MIH-Affected Substrate: An Overview of Adhesive Challenges to the Dental Structures.

Based on the current state of the art regarding molar incisor hypomineralisation (MIH)-affected enamel, bonding systems are expected to play a relevant role on the restorative procedures when required. MIH-affected enamel is often subjected to posteruptive breakdown combined or not with carious lesions, predominantly on molars, and may also affect the aesthetics of anterior teeth. As unbalanced mineral and protein contents occur, understanding these alterations is essential before selecting the most appropriate adhesive systems, while bearing in mind their limitations. In particular, when dentin is involved due to enamel breakdown, the use of functional monomer-based bonding systems present in self-etching and universal systems produce a chemical interaction that enhance the bonding. So far, the overall recommendation relies on placing the margin of the restoration on clinically sound enamel, regardless of the category of the adhesive system.

Factors influencing food-related quality of life in patients with inflammatory bowel disease: A systematic review.

BACKGROUND: People diagnosed with Inflammatory bowel disease (IBD) often have severe dietary restrictions and avoidance due to the uncertainty of intestinal symptoms. Inadequate dietary intake may increase the risk of malnutrition and result in impaired food-related quality of life (FRQoL). Few studies investigated factors influencing FRQoL in patients with IBD. This study aimed to synthesize the existing evidence regarding FRQoL among patients with IBD, including the current situation, measurement instruments, and related influencing factors. METHOD: The comprehensive literature search was conducted in databases including PubMed, Embase, CINAHL, PsycInfo, Cochrane Library, as well as the most commonly used Chinese databases (CNKI, Wanfang and CBM). Studies published between January 2015 and December 2023 on FRQoL in patients with IBD were included. The Joanna Briggs Institute (JBI) critical appraisal checklist was utilized to evaluate the methodological quality of the selected studies. RESULTS: Finally, only five studies met the inclusion criteria were reviewed, including three cross-sectional studies and two case-control studies. The Food-related quality of life-29 Scale (FR-QoL-29) with a total core of 145 was the most used instrument measuring FRQoL in patients with IBD. The mean scores of FRQoL ranged from 69.9 to 102.3 in adult patients with IBD and 94.3 in children. A diverse range of factors were associated with FRQoL, including socio-demographic, clinical, psychological, diet-related, and nutrient intake factors. CONCLUSIONS: The main influencing factors of FRQoL among patients with IBD included disease activity status, severe symptoms, history of IBD surgery, negative emotion reaction, and restrictive eating behaviour. Clinicians should work in concert with dietitians, keeping an eye on the disease status, nutrition intake, and restrictive eating habits, assessing FRQoL and providing personalized dietary recommendation for the patients with IBD.

From the kitchen to the medicine cabinet: Examples of functional herbs and spices.

In many cultures, "food as medicine" has existed for centuries as the foundation of health. It is a practice built on the knowledge that food and diet play important roles in disease prevention and management. Foods possessing therapeutic properties are often referred to as functional foods. Many herbs and spices contain numerous nutritional and non-nutritional components that can interact with pharmacologically relevant receptors, either directly or indirectly via their metabolites, to regulate cellular biochemical processes. Although opinions are changing, the concept of food as a therapeutic intervention goes against conventional Western medicine. To provide guidance to clinicians interested in using these products, members of the Food as Medicine working group of the Nutrition Committee NASPGHAN, as part of a two-part review series, have identified frequently used foods, supplements, herbs, and spices that are utilized for therapeutic intent and have created summaries of commonly used indications, doses, and caveats. In this review, the focus is the use of select herbs and spices for medicinal purposes. Gaps in our knowledge in how to effectively use these agents in pediatric patients are discussed. Evidence supporting their use for management of gastrointestinal conditions, especially in the pediatric population, is provided when available. Circumstances in clinical settings and patient indications may require actions different from those recommended in this review and professional judgment should prevail.

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Brazilian undergraduates' and dentists' knowledge on preventing, diagnosing and managing dentin hypersensitivity: A cross-sectional questionnaire study.

OBJECTIVES: To analyse the knowledge of dental undergraduates and dentists on the prevention, diagnosis and management of dentin hypersensitivity (DH); to compare their knowledge scores; and to understand the related variables using a regression model. METHODS: An original online questionnaire investigated the attitudes, self-reported knowledge ('how much they thought they knew') and real knowledge ('how much they really knew') of 132 students and 338 dentists. Data were analysed descriptively, both knowledge scores were compared using Mann-Whitney and Wilcoxon signed-rank tests and data were subjected to two multiple linear regression analyses considering real knowledge scores as the dependent variable (α < 0.05). RESULTS: The self-reported knowledge on DH was higher than the real knowledge for both students and dentists, but dentists presented the highest scores. Gingival recession and acidic diet were reported as the main predisposing factors for DH by undergraduates and dentists. Students normally managed DH with dietary and hygiene instructions followed by a desensitizing agent application, while dentists managed with occlusal adjustments. The mechanism of glutaraldehyde/HEMA and bioactive fillers on DH is widely unknown by students and dentists. The majority of the questioned individuals cannot differentiate DH from sensitivity of caries or molar-incisor hypomineralization. CONCLUSION: Both students and dentists overestimate their knowledge of DH, revealing deficiencies in prevention, diagnosis and management. Students' knowledge improves towards the end of the Dentistry course, while younger dentists and PhD holders are more knowledgeable. Institutions should implement ongoing DH education for undergraduates and conduct interventions for experienced professionals, especially older ones.

Practical training using BEWE aimed at improving the diagnosis ability of erosive tooth wear for dental students-A randomized trial.

INTRODUCTION: Erosive tooth wear (ETW) has been gaining attention due to its high prevalence. However, ETW clinical diagnosis is difficult and may go unnoticed by many professionals. The present study aimed to develop, implement and evaluate a theoretical-practical training using active methodologies in the development of undergraduate students' skills for the diagnosis of ETW compared to the traditional teaching method. MATERIALS AND METHODS: This randomized controlled study involved two parallel groups: control group (n = 22), with learning based only on theoretical content and test group (n = 24), learning by theoretical-practical activity mediated by monitors/tutors. The theoretical class covered the current concepts of ETW, aetiology, diagnosis, use of the BEWE index, prevention and treatment. The practical training included exercises and discussions based on the diagnosis using BEWE scores of a collection of images and extracted teeth. To evaluate the efficacy of the teaching-learning methods, a theoretical multiple-choice questionnaire and a practical test using images and extracted teeth were applied. The outcome was the number of correct answers. Groups were compared by Mann-Whitney (theoretical knowledge) and T tests (practical ability in diagnosis) (p < .05). RESULTS: There was no significant difference between groups in the theoretical evaluation (p = .866). The test group showed higher ability to diagnose ETW lesions compared to the control group in the practical tests (p = .001). The performance of ETW diagnosis was similar when images were used in comparison to extracted teeth (p = .570). CONCLUSION: The practical activity associated with theoretical classes can be a promising strategy to improve the development of undergraduate students' skills in the diagnosis of ETW.

Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura.

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) results from severe hereditary deficiency of ADAMTS13. The efficacy and safety of recombinant ADAMTS13 and standard therapy (plasma-derived products) administered as routine prophylaxis or on-demand treatment in patients with congenital TTP is not known. METHODS: In this phase 3, open-label, crossover trial, we randomly assigned patients in a 1:1 ratio to two 6-month periods of prophylaxis with recombinant ADAMTS13 (40 IU per kilogram of body weight, administered intravenously) or standard therapy, followed by the alternate treatment; thereafter, all the patients received recombinant ADAMTS13 for an additional 6 months. The trigger for this interim analysis was trial completion by at least 30 patients. The primary outcome was acute TTP events. Manifestations of TTP, safety, and pharmacokinetics were assessed. Patients who had an acute TTP event could receive on-demand treatment. RESULTS: A total of 48 patients underwent randomization; 32 completed the trial. No acute TTP event occurred during prophylaxis with recombinant ADAMTS13, whereas 1 patient had an acute TTP event during prophylaxis with standard therapy (mean annualized event rate, 0.05). Thrombocytopenia was the most frequent TTP manifestation (annualized event rate, 0.74 with recombinant ADAMTS13 and 1.73 with standard therapy). Adverse events occurred in 71% of the patients with recombinant ADAMTS13 and in 84% with standard therapy. Adverse events that were considered by investigators to be related to the trial drug occurred in 9% of the patients with recombinant ADAMTS13 and in 48% with standard therapy. Trial-drug interruption or discontinuation due to adverse events occurred in no patients with recombinant ADAMTS13 and in 8 patients with standard therapy. No neutralizing antibodies developed during recombinant ADAMTS13 treatment. The mean maximum ADAMTS13 activity after recombinant ADAMTS13 treatment was 101%, as compared with 19% after standard therapy. CONCLUSIONS: During prophylaxis with recombinant ADAMTS13 in patients with congenital TTP, ADAMTS13 activity reached approximately 100% of normal levels, adverse events were generally mild or moderate in severity, and TTP events and manifestations were rare. (Funded by Takeda Development Center Americas and Baxalta Innovations; ClinicalTrials.gov number, NCT03393975.).

Are S-PRG composites able to resist against erosive and abrasive challenges and protect surrounding enamel in situ?

OBJECTIVES: This study evaluated the resistance of S-PRG (Surface Pre-Reacted Glass-ionomer) composites and other restorative materials against erosive and abrasive challenges and their protective effect on enamel adjacent to the restorations. MATERIALS AND METHODS: Bovine enamel blocks were prepared and randomized into 12 groups, including 6 types of material, each of them subjected to erosion_e or erosion+abrasion_ea: Beautifil II (S-PRG); Beautifil Bulk Restorative (S-PRG); Filtek Z250 XT; Filtek Bulk Fill; EQUIA Forte; Riva Light Cure. Cavities were prepared in the middle of enamel blocks and restored with the materials. Initial profiling measurement was performed on the material and on adjacent enamel (100, 200, 300, 600 and 700 µm from the restoration margin). Palatal intraoral appliances with the restored enamel blocks were used by the volunteers (n = 10). During 5 days appliances were immersed in 2.5 % citric acid for 2 min; 6 × /day (erosion_e). For ea condition, blocks were brushed for 1 min after each acid immersion. Final profile assessment was performed. Data were analysed by two and three way ANOVA followed by Tukey's test (p < 0.05). RESULTS: Material wear: Riva Light Cure showed the highest wear followed by EQUIA Forte and then all resin composites, including the ones with S-PRG (p = 0.000). Enamel wear: there was significant interaction among type of restorative material, wear condition and distance (p = 0.014), enamel around materials showed similar wear (p = 0.983) and the enamel subjected to ea exhibited highest wear (p = 0.000). CONCLUSION: SPRG based composites showed resistance against erosive and abrasive challenges but were not able to protect enamel adjacent to the restorations. CLINICAL SIGNIFICANCE: S-PRG composites exhibit resistance to material wear comparable to resin composites. However, they have shown an inability to effectively protect the adjacent enamel under in situ erosive-abrasive conditions, despite the presence of mineral-loss-preventing ions surrounding materials.

Awake intraoperative mapping for the prevention of amusia.

The authors describe the awake surgical mapping of music skills for patients who require resection in brain areas that may support musical abilities. A 65-year-old man was diagnosed with an anterolateral right temporal nonenhancing lesion, likely a diffusely infiltrating glioma, after presenting with several episodes of altered taste and smell and one episode of loss of consciousness. The patient specializes in music and music technology and has composed scores for films. An awake surgery was planned in a semiseated position. Prerecorded melodies were designed preoperatively as a surrogate for a composition skill task. These consisted of 10- to 15-second musical clips played during bipolar electrical stimulation of the overlying cortex and were divided into three segments: listen, play, and accuracy check. During the "listen" phase, the patient listened to a musical prompt. During the "play" phase, he played a musical response on a keyboard. Stimulation at multiple temporal neocortical sites was negative for any alteration in task performance. The patient did well postoperatively with excellent clinical and radiographic results and returned to composing music without functional compromise. Musical composition tasks can be performed safely intraoperatively for patients with musical expertise. Whether stimulating more posterior nondominant temporal neocortex or other cortical or white matter locations can disrupt this task remains undetermined.

Analysis of color stability and degree of conversion of different types of resin composites.

Resin composites containing surface pre-reacted glass (S-PRG) have been introduced to reduce demineralization and improve remineralization of the tooth structure. However, water diffusion within the material is necessary for its action, which can impair its overall physicomechanical properties over time, including color stability. This study aimed to evaluate the color stability and related degree of conversion (DC) of four resin composites. Discs (6 x 4 mm, n = 5/group) of microhybrid (MH), nanofilled (NF), nanohybrid (NH), and S-PRG-based nanohybrid (S-PRG-NH) composites with two opacities (A2/A2E and A2O/A2D) were prepared. Color (CIELab and CIEDE2000) was evaluated with a spectrophotometer after aging in grape juice (2 x 10 min/10mL/7days). The DC was analyzed by using Fourier transform infrared spectroscopy before and after light-curing. Data were statistically analyzed by using two-way analysis of variance and post-hoc least significant difference tests (p<0.05). In the color stability analysis, the interaction between filler type and opacity was significant (CIELab, p = 0.0015; CIEDE2000, p = 0.0026). NH presented the highest color stability, which did not differ from that of MH. The greatest color alteration was observed for S-PRG-NH. S-PRG fillers also influenced DC (p < 0.05). The nanohybrid resin composite presented favorable overall performance, which is likely related to its more stable organic content. Notwithstanding the benefits of using S-PRG-based nanohybrid resins, mostly in aesthetic procedures, professionals should consider the susceptibility of such resins to color alteration, probably due to the water-based bioactive mechanism of action.

Association between cooking patterns and the prevalence of hyperlipidemia in Eastern China.

BACKGROUND: Hyperlipidemia is a major risk factor for many diseases. Previous studies have shown that diet is closely associated with hyperlipidemia. However, the relationship between cooking methods and hyperlipidemia remains unclear. The objective of this study was to identify the major cooking patterns existing in the Eastern Chinese population and evaluate their association with the prevalence of hyperlipidemia. METHODS: We interviewed 4,710 residents in Eastern China regarding the consumption frequency of each cooking method when they prepare food at home or when eating out and regarding the prevalence of hyperlipidemia. Factor analysis, Chi-square tests, analysis of variance, and binary logistic regression analysis were used to identify the cooking patterns and analyze the characteristics of participants' categories of cooking patterns and the relationship between different cooking patterns and prevalence of hyperlipidemia. RESULTS: Three major cooking patterns were identified: Traditional Chinese, Bland (little or no oil is used to process the food), and High-temperature cooking patterns. After controlling for potential confounders, participants in the highest quartile of the Bland cooking pattern had lower odds of hyperlipidemia than those in the lowest quartile. Nevertheless, no significant associations were observed between the Traditional Chinese and High-temperature cooking patterns and the prevalence of hyperlipidemia. CONCLUSIONS: This study confirms the association between cooking patterns and the prevalence of hyperlipidemia and indicates that the Bland cooking pattern is associated with a reduced prevalence of hyperlipidemia.

A balancing act: drifting away from the reflexive use of "ab"normal saline.

Maintenance intravenous fluids are the most frequently ordered medications for hospitalized children. Since the American Association of Pediatrics published national guidelines, there has been an increased reflexive use of isotonic solutions, especially 0.9% saline, as a prophylaxis against hyponatremia. In this educational review, we discuss the potential deleterious effects of using 0.9% saline, including the development of hyperchloremia, metabolic acidosis, acute kidney injury, hyperkalemia, and a proinflammatory state. Balanced solutions with anion buffers cause relatively minimal harm when used in most children. While the literature supporting one fluid choice over the other is variable, we highlight the benefits of balanced solutions over saline and the importance of prescribing fluid therapy that is individualized for each patient.

Synthesis of α-sulfenylated carbonyl compounds under metal-free conditions.

An efficient synthesis of α-sulfenylated carbonyl compounds from propargylic alcohols and aryl thiols under heating conditions is described. The method is characterized by mild conditions, simple operation, metal-free catalysis and good functional group tolerance. Mechanistic studies suggest that the reaction involves a radical pathway and an isomerization process.

Analysis of color stability and degree of conversion of different types of resin composites

Abstract Resin composites containing surface pre-reacted glass (S-PRG) have been introduced to reduce demineralization and improve remineralization of the tooth structure. However, water diffusion within the material is necessary for its action, which can impair its overall physicomechanical properties over time, including color stability. This study aimed to evaluate the color stability and related degree of conversion (DC) of four resin composites. Discs (6 x 4 mm, n = 5/group) of microhybrid (MH), nanofilled (NF), nanohybrid (NH), and S-PRG-based nanohybrid (S-PRG-NH) composites with two opacities (A2/A2E and A2O/A2D) were prepared. Color (CIELab and CIEDE2000) was evaluated with a spectrophotometer after aging in grape juice (2 x 10 min/10mL/7days). The DC was analyzed by using Fourier transform infrared spectroscopy before and after light-curing. Data were statistically analyzed by using two-way analysis of variance and post-hoc least significant difference tests (p<0.05). In the color stability analysis, the interaction between filler type and opacity was significant (CIELab, p = 0.0015; CIEDE2000, p = 0.0026). NH presented the highest color stability, which did not differ from that of MH. The greatest color alteration was observed for S-PRG-NH. S-PRG fillers also influenced DC (p < 0.05). The nanohybrid resin composite presented favorable overall performance, which is likely related to its more stable organic content. Notwithstanding the benefits of using S-PRG-based nanohybrid resins, mostly in aesthetic procedures, professionals should consider the susceptibility of such resins to color alteration, probably due to the water-based bioactive mechanism of action.

Consensus for teaching dental caries in the Portuguese Language at Brazilian dental schools.

The aim of this paper was to present a summary of the process of developing and preparing the final documents of the national consensus for teaching undergraduate Brazilian dental students the dental caries curriculum in the Portuguese language. The final document was developed in three steps: a) The ABENO and LAOHA cariology group invited experts from all five regions of Brazil to participate in the discussion. The theoretical support for crafting the first draft of the consensus was based on two publications: National Curriculum Guidelines of the Dentistry graduation in Brazil, Ministry of Education (2021) and the competences described in the European Core Curriculum for Cariology (ORCA-ADEE, 2011); b) The group of experts was divided into 5 working groups: G1-Domain, Main and Specific Competences, G2-Essential knowledge, G3-Life course perspective, G4-Social determinants and dental caries, G5- Glossary. The document was finalized by thoroughly reviewing the process using Delphi methodology; c) The 5-chapter document (one from each working group) was submitted to three open public consultations in 2022 (May-June, August, and October) using Google-forms. The suggestions (content/wording) were discussed within the group as: totally accepted, partially accepted, and rejected. A total of 192 suggestions were registered from 31 dental schools in all regions of Brazil. The number of suggestions received per Group were: 84, 28, 26, 24, 30 suggestions for G1, G2, G3, G4 and G5, respectively. The majority of suggestions were totally accepted by the group of experts (n = 172, 89.6%), 15 were partially accepted (7.8%), and 5 were rejected. Conclusion The final document could be considered to be the first national consensus for teaching the dental caries curriculum in Brazil.

Guardianship: The Implications of Resident Physician Perceptions of Caring for Incapacitated Older Adults Without Advocates.

As the incidence of dementia rises, increased utilization of surrogate decision-makers, including legal guardians, is anticipated. This manuscript presents an analysis of resident physicians' experiences and perceptions regarding requirements, roles, and responsibilities of caring for older adults in need of, or already under, legal guardianship. This is a cross-sectional study, conducted at a tertiary academic medical center. A survey was sent, via Qualtrics, to all emergency medicine, family medicine, internal medicine, general surgery, and medicine-pediatric resident physicians. Eighty-eight out of three hundred thirty-three (26.4%) eligible residents physicians completed the survey. Most (98.9%) reported caring for patients under guardianship, yet many resident physicians reported significant uncertainty regarding the roles and responsibilities of guardianship, including its potential benefits and limitations. They also displayed misconceptions and overconfidence about guardians' abilities to facilitate disposition, ensure financial security, and assign code status, among other matters. Our study highlights the importance of structured and directed education on the topic of guardianship for medical trainees.

Patients' perspectives on marijuana use for inflammatory bowel disease: a multicenter survey.

Background: As marijuana use is rising among patients with inflammatory bowel disease (IBD), so is interest in its potential use as a therapeutic agent. We sought to survey IBD patients regarding marijuana use, self-reported impact on IBD symptoms, and perceptions of safety. Methods: A multicenter anonymous survey was administered to patients with IBD between October 2020 and June 2021. The 70-question survey collected demographic variables, clinical variables, attitudes about marijuana, and perceptions of its safety and efficacy in IBD. Participants were classified by their marijuana use: "rarely/never," "current," and "former". Percentage and chi-square tests were used to compare categorical variables between the 3 groups, and means and 2-group ANOVA were used for continuous variables. Results: Of 181 patients surveyed, 166 were eligible for the study. Of these, 70 (42.2%) participants were rare/never marijuana users, 44 (26.5%) were current users, and 52 (31.3%) were former users. Fifty-three percent thought marijuana would help with IBD inflammation and 80% thought it would help with IBD pain. Over 70% of patients from all groups thought marijuana had a low-to-moderate risk of harm, and 69.6% of the participants who never or rarely used marijuana thought marijuana was addictive, compared to 20.5% of the current users and 44% of the former marijuana users. Conclusions: While many patients thought marijuana use helps with IBD-related pain and inflammation, many expressed concerns about addiction to marijuana and a possible risk of harm. Further studies are needed to examine the benefit and harm of marijuana in IBD.

The introduction of clozapine at the Nathan Kline Institute in New York and its long-term consequences.

Nathan S. Kline was a pioneer in psychopharmacology in the United States (US). In 1952, Kline started a research unit at Rockland State Hospital, New York. Kline brought clozapine from Switzerland since it was not yet available in the US. At Rockland State Hospital, George Simpson had conducted antipsychotic trials and had developed scales to assess movement disorders. In 1974, Simpson published the first US clozapine trial. In 1978, he published on 1) the effect of clozapine on tardive dyskinesia and 2) high plasma clozapine concentrations in two patients with seizures. His experience of clozapine withdrawal symptoms in his first 2 trials led in the future to more articles in this area. In Philadelphia, Simpson designed a double-blind randomized clinical trial (RCT) with 3 doses (100, 300 and 600 mg/day) which was published in 1999. From the 50 patients started on the RCT, 47 provided repeated plasma clozapine concentrations every other week of the RCT. This rich database of plasma clozapine concentrations under controlled conditions has contributed to many of the advances in clozapine pharmacokinetics in the last 5 years including: 1) obesity can be associated with clozapine poor metabolism (PM) status, 2) a clozapine ultrarapid metabolizer (UM) with a minimum therapeutic dose of 1591 mg/day, 3) a case of clozapine intoxication dropped from the RCT due to pneumonia, 4) cases of increased plasma concentrations during clozapine-induced fever, 5) the possibility that African-Americans may need higher clozapine doses than those of European ancestry, and 6) three indices of non-adherence.

Malignant Glioma.

This chapter provides a comprehensive overview of malignant gliomas, the most common primary brain tumor in adults. These tumors are varied in their cellular origin, genetic profile, and morphology under the microscope, but together they share some of the most dismal prognoses of all neoplasms in the body. Although there is currently no cure for malignant glioma, persistent efforts to improve outcomes in patients with these tumors have led to modest increases in survival, and researchers worldwide continue to strive toward a deeper understanding of the factors that influence glioma development and response to treatment. In addition to well-established epidemiology, clinical manifestations, and common histopathologic and radiologic features of malignant gliomas, this section considers recent advances in molecular biology that have led to a more nuanced understanding of the genetic changes that characterize the different types of malignant glioma, as well as their implications for treatment. Beyond the traditional classification of malignant gliomas based on histopathological features, this chapter incorporates the World Health Organization's 2016 criteria for the classification of brain tumors, with special focus on disease-defining genetic alterations and newly established subcategories of malignant glioma that were previously unidentifiable based on microscopic examination alone. Traditional therapeutic modalities that form the cornerstone of treatment for malignant glioma, such as aggressive surgical resection followed by adjuvant chemotherapy and radiation therapy, and the studies that support their efficacy are reviewed in detail. This provides a foundation for additional discussion of novel therapeutic methods such as immunotherapy and convection-enhanced delivery, as well as new techniques for enhancing extent of resection such as fluorescence-guided surgery.