Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study.

PURPOSE: No approved targeted therapy for the treatment of patients with neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS)-mutant melanoma is currently available. PATIENTS AND METHODS: In this phase Ib escalation/expansion study (ClinicalTrials.gov identifier: NCT02974725), the safety, tolerability, and preliminary antitumor activity of naporafenib (LXH254), a BRAF/CRAF protein kinases inhibitor, were explored in combination with trametinib in patients with advanced/metastatic KRAS- or BRAF-mutant non-small-cell lung cancer (escalation arm) or NRAS-mutant melanoma (escalation and expansion arms). RESULTS: Thirty-six and 30 patients were enrolled in escalation and expansion, respectively. During escalation, six patients reported grade ≥3 dose-limiting toxicities, including dermatitis acneiform (n = 2), maculopapular rash (n = 2), increased lipase (n = 1), and Stevens-Johnson syndrome (n = 1). The recommended doses for expansion were naporafenib 200 mg twice a day plus trametinib 1 mg once daily and naporafenib 400 mg twice a day plus trametinib 0.5 mg once daily. During expansion, all 30 patients experienced a treatment-related adverse event, the most common being rash (80%, n = 24), blood creatine phosphokinase increased, diarrhea, and nausea (30%, n = 9 each). In expansion, the objective response rate, median duration of response, and median progression-free survival were 46.7% (95% CI, 21.3 to 73.4; 7 of 15 patients), 3.75 (95% CI, 1.97 to not estimable [NE]) months, and 5.52 months, respectively, in patients treated with naporafenib 200 mg twice a day plus trametinib 1 mg once daily, and 13.3% (95% CI, 1.7 to 40.5; 2 of 15 patients), 3.75 (95% CI, 2.04 to NE) months, and 4.21 months, respectively, in patients treated with naporafenib 400 mg twice a day plus trametinib 0.5 mg once daily. CONCLUSION: Naporafenib plus trametinib showed promising preliminary antitumor activity in patients with NRAS-mutant melanoma. Prophylactic strategies aimed to lower the incidence of skin-related events are under investigation.

Clean intermittent catheterization in long-term management of neurogenic bladder in spinal cord injury: Patient perspective and experiences.

OBJECTIVES: Bladder dysfunction due to spinal cord injury has a significant impact on the overall health and quality of life of an individual. Clean intermittent catheterization is the gold standard for bladder management and is recommended due to having the lowest complication rate. Transitions from intermittent catheterization to other less optimal strategies, such as indwelling catheter, are quite common. However, the research documenting patient perspectives, and epidemiological and demographic factors related to such transition is limited. METHODS: Data from patients with spinal cord injury rehabilitated with clean intermittent catheterization were collected. Demographic and epidemiological details of the patients were documented from the inpatient records. Appropriate statistical tests were applied to the values. RESULTS: Among the 45 participants, 68.89% continued clean intermittent catheterization. In those who discontinued clean intermittent catheterization, the median duration of practicing clean intermittent catheterization was 3.5 months. The commonest difficulty among compliant patients was carrying out clean intermittent catheterization in outdoor environments due to the unavailability of toilet facilities. Urinary tract infection was the most common (17.78%) complication noted. Dependence (20.00%) was a major procedural difficulty followed by pain. Adaptations to remain continent in special conditions were diapers and condom catheters. The duration of clean intermittent catheterization practiced influenced discontinuation of clean intermittent catheterization. With an increase in the duration of clean intermittent catheterization practiced after discharge, the risk of discontinuation of clean intermittent catheterization decreased with an adjusted odds ratio of 0.773 (95% confidence interval 0.609-0.982). CONCLUSIONS: People with spinal cord injury have many challenging issues in the regulation of bladder function at their level inclusive of procedural difficulties, environmental barriers and medical complications, and understanding of which will help to establish a comprehensive and a holistic program to provide remote/community care.

Prevalence of depression and quality of life in primary caregiver of children with cerebral palsy.

OBJECTIVE: Study the correlation of depression and quality of life (QoL) in primary caregivers (mothers) of children with cerebral palsy (CP). METHODS: An observational cross-sectional study was conducted on a total of 203 primary caregivers (mothers) of children with CP. The depression and QoL in the caregivers were assessed using the Montgomery and Asberg Depression Rating Scale and World Health Organization Quality of Life Instrument (WHOQOL-BREF) (physical, psychological, social and environmental domains), respectively. The child's gross motor function level was determined using the Gross Motor Functional Classification System-Expanded and Revised (GMFCS-ER). The association of depression and QoL in mothers to functional limitation in children were assessed. For statistical methods, P < 0.05 was considered significant. RESULTS: The severity of the depression showed a statistically significant negative correlation with the physical domain (r = -0.498, P < 0.0001), psychological domains (r = -0.486, P < 0.0001), social relationships (r = -0.165, P = 0.019) and environmental domains (r = -0.195, P = 0.005). The mean QoL domains scores showed a decreasing trend with increasing motor dysfunction of the child, with a statistical association for physical (r = -0.327, P < 0.0001) and psychological domains (r = -0.440, P < 0.0001). Out of all the baseline demographic factors, the child's age was a significant risk factor affecting the mother's QoL (P = 0.041). CONCLUSION: CP, being a debilitating disease, requires around-the-clock caregiving for the child. However, caregiving causes a significant impact on the QoL with increasing severity of depression among the mothers.

Health-related quality of life in premenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer treated with ribociclib plus endocrine therapy: results from a phase III randomized clinical trial (MONALEESA-7).

BACKGROUND: This analysis evaluated patient-reported outcomes (PROs) to assess health-related quality of life (HRQoL) in the phase III MONALEESA-7 trial, which previously demonstrated improvements in progression-free survival (PFS) and overall survival (OS) with ribociclib (cyclin-dependent kinase 4/6 inhibitor) + endocrine therapy (ET) compared with placebo + ET in pre- and perimenopausal patients with hormone-receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC). METHODS: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire C30 (QLQ-C30) and the EQ-5D-5L were used to evaluate HRQoL. RESULTS: EORTC QLQ-C30 assessments were evaluable for 335 patients in the ribociclib arm and 337 patients in the placebo arm. Adherence rates at baseline and ⩾1 postbaseline time point were 90% and 83%, respectively. Patients treated with ribociclib + ET had a longer time to deterioration (TTD) ⩾ 10% in global HRQoL {hazard ratio (HR), 0.67 [95% confidence interval (CI), 0.52-0.86]}. TTD ⩾ 10% in global HRQoL was delayed in ribociclib-treated patients without versus with disease progression [HR, 0.31 (95% CI, 0.21-0.48)]. TTD ⩾ 10% in pain was longer with ribociclib + ET than with placebo + ET [HR, 0.65 (95% CI, 0.45-0.92)]. Patients who received a nonsteroidal aromatase inhibitor experienced similar benefits with ribociclib versus placebo in global HRQoL and pain. CONCLUSION: HRQoL was maintained longer in patients who received ribociclib + ET versus placebo + ET. These data, combined with previously reported improvements in PFS and OS, support a strong clinical benefit-to-risk ratio with ribociclib-based treatment in pre- and perimenopausal patients with HR+/HER2- ABC.

Proximal femoral focal deficiency associated with fibular duplication and diplopodia and complete agenesis of the tibia: a case report.

A 14-year-old boy reported with congenital deformity of the left lower limb, with gross shortening, hip and knee flexion deformities, ankle with equinus deformity, and polydactyly of the left foot. Radiologic examination showed proximal femoral focal deficiency, double fibula, and duplication of the tarsal bones, and a diagnosis of 'proximal femoral focal deficiency associated with fibular duplication and diplopodia with complete agenesis of tibia' was made. Such association of deformities is very rare and poses difficulties in rehabilitation of the case. This patient was managed with elective knee disarticulation, early prosthetic fitment, and gait training.

Phenol Versus Botulinum Toxin A Injection in Ambulatory Cerebral Palsy Spastic Diplegia: A Comparative Study.

The aim of this study is to compare the treatment effectiveness of botulinum toxin type A (BTX-A) and phenol blocks in the management of lower limb spasticity and to measure improvement in gross motor functional outcome in children with cerebral palsy (CP). This is a hospital-based prospective, noncontrolled randomized study that took place in a tertiary care center. A total of 61 ambulatory children with CP spastic diplegia, aged from 4 to 10 years, were randomly divided into two groups and included in this study. Twenty-eight children with CP received BTX-A injections and 33 received phenol motor point blocks. The measures performed were as follows: outcome assessment spasticity by the Modified Ashworth scale (MAS), active range of motion (AROM) of lower limb joint by goniometer, and functional improvement by Gross Motor Function Measures (GMFM). Postinjection follow-up done at 2, 6, 12, 24, and 48 weeks. Significant improvement in reduction of spasticity, increased AROM of all joints of lower limbs, and improvement in functional outcome were observed in CP with spastic diplegia after BTX-A injections as compared with the phenol motor point block group. There was no significant side effect after BTX-A injections as compared with phenol injections. BTX-A injections showed superior treatment effects in the reduction of spasticity and improvement in AROM and functional outcome measures with spastic diplegia as compared with phenol blocks. BTX-A injections also revealed fewer clinical side effects and were well tolerated by children with CP.

Effective and Economic Offloading of Diabetic Foot Ulcers in India with the Bohler Iron Plaster Cast.

Economic constraints are a major obstacle to the implementation of offloading casts in India. The aim of this study is to monitor the healing and activity limitations related to Bohler iron plaster cast (BIPC) when used for offloading diabetic neuropathic plantar foot ulcers. Thirty patients were cast for 1 month and evaluated for healing using the Pressure Ulcer Scale for Healing (PUSH), and for activity limitation using the Lower Extremity Functional Scale (LEFS). The change in the scores after intervention was the outcome measure. There was good healing as evidenced by a statistical difference in mean PUSH scores. The baseline PUSH score of 9.76-0.41 (T1-SEM) was greater than follow-up PUSH score of 6.32 + 0.41 (T2 + SEM) and the p value <0.0001. Improvement was seen in ulcer area, exudate, and tissue type. There was no mobility effect as there was no significant difference in LEFS. Significant negative correlation was there between PUSH and LEFS. The r value was less than -0.7 both at baseline and after intervention. The combined benefits of good healing, lack of affect on lower extremity function, the ease of application and dressing, and relative affordability make BIPC a commendable offloading modality for the management of diabetic plantar ulcers.

Percutaneous A1 pulley release by the tip of a 20-g hypodermic needle before open surgical procedure in trigger finger management.

The objective of the study was to assess the safety, the efficacy, and the result of percutaneous A1 pulley release, using the tip of a 20-G hypodermic needle; the study included 17 patients with 27 trigger digits (18 grade IIIA, 8 grade IIIB, and 1 grade IV). All the patients were assessed by the total range of motion of the affected digit, the visual analog scale score, and the Disability of Arm Shoulder Hand score, before and after the procedure and during the follow-up at 2, 6, 12, and 24 weeks, and then every 3 months, and the improvement was assessed by one sample t test. Sixteen patients with 26 trigger digits (95.4%) showed complete relief of symptoms with no recurrence and a statistically significant improvement in the range of motion, the visual analog scale score, and the Disability of Arm Shoulder Hand score with a P-value <0.0001, which concludes that the procedure is safe, effective, and highly successful with good results and lower complications, comparable to those reported in papers on open release for grade III and IV trigger fingers.