Tag: pubmed

Mov Disord. 2021 May 20. doi: 10.1002/mds.28650. Online ahead of print.

ABSTRACT

BACKGROUND: Potential therapeutic targets and clinical trials for Huntington’s disease have grown immensely in the last decade. However, to improve clinical trial outcomes, there is a need to better characterize profiles of signs and symptoms across different epochs of the disease to improve selection of participants.

OBJECTIVE: The objective of the present study was to best distinguish longitudinal trajectories across different Huntington’s disease progression groups.

METHODS: Clinical and morphometric imaging data from 1082 participants across IMAGE-HD, TRACK-HD, and PREDICT-HD studies were combined, with longitudinal times ranging between 1 and 10 years. Participants were classified into 4 groups using CAG and age product. Using multivariate linear mixed modeling, 63 combinations of markers were tested for their sensitivity in differentiating CAG and age product groups. Next, multivariate linear mixed modeling was applied to define the best combination of markers to track progression across individual CAG and age product groups.

RESULTS: Putamen and caudate volumes, individually and/or combined, were identified as the best variables to both differentiate CAG and age product groups and track progression within them. The model using only caudate volume best described advanced disease progression in the combined data set. Contrary to expectations, combining clinical markers and volumetric measures did not improve tracking longitudinal progression.

CONCLUSIONS: Monitoring volumetric changes throughout a trial (alongside primary and secondary clinical end points) may provide a more comprehensive understanding of improvements in functional outcomes and help to improve the design of clinical trials. Alternatively, our results suggest that imaging deserves consideration as an end point in clinical trials because of the prospect of greater sensitivity. © 2021 International Parkinson and Movement Disorder Society.

PMID:34014005 | DOI:10.1002/mds.28650

Int J Dermatol. 2021 May 20. doi: 10.1111/ijd.15628. Online ahead of print.

ABSTRACT

BACKGROUND: Drug survival is useful to evaluate long-term drug performance in daily practice. The aim of this study was to evaluate drug survival for methotrexate (MTX) monotherapy in patients with plaque-type psoriasis.

METHODS: We reviewed 3,512 follow-up charts of patients with psoriasis at five tertiary referral centers between January 2012 and January 2020. We analyzed baseline data and treatment outcomes of patients under MTX monotherapy. Drug survival was analyzed using Kaplan-Meier and Cox regression analyses.

RESULTS: Patients with psoriasis who were treated with MTX monotherapy were enrolled (N = 649). The median duration of drug survival was 15 months (95% CI: 13.2-16.8). The overall drug survival rate was 54.7%, 17.4%, and 8% after 1, 3, and 5 years, respectively. The main reasons for discontinuation were adverse effects (n = 209, 32.2%) and inefficacy (n = 105, 15.6%). Based on multivariate Cox regression analysis, the presence of nausea/vomiting (HR: 2.01, 95% CI: 1.49-2.71; P < 0.001) was observed as a statistically significant risk factor for drug discontinuation. Age over 50 years (HR: 0.68, 95% CI: 0.48-0.97; P = 0.03) and using MTX dose ≥15 mg/weekly were positive predictors for drug survival (HR: 0.72, 95% CI: 0.54-0.95; P = 0.02).

CONCLUSIONS: The average drug survival of MTX was 15 months. MTX is still the first-line treatment of moderate-to-severe plaque psoriasis, as highlighted in guidelines. To prevent premature discontinuation, physicians need to look at the response time of at least 16-24 weeks, especially when a stepwise dose increment is used. The presence of nausea/vomiting seemed to be associated with an approximately twofold risk of discontinuation.

PMID:34013975 | DOI:10.1111/ijd.15628

Laryngoscope. 2021 May 20. doi: 10.1002/lary.29628. Online ahead of print.

ABSTRACT

OBJECTIVES: Assesses whether preoperative functional testing can distinguish vestibular schwannomas from facial nerve schwannomas medial to the labyrinthine segment.

STUDY DESIGN: Retrospective cohort.

METHODS: Retrospectively review surgically managed intracranial facial and vestibular schwannomas between January 2015 and December 2019 at two tertiary care centers. Patients with neurofibromatosis 2 and surgery for recurrence were excluded. Preoperative functional testing to include House-Brackmann scores, electroneuronography (ENoG), cervical vestibular evoked myogenic potentials (cVEMP), caloric testing, acoustic brainstem responses (ABRs), acoustic reflexes, and audiograms was compared between the two groups of schwannomas.

RESULTS: Twelve facial and 128 vestibular schwannomas met inclusion criteria. In only one case was a facial schwannoma diagnosed preoperatively from imaging. No statistically significant difference was found in preoperative House-Brackmann scores, ENoG, cVEMP, caloric testing, ABRs, or acoustic reflexes. Pure tone average was worse in the vestibular schwannoma group (63 dB [95% CI: 58-68 dB] vs. 46 dB [95% CI: 34-58 dB], P = .01), and the difference was more apparent in the lower frequencies. Word recognition score was better in the facial schwannoma group (66% [95% CI: 45-86%] vs. 41% [95% CI: 34-47%], P = .02).

CONCLUSION: Specialized preoperative functional evaluation of the nerves of the internal auditory canal cannot reliably predict the presence of an intracranial facial schwannoma. Hearing is better in facial schwannomas, particularly in the lower frequencies. This should raise the index of suspicion for an intracranial facial schwannoma, especially in candidates for hearing preservation vestibular schwannoma surgery.

LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2021.

PMID:34013983 | DOI:10.1002/lary.29628

Headache. 2021 May 20. doi: 10.1111/head.14120. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the methodology and implications of the patient-identified most bothersome symptom (PI-MBS) measure used in the phase 3, multicenter, randomized, double-blind, placebo-controlled, and parallel-group PROMISE-2 trial and to evaluate the contribution of this measure to the assessment of the preventive migraine benefits of treatment.

BACKGROUND: Although freedom from MBS is a coprimary endpoint in acute migraine treatment trials, its evaluation in preventive migraine trials is limited. The PROMISE-2 study assessed a unique PI-MBS measure as a secondary endpoint.

METHODS: This was a secondary analysis of data from the PROMISE-2 study. Adults with chronic migraine (CM) were randomized to receive intravenous (IV) eptinezumab 100 mg, eptinezumab 300 mg, or placebo, administered on day 0 and every 12 weeks. At the screening visit, patients were asked to verbally describe the MBS associated with their CM; the question format was open ended. At subsequent visits, patients were asked to rate the overall change in severity of their MBS from study inception to that time point, using a 7-point ordinal scale ranging from “very much worse” (-3) to “very much improved” (+3). Patients completed the Patient Global Impression of Change (PGIC) assessment during the same visits, using an identical rating scale and recall period. Endpoints were summarized descriptively; post hoc correlations using the methodologies of Pearson and Spearman were calculated to evaluate relationships between PGIC and PI-MBS and between PGIC and mean monthly migraine days (MMDs; primary efficacy endpoint in PROMISE-2).

RESULTS: Altogether, 1072 patients received treatment (eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366) and were included in the analysis. There were 23 unique MBS identified; those reported by ≥10 patients included light sensitivity (18.7%), nausea/vomiting (15.1%), pain with activity (13.7%), pain (12.4%), headache (11.2%), sound sensitivity (7.3%), throbbing/pulsating pain (4.7%), cognitive disruption (4.1%), fatigue (2.4%), mood changes (1.5%), and sensitivity to smell (0.9%). Four weeks after the first dose (week 4), the rates of much or very much improvement in PI-MBS were higher with eptinezumab 100 mg (45%) and 300 mg (57%) than with placebo (29%). Four weeks after the second dose (week 16), the proportions with much or very much improvement in PI-MBS had increased to 58%, 65%, and 36%, respectively. At each time point, the percentages of patients with PGIC ratings of much or very much improved were similar to those for patient-reported improvement in PI-MBS. Patient ratings of changes in PI-MBS and PGIC correlated strongly across time points (Pearson, r range, 0.83-0.88; Spearman, r range, 0.83-0.89); the absolute value of the correlations was greater than the correlation among changes in MMDs and PGIC (Pearson, r range, -0.49 to -0.52; Spearman, r range, -0.49 to -0.52).

CONCLUSIONS: Among patients with CM in the PROMISE-2 study, a broad range of PI-MBS was reported at baseline. Throughout the study, patients treated with eptinezumab reported greater improvement in their PI-MBS severity compared with placebo recipients, and this improvement correlated strongly with PGIC findings. Collectively, these results indicate that PI-MBS is a promising and novel outcome measure for preventive trials of CM and thus may provide a unique patient-centered approach for identifying and measuring the burden of migraine symptoms that matter most to each patient, as well as the benefits of treatment.

PMID:34013992 | DOI:10.1111/head.14120

Leuk Lymphoma. 2021 May 20:1-7. doi: 10.1080/10428194.2021.1929962. Online ahead of print.

ABSTRACT

There are only a few predictive markers that can truly aid therapy decisions in patients with acute myeloid leukemia (AML). The current study aimed to examine the impact of easily available common laboratory parameters on the course and prognosis of patients with AML. Gender, initial bone marrow blast percentage, mean platelet volume (MPV), lymphocyte-to-monocyte ratio, treatment regimen, and complete remission (CR1) were found to have a statistically significant effect on both OS and PFS (p < 0.05). Only MPV, LDH, and initial treatment regimen were found to have a significant effect on CR1 achievement (p < 0.05). According to the current study, besides the induction regimen, only MPV was seen to affect short and long-term outcomes including both CR achievement, OS and PFS. MPV can be considered as a predictive or prognostic marker in patients with AML. Patients with higher MPV at the time of diagnosis should be evaluated carefully.

PMID:34013848 | DOI:10.1080/10428194.2021.1929962

J Pediatric Infect Dis Soc. 2021 May 20:piab010. doi: 10.1093/jpids/piab010. Online ahead of print.

ABSTRACT

BACKGROUND: The Zika virus (ZIKV) epidemic had devastating consequences in Brazil. We investigated whether a radiologic finding (ie, infratentorial abnormalities) was associated with sight-threatening defects in children born with congenital Zika syndrome (CZS). We also investigated whether ophthalmic abnormalities correlated with head circumference (HC) and gestational age of infection.

METHODS: Cross-sectional evaluation based upon a previous cohort from March 2016 to December 2018, in Paraíba, Brazil. The study population was comprised of children born to mothers with laboratory-confirmed ZIKV infection during pregnancy (ZIKV reverse transcriptase polymerase chain reaction [RT-PCR]+) and children born with clinical and radiologic features of CZS.

RESULTS: A total of 75 infants had complete data. All 75 had brain calcifications. Microcephaly was present in 53 (71%) of them. Infratentorial abnormalities were present in 17 infants (22.7%). Ophthalmic abnormalities were seen in 16 of the 17 children (94%) with infratentorial abnormalities, while 28% of children without infratentorial abnormalities had ophthalmic findings (odds ratio [OR]: 42.0; 95% confidence interval [CI]: 5.1-342.9). Similar associations were observed when macular chorioretinal atrophy and optic nerve abnormalities were analyzed individually (OR: 23.7; 95% CI: 6.0-93.3 and OR: 11.5; 95% CI: 3.3-40.0, respectively). Infratentorial abnormalities were more frequently associated with ophthalmic abnormalities (94%) than microcephaly (43.4%) (P < .001). Mean HC was statistically different between groups with and without ophthalmic abnormalities (P = .01). A statistically significant difference in gestational age between both groups was not noted (P = .12).

CONCLUSIONS: In children with CZS, the presence of infratentorial abnormalities is a significant predictor of ophthalmic abnormalities. All neonates whose mothers had ZIKV exposure during pregnancy should have an ophthalmologic examination.

PMID:34013960 | DOI:10.1093/jpids/piab010

J Feline Med Surg. 2021 May 20:1098612X211013745. doi: 10.1177/1098612X211013745. Online ahead of print.

ABSTRACT

OBJECTIVES: Bisphenol A (BPA) is one of the most widely used synthetic compounds on the planet. It is used in the synthesis of polycarbonate plastics, epoxy resins and other polymer materials. Owing to its excellent chemical and physical properties, it is used to produce food and beverage containers or the linings for metal products. BPA has been mentioned as a possible cause of feline hyperthyroidism. Cat food is considered one of the main sources of BPA intake. The purpose of this study was to evaluate BPA concentration in various types of commercial cat food available in the Czech Republic.

METHODS: In total, 172 samples prepared from 86 different types of commercial cat food were assessed. The concentration of BPA was measured using liquid chromatography-tandem mass spectrometry.

RESULTS: Measurable concentration of BPA was found in all samples (range 0.065-131 ng/g), with the highest concentration (mean ± SD) of BPA in canned food (24.6 ± 34.8 ng/g). When comparing BPA concentration in food trays (1.58 ± 0.974 ng/g), pouches (0.591 ± 0.592 ng/g) and dry food (1.18 ± 0.518 ng/g), concentrations of BPA in food trays and dry food were significantly higher (P <0.01) compared with pouches. Comparing BPA concentrations in canned food of different manufacturers, statistically significant differences were found as well.

CONCLUSIONS AND RELEVANCE: The highest concentrations of BPA were found in cans. Thus, cans represent the highest possibility of exposure to BPA in comparison with other types of commercial feline food.

PMID:34013813 | DOI:10.1177/1098612X211013745

Lupus. 2021 May 20:9612033211016074. doi: 10.1177/09612033211016074. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE) increases the incidence of adverse pregnancy outcomes (APOs). Nevertheless, most of the data on SLE pregnancies were derived from database studies in which details of the pregnancies were unavailable, and no consensus exists on the risk of APO in patients with prior severe organ manifestations.

METHODS: SLE patients followed by rheumatologists and gynecologists throughout pregnancy at our institute were retrospectively identified, and their data between April 2003 and December 2020 were reviewed from electronic records. We assigned patients based on the presence of prior severe organ manifestation (renal/neurological manifestation, prior treatment with methylprednisolone pulse therapy/prednisolone 1 mg/kg/day/biological or cytotoxic therapy) and compared the incidence of overall and serious APO (maternal death, pregnancy loss, preterm birth <32 weeks, birthweight <1500 g, Apgar score <7 at 5 min and birth defect).

RESULTS: This study included 34 pregnancies in 32 patients; 23 pregnancies in 22 patients were classified as SLE with prior severe organ manifestation. There was no statistical difference in the incidence of overall APO between the two groups (52.2% vs 45.5%, P = 1). Among patients with prior severe organ manifestation, 17.4% had serious APO. A detailed electronic health record search revealed specific causes of APO in all pregnancies with serious APO, except the presence of prior severe organ manifestation.

CONCLUSION: The incidence of overall APO in SLE patients was not affected by prior severe organ manifestation. Although the incidence of serious APOs increased in patients with previous severe organ manifestation, there were other risk factors for poor pregnancy outcomes besides prior lupus severity. Therefore, proper management by rheumatologists and gynecologists may enable patients with prior severe organ manifestation to safely deliver healthy babies.

PMID:34013819 | DOI:10.1177/09612033211016074

Int J Hyperthermia. 2021;38(1):781-785. doi: 10.1080/02656736.2021.1926561.

ABSTRACT

OBJECTIVE: To compare the efficacy and safety of the treatment of vulvar lichen simplex chronicus (VLSC) using high-intensity focused ultrasound (HIFU) at different powers.

METHODS: This retrospective study included 152 patients with VLSC. Among these patients, 70 were treated with HIFU at low power (level 2), and 82 were treated at normal power (level 3). The treatment responses, recurrence rates and intra- and postoperative complications were all compared.

RESULTS: No statistically significant differences were found between the two groups in age, disease course, menopause status, lesion size and severity of symptoms. All patients received one session of HIFU therapy, and the treatment process was successful. No difference was found in the total response rate between the two groups at 1 (85.7% versus 87.8%, p = .35), 6 (80% versus 80.5%, p = .65) and 12 (80% versus 80.5%, p = .73) months after HIFU therapy. No significant difference was observed in the recurrence rate between the two groups at 6 (5.7% versus 9.8%, p = .36) and 12 (22.9% versus 26.8%, p = .57) months after HIFU treatment. Patients in the low-power group had a lower incidence of blisters (10% versus 23.3%, p = .04).

CONCLUSION: Based on our results, low-power HIFU treatment can achieve a therapeutic effect similar to normal power HFU treatment for VLSC, but its incidence of side effects is lower.

PMID:34013843 | DOI:10.1080/02656736.2021.1926561

J Hand Surg Eur Vol. 2021 May 20:17531934211016668. doi: 10.1177/17531934211016668. Online ahead of print.

ABSTRACT

The incidence of distal radioulnar joint instability following a distal radius fracture is estimated around one in three based upon clinical examination. Using a validated rig, we objectively measured distal radioulnar joint translation in vivo following distal radius fracture. Dorsopalmar translation of the distal radioulnar joint was measured in 50 adults with previous distal radius fractures. Measurements were compared with the uninjured wrist and against a database of previous measurements within healthy and clinically lax populations. Translation at the distal radioulnar joint was greater in injured wrists at 12.2 mm (range 10-15, SD 1.2) than the uninjured wrists at 6.4 (range 4-9, SD 0.8) (p < 0.001) and was always outside the established normal range. There was no statistically significant link between translation and the severity of the injury. Instability appears almost inevitable following a distal radius (wrist) fracture, albeit subclinical in the vast majority.

PMID:34013791 | DOI:10.1177/17531934211016668