Hypertonic Saline Compared to Mannitol for the Management of Elevated Intracranial Pressure in Traumatic Brain Injury: A Meta-Analysis

Background: We performed a meta-analysis to evaluate the effect of hypertonic saline compared to mannitol for the management of elevated intracranial pressure in traumatic brain injury.Methods: A systematic literature search up to July 2021 was performed and 17 studies included 1,392 subjects with traumatic brain injury at the start of the study; 708 of them were administered hypertonic saline and 684 were given mannitol. They were reporting relationships between the effects of hypertonic saline compared to mannitol for the management of elevated intracranial pressure in traumatic brain injury. We calculated the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to assess the effect of hypertonic saline compared to mannitol for the management of elevated intracranial pressure in traumatic brain injury using the dichotomous or continuous method with a random or fixed-effect model.Results: Hypertonic saline had significantly lower treatment failure (OR, 0.38; 95% CI, 0.15–0.98, p = 0.04), lower intracranial pressure 30–60 mins after infusion termination (MD, −1.12; 95% CI, −2.11 to −0.12, p = 0.03), and higher cerebral perfusion pressure 30–60 mins after infusion termination (MD, 5.25; 95% CI, 3.59–6.91, p < 0.001) compared to mannitol in subjects with traumatic brain injury.However, hypertonic saline had no significant effect on favorable outcome (OR, 1.61; 95% CI, 1.01–2.58, p = 0.05), mortality (OR, 0.59; 95% CI, 0.34–1.02, p = 0.06), intracranial pressure 90–120 mins after infusion termination (MD, −0.90; 95% CI, −3.21–1.41, p = 0.45), cerebral perfusion pressure 90–120 mins after infusion termination (MD, 4.28; 95% CI, −0.16–8.72, p = 0.06), and duration of elevated intracranial pressure per day (MD, 2.20; 95% CI, −5.44–1.05, p = 0.18) compared to mannitol in subjects with traumatic brain injury.Conclusions: Hypertonic saline had significantly lower treatment failure, lower intracranial pressure 30–60 mins after infusion termination, and higher cerebral perfusion pressure 30–60 mins after infusion termination compared to mannitol in subjects with traumatic brain injury. However, hypertonic saline had no significant effect on the favorable outcome, mortality, intracranial pressure 90–120 mins after infusion termination, cerebral perfusion pressure 90–120 mins after infusion termination, and duration of elevated intracranial pressure per day compared to mannitol in subjects with traumatic brain injury. Further studies are required to validate these findings.

Natural Compounds as Potential Regulators of the Phosphatidylinositol 3′ Kinase (PI3K) Pathway in Breast Cancer

Breast cancer is one of the most prevalent forms of cancer in women both globally and in India. Although breast cancer is characterized by different molecular subtypes, a majority of breast cancers appear to have mutations in the phosphatidylinositol 3′ kinase (PI3K)/ protein kinase B (Akt) pathway. Dysregulation of the PI3K/ Akt pathway in breast cancers plays important roles in promoting tumour growth, proliferation and invasion. Targeting PI3K mediated signalling cascades could be therefore of value for breast cancer treatment. Studies with synthetic inhibitors of the PI3K/ Akt pathway have yielded positive results but the efficacy shown by many of these inhibitors appear to be compromised by deleterious side effects. An alternative to syn-thetic inhibitors is the use of natural phytochemical compounds with anti-tumorigenic potential like apigenin, pomolic acid, resveratrol and its deriva-tives, curcumin, epigallocatechin-3 gallate and thymoquinone as potential inhibitors of PI3K/Akt signalling in breast cancer and such a strategy could lead to lesser side effects and a lower treatment cost. The current study ex-amines the importance of the PI3K pathway in breast cancer and discusses how regulation of aberrant signalling through this pathway by natural com-pounds could play an important role in breast cancer therapy.

The Effect of Sociodemographic Factors, Parity and Cervical Cancer on Antibiotic Treatment for Uncomplicated Cystitis in Women: A Nationwide Cohort Study

Background: Uncomplicated cystitis is one of the most common reasons for antibiotic treatment in otherwise healthy women. Nationwide studies on antibiotic treatment for this infection and in relation to factors beyond the infection itself have hitherto not been available. Methods: This was a nationwide open cohort study consisting of 352,507 women aged 15–50 years with uncomplicated cystitis (2006–2018). The outcome was a redeemed antibiotic prescription within five days from the cystitis diagnosis. Logistic regression models were used to examine the relationship between the outcome and the predictor variables. Results: This study identified 192,065 redeemed treatments (54.5%). Several sociodemographic variables were associated with antibiotic treatment. For example, women with the lowest income had an odds ratio (OR) of 1.26 (95% CI 1.23–1.28) compared to those with the highest income. History of cervical cancer and high parity were also associated with lower treatment rates. Conclusion: This study presents novel factors beyond the infection which seem to affect the antibiotic treatment for uncomplicated cystitis in women. Future studies to investigate possible mechanisms are warranted in order to properly use our findings. This may help healthcare workers and planners to provide a more equal treatment plan for this common infection, which may reduce misuse of antibiotics, decrease costs and improve efforts against antibiotic resistance.

A.5 Identification of predictors of response to Erenumab in episodic and chronic migraine in a cohort of patients: a preliminary analysis

Background: Erenumab is an antibody anti-calcitonin gene related peptide (CGRP) receptor approved for the treatment of episodic (EM) and chronic migraine (CM). In this study, we aimed to identify the predictors of response to the treatment. Methods: This is an ongoing retrospective cohort study of 120 patients (49 with cervicalgia) with EM or CM treated with Erenumab. The first endpoint was to identify the success rate of this treatment (at least 50% reduction in monthly migraine days during the third month of the treatment). The second endpoint was to identify the predictors of response to Erenumab treatment. Results: Seventy one percent of patients achieved a favorable response (P-value<0.001) to Erenumab. Patients with cervicalgia showed a lower treatment success rate (21.1% with vs 40.8% without cervicalgia) while patients without cervicalgia showed a higher treatment success rate (78. 9% without vs 59.2% with cervicalgia) with a P-value of 0.025 and an odd ratio of 0.388 (95% CI 0.174-0.869, P-value=0.021). A similar trend was observed in patients with occipital neuralgia and obesity (P-value<0.08). Conclusions: The preliminary analysis of this study demonstrates that cervicalgia (and to a lesser extend occipital neuralgia and obesity) is a negative predictor of response to Erenumab in patients with migraine.

Electronically monitored occlusion therapy in amblyopia with eccentric fixation

Purpose Amblyopia with eccentric fixation, especially when not diagnosed early, is a therapeutic challenge, as visual outcome is known to be poorer than in amblyopia with central fixation. Consequently, treatment after late diagnosis is often denied. Electronic monitoring of occlusion provides us the chance to gain first focussed insight into age-dependent dose response and treatment efficiency, as well as the shift of fixation in this rare group of paediatric patients. Methods In our prospective pilot study, we examined amblyopes with eccentric fixation during 12 months of occlusion treatment. We evaluated their visual acuity, recorded patching duration using a TheraMon®-microsensor, and determined their fixation with a direct ophthalmoscope. Dose-response relationship and treatment efficiency were calculated. Results The study included 12 participants with strabismic and combined amblyopia aged 2.9–12.4 years (mean 6.5). Median prescription of occlusion was 7.7 h/day (range 6.6–9.9) and median daily received occlusion was 5.2 h/day (range 0.7–9.7). At study end, median acuity gain was 0.6 log units (range 0–1.6) and residual interocular visual acuity difference (IOVAD) 0.3 log units (range 0–1.8). There was neither significant acuity gain nor reduction in IOVAD after the 6th month of treatment. Children younger than 4 years showed best response with lowest residual IOVAD at study end. Efficiency calculation showed an acuity gain of approximately one line from 100 h of patching in the first 2 months and half a line after 6 months. There was a significant decline of treatment efficiency with age (p = 0.01). Foveolar fixation was achieved after median 3 months (range 1–6). Three patients (> 6 years) did not gain central fixation. Conclusion Eccentric fixation is a challenge to therapy success. Based on electronic monitoring, our study quantified for the first time the reduction of treatment efficiency with increasing age in amblyopes with eccentric fixation. Despite some improvement in patients up to 8 years, older patients showed significantly lower treatment efficiency. In younger patients with good adherence, despite poor initial acuity, central fixation and low residual IOVAD could be attained after median 3 months. Hence, the necessity of early diagnosis and intensive occlusion should be emphasized.

Combined Model of Technology Use and Medical Adherence in eHealth Technology Implementation

eHealth applications are expected to improve the effectiveness and efficiency of healthcare systems by providing improved medical information flow between medical providers and patients. Although the technology is expected to empower patients, lower treatment costs, and provide real-time collection of health data, individuals may be apprehensive about the use and efficacy of eHealth technologies. Medical professionals are often unaware of human factors technology acceptance or usability models which impact the use of medically focused technology, such as eHealth applications. Similarly, human factors professionals are often unaware of treatment adherence models which map the relationship of illness factors and individual differences to treatment protocols. The present paper presents a theoretical approach through which technology acceptance and usability models should be combined with medical treatment adherence models to ensure that eHealth applications are used properly and effectively.

1544Baseline predictors of attrition in a randomised controlled trial of treatments for people with recurrent binge eating episodes associated to overweight or obesity

Purpose Understanding the high rate of treatment attrition in trials of people with eating disorders is important as it can compromise the quality of the trials. In clinical practice, it may also contribute to illness chronicity, relapse, and costs. Thus, we investigated factors associated with treatment attrition to a new manualised psychotherapy HAPIFED compared to CBT-E, for individuals with Bulimia Nervosa or Binge Eating Disorder comorbid with overweight or obesity. Methods In total, 98 participants were recruited with 50 randomised to HAPIFED and 48 to the control intervention CBT-E, all administered in groups of up to 10 participants. An investigator external to the site conducted the random allocation, which was concealed from the statistician involved in the analysis, and known only to the therapists until the finalization of the 12-month follow-up after the end of active treatment. Three scenarios in the timeline treatment of a total of 30 sessions were assessed: 33% or 60% or 75% of presence. Logistic regression analysis was performed to find the correlates of attrition. Results None of the six variables - frequency of binge eating episodes, purging, eating disorder symptom severity, weight, illness duration and mental health-related quality of life - significantly predicted attrition at 33%, but longer illness duration predicted lower treatment attrition at both 60% and 75% presence of the interventions. Also for 75% presence, lower body weight predicted lower treatment attrition. Conclusions Lower attrition due to late treatment completion was associated with longer binge eating illness length and a lower body weight. More research is needed to recognize factors that may interfere with engagement in treatments aiming to avoid early dropout. Keywords binge eating disorder, bulimia nervosa, cognitive therapy, obesity, patient dropout Trial registration US National Institutes of Health clinical trial registration number NCT02464345, date of registration 1 June 2015.

Features of minimally invasive ligamentotomy of the thumb A1 pulley (our experience)

Objective. Stenosing tenosynovitis (Nott’s disease, "trigger finger") is one of the most common pathologies of the hand which hand surgeons and orthopedic surgeons have to deal with. A variety of conservative methods are used to treat “trigger finger", including individual splinting and corticosteroid injections. Surgical treatment consists of dissection of the A1 pulley. Traditionally, the operation starts with a small incision. However, in recent years, a number of articles have appeared that report that percutaneous ligamentotomy on II-V fingers is a safe and effective alternative to an open surgery. Due to anatomical features, some authors do not recommend performing a percutaneous ligamentotomy on the thumb, fearing the damage it can cause to the digital nerves.The purpose of this research is to show that the minimally invasive needle ligamentotomy of the thumb A1 pulley is a safe procedure and to conduct the approbation of the offered method.Material and methods. The research consisted of two parts - anatomical and clinical. In the anatomical part of the research (8 upper extremities of 4 unfixed corpses), we proposed the safe accesses in order to conduct percutaneous ligamentotomy of the thumb A1 pulley.In the clinical part of the study we tested a minimally invasive ligamentotomy and analysed the results of treatment in 109 patients with stenosing tenosynovitis of the thumb II-IV stage by Green aged from 28 to 80. All patients received minimally invasive ligamentotomy of the A1 pulley with 18g needle under local anaesthesia (120 surgeries). Average length of the operation was several minutes. All procedures were performed outpatiently. Evaluation of the results of treatment was performed using the Visual Analog Scale (VAS) and Gilberts questionnaire. The observation period was from 12 months up to 24 months.The results. In most cases both clinical and esthetical results were excellent. It was possible to eliminate the “trigger” of the finger intraoperatively for all patients. However, 6 (5.5%) patients complained about the presence of residual clicks due to incomplete dissection of the ligament at the control examination a week later. Percutaneous ligamentotomy was conducted again on all patients with successful outcomes. No recurrence of the disease was noted. 17% of patients tend to complain about pain in the A1 pulley localization during the first week after the operation.Conclusion. The empirical findings prove the efficiency and safety of percutaneous ligamentotomy of the thumb A1 pulley. One of the merits of this technique is a lower risk of postoperative complications and lower treatment expenses. This technique can be successfully used in the practice of hand surgeons in the outpatient setting that have the experience with the conduction of open operations.

COVID-19 Pandemic-Adapted Radiotherapy Guidelines: Are They Really Followed?

Background: In our department, we provided guidelines to the radiation oncologists (ROs) regarding the omission, delay, or shortening of radiotherapy (RT). The purpose was to reduce the patients’ exposure to the hospital environment and to minimize the departmental overcrowding. The aim was to evaluate the ROs’ compliance to these guidelines. Methods: ROs were asked to fill out a data collection form during patients’ first visits in May and June 2020. The collected data included the ROs’ age and gender, patient age and residence, RT purpose, treated tumor, the dose and fractionation that would have been prescribed, and RT changes. The chi-square test and binomial logistic regression were used to analyze the correlation between the treatment prescription and the collected parameters. Results: One hundred and twenty-six out of 205 prescribed treatments were included in this analysis. Treatment was modified in 61.1% of cases. More specifically, the treatment was omitted, delayed, or shortened in 7.9, 15.9, and 37.3% of patients, respectively. The number of delivered fractions was reduced by 27.9%. A statistically significant correlation (p = 0.028) between younger patients’ age and lower treatment modifications rate was recorded. Conclusion: Our analysis showed a reasonably high compliance of ROs to the pandemic-adapted guidelines. The adopted strategy was effective in reducing the number of admissions to our department.

Baseline Predictors of Attrition in a Randomised Controlled Trial of a New Group Psychological Intervention for People with Recurrent Binge Eating Episodes Associated to Overweight or Obesity

Purpose: Understanding the high rate of treatment attrition in trials of people with eating disorders is important as it can compromise the quality of the trials. In clinical practice, it may also contribute to illness chronicity, relapse, and costs. Thus, we investigated factors associated with treatment attrition to a new manualised psychotherapy HAPIFED compared to CBT-E, for individuals with Bulimia Nervosa or Binge Eating Disorder comorbid with overweight or obesity.Methods: In total, 98 participants were recruited with 50 randomised to HAPIFED and 48 to the control intervention CBT-E, all administered in groups of up to 10 participants. An investigator external to the site conducted the random allocation, which was concealed from the statistician involved in the analysis, and known only to the therapists until the finalization of the 12-month follow-up after the end of active treatment. Three scenarios in the timeline treatment of a total of 30 sessions were assessed: 33% or 60% or 75% of presence. Logistic regression analysis was performed to find the correlates of attrition.Results: None of the six variables - frequency of binge eating episodes, purging, eating disorder symptom severity, weight, illness duration and mental health-related quality of life - significantly predicted attrition at 33%, but longer illness duration predicted lower treatment attrition at both 60% and 75% presence of the interventions. Also for 75% presence, lower body weight predicted lower treatment attrition. Conclusions: Lower attrition due to late treatment completion was associated with longer binge eating illness length and a lower body weight. More research is needed to recognize factors that may interfere with engagement in treatments aiming to avoid early dropout.Trial registration: US National Institutes of Health clinical trial registration number NCT02464345, date of registration 1 June 2015.