprotection.
The aim of this study was to explore the upper motor neurons (UMN) and lower motor neurons (LMN) degeneration in amyotrophic lateral sclerosis (ALS) from the perspective of the clinical neurological examination and MRI-electromyography manifold detection, respectively.
The clinical data, cortical thickness of corresponding areas in different body regions in MRI and electromyography data were collected from 108 classical ALS patients.
The kappa value of UMN and LMN involvement signs in the bulbar region (0.31) was higher than that of the left upper limb (-0.13), right upper limb (-0.27), left lower limb (-0.05) and right lower limb (-0.08). The cortical thickness in the positive LMN damage group was thinner than that of the negative LMN damage group in the left head-face area (P < 0.05; Cohen’s d = 0.84); however, cortical thickness showed no significant differences in the right head-face, bilateral tongue-larynx, upper-limb, trunk and lower-limb areas between LMN-damage-positive and LMN-damage-negative groups.
The degeneration of motor neuron could be independent through UMN and LMN levels. The degenerative process was not only confined to UMN and LMN levels but can also expand to white matter fiber tracts. Thus, the degeneration of UMN and LMN might be independent of the motor system’s three-dimensional anatomy.
The degeneration of motor neuron could be independent through UMN and LMN levels. The degenerative process was not only confined to UMN and LMN levels but can also expand to white matter fiber tracts. Thus, the degeneration of UMN and LMN might be independent of the motor system’s three-dimensional anatomy.
Lidocaine is well known as a local anesthetic that has been reported to play an antitumor role in numerous cancers, including glioma. Circular RNAs (circRNAs) play multiple biological roles in cancers. The aim of this study was to determine the effects of lidocaine in glioma in vitro and in vivo and explore functional mechanisms.
The effects of lidocaine on glioma progression were investigated by cell proliferation, migration and invasion using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and transwell assay. The expression of CD133 and glial fibrillary acidic protein (GFAP) was quantified by western blot to assess cell differentiation. The expression of circEZH2 and miR-181b-5p was detected by a quantitative real-time PCR (qRT-PCR). The target relationship between circEZH2 and miR-181b-5p was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The effect of lidocaine on tumor growth in vivo was investigated by establishing Xenograft models.
Lidocaine inhibited proliferation, migration, invasion and induced differentiation of glioma cells in vitro. Lidocaine suppressed the expression of circEZH2, and circEZH2 was highly expressed in glioma tissues and cells. CircEZH2 overexpression partly inhibited the function of lidocaine. CircEZH2 was a sponge of miR-181b-5p, and miR-181b-5p was downregulated in glioma tissues and cells. Besides, miR-181b-5p restoration reversed the effects of circEZH2 overexpression to repress the malignant behaviors of glioma cells. In addition, lidocaine mediated the circEZH2/miR-181b-5p axis to inhibit tumor growth in vivo.
Lidocaine suppressed glioma progression by modulating the circEZH2/miR-181b-5p pathway.
Lidocaine suppressed glioma progression by modulating the circEZH2/miR-181b-5p pathway.
Competent neurologic examination and clinical skills are essential components in the care for patients in acute hospital and rehabilitation settings. To enhance the evaluation and education of Physical Medicine and Rehabilitation residents, the authors developed an educational objective structured clinical examination, the Neurological Exam Assessment Competency Evaluation System, and gathered 2 yrs of baseline data. The Neurological Exam Assessment Competency Evaluation System consisted of nine 9-min examination stations, seven with written clinical scenario with instructions for junior residents to complete the appropriate examination (stations Altered Mental Status, Mild Traumatic Brain Injury, Dementia, Stroke, Falls, and the International Standards for Neurological Classification of Spinal Cord Injury Sensory and Motor Examinations). Examinees provided written responses to posed questions for the other two stations-Modified Ashworth Scale and brachial plexus. The assessment tools for this examination wns for junior residents to complete the appropriate examination (stations Altered Mental Status, Mild Traumatic Brain Injury, Dementia, Stroke, Falls, and the International Standards for Neurological Classification of Spinal Cord Injury Sensory and Motor Examinations). Examinees provided written responses to posed questions for the other two stations-Modified Ashworth Scale and brachial plexus. The assessment tools for this examination were designed for residency programs to evaluate the basic competencies as outlined by the Accreditation Council for Graduate Medical Education and Physical Medicine and Rehabilitation milestones. Based on the feedback received from the examinees and examiners, the Neurological Exam Assessment Competency Evaluation System can serve as an educational objective structured clinical examination for the improvement of trainee core competencies.
Intramuscular Botulinum toxin A (BTX-A) is used in the management of focal spasticity in cerebral palsy (CP). We aimed to conduct a systematic review to assess current literature on the use of BTX-A in the management of mobility related outcomes among adult persons with spastic CP.
All studies reporting on the use of BTX-A in the management of spastic CP among adult persons were identified by searching the following electronic databases PubMed, CINAHL, the Cochrane Library, and EMBASE.
Six studies were included in the review. Most studies were conducted in mixed patient groups comprising patients with movement disorders, traumatic brain injury, cerebral palsy and other disorders requiring therapy for spasticity. BTX-A was shown to be effective in improving spasticity related outcomes among persons with CP but mixed results were shown for functional outcomes.
More studies are required on exclusive CP cohorts using recommended and currently used scales, incorporating Quality of life and patient satisfaction scales. Results from long term follow up studies will be valuable for better evaluation of the effectiveness of BTX-A in the management of spasticity related outcomes among adult persons with CP.
More studies are required on exclusive CP cohorts using recommended and currently used scales, incorporating Quality of life and patient satisfaction scales. Results from long term follow up studies will be valuable for better evaluation of the effectiveness of BTX-A in the management of spasticity related outcomes among adult persons with CP.Interest in global health is rising in graduate medical education. Trainees are increasingly seeking high quality, ethically sound, and educationally robust opportunities for global medical rotations. When based on best educational practices, these opportunities can provide a unique learning experience for residents in traditional Physical Medicine and Rehabiliation (PM&R) programs. This article describes the development of an international rotation in PM&R including specific competency-based PM&R global health learning objectives, predeparture training, rotation structure, and post-rotation feedback mechanisms. The aim is to present the development of the program as a resource for both residents and program directors to help create and maximize existing rotations at their own institutions. Learners must complete predeparture requirements that include completion of a musculoskeletal rotation and global health didactics intended to provide foundational knowledge in physiatry and global health. Postrotation requirements include the residency program’s standardized evaluation form, resident survey, and self-reflection essay. Experience from a novel 4-week pilot rotation to Punta Gorda, Belize is described to exemplify ACGME based learning objectives as well as the benefits of a formalized rotation structure. Using this unique set of learning objectives and proposed rotation requirements, we believe that PM&R residency programs can develop valuable global health learning experiences.The American Board of Physical Medicine and Rehabilitation’s revised mission and vision emphasize lifelong learning throughout its board certification processes. More formative approaches have been incorporated into both initial and continuing certification. These changes are based in adult learning theory and are supported by an ongoing board research endeavor. Board certification in the future is envisioned as a partnership with physicians to facilitate ongoing learning and positively impact patient outcomes.
In 2015, the Accreditation Council for Graduate Medical Education published the Physical Medicine and Rehabilitation Milestones 1.0 as part of the Next Accreditation System. This was the culmination of more than 20 yrs of work on the part of the Accreditation Council for Graduate Medical Education to improve graduate medical education competency assessments. The six core competencies were patient care, medical knowledge, systems-based practice, practice-based learning and improvement, professionalism, and interpersonal and communication skills. While providing a good foundation for resident assessment, the Physical Medicine and Rehabilitation Milestones 1.0 was not without faults. With input from program directors, national organizations, and the public, the Physical Medicine and Rehabilitation Milestones 2.0 strives to further advance resident assessment, providing improvements through the integration of the harmonized Milestones and the addition of a supplemental guide.
In 2015, the Accreditation Council for Graduate Medical Education published the Physical Medicine and Rehabilitation Milestones 1.0 as part of the Next Accreditation System. This was the culmination of more than 20 yrs of work on the part of the Accreditation Council for Graduate Medical Education to improve graduate medical education competency assessments. The six core competencies were patient care, medical knowledge, systems-based practice, practice-based learning and improvement, professionalism, and interpersonal and communication skills. While providing a good foundation for resident assessment, the Physical Medicine and Rehabilitation Milestones 1.0 was not without faults. With input from program directors, national organizations, and the public, the Physical Medicine and Rehabilitation Milestones 2.0 strives to further advance resident assessment, providing improvements through the integration of the harmonized Milestones and the addition of a supplemental guide.
Facial suspension threads have been successfully used for facial soft-tissue repositioning. When using facial suspension threads, it is unclear which technique and/or material has the greatest lifting effect for the middle and lower face or which technique/material best reduces the appearance of the jowls.
Three female and 2 male cephalic specimens of Caucasian ethnicity (65.2 ± 8.3 years; 20.72 ± 2.6 kg/m) were analyzed in an upright secured position. Polydioxanone and polycaprolactone bidirectional barbed facial suspension threads were introduced by an 18 G, 100 mm cannula. The single-vector technique aimed toward the labiomandibular sulcus, and the dual-vector technique aimed toward the labiomandibular sulcus and the mandibular angle. Computation of vertical lifting, horizontal lifting, and volume reduction at the jowls and along the jawline were calculated using 3D imaging.
The dual-vector technique effected a greater vertical lifting effect (4.45 ± 2.78 mm vs 2.99 ± 2.23 mm) but a reduced horizontal lifting effect (0.33 ± 1.34 mm vs 0.49 ± 1.32 mm). The dual-vector technique effected less volume reduction at the jowls 0.32 ± 0.24 cc versus 0.41 ± 0.46 cc and less volume reduction along the jawline 0.46 ± 0.48 cc versus 0.87 ± 0.53 cc (dual-vector vs single-vector).
This study provides evidence resulting from cadaveric observations for the overall nonsuperiority of the dual-vector technique compared with the single-vector technique.
This study provides evidence resulting from cadaveric observations for the overall nonsuperiority of the dual-vector technique compared with the single-vector technique.
Cherry angiomas are benign vascular proliferations of endothelial cells associated with aging. Currently, no mainstay of treatment for these vascular anomalies exists.
To review existing evidence-based therapies for the treatment of cherry angiomas.
A literature search in May 2019 was performed with PubMed Database and Cochrane Library using the following terms „cherry angioma,” „senile hemangioma,” „senile angioma,” „cherry hemangioma,” and „Campbell de Morgan spots.”
Ten studies included in this systematic review reported laser therapy and nonlaser therapy as efficacious treatments for cherry angiomas. Among the laser therapies, pulsed dye laser (PDL) was preferred over potassium-titanyl-phosphate (KTP) and electrodessication (ED), based on decreased procedure-related pain. The neodymium-doped yttrium aluminum garnet (NdYAG) laser 1064 nm produced less pigmentary complications, whereas KTP and PDL risked pigmentary changes in darker-skinned individuals. Nonlaser therapies included cryotherapy, sclerotherapy, electrosurgery (i.e., ED, electrocoagulation), and radiofrequency ablation. No therapy proved to be superior.
A variety of therapeutic modalities exist for the treatment of cherry angiomas. However, a limited number of high-quality studies explored the efficacy of treatments and compared treatment modalities. Light-based methods such as argon, KTP, NdYAG, intense pulsed light, and PDL, along with non-light-based interventions such as cryotherapy, electrosurgery, and sclerotherapy effectively treated cherry angiomas.
A variety of therapeutic modalities exist for the treatment of cherry angiomas. However, a limited number of high-quality studies explored the efficacy of treatments and compared treatment modalities. Light-based methods such as argon, KTP, NdYAG, intense pulsed light, and PDL, along with non-light-based interventions such as cryotherapy, electrosurgery, and sclerotherapy effectively treated cherry angiomas.
Historically, soft-tissue hyaluronic acid (HA) fillers have been mixed with agents to reduce pain or alter physicochemical properties.
Evaluate the impact of dilution and mixing on HA filler physicochemical properties.
Crosslinked HA filler (VYC-20L, 20 mg/mL) was diluted to 15 mg/mL using saline through 5 or 10 passes between 2 syringes connected using a luer connector. Extrusion force, rheological properties, and microscopic appearance were assessed. Undiluted VYC-15L (15 mg/mL) served as the control.
Average extrusion force was higher for diluted VYC-20L versus the control, with an increase in slope for gel diluted using 5 passes (0.65) and 10 passes (0.52) versus the control (<0.1). For diluted samples mixed with 5 or 10 passes, the rheological profile was different between the 2 halves of the syringe, with the second half more elastic than the first half, compared with the consistent profile of undiluted samples. Microscopically, diluted VYC-20L samples seemed more liquid near the luer and more particulate near the piston compared with the control, which was smooth throughout.
In addition to potentially introducing contamination, diluting or mixing soft-tissue HA fillers yields a heterogeneous product with physicochemical characteristics that vary substantially throughout the syringe.
In addition to potentially introducing contamination, diluting or mixing soft-tissue HA fillers yields a heterogeneous product with physicochemical characteristics that vary substantially throughout the syringe.
Venous malformations (VM) are common vascular malformations. Percutaneous injection of sclerosants into the lesion has become mainstream therapy. The most commonly used sclerosants are ethanol, polidocanol, bleomycin, and the like. But few articles have reported that sclerosants are more effective and safer.
We performed a search on Cochrane, Embase, PubMed, China National Knowledge Infrastructure, CBM, and Wan Fang databases of Controlled Trials (from January 1, 2010, launch up to April 10, 2019) reporting outcome of intralesional ethanol, polidocanol, and bleomycin injections in patients with VM (n ≥ 20). A meta-analysis was conducted using Rev-man 5.3 software.
A total of 9 articles, 632 participants and 676 lesions were included. Quality of evidence was generally low. Meta-analysis showed that absolute ethanol treatment was better than polidocanol in treating VM (p = .001), and absolute ethanol elicited a better response than bleomycin (p = .01). Ethanol therapeutic effect was not statistically significant compared with ethanol alone (p = .07), but the combination effect was better than polidocanol (p = .04). Ethanol treatment showed significantly more adverse reactions than polidocanol and combination therapy.
Absolute ethanol combined with polidocanol is more effective in treating VM and has fewer adverse reactions.
Absolute ethanol combined with polidocanol is more effective in treating VM and has fewer adverse reactions.
The large-scale social distancing efforts to reduce SARS-CoV-2 transmission have dramatically changed human behaviors associated with traumatic injuries. Trauma centers have reported decreases in trauma volume, paralleled by changes in injury mechanisms. We aimed to quantify changes in trauma epidemiology at an urban Level I trauma center in a county that instituted one of the earliest shelter-in-place orders to inform trauma care during future pandemic responses.
A single-center interrupted time-series analysis was performed to identify associations of shelter-in-place with trauma volume, injury mechanisms, and patient demographics in San Francisco, California. To control for short-term trends in trauma epidemiology, weekly level data were analyzed 6 months before shelter-in-place. To control for long-term trends, monthly level data were analyzed 5 years before shelter-in-place.
Trauma volume decreased by 50% in the week following shelter-in-place (p < 0.01), followed by a linear increase each successive week (p < 0.01). Despite this, trauma volume for each month (March-June 2020) remained lower compared with corresponding months for all previous 5 years (2015-2019). Pediatric trauma volume showed similar trends with initial decreases (p = 0.02) followed by steady increases (p = 0.05). Reductions in trauma volumes were due entirely to changes in nonviolent injury mechanisms, while violence-related injury mechanisms remained unchanged (p < 0.01).
Although the shelter-in-place order was associated with an overall decline in trauma volume, violence-related injuries persisted. Delineating and addressing underlying factors driving persistent violence-related injuries during shelter-in-place orders should be a focus of public health efforts in preparation for future pandemic responses.
Epidemiological study, level III.
Epidemiological study, level III.
Rehabilitation therapists do not consistently utilize standardized outcome measures. The purpose of this study was to develop and implement a tailored knowledge translation (KT) intervention to facilitate application of standardized outcome measures used in patients with Parkinson disease (PD) receiving outpatient rehabilitation.
Four clinics within a hospital-based outpatient system including physical therapists (n = 7) and occupational therapists (n = 2) collaborated with researcher clinicians. A mixed-methods study, using the knowledge to action (KTA) framework, was executed to standardize the assessment battery completed on patients with PD. The project was titled iKNOW-PD (integrating KNOWledge translation for Parkinson Disease).
Four measures were selected for iKNOW-PD (9-Hole Peg Test, miniBESTest, 10-m walk test, and 5 times sit-to-stand). A multimodal intervention that overcame specific identified barriers (equipment, time) was implemented to ensure successful uptake. Consistency of utilizing ivercoming identified barriers and capitalizing on facilitators promoted the uptake of standardized outcomes. Following the 6-month intervention period, therapists endorsed an improvement in their application of standardized measures and labeled iKNOW-PD as a positive experience that allowed them to minimize variability in practice.Video Abstract available for more insights from the authors (see the Video, Supplemental Content 1, available at http//links.lww.com/JNPT/A329).
We aimed to assess rates and predictors of hepatocellular carcinoma (HCC) screening among patients with cirrhosis.
We reviewed electronic health records of 11,361 patients with cirrhosis from 11 U.S. Veterans Health Administration facilities for receipt of HCC screening in the 6 months preceding October 1, 2019.
Nearly half of the cohort (46%) received HCC screening over a 6-month period. Screening rates and modalities (ultrasound, computed tomography, magnetic resonance imaging, serum alpha fetoprotein) varied by facility. Screening was associated with race/ethnicity, body mass index ≥ 25, cirrhosis etiology, thrombocytopenia, Fibrosis-4 ≥ 3.25, and lower Model for End-Stage Liver Disease-Sodium.
HCC screening rates varied by facility. Higher risk patients were more likely to receive screening.
HCC screening rates varied by facility. Higher risk patients were more likely to receive screening.
Metabolic-associated fatty liver disease is common, with fibrosis the major determinant of adverse outcomes. Population-based screening tools with high diagnostic accuracy for the staging of fibrosis are lacking.
Three independent cohorts, 2 with both liver biopsy and liver stiffness measurements (LSMs, n = 254 and 65) and a population sample (n = 713), were studied. The performance of a recently developed noninvasive algorithm (ADAPT [age, diabetes, PRO-C3 and platelets panel]) as well as aspartate aminotransferase-to-platelet ratio index, fibrosis-4, nonalcoholic fatty liver disease fibrosis score, and LSM was used to stage patients for significant (≥F2) and advanced (≥F3) fibrosis.
In the hospital-based cohorts, the N-terminal propeptide of type 3 collagen (Pro-C3) increased with fibrosis stage (P < 0.0001) and independently associated with advanced fibrosis (odds ratio = 1.091, 95% confidence interval [CI] 1.053-1.113, P = 0.0001). ADAPT showed areas under the receiver operating characteristics cow down those patients who would need to be referred to specialty clinics.
PRO-C3 and ADAPT reliably exclude advanced fibrosis in low-risk populations. The serial combination of ADAPT with LSM has high diagnostic accuracy with a low requirement for liver biopsy. The proposed algorithm would help stratify those who need biopsies and narrow down those patients who would need to be referred to specialty clinics.
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are rare myeloid clonal disorders that commonly affect the elderly population and have poor prognosis. There are limited data on the risk of AML/MDS among patients with inflammatory bowel disease (IBD), especially on the impact of thiopurines (TPs).
We conducted a retrospective cohort study among patients with IBD from Veteran Affairs data set. The exposure of interest was TP exposure (i) never exposed to TPs, (ii) past TP use (discontinued >6 months ago), (iii) current TP use with a cumulative exposure of <2 years, and (iv) current TP use with a cumulative exposure of ≥2 years. The outcome of interest was a composite outcome of incident diagnosis of AML and/or MDS. Cox regression was used to estimate the adjusted and unadjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for AML/MDS risk associated with TP use defined as a time-varying exposure.
Among 56,314 study patients, 107 developed AML/MDS. The overall incidence of use.A large body of animal and human studies indicates that blocking peripheral calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) signaling pathways may prevent migraine episodes and reduce headache frequency. To investigate whether recurring migraine episodes alter the strength of CGRP and PACAP signaling in trigeminal ganglion (TG) neurons, we compared the number of TG neurons that respond to CGRP and to PACAP (CGRP-R and PACAP-R, respectively) under normal and chronic migraine-like conditions. In a mouse model of chronic migraine, repeated nitroglycerin (NTG) administration significantly increased the number of CGRP-R and PACAP-R neurons in TG but not dorsal root ganglia. In TG neurons that express endogenous αCGRP, repeated NTG led to a 7-fold increase in the number of neurons that respond to both CGRP and PACAP (CGRP-R&PACAP-R). Most of these neurons were unmyelinated C-fiber nociceptors. This suggests that a larger fraction of CGRP signaling in TG nociceptors may be mediated through the autocrine mechanism, and the release of endogenous αCGRP can be enhanced by both CGRP and PACAP signaling pathways under chronic migraine condition. The number of CGRP-R&PACAP-R TG neurons was also increased in a mouse model of posttraumatic headache (PTH). Interestingly, low-dose interleukin-2 treatment, which completely reverses chronic migraine-related and PTH-related behaviors in mouse models, also blocked the increase in both CGRP-R and PACAP-R TG neurons. Together, these results suggest that inhibition of both CGRP and PACAP signaling in TG neurons may be more effective in treating chronic migraine and PTH than targeting individual signaling pathways.
During self-induced pain, a copy of the motor information from the body’s own movement may help predict the painful sensation and cause downregulation of pain. This phenomenon, called sensory attenuation, enables the distinction between self-produced stimuli vs stimuli produced by others. Sensory attenuation has been shown to occur also during imagined self-produced movements, but this has not been investigated for painful sensations. In the current study, the pressure pain thresholds of 40 healthy participants aged 18 to 35 years were assessed when pain was induced by the experimenter (other), by themselves (self), or by the experimenter while imagining the pressure to be self-induced (imagery). The pressure pain was induced on the participants left lower thigh (quadriceps femoris) using a handheld algometer. Significant differences were found between all conditions other and self (P < 0.001), other and imagery (P < 0.001), and self and imagery (P = 0.004). The mean pressure pain threshold for other of sensory attenuation might also be used to alleviate the pain experience for patients undergoing procedural pain.
The aims of the study were to assess the clinical and histopathological characteristics of a comprehensive cohort of women with vulvovaginal melanoma (VVM) treated at our institution and to study the treatment response of checkpoint inhibitors in this patient cohort.
This is a retrospective study of women with invasive VVM treated at the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, over a period of 15 years. Clinical and histopathological characteristics, treatment, as well as treatment-related outcome were analyzed in 32 women. Treatment response was evaluated retrospectively using the „response criteria for use in trials testing immunotherapeutics” (iRECIST). The objective response rate was defined as the proportion of patients with complete or partial response based on the best overall response.
At a median follow-up of 37.8 months (5.8-110.4), 26 women (81.3%) had disease progression and 16 (50%) died. Thirteen patients with locally unresectable or metastatic melanoma were treated with immune checkpoint inhibitors. Ten additional cases were identified from previously published reports. The best objective response rate for immune checkpoint inhibitors was 30.4% (95% CI = 11.6%-49.2%) and the clinical benefit rate was 52.2% (95% CI = 31.8%-72.6%). The clinical benefit rate was significantly better for programmed cell death protein 1 inhibitors (or a combination) compared with ipilimumab alone (Fisher exact, p = .023). Grade 3/4 adverse events were observed in 3 (13.0%) of the 23 patients.
Women with VVM constitute a high-risk group with poor overall prognosis. Immune checkpoint inhibitors are effective in the treatment of metastatic melanoma in this patient cohort.
Women with VVM constitute a high-risk group with poor overall prognosis. Immune checkpoint inhibitors are effective in the treatment of metastatic melanoma in this patient cohort.
Compare anterior minimally invasive plate osteosynthesis (MIPO) to open reduction/internal fixation (ORIF) for humeral shaft fractures, assessing complications and clinical outcomes.
Retrospective matched case-controlled cohort.
Tertiary referral trauma centre.
Humeral shaft fractures identified retrospectively over 5-years; 31 were treated by MIPO and 54 by ORIF. Case-matched cohort assembled according to fracture pattern, gender, age, and comorbidities, with 56 total patients (28 per group).
MIPO and ORIF MAIN OUTCOME MEASURES Complication rate was the primary outcome (radial nerve injury, nonunion, infection, and re-operation). Radiographic alignment and the DASH Score were secondary outcomes.
Cumulative complication rates were 3.6% following anterior MIPO, and 35.7% after ORIF (p=0.0052). The only complication following anterior MIPO was a nonunion, managed with revision ORIF and bone graft. The ORIF group had 10 complications, including 5 superficial infections, 4 iatrogenic radial nerve injuries, and 1 nonunion. The mean DASH score following MIPO was 17.0 ± 18.0, and after ORIF was 24.9 ± 19.5. The mean coronal plane angulation following MIPO was 1.8 ± 1.3, and after ORIF was 1.0 ± 1.2. The mean sagittal plane angulation following MIPO was 3.0 ± 2.9, and after ORIF was 1.0 ± 1.2.
The cumulative complication rate was 10 times higher following ORIF of humeral shaft fractures compared to the MIPO technique. MIPO achieved nearly equivalent radiographic alignment, with no clinically meaningful differences observed. MIPO is the safer option, and should be considered for patients with humeral shaft fractures that would benefit from surgical intervention.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
To assess agreement among experts in pelvic fracture management regarding stability and need for operative repair of lateral compression (LC) type pelvic fractures with static radiographs compared to static radiographs and exam under anesthesia (EUA).
Online surveyPatients/Participants Ten patients who presented to our level-1 trauma center with a pelvic ring injury were selected. Vignettes were distributed to 11 experienced pelvic surgeons.
Exam under anesthesia MAIN OUTCOME MEASUREMENTS Agreement regarding pelvic fracture stability, need for surgical fixation.
Agreement on stability was achieved in 4 (40%) cases without EUA compared to 8 (80%) cases with EUA. Inter-reviewer reliability was poor without EUA and moderate with EUA (0.207 vs. 0.592). Agreement on need to perform surgery was achieved in 5 (50%) cases compared to 6 (60%) cases with EUA. Inter-reviewer reliability was poor without EUA and moderate with EUA (0.250 vs. 0.432). For reference cases with agreement, surgeons were able to predict stability or instability using standard imaging in 57 of a possible 88 reviewer choices (64.8%) compared to 82 of 88 choices (93.2%) with the addition of EUA (p<0.0001).
EUA increased agreement among experienced pelvic surgeons regarding the assessment of pelvic ring stability and the need for operative intervention. Further research is necessary to define specific indications for which patients may benefit from EUA.
Diagnostic Level V. See Instructions for authors for a complete description of levels of evidence.
Diagnostic Level V. See Instructions for authors for a complete description of levels of evidence.
We hypothesize that in adequately resuscitated borderline polytrauma patients with long bone fractures (femur and tibia) or pelvic fractures; early (within 4 days) definitive stabilization (EDS) can be performed without an increase in post-operative ventilation and post-operative complications.
Retrospective Cohort Study SETTING Level 1 Trauma Centre PATIENTS In total 103 patients were included in this study of which 18 (17.5%) were female and 85(82.5%) were male. These patients were borderline trauma patients who had the following parameters prior to definitive surgery, normal coagulation profile, lactate < 2.5 mmol/L, pH ≥ 7.25, and base excess (BE) ≥ 5.5.
These patients were treated either according to Early Total Care (ETC), definitive surgery on day of admission, or Damage Control Orthopaedics (DCO) principles, temporizing external fixation followed by definitive surgery at a later date. Timing of definitive surgical fixation was recorded as EDS or late definitive surgical fixation (LDS) (>4 tions for Authors for a complete description of levels of evidence.
To determine if orthogonal or parallel plate position provides superior fixation of the separate capitellar fragment often present in intra-articular distal humerus fractures. We hypothesized that orthogonal plating would provide stiffer fixation given a greater number of opportunities for capitellar fixation as well as screw trajectories perpendicular to the fracture plane offered by a posterolateral plate compared to a parallel plate construct.
Ten matched pairs of cadaveric distal humeri were used to compare parallel and orthogonal plating in a fracture gap model with an isolated capitellar fragment. The capitellum was loaded in 20 of flexion utilizing a cyclic, ramp-loading protocol. Fracture displacement was measured using video tracking software. The primary outcome was axial stiffness for each construct. Secondary outcomes included maximum axial and angular fracture displacement.
The parallel plate construct was more than twice as stiff as the orthogonal plate construct averaged across all loads dy. In the setting of an articular fracture, in which absolute stability and primary bone healing are desirable, parallel fixation should be considered even in fractures with a separate capitellar fragment if the size of fragment and fracture orientation allows.
To clarify the incidence, associated conditions, and timing of fasciotomy for compartment syndrome (CS) in children with a supracondylar (SC) fracture of the humerus.
A retrospective trauma system database study.
Accredited trauma centers in Pennsylvania.
A statewide trauma database was searched for children age 2-12 years old admitted with a SC fracture between 1/2001 and 12/2015. 4308 children met inclusion criteria.
Treatment of a SC fracture.
Diagnosis of CS /performance of a fasciotomy.
During the study period 21 (0.49%) children admitted with a SC fracture of the humerus were treated with fasciotomy. CS / fasciotomy was more likely in males (p = 0.031), those with a nerve injury (p = 0.049), and /or ipsilateral forearm fracture (p < 0.001). Vascular procedure, performed in 18 (0.42%), was strongly associated with CS / fasciotomy (p < 0.001). Closed reduction and fixation of a forearm fracture was associated with CS (p = 0.007). Timing of SC fracture treatment did not influence outcome. Fasciotomy was performed subsequent to reduction in 13 subjects, mean interval between procedures was 23.4 hrs. (r 4.5 – 51.3).
Risk factors for CS exist, however are not required for the condition to develop. CS may develop subsequent to admission and /or SC fracture treatment. In terms of timing of operative management and hospitalization, the results support contemporary practice.
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
To compare piriformis fossa to greater trochanteric entry cephalomedullary implants in an evaluation of femoral neck load to failure when the device is used for femoral shaft fractures with prophylaxis of an associated femoral neck fracture.
Thirty fourth-generation synthetic femur models were separated into 5 groups; intact femora, entry sites alone at the piriformis fossa or greater trochanter, and piriformis fossa and greater trochanteric entry sites after the insertion of a cephalomedullary nail. Each model was mechanically loaded with a flat plate against the superior femoral head along the mechanical axis and load to failure was recorded.
Mean load to failure was 5487 ± 376 N in the intact femur, 3126 ± 387 N in the piriformis fossa entry site group, 3772 ± 558 N in the piriformis entry nail, 5332 ± 292 N for the greater trochanteric entry site, and 5406 ± 801 N for the greater trochanteric nail group. Both piriformis groups were significantly lower compared to the intact group. Both greater trochanteric groups were similar to the intact group and were statistically higher than the piriformis groups.
A piriformis fossa entry site with or without an intramedullary implant weakens the femoral neck in load to failure testing. A greater trochanteric entry yields a load to failure equivalent to that of an intact femoral neck. Instrumentation with a greater trochanteric cephalomedullary nail is significantly stronger than a piriformis fossa cephalomedullary nail during axial loading in a composite femur model.
A piriformis fossa entry site with or without an intramedullary implant weakens the femoral neck in load to failure testing. A greater trochanteric entry yields a load to failure equivalent to that of an intact femoral neck. Instrumentation with a greater trochanteric cephalomedullary nail is significantly stronger than a piriformis fossa cephalomedullary nail during axial loading in a composite femur model.
To compare the volume of embolic load during intramedullary fixation of femoral and tibial shaft fractures. Our hypothesis was that tibial IM nails would be associated with less volume of intravasation of marrow than IM nailing of femur fractures.
Prospective observational study.
Urban Level I trauma center.
Twenty-three patients consented for the study 14 with femoral shaft fractures and 9 with tibial shaft fractures.
All patients underwent continuous transesophageal echocardiography (TEE), and volume of embolic load was evaluated during five distinct stages post induction, initial guidewire, reaming, nail insertion, and postoperative.
Volume of embolic load was measured based on previously described luminosity scores. The embolic load based on fracture location and procedure stage was evaluated using a mixed effects model.
The IMN procedure increased the embolic load by 215% (-12 – 442%, p=0.07) in femur patients relative to tibia patients after adjusting for baseline levels. Of the five steps measured, reaming was associated with the greatest increase in embolic load relative to the guide wire placement and controlling for fracture location (421%, 95% CI 169 – 673%, p<0.01) CONCLUSIONS Femoral shaft IMN fixation was associated with a 215% increase in embolic load in comparison to tibial shaft IMN fixation, with the greatest quantitative load during the reaming stage, however both procedures produce embolic load.
Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.