Likelihood Ratio Test and the Evidential Approach for 2 × 2 Tables.

Categorical data analysis of 2 × 2 contingency tables is extremely common, not least because they provide risk difference, risk ratio, odds ratio, and log odds statistics in medical research. A χ2 test analysis is most often used, although some researchers use likelihood ratio test (LRT) analysis. Does it matter which test is used? A review of the literature, examination of the theoretical foundations, and analyses of simulations and empirical data are used by this paper to argue that only the LRT should be used when we are interested in testing whether the binomial proportions are equal. This so-called test of independence is by far the most popular, meaning the χ2 test is widely misused. By contrast, the χ2 test should be reserved for where the data appear to match too closely a particular hypothesis (e.g., the null hypothesis), where the variance is of interest, and is less than expected. Low variance can be of interest in various scenarios, particularly in investigations of data integrity. Finally, it is argued that the evidential approach provides a consistent and coherent method that avoids the difficulties posed by significance testing. The approach facilitates the calculation of appropriate log likelihood ratios to suit our research aims, whether this is to test the proportions or to test the variance. The conclusions from this paper apply to larger contingency tables, including multi-way tables.

Cardiovascular adverse events of antineoplastic monoclonal antibodies among cancer patients: real-world evidence from a tertiary healthcare system.

BACKGROUND: Antineoplastic monoclonal antibodies (mAbs), such as trastuzumab, bevacizumab, and pertuzumab have been the mainstay of therapy in cancer patients. Despite proven efficacy of the monoclonal antibodies, cardiovascular-induced adverse events such as heart failure, hypertension, ischemic heart disease, arrhythmias, thromboembolic events, and hemorrhage remain a major complication. The European society of cardiology address that concern with antineoplastic monoclonal antibodies issuing a guideline to manage and monitor chemotherapy-induced cardiotoxicity. There is limited evidence of the real-world prevalence of cardiovascular (CV) events induced by monoclonal antibodies among patients with cancer in Saudi Arabia. OBJECTIVE: To evaluate the prevalence of cardiovascular adverse events among patients with cancer treated with monoclonal antibodies in Saudi Arabia. METHODS: This is a retrospective study conducted in a tertiary care hospital, Riyadh, Saudi Arabia. Data were obtained from an electronic medical record of patients with cancer treated with one of the selected monoclonal antibodies, who met the inclusion criteria between January 2005 until June 2015 and have been followed up for at least one year. Patients were stratified into groups according to monoclonal antibodies treatment: trastuzumab, bevacizumab, pertuzumab, and combined mAbs. RESULTS: A total of 1067 patient were included in the study, within the pre-determined study period. The prevalence of cardiovascular disease among patients with cancer treated with monoclonal antibodies was 16.3%. The prevalence of heart failure was relatively higher in the trastuzumab group (46/626 patients, 7.3%). Among 418 patients treated with bevacizumab, hypertension was the most frequent adverse event, reported in 38 patients (9.1%), followed by thromboembolism reported in 27 patients (6.5%). Treatment discontinuation owing to cardiovascular adverse events was reported in 42/1,067 patients (3.9%). CONCLUSION AND RELEVANCE: Prevalence of antineoplastic monoclonal antibody induced cardiovascular adverse events among patients with cancer is substantially high in Saudi Arabia. There is an urgent need to streamline the practice for identifying high risk patients and flexible referral system for cardio-oncology care.

Effects of potassium channel modulators on the responses of mammalian slowly adapting mechanoreceptors.

Introduction: slowly adapting mechanoreceptors in the skin provide vital tactile information to animals. The ionic channels that underlie their functioning is the subject of intense research. Previous work suggests that potassium channels may play particular roles in the activation and firing of these mechanoreceptors. Objective: We used a range of potassium channel blockers and openers to observe their effects on different phases of mechanoreceptor responses. Methods: Extracellular recording of neural activity of slowly adapting mechanoreceptors was carried out in an in vitro preparation of the sinus hair follicles taken from rat whisker pads. A range of potassium (K+) channel modulators were tested on these mechanoreceptor responses. The channel blockers tested were: tetraethylammonium (TEA), barium chloride (BaCl2), dequalinium, 4-aminopyridine (4-AP), paxilline, XE 991, apamin, and charybdotoxin. Results: Except for charybdotoxin and apamin, these drugs increased the activity of both types of slowly adapting units, St I and St II. Generally, both spontaneous and evoked (dynamic and static) activities increased. The channel opener NS1619 was also tested. NS1619 clearly decreased evoked activity (both dynamic and static) while leaving spontaneous activity relatively unaffected, with no clear discrimination of effects on the two types of St receptor. Conclusion: These findings are consistent with the targets of the drugs suggesting that K+ channels play an important role in the maintenance of spontaneous firing and in the production of and persistence of mechanoreceptor activity.

Effects of camphor and related compounds on slowly adapting mechanoreceptors in the rat sinus hair follicle.

Introduction: Camphor is a popular compound for therapeutic and cosmetic use with a distinctive odour, and somatosensory warming and cooling properties. The mechanisms for its action remain unclear. Objective: The current study examined the effects of two enantiomers of camphor and related monoterpenoid compounds on mechanoreceptors. Methods: Extracellular recordings were made in an in vitro bath preparation. Camphor, borneol, eugenol, carveol, and thymol were tested on the neural activity of St I and St II slowly adapting mechanoreceptors in the rat vibrissal hair follicle preparation. Results: All compounds tested (0.5 - 2 mM bath concentrations) resulted in dose-dependent depression of spontaneous and mechanically evoked firing (dynamic and static phases). The mean latency of responses also increased. Both St I and St II were similarly affected, although (-)-camphor had a greater depressant effect on St II than on St I units. Differences were found across the different compounds for their effect on the dynamic and static phases. Thymol was found to have the greatest depressant effect on these phases. The broad spectrum TRP blocker ruthenium red did not reverse the depressant effects of camphor. The depressant effects of the compounds appeared similar to those obtained using the local anaesthetic lignocaine. The depressant effects of camphor and of lignocaine were partially reversed by the K+ channel blocker tetraethylammonium. Conclusions: The results question whether the depressant effects of camphor and related compounds act through TRP channels. Perhaps the use of more selective blockers may reveal the molecular mechanisms through which these compounds act.

Evaluation of COVID-19 myths in Saudi Arabia.

OBJECTIVES: To examine the awareness level of COVID-19 and to highlight the frequency of myths and misconceptions among Saudi Arabia's population. METHODS: We conducted a cross-sectional study from June 13 to 20, 2020 by distributing a 16-item online Google forms questionnaire among adults (18-65 years old) living in Saudi Arabia. We utilized the convenience sampling. Data analysis was performed using Chi-square and multiple regression analysis on Jamovi. RESULTS: A total of 1436 responses were analyzed with 43.5% males and 56.5% females. Most respondents (89.1%) thought that only the elderly above 60 years old are considered at high risk of contracting COVID-19. Most respondents (86.5%) agreed that people with other health conditions could be more affected by COVID-19. Approximately 97.2% agreed that wearing a mask and avoiding touching eyes, nose, and mouth with unwashed hands was the leading preventive action. Most participants (99.4%) chose fever as an associated symptom. Respondents from the healthcare sector presented statistically higher scores than those in non-healthcare sectors (p<0.001). Higher education and higher salary were important predictors of better COVID-19 knowledge. CONCLUSION: Public health officials need to increase awareness measures on COVID-19 to limit myths and misconceptions and reduce psychological distress associated with it.

Does Hyaluronidase Enhance Drug Penetration to Mechanoreceptors?

BACKGROUND: The pharmacological study of mechanoreceptors embedded within tissue is hampered by tissue barriers to applied research drugs. METHODS: Hyaluronidase increases the permeability of tissues and is used clinically to facilitate the distribution of injected drugs. An in vitro rat sinus hair preparation was used to determine whether hyaluronidase (1,500 or 3,000 IU/10 mL) had an effect on drug access to receptor sites on slowly adapting St I and St II mechanoreceptors. Electrical recordings were made from single mechanoreceptor units that were activated by trapezoid ramp stimuli. Cinnamaldehyde (500-1,500 µM) and capsazepine (100 µM) were used as test drugs. Changes in onset time and degree of depression of firing due to test drugs were compared to control experiments not employing hyaluronidase. RESULTS: There were no statistical effects on any of the observed measures. Often the effects were opposite to those predicted. Using a likelihood approach, it was calculated that there was strong evidence (log-likelihood ratios from -0.5 to -6.5) to support a null effect over a facilitatory effect. There was no evidence of loss of integrity of mechanoreceptor mechanotransduction mechanisms following hyaluronidase applications. Comparison with Existing Method: The use of hyaluronidase does not facilitate drug access to receptors. CONCLUSIONS: In the in vitro sinus hair preparation, the addition of hyaluronidase does not allow easier access to slowly adapting mechanoreceptors within the follicle.

Comparative Analysis of Prescription Drug Prices in South Asian Association for Regional Cooperation Countries.

OBJECTIVES: The SAARC (South Asian Association for Regional Cooperation) is a geopolitical organization composed of 8 neighboring countries: Afghanistan, Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka. The objective of this study was to compare the prices of some selected drugs in SAARC countries. METHODS: A list of 24 drugs was prepared based on certain inclusion and exclusion criteria. The retail prices of the drugs were determined from different sources and verified manually in the open market. The prices obtained in local currencies were converted into US dollars for comparison purposes. In another analysis, the gross domestic product (GDP) of each country was factored for comparative analysis. RESULTS: Out of the 23 drugs, 17 comparisons across countries were statistically different at P < .05. These analyses revealed large differences in drug prices among SAARC countries. The GDP-adjusted median drug prices revealed a more polarized picture, with Nepal generally having the highest prices (19 out of 24 drugs) and Sri Lanka having the lowest (19 out of 24 drugs). For example, the widely used antipsychotic drug risperidone was 7 times more expensive in Pakistan ($0.316) compared with Sri Lanka ($0.045). Adjusting for GDP made risperidone more than 18 times more expensive ($21.90 and $1.20) across the same 2 countries. CONCLUSION: Prices of selected drugs varied markedly in SAARC countries. After adjusting for GDP, drug prices became more polarized across countries, with Nepal featuring the highest prices. In determining drug prices, the country's GDP and the population's purchasing power need to be taken into account.

Selective decline in the prevalence of slowly adapting type I mechanoreceptors during development.

Merkel nerve endings are identified physiologically as slowly adapting type I mechanoreceptor units. They are important for fine acuity tactile perception. We examined the effect of age on the electrophysiological availability of different types of slowly adapting mechanoreceptor units. Using 6-50 week old rats, we observed an obvious decline with age in the probability of recording from St I units of the deep vibrissal nerve. The precipitous decline occurred between ages 6-14 weeks and then stabilized. By contrast, the prevalence of St II units, the other type of slowly adapting mechanoreceptor, remained constant over the age range studied. These observations correlate with anatomical findings reported elsewhere.

Use of beta blockers is associated with hearing loss.

OBJECTIVE: This study was conducted to investigate the hypothesis that patients using ß-blockers will develop hearing loss. DESIGN: A cross-sectional study. STUDY SAMPLE: A total of 125 patients completed the study. A total of 63 patients were on ß-blockers and 62 were not on ß-blockers. RESULTS: Carvedilol was significantly associated with hearing loss. Other beta-blockers including metoprolol and atenolol showed no association with hearing loss. Linear multiple regression analysis was run including variables of gender, age, ischaemic heart disease, cardiac failure/dilated cardiomyopathy, frusemide and carvedilol use as predictors for total hearing loss severity at all frequencies. Age and gender, as well as carvedilol, were found to be the only statistically significant predictors for hearing loss severity. CONCLUSION: Chronic use of carvedilol was associated with significant hearing loss. This may need to be taken into account when prescribing the drug. Further randomised controlled studies with baseline audiometric hearing tests before starting treatment, and periodic follow-up tests, would provide a better assessment of the effect of carvedilol on hearing.

Action research in rehabilitation with chronic stroke recovery: A case report with a focus on neural plasticity.

BACKGROUND: Chronic stroke patients are primarily referred to general rehabilitation, rather than to specific neurorehabilitation. Currently, there are no Danish clinical guidelines for chronic stroke, but recent research in neuroplasticity has contributed to possible rehabilitation interventions for these patients. OBJECTIVE: The purpose of this project is to describe the use of a specialized neuroplastic approach in combination with an already existing training program. METHODS: The project is designed as an action research project concerning four participants with chronic stroke. Through ten intervention, a neuroplastic focus has been added to their group training program including daily home training. Participants were tested before and after the intervention with MAS, DGI, 6MWT, SSQLS. RESULTS: All four participants improved their functional levels and their quality of life following the intervention. CONCLUSIONS: This report indicates that a specific neuroplastic focus in combination with action research has an impact on the participants with chronic stroke. However, there is still no clarity regarding what type of rehabilitation methods can be considered the most efficacious in promoting neuroplasticity. This case report serves as a pilot project for further studies of how to implement neuroplasticity in physical therapy.

Combined Recording of Mechanically Stimulated Afferent Output and Nerve Terminal Labelling in Mouse Hair Follicle Lanceolate Endings.

A novel dissection and recording technique is described for monitoring afferent firing evoked by mechanical displacement of hairs in the mouse pinna. The technique is very cost-effective and easily undertaken with materials commonly found in most electrophysiology laboratories, or easily purchased. The dissection is simple and fast, with the mechanical displacement provided by a generic electroceramic wafer controlled by proprietary software. The same software also records and analyses the electroneurogram output. The recording of the evoked nerve activity is through a commercial differential amplifier connected to fire-polished standard glass microelectrodes. Helpful tips are given for improving the quality of the preparation, the stimulation and the recording conditions to optimize recording quality. The system is suitable for assaying the electrophysiological and optical properties of lanceolate terminals of palisade endings of hair follicles, as well as the outcomes from their pharmacological and/or genetic manipulation. An example of combining electrical recording with mechanical stimulation and labeling with a styryl pyridinium vital dye is given.

Patient outcomes after treatment with percutaneous cholecystostomy for biliary sepsis.

INTRODUCTION: Acute cholecystitis is among the most common general surgical presentations. There is a cohort of patients who develop systemic sepsis and complications of acute cholecystitis. These patients are often elderly and co-morbid. Conservative management with percutaneous cholecystostomy has been shown to be a safe and effective management option in the acute setting. However, there is currently no consensus for the further management of these patients. In particular, there is a paucity of data on readmission rates and subsequent operative or non-operative management. METHODS: A retrospective study was carried out of patients treated with a percutaneous cholecystostomy for biliary sepsis over a three-year period in a UK teaching hospital. Outcome measures were subsequent operative or conservative management, conversion rates, operative complications and readmission rates. RESULTS: Twenty-five patients had a percutaneous cholecystostomy for the treatment of acute biliary sepsis. The median follow-up duration was 35 months. Thirteen patients (52%) had operative treatment. In the operative group, 6/13 had a laparoscopic cholecystectomy, 2/13 had a planned open cholecystectomy, 2/13 had abandoned procedures and 3/13 had a converted procedure. Complications in the operative group included: postoperative mortality (1/13), common bile duct injury requiring drainage and endoscopic stenting (1/13) and one patient required readmission with recurrent pain. In the non-operative group, 5/12 patients were readmitted with biliary sepsis, 5/12 had no readmissions, 1/12 died in the community and 1/12 was readmitted with biliary colic. CONCLUSIONS: Percutaneous cholecystostomy is a recognised treatment modality for elderly, co-morbid patients with biliary sepsis. Nevertheless, the readmission rate in this group is relatively high at 5/12 (42%). Patients who undergo subsequent operative management have a conversion rate of 3/13 (23%) and a significant complication rate of 2/13 (15%). The further management of patients having undergone percutaneous cholecystostomy requires careful consideration on an individual case basis. The P-POSSUM (Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) may aid decision making.