First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC.

BACKGROUND: Selpercatinib, a highly selective potent and brain-penetrant RET inhibitor, was shown to have efficacy in patients with advanced RET fusion-positive non-small-cell lung cancer (NSCLC) in a nonrandomized phase 1-2 study. METHODS: In a randomized phase 3 trial, we evaluated the efficacy and safety of first-line selpercatinib as compared with control treatment that consisted of platinum-based chemotherapy with or without pembrolizumab at the investigator's discretion. The primary end point was progression-free survival assessed by blinded independent central review in both the intention-to-treat-pembrolizumab population (i.e., patients whose physicians had planned to treat them with pembrolizumab in the event that they were assigned to the control group) and the overall intention-to-treat population. Crossover from the control group to the selpercatinib group was allowed if disease progression as assessed by blinded independent central review occurred during receipt of control treatment. RESULTS: In total, 212 patients underwent randomization in the intention-to-treat-pembrolizumab population. At the time of the preplanned interim efficacy analysis, median progression-free survival was 24.8 months (95% confidence interval [CI], 16.9 to not estimable) with selpercatinib and 11.2 months (95% CI, 8.8 to 16.8) with control treatment (hazard ratio for progression or death, 0.46; 95% CI, 0.31 to 0.70; P<0.001). The percentage of patients with an objective response was 84% (95% CI, 76 to 90) with selpercatinib and 65% (95% CI, 54 to 75) with control treatment. The cause-specific hazard ratio for the time to progression affecting the central nervous system was 0.28 (95% CI, 0.12 to 0.68). Efficacy results in the overall intention-to-treat population (261 patients) were similar to those in the intention-to-treat-pembrolizumab population. The adverse events that occurred with selpercatinib and control treatment were consistent with those previously reported. CONCLUSIONS: Treatment with selpercatinib led to significantly longer progression-free survival than platinum-based chemotherapy with or without pembrolizumab among patients with advanced RET fusion-positive NSCLC. (Funded by Eli Lilly and others; ClinicalTrials.gov number, NCT04194944.).

A review of the Turned-down Onto Pericapsular-tissue Hemisectioned Amputated Toe (TOPHAT) flap for wound coverage during ray amputations of the toes.

INTRODUCTION: Exposure of the adjacent Metatarsal-Phalangeal Joint (MTPJ) commonly occurs after application of Topical Negative Pressure Wound Therapy (TNPWT) for a ray amputation wound. This is due to mechanical soft tissue erosion or trauma to the adjacent digital artery from direct pressure effect. This results in toe gangrene requiring a ray amputation and ultimately a larger wound bed. We describe the use of the Turned-down Onto Pericapsular-tissue Hemisectioned Amputated Toe (TOPHAT) flap - a filleted toe flap to protect the adjacent MTPJ capsule combined with a novel Negative Pressure Wound Therapy with instillation and dwell-time (NPWTi-d) dressing technique. The flap protects the adjacent joint capsule and reduces the wound burden whilst allowing the wound to benefit from TNPWT, thereby accelerating wound healing. MATERIAL AND METHODS: A retrospective review was conducted of patients with toe gangrene requiring ray amputation that underwent the TOPHAT flap on in our institution from 2019 and 2020. Complications such as wound dehiscence, hematoma, flap necrosis and secondary infection were recorded. Other outcomes recorded were time taken to final skin grafting and time taken for complete wound epithelialization. RESULTS: 9 patients underwent treatment with the TOPHAT flap. 2 patients had flap necrosis. 7 patients progressed to definitive skin coverage with skin grafting. One patient subsequently had progressive arterial disease despite successful skin grafting and required above knee amputation. The mean time to final skin grafting and complete wound epithelialization was 49.5 days and 107.5 days respectively. All patients were satisfied with the outcomes and were able to return to their pre-morbid function. CONCLUSIONS: The TOPHAT flap has a consistent vascular supply that provides durable soft tissue coverage. It is a robust and easily reproducible technique to accelerate wound healing after ray amputations even in patients with peripheral vascular disease.

Morton's neuroma: review of anatomy, pathomechanism, and imaging.

Morton's neuroma is a commonly encountered cause of forefoot pain, which may limit weight-bearing activities and footwear choices. Although the aetiology and pathomechanism of this condition is controversial, the histological endpoint is well established as benign perineural fibrosis of a common plantar digital nerve, typically within the third intermetatarsal space. The diagnosis of Morton's neuroma is mainly based on characteristic symptoms and clinical findings, but may be confirmed by ultrasonography. Although ultrasound is a highly accurate diagnostic tool for Morton's neuroma, it is subject to interoperator variability due to differences in technique and level of experience. In this paper, the authors review the anatomy of the common plantar digital nerves and surrounding structures in the forefoot, which are deemed relevant to the understanding of Morton's neuroma, especially from a sonographic point of view. Several theories of the pathomechanism of Morton's neuroma are briefly discussed. The main purpose of this article is to illustrate the ultrasound techniques for evaluating Morton's neuroma and performing ultrasound-guided corticosteroid injections.

Advancing practice in dietitians' communication and nutrition counselling skills: a workplace education program.

BACKGROUND: Communication is the primary method in which dietitians conduct their practice. However, continuing education and competency standards are often focused on clinical knowledge and skills, with few programs being available to improve the communication and nutrition counselling skills of dietitians. Dietitians have reported reduced confidence in the knowledge and use of these skills, particularly when dealing with people who are struggling to find motivation to change their eating behaviours. The present study aimed to evaluate the effect of a workplace education program on the self-reported communication and nutrition counselling skills of dietitians. METHODS: An education program was developed using techniques from motivational interviewing, patient-centred therapy, solution-focused therapy and narrative therapy. These techniques were chosen based on evidence of potential application to dietetic practice for behaviour change. Dietitians working in acute care hospitals and community health services completed the program. Pre- and post-written surveys incorporating five-point Likert scales (1-5) were used to evaluate the program. The results were analysed using parametric and nonparametric statistics. RESULTS: Fifty dietitians completed the program and evaluation. The dietitians' self-rating of their communication and nutrition counselling skills improved significantly (median = 3 versus 4, Z = 4.562, P < 0.001, r = 0.65). Dietitians also reported knowledge of a greater variety of behaviour change techniques to use with their patients post-program. CONCLUSIONS: To our knowledge, this is the first dietitian-specific workplace education program of its type to address essential skills for better communication with patients. Ongoing workplace support, such as peer observation, is recommended to assist with skill development and sustainability.

Carbohydrate knowledge, lifestyle and insulin: an observational study of their association with glycaemic control in adults with type 1 diabetes.

BACKGROUND: The ability to achieve optimal glycaemic control varies widely among individuals with type 1 diabetes. The present study aimed to explore the factors that are associated with optimal glycaemic control compared to suboptimal control. METHODS: An observational study design was used to explore the association of various factors with glycaemic control. Surveys were completed by individuals who attended the type 1 diabetes clinic at a tertiary hospital in New South Wales (NSW), Australia. Clinical and demographic information and attendance at dietary review were also collected. RESULTS: One hundred and three individuals completed the survey. Those with optimal control [glycated haemoglobin ≤7.0% (53 mmol mol-1 )] had a significantly shorter mean (SD) duration of diabetes [10.1 (12.6) years versus 18.8 (12.8) years, P = 0.005), were less likely to omit basal and bolus insulin (18.2% versus 47.5%, P = 0.016; 36.4% versus 61.8%, P = 0.034, respectively), and were less likely to report low confidence in managing their diabetes (9.1% versus 35.4%, P = 0.017). Participants who were able to identify carbohydrate sources were significantly more likely to have attended dietary review in the past 12 months (60.5% versus 20.0%, P = 0.001). However, they were not more likely to have better glycaemic control. CONCLUSIONS: The present study identified that consistency in taking insulin and confidence in self-management was associated with better glycaemic control. An association was also found between recent dietary review and better carbohydrate knowledge, although this did not translate into better glycaemic control. Future investigation into the application of carbohydrate knowledge is required.

Tuberous sclerosis and its rare association with macrodactyly and fibrous hamartomas.

Tuberous sclerosis complex is a genetic disease that results in abnormal cellular proliferation and hamartoma growths in multiple organ systems. However, macrodactyly and subcutaneous fibrous harmatomas are very uncommon associations with this disease. We see these rare manifestations in our case report of a 16-year-old female with tuberous sclerosis complex and discuss the imaging findings and pathogenetics of these manifestations. Through this, our report aims to expand the known clinical spectrum of features seen in tuberous sclerosis and aid in its diagnosis.

Orbital apex syndrome affecting head and neck cancer patients: A case series.

BACKGROUND: Orbital apex syndrome (OAS) is a complex and uncommon disorder that typically damages multiple cranial nerves in association with optic nerve dysfunction. OAS is associated with several different pathologies, however; only a few cases have been reported in association with head and neck cancer (HNC) so far. MATERIAL AND METHODS: A case series of HNC patients diagnosed with OAS is described including clinicopathological data, image findings, and disease outcome. RESULTS: Ptosis and diplopia were diagnosed in four male patients with mean age of 61.2 years who were undergoing treatment for late-stage carcinomas of the tongue, larynx, and nasopharynx, eventually leading to the diagnosis of OAS. The mean overall survival rate after the diagnosis of OAS was 9.5 months. CONCLUSIONS: The current study reinforces evidence that OAS indicates poor prognosis and highlights the importance of early diagnosis.

Pre-NELA vs NELA - has anything changed, or is it just an audit exercise?

BACKGROUND Following evidence suggestive of high mortality following emergency laparotomies, the National Emergency Laparotomy Audit (NELA) was set up, highlighting key standards in emergency service provision. Our aim was to compare our NHS trust's adherence to these recommendations immediately prior to, and following, the launch of NELA, and to compare patient outcome. METHODS This was a retrospective study of patients who underwent an emergency laparotomy over the course of 6 months - 3 months either side of the initiation of NELA. RESULTS There were 44 patients before the initiation of NELA (pre-NELA, PN group) and 55 in the first 3 months of NELA (N group). We saw a significant increase in the proportion of patients whose decision to operate was made by the consultant: 75.0% in the PN group vs 100% in N group (subsequent data presented in this order) (P < 0.001). The presence of a consultant surgeon (75.0% vs 83.6%, P = 0.321) and anaesthetist (100.0% vs 90.9%, P = 0.064) in theatres were comparable in both groups. Risk stratification based on Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (P-POSSUM) score showed no difference in high-risk patients in both groups (47.7% vs 36.4%, P = 0.306). With the NELA initiative, however, significantly more patients were admitted directly from theatres to the critical care unit, when compared with the pre-NELA period (9.1% vs 27.3%, P = 0.038). This also reflected a significant reduction in unexpected escalation to a higher level of care during this period (10.0% vs 0%, P = 0.036). Significantly more patients had uneventful recovery in the NELA period (52.3 vs 76.4%, P = 0.018), although there was no difference in 30-day mortality between the groups (2.3% vs 7.3%, P = 0.378). CONCLUSIONS This study demonstrated a greater degree of consultant involvement in the decision to operate during NELA. More high-risk patients have been identified preoperatively with diligent risk assessment and, hence, have been proactively admitted to critical care units following laparotomy, which may account for the significant reduction in unexpected escalation to level 2 or level 3 care and thus in overall better patient outcomes.

Effect of Repetitive Transcranial Magnetic Stimulation on Physical Function and Motor Signs in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: The short-term beneficial effects of repetitive transcranial magnetic stimulation (rTMS) on motor signs in Parkinson's disease (PD) have been addressed by previous meta-analyses while its long-term effects remain undetermined. Although deterioration of walking and upper limb function greatly affects the participation in activities and quality of life of PD sufferers, the effect of rTMS thereon has not been systematically studied. OBJECTIVE: This systematic review aimed to examine the efficacy of rTMS on improving physical function and motor signs over the short- and long-terms in people with PD. METHODS: Five electronic databases were systematically searched for English language full-text articles using relevant search terms. Only randomized placebo-controlled trials investigating the effects of rTMS in PD were considered. The primary outcomes were walking performance, upper limb function, and unified Parkinson's disease rating scale (UPDRS) section III. Trials with similar outcomes were pooled by calculating Hedges' g using random-effects model. RESULTS: Twenty-two trials comprising 555 people with PD were included. Pooled estimates of effect of rTMS indicated significantly improved short-term upper limb function (Hedges' g, 0.40, P = 0.007), short-term (Hedges' g, 0.61, P = 0.03) and long-term walking performance (Hedges' g, 0.89, P = 0.03), short-term (Hedges' g, 0.31, P = 0.003) and long-term (Hedges' g, 0.54, P = 0.003) UPDRS III scores. Subgroup analyses suggest a more prominent effect for M1 stimulation. Meta-regression revealed that a greater number of total stimulation pulses were associated with more UPDRS III improvements over the long-term. CONCLUSION: The pooled evidence suggests that rTMS improves upper limb function in the short-term, walking performance and UPDRS III in the short- and long-terms in PD sufferers. Further studies are required to develop optimal rTMS therapeutic protocols for PD.

Measuring outcome after cardiac arrest: construct validity of Cerebral Performance Category.

INTRODUCTION: Approximately half of the survivors of cardiac arrest have cognitive impairments due to hypoxic brain injury. To describe the outcome after a cardiac arrest, the Cerebral Performance Category (CPC) is frequently used. Although widely used, its validity is still debatable. OBJECTIVE: To investigate the construct validity of the Cerebral Performance Category in survivors of a cardiac arrest. Participants were 18 years and older that survived a cardiac arrest more than six months. METHODS: Cross-sectional design. A method to administer the CPC in a structured and reproducible manner was developed. This 'Structured CPC' was administered by a structured interview. Construct variables were Cognitive Failure Questionnaire (CFQ), Barthel Index (BI), Frenchay Activity Index (FAI), Community Integration Questionnaire (CIQ) and Quality of Life after Brain Injury (Qolibri). Associations were tested based on Spearman correlation coefficients. RESULTS: A total of 62 participants responded. In 58 (94%) patients the CPC was determined, resulting in CPC 1 (48%), CPC 2 (23%) and CPC 3 (23%). The CPC-scoring correlated significantly with the CFQ (r=-0.40); BI (r=-0.57); FAI (r=-0.65), CIQ (r=-0.53) and Qolibri (r=-0.67). DISCUSSION AND CONCLUSIONS: In this study we developed the 'Structured CPC' to improve the transparency and reproducibility of the original CPC. A moderate correlation between the 'Structured CPC' and the constructs 'activities', 'participation' and 'quality of life' confirmed the validity of the 'Structured CPC'. CLINICAL MESSAGE: The 'Structured CPC' can be used as an instrument to measure the level of functioning after cardiac arrest.

HLA-B*38:02:01 predicts carbimazole/methimazole-induced agranulocytosis.

Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.

Use of Jebsen Taylor Hand Function Test in evaluating the hand dexterity in people with Parkinson's disease.

OBJECTIVES: To investigate the test-retest reliability of JTT in older patients with Parkinson's disease (PD); and to compare the Jebsen Taylor Hand Function Test (JTT) scores between PD and healthy subjects. STUDY DESIGN: Cross-sectional comparative study. METHODS: Fifteen PD and fifteen healthy subjects performed the JTT and the time taken to complete the JTT was recorded. RESULTS: Test-retest reliabilities of JTT subtests and total score of both dominant and non-dominant hand were good to excellent (ICCs = 0.77-0.97) except J5 checkers which had moderate reliability. PD subjects required significantly longer time to finish subtests and the whole JTT (p < 0.05), except the subtest J1 writing of dominant hand that showed marginal significance (p = 0.059). CONCLUSION: JTT is a reliable and easily available assessment tool for assessing the hand function of PD subjects. PD subjects took a longer time to complete the JTT, suggesting that they have deficits in gross and fine functional dexterity.

Managing hyperglycaemia in patients with diabetes on enteral nutrition: the role of a specialized diabetes team.

BACKGROUND/OBJECTIVES: Hyperglycaemia is commonly observed in patients with diabetes mellitus (DM) while receiving enteral nutrition (EN) in hospital, and hyperglycaemia has been shown to be associated with poor clinical outcomes. The aim of this study was to assess the glycaemic status of patients with DM who received EN during hospital admission and evaluate the impact of intervention by a specialist diabetes team (SDT) on glycaemic control and clinical outcomes of these patients. SUBJECTS/METHODS: A retrospective review of patients with DM who required EN during hospital admission was conducted. We compared patient characteristics, glycaemic profile and clinical outcomes between patients who were managed by SDT and those who were managed by the admitting team. RESULTS: Seventy-four patients with DM on EN were included in this study, of whom 27 were managed by SDT while on EN. Compared with patients managed by the admitting team, those who were reviewed by SDT had better glycaemic control during the period of EN as well as during the 24 h after EN was ceased. These patients also had shorter length-of-stay in hospital and lower in-patient mortality. CONCLUSIONS: Our findings confirmed that there was a role for SDT in managing patients with DM who received EN during their hospital admission. These patients had improved glycaemic control while receiving EN and had better clinical outcomes. Further prospective studies will be required to validate the findings of this study.

The immediate effect of a novel audio-visual cueing strategy (simulated traffic lights) on dual-task walking in people with Parkinson's disease.

BACKGROUND: Gait deficits are exacerbated during the addition of a concurrent cognitive task in individuals with Parkinson's disease (PD). The provision of auditory and/or visual cues has been reported to facilitate gait performance in these patients. AIM: To investigate whether individuals with PD could use traffic lights as an audio-visual cueing strategy to enhance dual-task walking performance. DESIGN: Cross-sectional comparative study. SETTING: The Hong Kong Polytechnic University. POPULATION: Fifteen PD and 13 healthy individuals. METHODS: All participants were instructed to walk at their natural pace, followed by 2 randomized conditions: 1) walking while doing serial subtractions of three, starting from a random number between 60 to 100; 2) doing the same tasks with the addition of traffic lights signals as audio-visual cues. Primary outcomes included stride length, cadence and gait velocity. RESULTS: Individuals with PD had more deterioration in all gait parameters than healthy controls for both single- and dual-task walking. With the use of traffic lights, individuals with PD showed significant increases in stride length (by 8.8%), cadence (by 9.6%), and gait velocity (by 21.0%, P=0.000). CONCLUSION: Traffic lights could be used as combined preparatory and ongoing audio-visual cues to enhance dual-task walking performance in people with PD. CLINICAL REHABILITATION IMPACT: Positive findings from the present study suggest a promising treatment intervention to benefit people with PD, who often have to conduct concurrent cognitive task during walking in their daily activities.

Mortality due to pandemic (H1N1) 2009 influenza in England: a comparison of the first and second waves.

Deaths in England attributable to pandemic (H1N1) 2009 deaths were investigated through a mandatory reporting system. The pandemic came in two waves. The second caused greater population mortality than the first (5·4 vs. 1·6 deaths per million, P<0·001). Mortality was particularly high in those with chronic neurological disease, chronic heart disease and immune suppression (450, 100, and 94 deaths per million, respectively); significantly higher than in those with chronic respiratory disease (39 per million) and those with no risk factors (2·4 per million). Greater mortality in the second wave has been observed in all previous influenza pandemics. This time, the explanation appears to be behavioural. This emphasizes the importance of maintaining public and clinical awareness of risks associated with pandemic influenza beyond the initial high-profile period.