Evidence-based Medicine Approach Research Articles

The Omics Complexity in Sepsis: The Limits of the Personalized Medicine Approach.

Sepsis is one of the most common causes of morbidity and mortality worldwide. Despite the remarkable advances in modern medicine throughout the last century, the mortality rates associated with sepsis have remained significantly elevated, both in high- and low-income countries. The main difficulty in the diagnosis and treatment of septic patients is the tremendous heterogeneity of this condition. The vast heterogeneity that characterizes sepsis ranges from the clinical presentation to the biological aspects of the disease. Evidence-based medicine approaches sepsis as a homogenous syndrome and does not consider the individual discrepancies between septic patients. This approach may contribute to the poor outcomes of septic patients. In recent years, personalized medicine has gained significant interest. This novel form of medicine underlines the importance of understanding the genetic, epigenetic, and molecular basis of a disease in order to provide a more tailored approach for the patient. The study of "omics", such as cytomics, genomics, epigenomics, transcriptomics, proteomics, and metabolomics, provides a deeper comprehension of the complex interactions between the host, the disease, and the environment. The aim of this review is to summarize the potential role of a personalized approach in sepsis management, considering the interactions between various "omics".

Improvement of Russian clinical guidelines and reduction of mortality in perforated ulcers

To analyze the results of laparoscopic surgery in patients with perforated ulcers using evidence-based medicine approaches. We compared the efficacy and effectiveness of laparoscopic and open surgeries in patients with perforated ulcers. Meta-analysis of mortality after laparoscopic surgeries (randomized controlled trials) and trial sequential analysis were carried out. We clarified the differences between the efficacy and effectiveness of laparoscopic surgeries regarding postoperative mortality. In the Russian Federation, mortality after laparoscopic surgery is 9-11 times lower compared to open procedures. According to evidence-based researches (efficacy of laparoscopic interventions in 10 meta-analyses), these differences are less obvious (1.4-3.0 times) and not significant. The diversity-adjusted required information size to draw reasonable conclusions about differences in mortality in trial sequential analysis was 68 181 participants. Meta-analyses of RCTs also demonstrate lower incidence of wound complications (1.8-5.0% after laparoscopic surgery and 6.3-13.3% after laparotomy), shorter hospital-stay (mean difference from -0.13 to -2.84) and less severe pain syndrome (mean difference in VAS score from -2.08 to -2.45) after laparoscopic technologies. The obvious advantage of laparoscopic surgery in patients with perforated ulcers is fast-truck recovery following shorter hospital-stay, mild pain and rarer wound complications. Comparison of postoperative mortality regarding efficacy and effectiveness is difficult due to insufficient introduction of laparoscopic technologies in clinical practice and diversity-adjusted required information size.

Concepts of multi-level dynamical modelling: understanding mechanisms of squamous cell carcinoma development in Fanconi anemia.

Fanconi anemia (FA) is a rare disease (incidence of 1:300,000) primarily based on the inheritance of pathogenic variants in genes of the FA/BRCA (breast cancer) pathway. These variants ultimately reduce the functionality of different proteins involved in the repair of DNA interstrand crosslinks and DNA double-strand breaks. At birth, individuals with FA might present with typical malformations, particularly radial axis and renal malformations, as well as other physical abnormalities like skin pigmentation anomalies. During the first decade of life, FA mostly causes bone marrow failure due to reduced capacity and loss of the hematopoietic stem and progenitor cells. This often makes hematopoietic stem cell transplantation necessary, but this therapy increases the already intrinsic risk of developing squamous cell carcinoma (SCC) in early adult age. Due to the underlying genetic defect in FA, classical chemo-radiation-based treatment protocols cannot be applied. Therefore, detecting and treating the multi-step tumorigenesis process of SCC in an early stage, or even its progenitors, is the best option for prolonging the life of adult FA individuals. However, the small number of FA individuals makes classical evidence-based medicine approaches based on results from randomized clinical trials impossible. As an alternative, we introduce here the concept of multi-level dynamical modelling using large, longitudinally collected genome, proteome- and transcriptome-wide data sets from a small number of FA individuals. This mechanistic modelling approach is based on the "hallmarks of cancer in FA", which we derive from our unique database of the clinical history of over 750 FA individuals. Multi-omic data from healthy and diseased tissue samples of FA individuals are to be used for training constituent models of a multi-level tumorigenesis model, which will then be used to make experimentally testable predictions. In this way, mechanistic models facilitate not only a descriptive but also a functional understanding of SCC in FA. This approach will provide the basis for detecting signatures of SCCs at early stages and their precursors so they can be efficiently treated or even prevented, leading to a better prognosis and quality of life for the FA individual.

Immunological Responses of Arsenicum album 30CH to Combat COVID-19: Protocol for a Double-Blind, Randomized, Placebo-Controlled Clinical Trial in the Pathanamthitta District of Kerala.

COVID-19 is a recent major public health concern caused by the SARS-CoV-2 virus, with approximately 44.6 million COVID-19-positive cases and 530,000 deaths in India (as of February 1, 2023). The COVID-19 vaccination drive in India was initiated in January 2021; however, an effective preventive strategy with high efficacy and immunological safety remains elusive. The aim of this study is to assess the immunogenic responses of Arsenicum album 30CH (AA30CH) as COVID-19 prophylaxis, including assessment of immunological markers, innate and acquired immune responses, COVID-19 symptoms, and its associated antibody responses. This randomized controlled clinical trial (RCT) will include two parallel comparator groups of AA30CH and placebo with an allocation ratio of 1:1 conducted in the Pathanamthitta district of Kerala, India. The placebo or AA30CH will be administered in three intervention schedules and blood samples will be collected before and after each of the intervention schedules. Based on the inclusion and exclusion criteria, 112 participants per arm (with an expected dropout of 20%) will be screened. Immunogenic responses will be evaluated by determining the antigen density and modulation in immunological markers and lymphocyte subsets CD3, CD4, CD8, CD24, CD27, CD38, CD4 interferon-γ, CD4 CD17, CD4 CD25 (activated T lymphocytes), T cells, B cells, dendritic cells (mature and immature), and natural killer cells on days 1, 5, 23,27, 45, 49, and 66. The innate and acquired immune responses will also be evaluated by a real-time reverse-transcriptase polymerase chain reaction (RT-PCR) array profiler (84-gene set) before and after the study interventions. The toxicity status of AA30CH in study participants will be evaluated through hepatic, renal, and hematological parameters and peripheral smears on days 1, 5, 23, 27, 45, 49, and 66. The number of participants developing COVID-19-like symptoms per National Centre for Disease Control guidelines and the number of participants testing positive for COVID-19 in RT-PCR during follow-ups in any of the three intervention schedules will be identified. Moreover, a subgroup analysis will be used to assess the COVID-19 antibody responses between vaccinated and unvaccinated participants. This RCT protocol has been approved by various committees and funded by the Central Council for Research in Homoeopathy, Ministry of Ayush, Government of India. The project has been implemented in collaboration with the Department of Homoeopathy, Government of Kerala. The RCT was rolled out on January 25, 2023, and enrollment was completed April 3, 2023. The immunological assays will be conducted at the Department of Biotechnology-Translational Health Science and Technology Institute, Faridabad, India. This study will represent the first evaluation of the immunological efficacy and safety of AA30CH in an RCT, which may significantly impact the use of homeopathy as an evidence-based medicine approach. Clinical Trials Registry-India CTRI/2022/08/045089; https://tinyurl.com/mryrpkvk. DERR1-10.2196/48479.

Efficacy of using progesterone as an immunosuppressant for the prevention of preeclampsia in pregnant women with iron-deficiency anemia

BACKGROUND:In previous studies, our data on the activation of pro-inflammatory cytokines at the systemic and local levels indicated an inadequate maternal immune response to fetal egg antigens against the backdrop of endocrine system restructuring and iron-deficiency anemia, which is a fundamental mechanism underlying the pathogenesis of preeclampsia. The above was the basis for the use of immunotherapy at a high risk of developing preeclampsia in pregnant women.
 AIM:The aim of this study was to evaluate the use of micronized progesterone as an immunosuppressant for the prevention of preeclampsia in pregnant women with iron-deficiency anemia.
 MATERIALS AND METHODS:We examined 44 pregnant women with iron-deficiency anemia in dynamics by trimesters of pregnancy: patients before and after taking micronized progesterone (main group,n= 25) and untreated pregnant women (comparison group,n= 19). We used general clinical and laboratory methods, assessing serum progesterone levels at 46, 2528 and 3236 weeks of pregnancy before and after the treatment, as well as statistical methods using evidence-based medicine approaches.
 RESULTS:Taking micronized progesterone in pregnant women with iron-deficiency anemia from early gestation increased blood progesterone level by 1.5 times by 28 weeks of pregnancy (p 0.05) and by 2.5 times by 3234 weeks of pregnancy (p 0.05) compared to that in women who did not take the hormonal drug. In case of progesterone deficiency in pregnant women with iron-deficiency anemia and mild preeclampsia, the administration of micronized progesterone elevated its blood level by 2.4 times (p 0.05), but in severe preeclampsia in untreated women, the hormone concentrations were reduced. In women with iron-deficiency anemia, due to the inclusion of progestogen in standard antianemic therapy from early stages and throughout pregnancy, the incidence of severe preeclampsia and preterm birth was decreased in 93.3% of cases, which led to a live birth in most cases.
 CONCLUSIONS:Micronized progesterone in pregnant women may be used to correct progesterone deficiency conditions, one of which is iron-deficiency anemia, and, as an immunosuppressant, to protect the fetus from an aggressive maternal immune response, manifested by the development of preeclampsia and other complications. The use of the gestagen therapy from early pregnancy is a promising tool for the prevention of preeclampsia in pregnant women with iron-deficiency anemia. Undoubtedly, further and more extensive research is needed to better understand this issue.

A Modified Study Design for Blinded Randomized Controlled Trial in Orthobiologic Therapy

Background: The utility of cellular based therapeutic agents in management of various ailments and conditions is promising, particularly in the field of orthopedics. However, an evidence-based medicine approach must be implemented to validate these novel cellular based therapies before they can be translated into routine clinical practice. Given pain relief is a primary goal of novel treatments for orthopedic disease, future orthobiologic clinical trials will need to overcome challenges such as the placebo effect or the placebo response and difficult participant recruitment. In this paper, we describe a clinical study that evaluates the safety and efficacy of autologous stromal vascular fraction (SVF) cells that adheres to a patient blinded, randomized and placebo-controlled study design while still offering the patient the opportunity to participate in the therapeutic intervention by using cell preservation techniques. Methods: This pilot clinical trial studies the safety and feasibility of intra-articular transplantation of SVF cells in patients with knee osteoarthritis with secondary outcomes of improving pain relief. The RCT aims to recruit 30 patients. Liposuction is performed on each patient to isolate SVF cells. 15 subjects are randomized to receive SVF injection in the same surgical procedure and 15 subjects receive placebo injection directly into their affected knee joint. The placebo group’s SVF cells are then frozen and preserved. At the 6-month follow-up visit, those who received the placebo are unblinded and have the option to receive the SVF injection as a condition for participation in the trial. Feasibility of liposuction, SVF manufacturing, cell preservation/thaw techniques and adverse outcomes are all primarily tracked. Secondary outcomes include standardized patient reported outcomes score responses to the treatments. Discussion: The design of this pilot study offers study subjects the opportunity to receive a novel therapeutic intervention even within a placebo arm and enables the investigators to blind subjects without performing an unnecessary liposuction or discarding the resulting cellular product which could encourage hesitant individuals to participate in the trial. This may aid in overcoming the challenges associated with recruiting participants for cell therapy trials concerned with being randomized to a control arm. The results of this trial will help to assess both the safety and feasibility of SVF injections to treat knee osteoarthritis as well as help plan larger phase controlled trials. However, precautionary measures are necessary to ensure the safety and well-being of patients receiving cell-based therapy. Proper handling and storage of the cellular product must be considered and are demonstrated here. Trial Registration ClinicalTrials.gov Identifier: NCT03940950

Stroke risk management in carotid atherosclerotic disease: A Clinical Consensus Statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases.

Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (1) establishing a unified knowledge foundation and (2) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailores personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management encompassing statins, novel lipid-lowering and antithrombotic strategies and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multimorbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for interdisciplinary collaboration and prioritized patient-centric decision-making.

Obesity in the elderly: peculiarities of treatment in outpatient practice

Today there is a worldwide trend of population aging, in addition, the proportion of older people with obesity is increasing. In order to adequately manage these patients in the outpatient setting, it is critical to understand the dynamic relationship between body weight, chronic disease prevalence, development of functional disability, life expectancy, and health care costs. While the obesity epidemic has affected people of all age groups, empirical knowledge about the management of obese older people remains largely scarce. Currently, there is no single therapeutic approach to this problem. Weight loss should be treated with caution in people over 60 years of age. The risk of sarcopenia, malnutrition, bone loss, increased risk of falls and injury must be considered, which can lead to an increase in the number of people with disabilities and the associated costs of medical and social care. The analytical review focuses on the relationship between two of the greatest epidemiological trends: aging and obesity. This paper highlights the features of the pathophysiology of obesity in the elderly, the phenomenon of the «obesity paradox». Also from the perspective of evidence-based medicine approaches to the treatment of obesity in the elderly, including surgical interventions aimed at reducing body weight, are analyzed.

Network analysis to explore the pharmacological mechanism of Shenmai injection in treating granulocytopenia and evidence-based medicine approach validation.

Shenmai injection is frequently utilized in China to clinically treat granulocytopenia in oncology patients following chemotherapy. Despite this, the drug's therapeutic benefits remain a topic of contention, and its active components and potential treatment targets have yet to be established. The present study utilizes a network pharmacology approach to investigate the drug's active ingredients and possible therapeutic targets, and to evaluate the effectiveness of Shenmai injection in treating granulocytopenia through meta-analysis. In our subject paper, we utilized the TCMID database to investigate the active ingredients present in red ginseng and ophiopogon japonicus. To further identify molecular targets, we employed SuperPred, as well as OMIM, Genecards, and DisGeNET databases. Our focus was on targets associated with granulocytopenia. The DAVID 6.8 database was utilized to perform gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Additionally, a protein-protein interaction network was established. The resulting "drug-key component-potential target-core pathway" network was used to predict the mechanism of action of Shenmai injection in the treatment of granulocytopenia. In order to evaluate the quality of the studies included in our analysis, we utilized the Cochrane Reviewers' Handbook. We then conducted a meta-analysis of the clinical curative effect of Shenmai injection for granulocytopenia, utilizing the Cochrane Collaboration's RevMan 5.3 software. After conducting a thorough screening, the study identified 5 primary ingredients of Shenmai injection - ophiopogonoside a, β-patchoulene, ginsenoside rf, ginsenoside re, and ginsenoside rg1-that can potentially target 5 essential proteins: STAT3, TLR4, PIK3CA, PIK3R1, and GRB2. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that Shenmai injection can be beneficial in treating granulocytopenia by interacting with pathways such as HIF-1 signaling, T-cell receptor signaling, PI3K-Akt signaling, chemokine signaling, and FoxO signaling. The results of meta-analysis indicate that the treatment group exhibited superior performance in terms of both efficiency and post-treatment leukocyte count when compared to the control group. In summary, studies in network pharmacology demonstrate that Shenmai injection exerts an impact on granulocytopenia via various components, targets, and mechanisms. Additionally, evidence-based studies provide strong support for the effectiveness of Shenmai injection in preventing and treating granulocytopenia.

Abstract P1-08-02: Implementation of Integrative Medicine Program for Breast Medical Oncology Professionals in an Academic Cancer Center

Abstract BACKGROUND: Integrative medicine such as acupuncture, meditation, yoga and massage are highly desired by breast cancer survivors. Breast medical oncology professionals including physicians, advanced nurse practitioners and physician assistants are often the first clinicians that patients would expect to discuss the use of integrative medicine. Many distressing symptoms, such as hot flashes, insomnia, anxiety, and pain, are common and remain challenging to manage with limited pharmacological intervention available and potential toxicities. Evidence-based integrative medicine approaches, including acupuncture, meditation, yoga, and massage, may help reduce this symptom burden and improve quality of life. However, many breast medical oncology professions are not familiar with current evidence and knowledge in integrative medicine. Therefore, there is an urgent need to educate them on the fundamentals of evidence-based integrative medicine interventions that could improve quality of life for breast cancer survivors. METHODS: We designed the Integrative Oncology training Program for breast medicine professionals at our institution. The program faculty are composed of five breast medical oncologists, five integrative medicine faculty, and one education coordinator. RESULTS: We developed an online, interdisciplinary five-hour course on evidence-based integrative oncology with essential knowledge on integrative medicine approaches for breast cancer survivors. We determined the topic of interest based on feedback from the program faculty. The integrative medicine approaches in management of hot flashes, arthralgia, insomnia, are cannabis uses are some examples that were highly in-demand. The program summarizes high-quality evidence in herbal supplements, acupuncture, meditation, and yoga, pertinent to the audience, as well as the referral flow to our Integrative Medicine Service. CONCLUSIONS: Integrative medicine education programs for oncological professionals are needed to disseminate integrative medicine knowledge and to prepare them to guide our patients on integrative and complementary approaches during and after anticancer treatments. Citation Format: W. Iris Zhi, Rui Wanq, Ting Bao. Implementation of Integrative Medicine Program for Breast Medical Oncology Professionals in an Academic Cancer Center [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-08-02.

Global Statements to Produce and Implement Evidence in the Post-COVID-19 Era Provide a Path Forward for Rehabilitation - A Joint Initiative of Cochrane Rehabilitation and the Leading Journals in the Field.

Global Statements to Produce and Implement Evidence in the Post-COVID-19 Era Provide a Path Forward for Rehabilitation - A Joint Initiative of Cochrane Rehabilitation and the Leading Journals in the Field.

Evidence-Based Medicine and Patient-Centred Care

Proponents of Evidence-Based Medicine (EBM) argue that EBM’s approach to medicine promotes good clinical decisions while it escapes adverse issues such as implicit bias. However, EBM approaches the causation of diseases from a homogenous standpoint; that is, EBM overgeneralises evidence and the intervention measures it provides. As a result, proponents of Patient-Centred Care (PCC) allude that the strictness of EBM towards evidence impairs it from considering case-by-case treatment of patients but a generalised method of intervention. Given this problem, I argue that EBM cannot be considered a medical approach to practising medicine and conducting medical research that is in the best interest of individual patients, especially patients that prefer alternative interventions other than the methods of EBM. I conclude by drawing from the best features of EBM and PCC to create an alternative that accommodates the interests of both EBM and PCC patients.

The EBM+ movement.

In this paper, I provide an introduction for biostatisticians and others to some recent work in the philosophy of medicine. Firstly, I give an overview of some philosophical arguments that are thought to create problems for a prominent approach towards establishing causal claims in medicine, namely, the Evidence-Based Medicine (EBM) approach. Secondly, I provide an overview of further recent work in the philosophy of medicine, which argues that mechanistic studies can help to address these problems. Lastly, I describe a novel approach for establishing causal claims in medicine that has been informed by this recent work in the philosophy of medicine, namely, the EBM+ approach.

Usefulness of pancreatic stone protein measurement to screen and diagnose sepsis in the context of the Surviving Sepsis Campaign recommendations.

Sepsis occurs yearly in 48.9 million people worldwide of whom 11 million will die. Sepsis is defined as a life-threatening dysregulated reaction of the body in response to a bacterial infection, leading to organ dysfunction. The Surviving Sepsis Campaign (SSC) made numerous recommendations for sepsis diagnosis and treatment using an evidence-based medicine approach. Frequently, levels of evidence of these recommendations are poor and lack clear clinical guidance. Interestingly, the SSC guidelines strongly recommend, with a moderate quality of evidence, screening of nosocomial sepsis in acutely ill hospitalized “high-risk patients”. The definition of acutely ill and high-risk patients is not specified, nor it is indicated which tools should be used. The diagnosis of infection and the subsequent administration of antibiotics relies solely on rapid clinical assessment, as recommended by the Best Practice Statement. Again, the elements used for clinical assessment are poorly defined, encompassing patient history, clinical examination, and tests for both infectious and non-infectious causes of acute illness. In the real world, only 30 to 40% of empiric broad-spectrum antibiotic administrations are appropriate, contributing to the emergence of antimicrobial resistant bacteria, toxicity related to antibiotic administration, and costs. The aim of this review article is to show that the use of biomarkers, such as the Pancreatic Stone Protein (PSP) as an example, helps in guiding the clinician to diagnose and manage sepsis. Over 600 peer-reviewed publications have studied the physiology of PSP and more than 50 evaluated its usefulness to screen for the development of nosocomial sepsis and diagnose sepsis.

Analysis of traditional physical therapy programs in treating stage 2-3 coxarthrosis using evidence-based medicine approaches

Analysis of traditional physical therapy programs in treating stage 2-3 coxarthrosis using evidence-based medicine approaches

Soy beverages and women's health: evidence review and experts opinion

Soy drinks are an increasingly consumed option within the Western diet. However, there are concerns about potential endocrine disruptor effects and possible impact on women's reproductive health. This review evaluates scientific documents in gynecology and obstetrics under an evidence-based medicine approach. All methods adhered to PRISMA 2020 declaration guidelines. The evaluated studies do not support a positive association between soy intake and early puberty or breast cancer; instead, a protective effect against such neoplasm was observed. Transplacental passage of soy isoflavones and their presence in breast milk has been reported without any maternal-fetal complications nor congenital malformations. Exposure to soy-derived products appears to have a neutral effect on body weight and bone health. Studies performed in adults indicate that soy may promote a minimal increase in thyrotropin (TSH) in subjects with subclinical hypothyroidism. The impact of soy-based foods on gut microbiota appears favorable, especially when consuming fermented products. Many of the human studies have been conducted with isoflavones supplements, isolated or textured soy proteins. Therefore, the results and conclusions should be interpreted cautiously, as these are not entirely applicable to commercial soy beverages.

Integrative Approaches to the Treatment of Cancer.

A significant proportion of cancer patients use forms of complementary medicine or therapies. An integrative approach to cancer management combines conventional medicine with evidence-based complementary medicines/therapies and lifestyle interventions, for the treatment and prevention of disease and the optimisation of health. Its basis is a holistic one; to treat the whole person, not just the disease. It makes use of adjunct technologies which may assist the clinician in diagnosis of early carcinogenesis and monitoring of treatment effectiveness. Many factors contribute to the development of cancer including some which are largely modifiable by the patient and which oncologists may be in a position to advise on, such as stress, poor nutrition, lack of physical activity, poor sleep, and Vitamin D deficiency. An integrative approach to addressing these factors may contribute to better overall health of the patient and better outcomes. Evidence-based complementary medicine approaches include the use of supplements, herbal medicine, various practices that reduce stress, and physical therapies. Individualised to the patient, these can also help address the symptoms and signs associated with cancer and its orthodox treatment.

Decision Support Tools in Medicine: Evidence-Based Medicine Approach in Tamale Teaching Hospital

Objective: To determine whether laboratory results match the preliminary diagnosis, using a model of malaria diagnosis by clinical staff at Tamale Teaching Hospital (TTH), Ghana.Methods: Data of outpatients diagnosed with malaria in 2012 were collected retrospectively from clinical notes. Data of the clinicians who provided the preliminary diagnoses were collected by self-reporting questionnaire. Statistical analyses were performed with Epi-Info and SPSS software.Results: A total of 344 patients were diagnosed with malaria in 2012, consisting of 186 females and 158 males. The age ranges between one month and 80 years. Forty-four clinicians responded to the questionnaire, consisting of 12 females and 32 males with mean ± SD age of 40.2±10.0 years. Respondents included consultants, medical officers, house officers, physician assistants, physician specialists and senior nurses, with mean ± SD years since qualification of 11.6±9.8 (range: 1-40 years). Nearly one-half (49%) of the clinicians reported not normally requesting laboratory investigations for suspected cases of malaria, thus not following an evidence-based approach for preliminary diagnosis. Slightly over onehalf (51%) of the preliminary diagnoses of malaria in suspected cases were incorrect. However, statistical assessment of the clinician’s preliminary diagnosis and the results from laboratory tests for malaria parasites showed a correlation (p=0.6548 at 95% CI).Conclusion: Practice of evidence-based medicine and establishment of a technology-based healthcare system can lead to decrease incorrect diagnoses and inappropriate health care management

No service is an island: towards an ecosystem approach to mental health service evaluation.

No service is an island: towards an ecosystem approach to mental health service evaluation.

COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes.

SUMMARYConvalescent plasma (CP) recurs as a frontline treatment in epidemics because it is available as soon as there are survivors. The COVID-19 pandemic represented the first large-scale opportunity to shed light on the mechanisms of action, safety, and efficacy of CP using modern evidence-based medicine approaches. Studies ranging from observational case series to randomized controlled trials (RCTs) have reported highly variable efficacy results for COVID-19 CP (CCP), resulting in uncertainty. We analyzed variables associated with efficacy, such as clinical settings, disease severity, CCP SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antibody levels and function, dose, timing of administration (variously defined as time from onset of symptoms, molecular diagnosis, diagnosis of pneumonia, or hospitalization, or by serostatus), outcomes (defined as hospitalization, requirement for ventilation, clinical improvement, or mortality), CCP provenance and time for collection, and criteria for efficacy. The conflicting trial results, along with both recent WHO guidelines discouraging CCP usage and the recent expansion of the FDA emergency use authorization (EUA) to include outpatient use of CCP, create confusion for both clinicians and patients about the appropriate use of CCP. A review of 30 available RCTs demonstrated that signals of efficacy (including reductions in mortality) were more likely if the CCP neutralizing titer was >160 and the time to randomization was less than 9 days. The emergence of the Omicron variant also reminds us of the benefits of polyclonal antibody therapies, especially as a bridge to the development and availability of more specific therapies.