Effective Evidence-based Treatment Research Articles

The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline.

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.

Determination of inflammatory mediator levels in cerebrospinal fluid during the formation of cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage

Introduction. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CV) lead to poor outcomes in patients after aneurysmal subarachnoid hemorrhage (aSAH). The pathophysiology of these complications is not fully understood, preventing the adoption of a single definition. Reliable diagnostic tests and effective evidence-based treatment are lacking. Objective: to determine the relationship between the concentration of interleukin-6 (IL-6), IL-10, IL-17, tumor necrosis factor-α (TNF-α) in cerebrospinal fluid and formation of delayed complications of subarachnoid hemorrhage. Materials and methods. The study involved 45 patients with aSAH who were treated in Kharkiv Regional Hospital (18 men and 27 women aged 32 to 73 years (mean age ‒ 45.9±8.5 years). The control group consisted of 20 healthy individuals (8 men and 12 women aged from 32 to 73 years (mean age - 59.2±10.6 years). The occurrence of DCI or CV was recorded. The level of IL-6, IL-10, IL-17 and TNF-α in the cerebrospinal fluid (CSF) was measured in all subjects of the study using enzyme-linked immunosorbent assay. Results. Levels of IL-6, TNF-α, IL-17, and IL-10 in the CSF of patients with aSAH were higher than in control subjects. In patients with CV, the values of IL-6, IL-17 and TNF-α in CSF exceeded those of patients without CV. The concentration of IL-6 and TNF-α was also increased in the cerebrospinal fluid of patients with DCI. Conclusions. The obtained results indicate that IL-6 and TNF-α in CSF may be early markers for predicting vasospasm and DCI on the 3rd day after subarachnoid hemorrhage before clinical onset. The content of IL-17 correlates with the formation of cerebral vasospasm, but there is no connection between its level in the CSF and DCI. The concentration of IL-10 in the CSF on the 3rd day after aSAH had no prognostic value either for CV or for DCI formation.

EMPOWERING ADULTS SEEKING RECOVERY FROM SUBSTANCE AND OPIOID USE DISORDER IN THE DEEP SOUTH

Abstract Substance and opioid use disorder may be missed due to lack of consideration of physical, social, and emotional changes in midlife and later adulthood. This presentation uses data from a Graduate Psychology Education grant to examine predictors of alcohol use and misuse among treatment-seeking and primary care patients. Across three sites, 237 individuals completed behavioral health assessments; a rural (n = 54) and an urban federally qualified health center (n = 59), and a state-certified residential rehabilitation facility (n = 124). Participants ranged from 18 to 70 years of age (M = 40.05, SD = 1.75). Approximately 49.4% were female and 72.2% were non-Hispanic White, 23.3% African American, and 4.6% other. More than 28% of individuals had less than a high school education, and 38.4% reported a high school education or GED. Using the TAPS-II, 34.2% of participants reported alcohol use, and 13.5% reported prescription opioid misuse. Logistic regression analyses revealed that older age, prescription opioid misuse, and depression were significantly associated with alcohol use, χ2 (7) = 18.04, p = 0.12, while gender, report of adverse childhood experiences, and anxiety were not. Holding age, gender, and experiences constant, prescription opioid misuse had a significant effect on the probability of alcohol use, B = 1.092, SE = .429; Wald = 6.496, p = 0.01. The odds of alcohol use increased by a factor of 2.98 for individuals misusing prescription opioids. Treatment for problematic alcohol use must consider contextual influences including age, prescription opioids, and depression to implement effective evidence-based treatment.

Diagnosis and Treatment of Early-Stage Testicular Cancer: AUA Guideline Amendment 2023.

The purpose of this American Urological Association (AUA) guideline amendment is to provide a useful reference on the effective evidence-based treatment strategies for early-stage testicular cancer. The original methodology protocol included searches of PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 through August 2018. The search strategy used medical subject heading (MeSH) terms and key words relevant to the diagnosis and treatment of early-stage testicular cancer. The searches conducted for the update presented herein utilized the same methodological protocol to capture literature published through March 2023. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. Updates were made to statements on imaging, seminoma management, non-seminoma management, surveillance for stage I testicular cancer, and additional survivorship. Further revisions were made to the methodology and reference sections as appropriate. This guideline seeks to improve clinicians' ability to evaluate and treat patients with early-stage testicular cancer based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Home treatment as an add-on to family-based treatment for adolescents with anorexia nervosa compared with standard family-based treatment and home-based stress reduction training: study protocol for a randomized clinical trial

BackgroundFamily-based treatment (FBT) is currently the most effective evidence-based treatment approach for adolescents with anorexia nervosa (AN). Home treatment (HT) as an add-on to FBT (FBT-HT) has been shown to be acceptable, feasible and effective. The described three-arm randomized clinical trial (RCT) is intended to investigate whether FBT-HT demonstrates higher efficacy compared to standard outpatient FBT with supplemental mindfulness-based stress reduction training (FBT-MBSR).MethodsThis RCT compares FBT-HT to standard outpatient FBT and FBT-MBSR as a credible home-based control group in terms of efficacy and delivery. Adolescents with AN or atypical AN disorder (n = 90) and their parent(s)/caregiver(s) are to be randomly assigned to either FBT, FBT-HT or FBT-MBSR groups. Eating disorder diagnosis and symptomatology are to be assessed by eating disorder professionals using standardized questionnaires and diagnostic instruments (Eating Disorder Examination, Eating Disorder Inventory, Body Mass Index). In addition, parents and caregivers independently provide information on eating behavior, intrafamily communication, stress experience and weight. The therapeutic process of the three treatments is to be measured and assessed among both participants and care providers. The feasibility, acceptability and appropriateness can thus also be evaluated.DiscussionWe hypothesize that FBT-HT will be an acceptable, appropriate and feasible intervention and, importantly, will outperform both established FBT and FBT-MBSR in improving adolescent weight and negative eating habits. Secondary outcome measures include the reduction in the stress experienced by caregivers, as well as the regulation of perceived expressed emotions within the family, while the intrafamily relationships are hypothesized to mediate/moderate the effectiveness of FBT. The proposed study has the potential to enhance the scientific and clinical understanding of the efficacy of FBT for AN, including whether the addition of HT to FBT versus another home-based adjunct intervention improves treatment outcomes. Furthermore, the study aligns with public health priorities to optimize the outcomes of evidence-based treatments and integrate the community setting.Trial registration This study is registered at ClinicalTrials.gov (NCT05418075).

Development and feasibility testing of an integrated PTSD and adherence intervention cognitive processing therapy-life steps (CPT-L) to improve HIV outcomes: Trial protocol

Despite high rates of Post-Traumatic Stress Disorder (PTSD) in persons living with HIV (PLWH) and poor HIV-related health outcomes associated with PTSD, an effective evidence-based treatment for PTSD symptoms in PLWH does not exist. Negative reinforcement conceptual models posit that avoidant behavior (hallmark symptom of PTSD) demonstrated by PLWH with co-occurring PTSD can contribute to poor antiretroviral therapy (ART) adherence. However, research evaluating the impact of evidence-based treatment for PTSD among HIV infected populations on HIV outcomes is scarce. The Cognitive Processing Therapy (CPT) protocol is an evidence-based PTSD treatment that may address internalized stigma with targeted modifications and improve ART adherence and subsequent viral suppression through reduction of avoidant coping. This study will be the first pilot open-label randomized control trial (RCT) to test feasibility of an integrated evidence-based PTSD treatment (CPT) with an adherence intervention (Lifesteps) delivered in a Ryan White clinic to improve PTSD symptoms, adherence to ART, and retention in HIV care. Primary aims are to (1) conduct theater testing of the CPT and Lifesteps research protocol and evaluate acceptability (n = 12) and (2) deliver a modified CPT protocol (CPT-Lifesteps, or CPT-L) in 60 PLWH/PTSD exploring impact of CPT-L on PTSD symptoms and HIV outcomes compared to a Lifesteps + Standard of Care condition. This innovative research extends PTSD treatment approaches as a paradigm to reduce barriers to ART adherence. Findings of this innovative study are significant because they support the Undetectable = Untransmittable (UU) campaign and can help prevent the transmission of HIV infection through increased viral suppression.

Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder

Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects. To determine the effect of a pharmacologically conditioned open-label placebo (C-OLP) on 90-day methadone dose, retention, drug use, withdrawal, craving, quality of life, and sleep. This 2-arm, open-label, single-blind randomized clinical trial was conducted between December 5, 2017, and August 2, 2019, in an academically affiliated community opioid treatment program. Analyses were conducted between October 1, 2019, and April 30, 2020. A total of 320 newly enrolled adults seeking treatment for moderate to severe OUD were assessed for study eligibility; 131 met eligibility criteria, provided informed consent, and were randomized to either C-OLP or treatment as usual (TAU) in an unequal-block (3:2) manner. Exclusion criteria were pregnancy, hospital/program transfers, and court-ordered treatment. Participants randomized to C-OLP received pharmacologic conditioning and a placebo pill and methadone, and participants randomized to TAU were given methadone only. Participants met with the study team 5 times: at baseline (treatment intake) and 2, 4, 8, and 12 weeks postbaseline. Interactions were balanced between the 2 groups. Outcomes included 90-day methadone dose (primary) and treatment retention, drug use, withdrawal, craving, quality of life, and sleep quality (secondary). Analyses were conducted as intention-to-treat. Of the 131 people enrolled in the study, 54 were randomized to TAU and 77 to C-OLP. Mean (SD) age was 45.9 (11.2) years; most of the participants were Black or African American (83 [63.4%]) and male (84 [64.1%]). No significant group differences were observed in the mean (SD) 90-day methadone dose (83.1 [25.1] mg for group TAU, 79.4 [19.6] mg for group C-OLP; t = 0.621991; P = .43), but the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP (χ21 = 4.356; P = .04; number needed to treat for the beneficial outcome of 3-month treatment retention, 6; 95% CI, 4-119). C-OLP participants also reported significantly better sleep quality. In this randomized clinical trial, C-OLP had no effect on the primary outcome of 90-day methadone dose. However, C-OLP participants were significantly more likely to remain in treatment. These findings support the use of C-OLP as a methadone treatment adjunct, but larger trials are needed to further examine the use of C-OLP. ClinicalTrials.gov Identifier: NCT02941809.

The Prognostic Value of Eryptosis Parameters in the Cerebrospinal Fluid for Cerebral Vasospasm and Delayed Cerebral Ischemia Formation

Delayed cerebral ischemia (DCI) and cerebral vasospasm (VS) contribute to poor outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). The pathophysiology of DCI is not fully understood, and this has hindered the adoption of a uniform definition. Reliable diagnostic tests and effective evidence-based treatment are lacking. This study explored the possibility of using eryptosis parameters in the cerebrospinal fluid (CSF) as a marker for early detection of VS and DCI. Twenty-one SAH patients were recruited and treated at Kharkiv Regional Hospital. The occurrence of DCI and VS was also recorded. Flow cytometry was used to assess eryptosis indices in the CSF by analyzing phosphatidylserine externalization in erythrocytes using annexin V staining and evaluating reactive oxygen species (ROS) generation using 2,7-dichlorodihydrofluorescein diacetate (DCF) staining. The percentage of annexin-positive red blood cells (RBCs) in the VS group was significantly higher than that in the non-vasospasm group (p = 0.0017). Furthermore, higher values of this index were significantly associated with DCI formation (p < 0.0001). Patients with VS had higher mean fluorescence intensity (MFI) values of DCF in RBCs compared to patients without VS (p = 0.0258). Patients with DCI also had higher MFI values of DCF in RBCs (p = 0.0282). A higher percentage of annexin-positive RBCs following 3 days of aSAH was correlated with poor 3-month neurological outcomes (r = 0.7). Our findings indicate a strong correlation between eryptosis level and DCI in a sizable series of patients with aSAH. Correlations between eryptosis indicators in the CSF and clinical and radiological manifestations suggest that eryptosis parameters are promising diagnostic biomarkers for DCI.

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine's wide-ranging superior efficacy - for treatment-resistant schizophrenia (TRS) and beyond - and make its safe use eminently feasible. Converging evidence indicates that TRS constitutes a distinct albeit heterogeneous subgroup of schizophrenias primarily responsive to clozapine. Most importantly, the predominantly early onset of treatment resistance and the considerable decline in response rates associated with its delayed initiation make clozapine an essential treatment option throughout the course of illness, beginning with the first psychotic episode. To maximize patients' benefits, systematic early recognition efforts based on stringent use of TRS criteria, a timely offer of clozapine, thorough side-effect screening and management as well as consistent use of therapeutic drug monitoring and established augmentation strategies for suboptimal responders are crucial. To minimize permanent all-cause discontinuation, re-challenges after neutropenia or myocarditis should be considered. Owing to clozapine's unique efficacy, comorbid conditions including substance use and most somatic disorders should not dissuade but rather encourage clinicians to consider clozapine. Moreover, treatment decisions need to be informed by the late onset of clozapine's full effects, which for reduced suicidality and mortality rates may not even be readily apparent. Overall, the singular extent of its efficacy combined with the high level of patient satisfaction continues to distinguish clozapine from all other available antipsychotics.

Craniomaxillofacial trauma in war-torn nations: Incidence, management gaps, and recommendations.

Craniomaxillofacial trauma (CMFT) is a type of injury that affects the face, neck, and scalp, and includes facial bone fractures, dentoalveolar trauma, and soft tissue injuries. Work, traffic accidents, sports, and daily activities commonly cause these injuries. However, they are widespread in war-torn countries where armed conflict leads to a high incidence of CMFT. The lack of resources, health care infrastructure, and surgical personnel in these areas result in subpar treatment and poor patient outcomes, contributing to the high mortality and morbidity rates among war victims. The importance of a multidisciplinary approach to CMFT management cannot be overstated, but current obstacles, such as a lack of access to proper medical care and rehabilitation services, impede the development of effective treatments. CMFT treatment is complex and prohibitively expensive for war-torn nations to afford, necessitating international intervention to provide life-saving surgical procedures for those suffering from CMFT in conflict zones. Despite efforts to improve CMFT treatments in war-torn countries, more must be done to improve treatment outcomes. Data collection and research must also be improved in order to develop effective evidence-based treatment methods.

Macrophage colony-stimulating factor potentially induces recruitment and maturation of macrophages in recurrent pituitary neuroendocrine tumors.

Although pituitary neuroendocrine tumors (PitNETs) are usually benign, some are highly invasive and recurrent. Recurrent PitNETs are often treatment-resistant and there is currently no effective evidence-based treatment. Tumor-associated macrophages (TAMs) promote tumor growth in many cancers, but the effect of TAMs on PitNETs remains unclear. This study investigated the role of TAMs in the incidence of recurrent PitNETs. Immunohistochemical analysis revealed that the densities of CD163- and CD204-positive TAMs tended to increase in recurrent PitNETs. Compared with TAMs in primary lesions, those in recurrent lesions were enlarged. To clarify the cell-cell interactions between TAMs and PitNETs, in vitro experiments were performed using a mouse PitNET cell line AtT20 and the mouse macrophage cell line J774. Several cytokines related to macrophage chemotaxis and differentiation, such as M-CSF, were elevated significantly by stimulation with macrophage conditioned medium. When M-CSF immunohistochemistry analysis was performed using human PitNET samples, M-CSF expression increased significantly in recurrent lesions compared with primary lesions. Although no M-CSF receptor (M-CSFR) expression was observed in tumor cells of primary and recurrent PitNETs, flow cytometric analysis revealed that the mouse PitNET cell line expressed M-CSFR. Cellular proliferation in mouse PitNETs was inhibited by high concentrations of M-CSFR inhibitors, suggesting that cell-to-cell communication between PitNETs and macrophages induces M-CSF expression, which in turn enhances TAM chemotaxis and maturation in the tumor microenvironment. Blocking the M-CSFR signaling pathway might be a novel therapeutic adjuvant in treating recurrent PitNETs.

The inter-relationship between various non-motor symptoms and with habitual physical activity in Parkinsonism: a scoping review protocol

Background Over 90% of individuals with neurodegenerative Parkinsonism present with non-motor symptoms (NMS), which have a significantly negative impact on their quality of life (QoL) more so than motor symptoms. Currently, NMS remain under-appreciated and under-researched compared to motor symptoms. This contributes to a limited understanding of the inter-relationship between various NMS (i.e. symptom-to-symptom interaction) and the scarcity of effective evidence-based treatment strategies. Physical activity (PA) and exercise are promising therapeutic options, but many people with Parkinsonism are inactive. Currently, there appears to be a limited understanding of the relationship between PA and NMS in this population. Objective This proposed review aims to explore and synthesise what is currently known about (1) the inter-relationship between various NMS and (2) their relationship with habitual PA among adults with neurodegenerative Parkinsonism. This review will also highlight potential research gaps in the literature. Methods Two independent scoping reviews will be completed to address the two distinct objectives. The reviews will follow recommended methodological and reporting guidelines. Conclusion Understanding the inter-relationship between various NMS and their relationship with PA behaviour might help guide which NMS to target therapeutically and help develop effective evidence-based PA recommendations that are feasible for people with neurodegenerative Parkinsonism.

Cognitive Processing Therapy Delivered in 5 Days via Telehealth to a Gay Latino Adolescent: A Clinical Case Study

Cognitive Processing Therapy (CPT) has been thoroughly investigated as an efficacious treatment for posttraumatic stress disorder (PTSD). However, for many, the barriers to receiving treatment in the traditional weekly, in-person format prevent engagement. Recent evidence suggests alternative modalities, such as telehealth, and condensed administration of treatment protocols may reduce barriers, increasing treatment completion. This case study reports the treatment of a gay-identifying adolescent Latino male who received 10 sessions of CPT over the course of 5 consecutive days (CPT-5). The patient experienced significant reduction in PTSD symptoms over the course of treatment, dropping below the clinical threshold for PTSD diagnosis by the 10th session. Treatment gains were maintained, and continued, 6 weeks posttreatment. Further, the patient reported marked reduction in suicidality and substance use. In conclusion, the administration of CPT-5 via telehealth holds promise as an effective evidence-based treatment for adolescents with PTSD, including those holding multiple historically marginalized identities, though further investigation through clinical trials is warranted.

Shifting Paradigms in the Pathophysiology and Treatment of Carcinoid Crisis.

Carcinoid crisis is a potentially fatal condition characterized by various symptoms, including hemodynamic instability, flushing, and diarrhea. The incidence of carcinoid crisis is unknown, in part due to inconsistency in definitions across studies. Triggers of carcinoid crisis include general anesthesia and surgical procedures, but drug-induced and spontaneous cases have also been reported. Patients with neuroendocrine tumors (NETs) and carcinoid syndrome are at risk for carcinoid crisis. The pathophysiology of carcinoid crisis has been attributed to secretion of bioactive substances, such as serotonin, histamine, bradykinin, and kallikrein by NETs. The somatostatin analog octreotide has been considered the standard of care for carcinoid crisis due to its inhibitory effect on hormone release and relatively fast resolution of carcinoid crisis symptoms in several case studies. However, octreotide's efficacy in the treatment of carcinoid crisis has been questioned. This is due to a lack of a common definition for carcinoid crisis, the heterogeneity in clinical presentation, the paucity of prospective studies assessing octreotide efficacy in carcinoid crisis, and the lack of understanding of the pathophysiology of carcinoid crisis. These issues challenge the classical physiologic model of carcinoid crisis and its common etiology with carcinoid syndrome and raise questions regarding the utility of somatostatin analogs in its treatment. As surgical procedures and invasive liver-directed therapies remain important treatment modalities in patients with NETs, the pathophysiology of carcinoid crisis, potential benefits of octreotide, and efficacy of alternative treatment modalities must be studied prospectively to develop an effective evidence-based treatment strategy for carcinoid crisis.

Large practice variations in diagnosis and treatment of delayed cerebral ischemia after subarachnoid hemorrhage

Delayed cerebral ischemia (DCI) contributes to poor outcomes after subarachnoid hemorrhage (SAH). The pathophysiology of DCI is not fully understood, which has hindered the adoption of a uniform definition. Furthermore, a reliable diagnostic test and an effective evidence-based treatment are lacking. This could lead to variations in care. A web-based survey on the variations in the definition, diagnosis, and treatment of DCI was designed and sent to 314 intensivists, neurologists, and neurosurgeons of all 9 hospitals in the Netherlands who care for patients with SAH. The responders were categorized into physicians responsible for the coordination of SAH care and those who were not. For questions on the definition and diagnosis, only the responses from the coordinating physicians were evaluated. For the treatment questions, all the responses were evaluated. The response rate was 34% (106 of 314). All 9 hospitals were represented. Of the responses, 27 did not provide answers for the definition, diagnosis, or treatment questions; 79 responses were used for analysis. Signs of vasospasm were required by 21 of the 47 coordinating physicians (44%) when considering DCI. Of the 47 coordinating physicians, 24 (51%) did not use a diagnostic test results for a positive diagnosis of DCI. When patients were discharged within 21 days, 33 of the 73 responders (45%) did not provide a prescription for nimodipine continuation. Finally, all but one hospital had treated DCI with hypertension induction. We found large variations in the definition, diagnosis, and treatment of DCI in the Netherlands. In the absence of evidence-based treatment, standardization of management seems warranted in an effort to optimize DCI care.

Thematic Analysis of Reddit Content About Buprenorphine-naloxone Using Manual Annotation and Natural Language Processing Techniques.

BackgroundOpioid use disorder (OUD) is a major public health crisis for which buprenorphine-naloxone is an effective evidence-based treatment. Analysis of Reddit data yields detailed information about firsthand experiences with buprenorphine-naloxone that has the potential to inform treatment of OUD.MethodsWe conducted a thematic analysis of posts about buprenorphine-naloxone from a Reddit forum in which Reddit users anonymously discuss topics related to opioid use. We used an application programming interface to retrieve posts about buprenorphine-naloxone, then applied natural language processing to generate meta-information and curate samples of salient posts. We manually categorized posts according to their content and conducted natural language processing-aided analysis of posts about buprenorphine tapering strategies, withdrawal symptoms, and adjunctive substances/behaviors useful in the tapering process.ResultsA total of 16,146 posts from 1933 redditors were retrieved from the /r/suboxone subreddit. Thematic analysis of sample posts (N = 200) revealed descriptions of personal experiences (74%), nonpersonal accounts (24%), and other content (2%). Among redditors who reported tapering to termination (N = 40), 0.063 mg and 0.125 mg were the most common termination doses. Fatigue, gastrointestinal disturbance, and mood disturbance were the most frequent adverse effects, and loperamide and vitamins/dietary supplements the most frequently discussed adverse effects adjunctive substances/behaviors respectively.ConclusionsDiscussions on Reddit are rich in information about buprenorphine-naloxone. Information derived from analysis of Reddit posts about buprenorphine-naloxone may not be available elsewhere and may help providers improve treatment of people with OUD through better understanding of the experiences of people who have used buprenorphine-naloxone.

Quality improvement project to increase screening and referral for biologic therapy for patients with uncontrolled asthma

Background Asthma is a treatable chronic disease of airway inflammation with varying levels of control and severity. Biological therapy is an effective evidence-based treatment for patients with allergic and eosinophilic phenotypes of asthma who are classified as poorly controlled moderate to severe asthma. Yet, evidence-based treatments are infrequently used to support effective care of poorly controlled moderate and severe asthma. This quality improvement (QI) project aimed to increase the number of patients with uncontrolled moderate to severe asthma at an outpatient asthma center who are screened and referred for biologic therapy when appropriate. Methods A guideline-based biologic screening protocol was implemented using plan-do-study-act (PDSA) methodology allowing for a systematic approach for implementation, monitoring and making adjustments. A pre- and post-independent groups comparative design was utilized to evaluate screening and referral data. Results Screening improved significantly from pre- (n = 30, 23.8%) to post-implementation (n = 17, 70.8%), p < 0.001; phi = .372. Referrals to biologics also improved from 42.4% (n = 28) to 93.3% (n = 14), p < 0.001; phi = .396. Providers reported increased knowledge, confidence, and satisfaction with the asthma screening protocol at post-implementation. Conclusions The implementation of an asthma screening protocol for asthma patients in an ambulatory center is an effective way of increasing screening for eligibility for biologic therapy. Adhering to the standard of care based on evidence-based guidelines increased access to biologic therapy with a higher percentage of patients being referred for therapy.

Etiology of Neuroinflammatory Pathologies in Neurodegenerative Diseases: A Treatise

Background:Conventional medical therapies for neurodegenerative diseases primarily target anti-inflammatory interventions, immune suppression of autoimmune pathologies, and, depending on the diagnosed pathological mechanisms, neurotransmitter reuptake inhibition, among other tactics. However, the incidence of neuroinflammatory pathologies appears to be progressively increasing. The National Institutes of Health, National Institute of Environmental Health Sciences in 2016, estimated that 5.4 million Americans were living with Alzheimer's. If no effective solutions are found and implemented, within 30 years of this publication, according to data from Harvard, more than 12 million Americans will suffer from neurodegenerative diseases.Methods:Rather than investigating greater etiological depth, modern medicine seems to have been designed to addressing obvious symptomologies to relieve suffering for as long as possible until neuropathological progress inevitably wins in achieving complete functional disability and death. Researchers are reporting herein evidence-based effective treatment therapies that are outside conventional medical standard of care therapies.Conclusion:These therapies are the result of a deeper exploration into etiological factors, including an expanded understanding of the role of anaerobic pathologies in the etiology of neuroinflammatory disorders and methods of reverting to a competent aerobic metabolism. Such therapies include a liquid VMP35 MNC; a greater focus on viral mechanistic pathologies and their remission; and understanding of the genetic basis for a loss of neurological interconnectivity and consequential reward deficiencies in combination with neuronutrient deficiencies, enabling neuronutrient repletion with nutrigenomic therapies such as the KB220Z.

The 15-Months Clinical Experience of SARS-CoV-2: A Literature Review of Therapies and Adjuvants.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19) that emerged in December 2019 in Wuhan, China, and rapidly spread worldwide, with a daily increase in confirmed cases and infection-related deaths. The World Health Organization declared a pandemic on the 11th of March 2020. COVID-19 presents flu-like symptoms that become severe in high-risk medically compromised subjects. The aim of this study was to perform an updated overview of the treatments and adjuvant protocols for COVID-19. Methods: A systematic literature search of databases was performed (MEDLINE PubMed, Google Scholar, UpToDate, Embase, and Web of Science) using the keywords: “COVID-19”, “2019-nCoV”, “coronavirus” and “SARS-CoV-2” (date range: 1 January 2019 to 31st October 2020), focused on clinical features and treatments. Results: The main treatments retrieved were antivirals, antimalarials, convalescent plasma, immunomodulators, corticosteroids, anticoagulants, and mesenchymal stem cells. Most of the described treatments may provide benefits to COVID-19 subjects, but no one protocol has definitively proven its efficacy. Conclusions: While many efforts are being spent worldwide in research aimed at identifying early diagnostic methods and evidence-based effective treatments, mass vaccination is thought to be the best option against this disease in the near future.

Stereotactic Radiosurgery for Intracranial Noncavernous Sinus Benign Meningioma: International Stereotactic Radiosurgery Society Systematic Review, Meta-Analysis and Practice Guideline.

BACKGROUNDStereotactic radiosurgery (SRS) for benign intracranial meningiomas is an established treatment.OBJECTIVETo summarize the literature and provide evidence-based practice guidelines on behalf of the International Stereotactic Radiosurgery Society (ISRS).METHODSArticles in English specific to SRS for benign intracranial meningioma, published from January 1964 to April 2018, were systematically reviewed. Three electronic databases, PubMed, EMBASE, and the Cochrane Central Register, were searched.RESULTSOut of the 2844 studies identified, 305 had a full text evaluation and 27 studies met the criteria to be included in this analysis. All but one were retrospective studies. The 10-yr local control (LC) rate ranged from 71% to 100%. The 10-yr progression-free-survival rate ranged from 55% to 97%. The prescription dose ranged typically between 12 and 15 Gy, delivered in a single fraction. Toxicity rate was generally low.CONCLUSIONThe current literature supporting SRS for benign intracranial meningioma lacks level I and II evidence. However, when summarizing the large number of level III studies, it is clear that SRS can be recommended as an effective evidence-based treatment option (recommendation level II) for grade 1 meningioma.