Post Chikungunya Fever and Post COVID-19 Bilateral Pedal Edema: A Case Report.

An 86-year-old male presented with fever and joint pain for seven days. Clinical features were suggestive of chikungunya fever, but reverse transcription-polymerase chain reaction (RT-PCR) was negative. After ruling out the differentials, the patient was clinically diagnosed with chikungunya fever. Chikungunya IgG antibody was positive two months after the onset of symptoms. He had a history of asymptomatic coronavirus disease (COVID-19) infection two months ago. About 20 days after his first symptom, he developed bipedal edema, refractory to diuretics. All other causes of pedal edema, including heart failure, renal failure, and liver failure, were ruled out. The bipedal edema was managed conservatively with compression bandages. Only a few case reports and studies on limb edema as a symptom post chikungunya fever have been published up to this point. Furthermore, it is difficult to say whether his COVID-19 infection is linked to the edema.

Analysis of effects of driver's evasive action time on rear-end collision risk using a driving simulator.

INTRODUCTION: Driver's evasive action is closely associated with collision risk in a critical traffic event. To quantify collision risk, surrogate safety measures (SSMs) have been estimated using vehicle trajectories. However, vehicle trajectories cannot clearly capture presence and time of driver's evasive action. Thus, this study determines the driver's evasive action based on his/her use of accelerator and brake pedals, and analyzes the effects of the driver's evasive action time (i.e., duration of evasive action) on rear-end collision risk. METHOD: Fifty drivers' car-following behavior on a freeway was observed using a driving simulator. An SSM called "Deceleration Rate to Avoid Crash (DRAC)" and the evasive action time were determined for each driver using the data from the driving simulator. Each driver tested two traffic scenarios - Cars and Trucks scenarios where conflicting vehicles were cars and trucks, respectively. The factors related to DRAC were identified and their effects on DRAC were analyzed using the Generalized Linear Models and random effects models. RESULTS: DRAC decreased with the evasive action time and DRAC was closely related to drivers' gender and driving experience at the road sections where evasive action to avoid collision was required. DRAC was also significantly different between Cars and Trucks scenarios. The effect of the evasive action time on DRAC varied among different drivers, particularly in the Trucks scenario. CONCLUSIONS: Longer evasive action time can significantly reduce crash risk. Driver characteristics are more closely related to effective evasive action in complex driving conditions. Practical Applications: Based on the findings of this study, driver warning information can be developed to alert drivers to take specific evasive action that reduces collision risk in a critical traffic event. The information is likely to reduce the variability of the driver's evasive action and the speed variations among different drivers.

Predicting driver reaction time and deceleration: Comparison of perception-reaction thresholds and evidence accumulation framework.

Prediction of driver reaction to the lead vehicle motion based on the perception-reaction time (PRT) is critical for prediction of rear-end crash risk. This study determines PRT at various spacings in approaching and braking conditions, and examines the association of PRT and deceleration rate with crash risk. For these tasks, a total of 50 drivers' behavior was observed in a driving simulator experiment with 4 different scenarios - reaction to a decelerating lead vehicle, reaction to a stopped lead vehicle, perception of a lead vehicle's speed change, and perception of a slow-moving lead vehicle. The study tested three hypotheses of PRT including perception and reaction thresholds and the evidence accumulation framework using a visual variable (tau-inverse). It was found that the drivers neither reacted after a specific PRT from the start of perception nor reacted at a specific value of tau-inverse. Rather, the drivers generally reacted when the accumulation of evidence (tau-inverse) over time reached a threshold. It was also found that the magnitude of deceleration rate depends on the tau-inverse at the start of braking and hence, higher crash risk was associated with higher level of urgency and insufficient brake force rather than longer PRT. This study demonstrates that the evidence accumulation framework is a promising method of predicting driver reaction in approaching and braking conditions for different types of lead vehicle, and the level of urgency is important for predicting the probability of crash.

Avatrombopag and lusutrombopag for thrombocytopenia in people with chronic liver disease needing an elective procedure: a systematic review and cost-effectiveness analysis.

BACKGROUND: There have been no licensed treatment options in the UK for treating thrombocytopenia in people with chronic liver disease requiring surgery. Established management largely involves platelet transfusion prior to the procedure or as rescue therapy for bleeding due to the procedure. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of two thrombopoietin receptor agonists, avatrombopag (Doptelet®; Dova Pharmaceuticals, Durham, NC, USA) and lusutrombopag (Mulpleta®; Shionogi Inc., London, UK), in addition to established clinical management compared with established clinical management (no thrombopoietin receptor agonist) in the licensed populations. DESIGN: Systematic review and cost-effectiveness analysis. SETTING: Secondary care. PARTICIPANTS: Severe thrombocytopenia (platelet count of < 50,000/µl) in people with chronic liver disease requiring surgery. INTERVENTIONS: Lusutrombopag 3 mg and avatrombopag (60 mg if the baseline platelet count is < 40,000/µl and 40 mg if it is 40,000-< 50,000/µl). MAIN OUTCOME MEASURES: Risk of platelet transfusion and rescue therapy or risk of rescue therapy only. REVIEW METHODS: Systematic review including meta-analysis. English-language and non-English-language articles were obtained from several databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, all searched from inception to 29 May 2019. ECONOMIC EVALUATION: Model-based cost-effectiveness analysis. RESULTS: From a comprehensive search retrieving 11,305 records, six studies were included. Analysis showed that avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy or rescue therapy only, and mostly with a statistically significant difference (i.e. 95% confidence intervals not overlapping the point of no difference). However, only avatrombopag seemed to be superior to no thrombopoietin receptor agonist in reducing the risk of rescue therapy, although far fewer patients in the lusutrombopag trials than in the avatrombopag trials received rescue therapy. When assessing the cost-effectiveness of lusutrombopag and avatrombopag, it was found that, despite the success of these in avoiding platelet transfusions prior to surgery, the additional long-term gain in quality-adjusted life-years was very small. No thrombopoietin receptor agonist was clearly cheaper than both lusutrombopag and avatrombopag, as the cost savings from avoiding platelet transfusions were more than offset by the drug cost. The probabilistic sensitivity analysis showed that, for all thresholds below £100,000, no thrombopoietin receptor agonist had 100% probability of being cost-effective. LIMITATIONS: Some of the rescue therapy data for lusutrombopag were not available. There were inconsistencies in the avatrombopag data. From the cost-effectiveness point of view, there were several additional important gaps in the evidence required, including the lack of a price for avatrombopag. CONCLUSIONS: Avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy, but they were not cost-effective given the lack of benefit and increase in cost. FUTURE WORK: A head-to-head trial is warranted. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019125311. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 51. See the NIHR Journals Library website for further project information.

Thrombocytopenia, which is a reduction in platelet numbers in the blood, is a common complication of chronic liver disease. It increases the risk of bleeding during procedures including liver biopsy and transplantation. It can delay or prevent procedures, leading to illness and death. Established treatment largely involves platelet transfusion before the procedure or as rescue therapy for bleeding. This report aims to systematically review the clinical effectiveness and estimate the cost-effectiveness of the first two recently licensed treatments, thrombopoietin receptor agonists avatrombopag (Doptelet^®; Dova Pharmaceuticals, Durham, NC, USA) (60 mg if platelet count is < 40,000/µl and 40 mg if platelet count is 40,000­< 50,000/µl) and lusutrombopag (Mulpleta^®; Shionogi Inc., London, UK) (3 mg if platelet count is < 50,000/µl), compared with established treatment. From a comprehensive search, six studies were included. Clinical effectiveness analysis showed that avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy. Only avatrombopag seemed superior to no thrombopoietin receptor agonist in reducing rescue therapy alone. Cost-effectiveness analysis found that lusutrombopag and avatrombopag were more expensive than no thrombopoietin receptor agonist over a lifetime, as the savings from avoiding platelet transfusions were exceeded by the drug cost, and without long-term health benefits. The probabilistic sensitivity analysis, which examined the effect of uncertainty, showed that no thrombopoietin receptor agonist had 100% probability of being cost-effective. Uncertainty about the price of avatrombopag and the content and costs of platelet transfusions and the potential under-reporting of use to estimate platelet transfusion-specific mortality had the greatest impact on results. If the price of avatrombopag was (confidential information has been removed) below the price of lusutrombopag, avatrombopag would become cost saving in the 40,000­< 50,000/µl subgroup. However, although in some scenarios avatrombopag costs could decrease in the 40,000­< 50,000/µl subgroup to around 10% more than the cost of no thrombopoietin receptor agonist, there would be negligible health benefits and the incremental cost-effectiveness ratios would remain very high, meaning that lusutrombopag and avatrombopag would still not be considered cost-effective.

Dangerous Territory: Racist Moments in the Psychoanalytic Space.

Racism and racist fantasies are inherent to being human yet have had profound traumatic effects on an individual and collective scale. Lurking in the shadows, racist images, fantasies, and attitudes can suddenly enter the analytic space and disrupt the psychic functioning of both the analyst and patient. A personal experience with racism outside the office is presented with clinical material involving my struggle in the countertransference around racist material that is brought up by my patient. Racial enactments, playfulness, racial humor, white privilege, and political/cultural differences are discussed focusing on my countertransference reactions to the patient and her responses.

Near full thickness macular hole with an intact overlying internal limiting membrane following resolution of fulminant acquired toxoplasma retinitis -A unique finding.

A 43-year-old immunocompetent male presented with focal macular retinitis with overlying vitritis in the right eye. His BCVA was counting fingers close to face. OCT showed increased intraretinal thickness at the area of retinitis with adjacent hypo reflectivity of the choroid. Serology was positive for IgM and IgG antibodies for toxoplasma. He received oral clindamycin 300 mg 4 times/day for 8 weeks. At 6 weeks, his BCVA was CF 2 metres. Fundus showed complete resolution of retinitis with formation of near, full thickness macular hole with intact overlying ILM. A small hyper reflective scar was seen at the base of the macular hole.

Fluocinolone Acetonide Intravitreal Implant for Treating Recurrent Non-infectious Uveitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited Alimera Sciences, the company manufacturing fluocinolone acetonide intravitreal implant (FAc) 0.19 mg (tradename ILUVIEN®), to submit evidence on the clinical and cost-effectiveness of FAc for treating recurrent non-infectious uveitis. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre + , was commissioned to act as the independent Evidence Review Group (ERG). This paper contains a summary of the clinical and cost-effectiveness evidence submitted by the company, the ERG's critique on the submitted evidence, and the guidance issued by the NICE Appraisal Committee (AC). The company submission (CS) was mainly informed by the PSV-FAI-001 trial in which FAc was compared with (limited) current practice [(L)CP], which was not considered to be representative of UK clinical practice by the ERG. There was no comparison of FAc to any treatment listed in the final scope, and especially to the dexamethasone intravitreal implant (dexamethasone), which was considered to be a relevant comparator by the AC. The primary outcome of the PSV-FAI-001 was recurrence of uveitis in the treated eye. Most of the events for the primary outcome were imputed during the PSV-FAI-001 trial, which probably led to an overestimation of the number of recurrences of disease, and a biased estimate of the relative effectiveness of FAc versus (L)CP. Finally, the place of FAc in the treatment pathway was not clearly defined by the company. Substantial uncertainty surrounded the cost-effectiveness results due to the shortcomings of the clinical evidence. Additionally, the quality of life of patients was not measured during the PSV-FAI-001 trial and long-term effectiveness data of FAc were lacking. The ERG adjusted several issues identified in the CS and added dexamethasone as a comparator in the decision analytic model. The ERG presented multiple analyses as base-cases because several elements of the assessment remained uncertain. The fully incremental ERG results ranged from dexamethasone (extendedly) dominating FAc (when assuming a hazard ratio of 1 or 0.7 for dexamethasone versus FAc) to an incremental cost-effectiveness ratio (ICER) of £30,153 per quality-adjusted life-year (QALY) gained for FAc versus (L)CP [when assuming a hazard ratio of 0.456 for dexamethasone versus (L)CP]. The ICER of FAc versus (L)CP ranged from £12,325 to £30,153 per QALY gained. After a second AC meeting where alternative company scenarios comparing FAc with dexamethasone were considered by the AC, the AC concluded that "the results of the company's analyses ranged from the fluocinolone acetonide implant being dominant (that is, it was more effective and costs less), to an ICER of £29,461 per QALY gained, and most of the ICERs were below £20,000 per QALY gained". Therefore, the AC recommended FAc as a cost-effective use of National Health Service (NHS) resources for treating recurrent non-infectious uveitis affecting the posterior segment of the eye in the final TA590 guidance (published July 2019).

Systematic review and network meta-analysis of the efficacy and safety of lidocaine 700 mg medicated plaster vs. pregabalin.

Objective: Neuropathic pain prevalence is estimated between 7% and 10% of the population. International guidelines recommend a variety of drugs at different therapy lines for pain relief. However, side effect profiles, for example, prompted the UK government recently to classify pregabalin and gabapentin as class C drugs. Lidocaine 700 mg medicated plaster (LMP) might be a safer alternative. A systematic review assessed how LMP and pregabalin compared in terms of efficacy and safety. The review focused on pain reduction, quality of life and adverse events in peripheral neuropathic pain (PNP) i.e. post-herpetic neuralgia, diabetic peripheral neuropathy, post-surgical/trauma, or other PNP conditions.Methods: Electronic databases were searched as well as a number of other sources up to November 2018. Sensitive strategies were used, with no restriction by language or publication status. Two independent reviewers screened records and extracted data with consensus determining final decisions. Risk of bias was assessed using the Cochrane Collaboration 2011 checklist for RCTs. Full network meta-analysis was conducted to compare LMP to pregabalin 300/600 mg in terms of pain reduction, quality of life, as well as serious adverse events and selected adverse events. Trials with enriched enrolment design were excluded.Results: Searches retrieved 7,104 records. In total 111 references pertaining to 43 RCTs were included for data extraction. Bayesian network meta-analysis of several pain outcomes showed no clear difference in efficacy between treatments However, LMP was clearly advantageous in terms of dizziness and any adverse event vs. pregabalin 600 mg/day and discontinuations vs. pregabalin 300 mg/day or 600 mg/day, as well as being associated with improved quality of life (albeit in this case based on weak evidence).Conclusions: LMP was found to be similar to pregabalin in reducing pain in all populations but had a better adverse events profile.

Comparative evaluation of the sealing ability of filling materials on root end cavities treated with smear layer removing agents: A confocal laser scanning microscopic study.

AIM: This study aims to evaluate and compare the sealing ability of Biodentine™ and mineral trioxide aggregate (MTA) plus® on root end cavities treated with 17% ethylene diamine tetraacetic acid (EDTA), 0.2% Chitosan and 1% Phytic acid using Confocal Laser Scanning Microscope (CLSM)-An in vitro study. MATERIALS AND METHODS: Sixty extracted single rooted teeth were instrumented and obturated with gutta-percha. The apical 3 mm of each tooth was resected and 3 mm root-end preparation was made using ultrasonic tip. 17% EDTA (n = 20), 0.2% Chitosan (n = 20) and 1% Phytic acid (n = 20) was used as a smear layer removing agent and each above group was further subdivided and restored with a root end filling material, Biodentine (n = 10) and MTA Plus (n = 10). The samples were coated with varnish except at the root end and after drying, they were immersed in Rhodamine B dye for 24 h. The teeth were then rinsed, sectioned longitudinally, and observed under CLSM. RESULTS: In the present study, MTA Plus® treated with 1% Phytic acid showed the least microleakage followed by Biodentine™ treated with 1% Phytic acid which was statistically not significant. MTA Plus® treated with 17% EDTA showed the highest microleakage when compared to other tested groups. There was a significant difference in microleakage between MTA Plus® and Biodentine™ when treated with 17% EDTA and 0.2% Chitosan. However, more microleakage was seen with Biodentine™ group than MTA plus® group. CONCLUSION: Root end cavities restored with MTA plus and treated with Phyitc acid showed superior sealing ability. Furthermore, smear layer removing agents will aid in better adaptability of root end filling material.

Comparison of profile of retinopathy of prematurity in semiurban/rural and urban NICUs in Karnataka, India.

PURPOSE: To identify and compare the profile of retinopathy of prematurity (ROP) in premature babies in urban and semiurban neonatal intensive care units (NICUs). METHODS: A prospective study of babies admitted to NICUs of two urban and seven semiurban centres. They were <36 weeks of gestational age and were subjected to fundus photography with a RetCam shuttle camera. Photos and NICU details were uploaded on a secure website. Photographs were read by a single observer. Infants were followed till retinal vascularisation was complete, or 45 weeks post conceptional age. Babies developing severe ROP were lasered. RESULTS: 500 babies were screened (243, urban group; 257, semiurban group). Incidence of ROP in the urban and semiurban groups was 16.5% (40) and 14.8% (38) respectively. Mean gestational age was 30.90 weeks and 31.53 weeks respectively. Mean birth weight was 1344 g and 1375 g respectively. 28 babies were lasered, 15 and 13 from each group respectively. There was no statistically significant difference between any of the parameters compared. Level of significance was fixed at 0.05. CONCLUSIONS: The magnitude of the burden of ROP is comparable between urban and semiurban NICUs stressing the need for effective screening strategies in semiurban and rural areas as well.

Transcranial magnetic stimulation: a device intended for the psychiatrist's office, but what is its future clinical role?

Repetitive transcranial magnetic stimulation (TMS) is a novel, noninvasive, office-based device technology that delivers focused stimulation to the cortex of the brain by means of magnetic pulses. It is a promising therapeutic approach in a variety of neuropsychiatric disorders. A large number of clinical trials have examined repetitive TMS as a novel treatment for major depression, with additional significant work in schizophrenia, anxiety disorders and pain syndromes. In this review, we describe how repetitive TMS is administered clinically and discuss how excitatory and inhibitory forms of stimulation are applied depending on what is known of the underlying pathophysiology of the disorder. Future putative clinical applications of repetitive TMS in psychiatry are discussed, with the authors' perspective on its likely role in clinical practice. TMS is a promising form of neuromodulation therapy that will most likely become a significant part of clinical practice in the future.

Functional neurosurgery in the treatment of severe obsessive compulsive disorder and major depression: overview of disease circuits and therapeutic targeting for the clinician.

Over the past 20 years, there has been a concerted effort to expand our understanding of the neural circuitry involved in the pathogenesis of psychiatric disorders. Distinct neuronal circuits and networks have been implicated in obsessive compulsive disorder (OCD) and major depressive disorder (MDD) involving feedback loops between the cortex, striatum, and thalamus. When neurosurgery is used as a therapeutic tool in severe OCD and MDD, the goal is to modulate specific targets or nodes within these networks in an effort to produce symptom relief.Currently, four lesioning neurosurgical procedures are utilized for treatment refractory OCD and MDD: cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. Deep brain stimulation (DBS) is a novel neurosurgical approach that has some distinct advantages over lesioning procedures. With DBS, the desired clinical effect can be achieved by reversible, high frequency stimulation in a nucleus or at a node in the circuit without the need to produce an irreversible lesion. Recent trials of deep brain stimulation in both OCD and MDD at several neuroanatomical targets have reported promising early results in highly refractory patients and with a good safety profile. Future definitive trials in MDD and OCD are envisaged.