Comparative clinical effectiveness and safety of super bioavailable itraconazole and conventional itraconazole in management of dermatophytosis: a retrospective data analysis

<p class="abstract"><strong>Background:</strong> A newer itraconazole formulation i.e., super bioavailable itraconazole has been launched recently in India which is claimed to overcome all the pharmacokinetic challenges faced with conventional itraconazole. The present retrospective data analysis was undertaken to evaluate the effectiveness and safety of super bioavailable itraconazole in comparison with conventional itraconazole in the treatment of dermatophytosis in Indian patients.</p><p class="abstract"><strong>Methods:</strong> The present multi-centric, retrospective data analysis was done at 12 dermatological centers across India from July 2020 to December 2020. Medical records of patients of dermatophytosis, who were prescribed with either super bioavailable itraconazole 50 mg twice daily for four weeks or conventional itraconazole 100 mg twice daily for four weeks were included in the study.<strong></strong></p><p class="abstract"><strong>Results:</strong> 56% patients (n=30) in super bioavailable itraconazole group achieved complete clearance of their symptoms (cured) compared to only 34% patients (n=17) in conventional itraconazole group and this difference was statistically significant (p=0.02). Significantly more patients achieved complete clearance of their lesions in super bioavailable itraconazole-37 patients (69%) compared to conventional itraconazole group-25 patients (49%) at the end of 4 week therapy (p=0.04). The difference in total symptom score (∆TSS) in super bioavailable itraconazole group was more (5.81) as compared to conventional itraconazole group (4.75) (p=0.09). Both the treatment were well tolerated.</p><p class="abstract"><strong>Conclusions:</strong> From the findings of the present study, super bioavailable itraconazole was more effective with similar safety profile as compared to conventional itraconazole in the treatment of dermatophytosis.</p>

IMMUNOTHERAPY VERSUS PHARMACOTHERAPY AMONG PATIENTS WITH ALLERGIC RHINITIS BASED ON TOTAL SYMPTOM SCORE AND MEDICATION SCORE.

Objective: To compare efcacy of immunotherapy and pharmacotherapy in patients with allergic rhinitis using total symptom score and rescue medication score. Prospective analysis of outcomes Design: of different treatment modalities in allergic rhinitis patients in a tertiary care centre. Hundred and ten pa Subjects: tients, diagnosed to have allergic rhinitis were included in this study, they were divided into 2 groups based on treatment modality i:e, pharmacotherapy (Group A) and immunotherapy group (Group B). Former contained 76 patients and latter 34 patients The pretreatment mean t Results: otal symptom score (TSS) in pharmacotherapy group was 7.76±3.8 and in immunotherapy group 10.88±2.45. Post treatment mean total symptom score was 7.31±3.68 and 6.29±3.01 respectively. Mean rescue medication score (RMS) in pharmacotherapy group was 0.40±0.22 and immunotherapy was 0.28±0.18. Conclusion: Both pharmacotherapy and immunotherapy was efcacious and safe in treating patients with AR , but the magnitude of reduction was more in immunotherapy group. Regardless of the sensitisation status of the patients (even if the patient is polysensitised ) they responded well with single allergen immunotherapy. Reduction in rescue medication score was statistically signicant in those receiving immunotherapy giving a stable control. Immunotherapy can also be used as anti symptomatic treatment and has the capacity to modify the course of illness

Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure

Background: Chronic heart failure with reduced ejection fraction impairs health-related quality of life (HRQL). Omecamtiv mecarbil (OM)—a novel activator of cardiac myosin—improves left ventricular systolic function and remodeling and reduces natriuretic peptides. We sought to evaluate the effect of OM on symptoms and HRQL in patients with chronic heart failure with reduced ejection fraction and elevated natriuretic peptides enrolled in the COSMIC-HF trial (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure). Methods: Patients (n=448) were randomized 1:1:1 to placebo, 25 mg of OM BID, or to pharmacokinetically guided dose titration (OM-PK) for 20 weeks. The Kansas City Cardiomyopathy Questionnaire was administered to assess HRQL at baseline, 16 weeks, and 20 weeks. The primary scores of interest were the Total Symptom Score, Physical Limitation Scale, and Clinical Summary Score. Results: Mean change in score from baseline to 20 weeks for the Total Symptom Score was 5.0 (95% CI, 1.8–8.1) for placebo, 6.6 (95% CI, 3.4–9.8) for OM 25 mg ( P =0.32 versus placebo), and 9.9 (95% CI, 6.7–13.0) for OM-PK ( P =0.03 versus placebo); for the Physical Limitation Scale, it was 3.1 for placebo (95% CI, −0.3 to 6.6), 6.0 (95% CI, 3.1–8.9) for OM 25 mg ( P =0.12), and 4.3 (95% CI, 0.7–7.9) for OM-PK ( P =0.42); for the Clinical Summary Score, it was 4.1 (95% CI, 1.4–6.9) for placebo, 6.3 (95% CI, 3.6–9.0) for OM 25 mg ( P =0.19), and 7.0 (95% CI, 4.1–10.0) for OM-PK ( P =0.14). Differences between OM and placebo were greater in patients who were more symptomatic at baseline. Conclusions: HRQL as measured by the Total Symptom Score improved in patients with heart failure with reduced ejection fraction assigned to the OM-PK group relative to placebo. Ongoing trials are prospectively testing whether OM improves symptoms and HRQL in heart failure with reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01786512.

Validation of a Modified Version of the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

Background Patients with myeloproliferative neoplasms (MPNs) are faced with severe disease-related fatigue among a range of other constitutional and spleen-related symptoms. The MPN-Symptom Assessment Form (SAF) is recommended for use to characterize symptom burden (Scherber R, et al. Blood 2011). Within the SAF, a profile of 18 symptom items are evaluated ranging in severity from 0 (absent) to 10 (worst imaginable). The SAF is often summarized to the MPN-SAF Total Symptom Score (TSS) for analysis purposes - a single computed sum of the 10 most clinically meaningful symptom scores, including fatigue (Emanuel R, et al. J Clin Oncol 2012). Though the SAF includes a fatigue item, initial deployments of the MPN-SAF TSS incorporated a 0-10 scaled fatigue item taken from the Brief Fatigue Inventory (BFI; Mendoza T, et al. Cancer 1999). A subsequent version of the MPN-SAF TSS for use within myelofibrosis clinical trials (called the MFSAF v4; Gwaltney C, et al. Leuk Res 2017) employed a harmonized fatigue item. This analysis employing data from two studies was carried out to assess the use of the SAF fatigue item within the MPN-SAF TSS for consistency with the MFSAF v4. Methods Both BFI and SAF fatigue items were included in an initial online survey evaluating disease burden among patients with MPNs. Participants were assigned to survey variants as a function of their age. Survey variants included those to receive 1 instance of either the BFI or SAF fatigue item, instances of both BFI and SAF, or 2 instances of the same fatigue item. Surveying was aimed to assess the worst symptom experience in the patient's last 24 hours. Additionally, an independent survey assessing the impact of COVID-19 among MPN patients was deployed using the SAF fatigue item for the MPN-SAF TSS. This modified version was then used to test internal validity. Pearson correlation (r) and t-tests were used to assess association, Bland-Altman methods were used to evaluate systematic agreement between BFI and SAF fatigue scores, and Cronbach's alpha was used to measure internal consistency. Results There were 229 participants assigned both BFI and SAF fatigue items within the same survey. Among them, 51% (n=117) received the BFI item first and 49% (n=112) the SAF item first. No difference was seen between first and second fatigue scores (mean difference [first-second] = 0.00; 95%CI -0.18, 0.17). BFI and SAF fatigue scores were highly correlated (r=0.88, p&lt;0.001) and showed 88.7% agreement in categorizing severe versus non-severe fatigue (score ≥ 7 versus &lt; 7). Overall concordance in severity category was 73.4% (category [score range]: absent [0]; mild [1-3]; moderate [4-6]; severe [7-10]). Constructing the MPN-SAF TSS using the BFI and SAF fatigue components separately, the original and modified MPN-SAF TSS were nearly identical (r=0.997, p&lt;0.001), and had equivalent internal consistency (both Cronbach's alpha=0.88). The Bland-Altman plot further indicates the 2 fatigue measures have high agreement with no evidence of directional bias and negligible overall bias (Figure 1: regression slope = -0.04, p=0.25; mean difference=0.22; 95%CI 0.05, 0.39). Within the COVID-19 survey (n=1217), the modified version of the MPN-SAF TSS was consistent with known correlates among disease characteristics (Emanuel R, et al. J Clin Oncol 2012). For example, more severe MPN-SAF TSS scores were highly correlated with low quality-of-life (n=1156, r = -0.50, p&lt;0.001), and associated with those reporting spleen enlargement (n=301) versus not (n=617) (p&lt;0.001; mean difference=7.7; 95%CI 5.4, 10.1). Conclusion The BFI and SAF fatigue items are highly consistent in raw score, severity category, and in contribution to the MPN-SAF TSS. There was no order effect seen in which fatigue item was asked first. The independent COVID-19 survey using the modified MPN-SAF TSS was validated and shows high internal consistent. In the ongoing development to capture the symptom experience, this analysis shows disease-related fatigue is equivalently measured using the SAF fatigue survey item in harmonization with the MFSAF v4. Disclosures Mesa: Bristol Myers Squibb: Research Funding; CTI BioPharma: Research Funding; Promedior: Research Funding; AbbVie: Research Funding; Samus Therapeutics: Research Funding; Genentech: Research Funding; Incyte: Research Funding; LaJolla Pharmaceutical Company: Consultancy; Novartis: Consultancy; Sierra Oncology: Consultancy.

HOW DO LEARNING DISORDERS IMPACT CLINICAL MEASURES FOLLOWING CONCUSSION?

Background: There is limited evidence examining the impact of learning disorders on testing and screening scores used in evaluation following concussion in adolescents. Purpose: To examine differences in clinical measures between adolescents with a history of dyslexia or ADD/ADHD and those without a history of learning disorder (LD) following concussion. Methods: Data were collected from participants enrolled in the North Texas Concussion Network Prospective Registry (ConTex). Participants ages 10-18 who had been diagnosed with a concussion sustained within 30 days of enrollment were included. Participants were separated into three groups based on self-reported prior diagnosis: dyslexia, ADD/ADHD, and no history of LD. Clinical measures from initial presentation were examined, including ImPACT®, King-Devick (KD), SCAT-5 symptom log, Patient Health Questionnaire (PHQ-8), and Generalized Anxiety Disorder (GAD-7) scale. Independent t-test analysis was performed to compare scores between groups. Results: A total of 993 participants were included; 68 with dyslexia, 141 with ADD/ADHD, and 784 with no history of LD. There was no difference in age, sex, time since injury, or history of concussion between the dyslexia group and no LD group. In the ADD/ADHD group, there were significantly more male participants (64.5% and 50.3% respectively, p=0.002). Participants with a history of dyslexia had a significant increase in KD time (63.7 sec vs 56.5 sec, p=0.019). Additionally, ImPACT® testing showed a decrease in visual motor speed (28.87 vs 32.99, p= 0.010). Total symptom score was higher in this group as well (36.22 vs 28.27, p=0.013). In those with a history of ADD/ADHD, multiple domains were found to be significantly different on ImPACT® testing including visual motor speed (30.05), reaction time (0.75), and cognitive efficiency (0.23) when compared to those with no LD (32.99, 0.71, and 0.27 respectively, p=0.004, 0.047, 0.027). KD time was also significantly higher in this group (62.1 sec vs 56.5 sec, p=0.008), as was the total symptom score (32.99 vs 28.27, p=0.043). PHQ-8 and GAD-7 were both significantly higher in the group with ADD/ADHD (5.79 and 5.06 respectively, p=0.001) than those with no LD (4.32 and 3.56, p=0.001). Conclusion: Differences were seen in participants with a history of dyslexia and ADD/ADHD on clinical concussion measures, including ImPACT® and KD testing, SCAT-5 symptom log, and screenings for depression and anxiety. A better understanding of the unique profiles seen in these patients will aid providers in their evaluation and assist as they counsel families regarding their child’s injury.

Efektivitas Penggunaan Kombinasi Vitamin B pada Pasien Neuropati Diabetikum

Pendahuluan: Neuropati diabetikum (ND) adalah salah satu bentuk neuropati yang paling umum dijumpai. Terapi yang ada saat ini lebih ditujukan untuk mengatasi gejala. Pemberian kombinasi vitamin B ditujukan bukan hanya untuk mengendalikan gejala, namun memperbaiki fungsi saraf. Penelitian terdahulu tentang vitamin untuk neuropati diabetika masih terbatas dan belum konklusif. Tujuan: Penelitian ini bertujuan untuk menilai efektivitas vitamin B kombinasi terhadap gejala klinis neuropati diabetika dan kualitas hidup (QoL) pada pasien diabetes melitus (DM). Metode: Metode yang digunakan dalam penelitian ini adalah metode penelitian observasional pada pasien DM dengan ND. Setiap subjek memperoleh vitamin B kombinasi yang terdiri dari vitamin B1, vitamin B6, dan vitamin B12 dengan dosis masing-masing secara berurutan 100 mg, 100 mg, dan 5 mg. Gejala klinis ND dinilai dengan menggunakan Total Symptom Score (TSS). QoL dinilai dengan menggunakan kuesioner SF-8. Penilaian dilakukan sebanyak 5 kali, yaitu penilaian awal hingga 3 bulan. Hasil: Total terdapat 104 subjek pada awal penelitian. Tujuh subjek tidak dapat mengikuti penelitian sampai selesai, sehingga tersisa 97 subjek pada akhir penelitian. Terdapat perbaikan berbagai gejala ND, yang meliputi sensasi nyeri tertusuk, sensasi nyeri terbakar, kesemutan, dan rasa kebas/baal, setelah pemberian vitamin B kombinasi. Perubahan tersebut bermakna secara statistik (p < 0,0001). Hal serupa juga tampak pada QoL. Terdapat perbaikan QoL dari awal penelitian hingga akhir penelitian. Perbedaan tersebut bermakna secara statistik (physical component summary dengan p < 0,0001 dan mental component summary dengan p = 0,0001). Kesimpulan: Vitamin B kombinasi efektif untuk memperbaiki gejala klinis dan meningkatkan kualitas hidup pada pasien ND.

Randomized Controlled Trial Evaluating Aerobic Training and Common Sport-Related Concussion Outcomes in Healthy Participants

Context Aerobic exercise interventions are increasingly being prescribed for concussion rehabilitation, but whether aerobic training protocols influence clinical concussion diagnosis and management assessments is unknown. Objective To investigate the effects of a brief aerobic exercise intervention on clinical concussion outcomes in healthy, active participants. Design Randomized controlled clinical trial. Setting Laboratory. Patients or Other Participants Healthy (uninjured) participants (n = 40) who exercised ≥3 times/week. Intervention(s) Participants were randomized into the acute concussion therapy intervention (ACTIVE) training or nontraining group. All participants completed symptom, cognitive, balance, and vision assessments during 2 test sessions approximately 14 days apart. Participants randomized to ACTIVE training completed six 30-minute exercise sessions that progressed from 60% to 80% of individualized maximal oxygen consumption (V˙o2max) across test sessions, while the nontraining group received no intervention. Main Outcome Measure(s) The CNS Vital Signs standardized scores, Vestibular/Ocular Motor Screening near-point convergence distance (cm), and Graded Symptom Checklist, Balance Error Scoring System, and Standardized Assessment of Concussion total scores. Results An interaction effect was found for total symptom score (P = .01); the intervention group had improved symptom scores between sessions (session 1: 5.1 ± 5.8; session 2: 1.9 ± 3.6). Cognitive flexibility, executive functioning, reasoning, and total symptom score outcomes were better but composite memory, verbal memory, and near-point convergence distance scores were worse at the second session (all P values &lt; .05). However, few changes exceeded the 80% reliable change indices calculated for this study, and effect sizes were generally small to negligible. Conclusions A brief aerobic training protocol had few meaningful effects on clinical concussion assessment in healthy participants, suggesting that current concussion-diagnostic and -assessment tools remain clinically stable in response to aerobic exercise training. This provides normative data for future researchers, who should further evaluate the effect of ACTIVE training on clinical outcomes among concussed populations. Trial Registration Number ClinicalTrials.gov: NCT02872480

ANALISIS KORELASI SKOR GEJALA TOTAL, NYERI, DAN KUALITAS HIDUP SETELAH PENGOBATAN VITAMIN B1, B6, DAN B12 DOSIS TINGGI PADA NEUROPATI PERIFER

CORRELATION ANALYSIS OF TOTAL SYMPTOM SCORE, PAIN, AND QUALITY OF LIFE POST HIGH DOSE VITAMIN B1, B6, DAN B12 TREATMENT IN PERIPHERAL NEUROPATHYABSTRACTIntroduction: Peripheral neuropathy (PN) is a clinical condition in which nerves of the peripheral nervous system are damaged and is associated with various symptoms affecting the patients’ quality of life (QoL).Aims: To understand the effect of Vitamin B1, B6, and B12 combination in mild to moderate PN.Methods: This is a prospective, open label, multicenter, single arm observational study involved 399 subjects with PN of different etiology. Subjects received the vitamin B1, B6, and B12 combination tablet orally once daily and were observed for 3 months. Total symptom score (TSS), visual analog score (VAS) and QoL were assessed, and the correlation between these parameters was analyzed.Results: Clinically significant reductions were observed from baseline to subsequent visits for TSS and VAS. Positive correlation was observed between TSS and components of VAS. The study treatment was associated with a significant improvement in QoL parameters. Inverse correlation was observed between QoL and TSS as well as QoL and components of VAS. The study treatment was found to be well tolerated.Discussion: The correlation analysis between different outcome measures demonstrated the beneficial effect of combination of vitamin B1, B6, and B12 in relief from symptoms and improvement in QoL of PN.Keyword: Correlation analysis, peripheral neuropathy, SF-8, TSS, VAS, vitamin B1, B6, and B12ABSTRAKPendahuluan: Neuropati perifer (NP) merupakan kondisi klinis akibat kerusakan pada sistem saraf tepi yang memengaruhi kualitas hidup (quality of life/QoL) pasien.Tujuan: Mengetahui efek pemberian kombinasi vitamin B1, B6, and B12 pada NP ringan hingga sedang.Metode: Penelitian observasional dan prospektif secara open label, multisenter, dan single arm, yang melibatkan 399 subjek penderita neuropati perifer dengan etiologi yang berbeda-beda. Subjek mengonsumsi tablet kombinasi vitamin B1, B6, and B12 secara oral satu kali sehari dan diamati selama 3 bulan. Dilakukan penilaian skor gejala total (total symptom score/TSS), visual analog scale (VAS), dan QoL, serta korelasi antara parameter-parameter tersebut.Hasil: Terdapat penurunan TSS dan VAS yang bermakna secara klinis antara baseline (awal) dengan kunjungan berikutnya. Terdapat korelasi yang positif antara TSS dengan komponen-komponen VAS. Pemberian perlakuan dalam penelitian berkorelasi secara bermakna dengan perbaikan parameter dalam QoL. Teramati juga adanya hubungan terbalik antara QoL dengan TSS serta QoL dan komponen VAS. Pengobatan pada penelitian ini juga terbukti dapat ditoleransi dengan baik.Diskusi: Analisis korelasi antara berbagai macam metode pengukuran yang berbeda menunjukkan manfaat dari pemberian kombinasi vitamin B1, B6, and B12 dalam mengurangi gejala dan perbaikan QoL pada pasien PN.Kata kunci: Analisis korelasi, neuropati perifer, kualitas hidup, SF-8, TSS, VAS, vitamin B1, B6, and B12