Real-world clinical management of individuals with Rett syndrome: a physician survey.

BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder. Management strategies are heterogeneous with no clear definition of success. This study describes physician decision-making regarding diagnosis, therapeutic goals, and management strategies to better understand RTT clinical management in the US. METHODS: This study was conducted among practicing physicians, specifically neurologists and pediatricians in the US with experience treating ≥2 individuals with RTT, including ≥1 individuals within the past two years. In-depth interviews with five physicians informed survey development. A cross-sectional survey was then conducted among 100 physicians. RESULTS: Neurologists had treated more individuals with RTT (median: 12 vs. 5, p < 0.001) than pediatricians throughout their career and were more likely to report being "very comfortable" managing RTT (31 vs. 4%, p < 0.001). Among physicians with experience diagnosing RTT (93%), most evaluated symptoms (91%) or used genetic testing (86%) for RTT diagnoses; neurologists used the 2010 consensus diagnostic criteria more than pediatricians (54 vs. 29%; p = 0.012). Improving the quality of life (QOL) of individuals with RTT was the most important therapeutic goal among physicians, followed by improving caregivers' QOL. Most physicians used clinical practice guidelines to monitor the progress of individuals with RTT, although neurologists relied more on clinical scales than pediatricians. Among all physicians, the most commonly treated symptoms included behavioral issues, epilepsy/seizures, and feeding issues. Management strategies varied by symptom, with referral to appropriate specialists being common across symptoms. A large proportion of physicians (37%) identified the lack of novel therapies and reliance on symptom-specific management as an unmet need. CONCLUSION: Although most physicians had experience and were comfortable diagnosing and treating individuals with RTT, better education and support among pediatricians is warranted. Additionally, novel treatments that target multiple symptoms associated with RTT could reduce the burden and improve the QOL of individuals with RTT and their caregivers.

Harnessing the Power of Precision Medicine and Novel Biomarkers to Treat Crohn's Disease.

Crohn's disease (CD) is a chronic inflammatory condition that affects the gastrointestinal tract. It is part of a spectrum of inflammatory Bowel Diseases (IBD). The disease is complex, characterized by significant inter and intra-individual heterogeneity, which contributes to a diverse and multifaceted portrayal of the disease. Consequently, applying specific and accurate treatment is challenging, and therapeutic success rates remain disappointing and insufficient. In recent years, significant advances in the therapeutic potential of CD have been made. Hope has been provided by these developments in the form of an expanding treatment toolkit. However, even with these beneficial adjustments, patients are frequently treated using an ineffective "one size fits all" treatment protocol, ultimately leading to a plateau in drug effectiveness and a decline in overall treatment success rates. Furthermore, with the advancement in the genome-wide association study, in combination with significant bioinformatic developments, the world of medicine has moved in the direction of personalized, tailored-treatment medicine, and this trend has not escaped the world of IBDs. Prediction models, novel biomarkers, and complex algorithms are emerging and inspiring optimism that CD patients will be treated with "precision medicine" in the near future, meaning that their treatments will be selected based on the patient's various unique features. In this review, we will outline the current diagnostic and therapeutic limitations that lead to a glass ceiling effect and thus send us in pursuit of discovering novel biomarkers. We will illustrate the challenges and difficulties in discovering relevant and innovative biomarkers and implementing them into everyday clinical practice. We will also heighten the progress made in practicing personalized medicine for CD patients and shed light on future directions and horizons.

Achieving long-term goals through early personalized management of schizophrenia: expert opinion on the role of a new fast-onset long-acting injectable antipsychotic.

Definition of an appropriate and personalized treatment plan focused on long-term outcomes is crucial in the management of schizophrenia. Following review of the literature, a panel of six leading psychiatrists discussed the importance of clear and shared long-term goals when initiating antipsychotic treatment in light of their clinical experience. The importance of establishing shared and progressive treatment objectives was stressed, which should be tailored based on the patient's characteristics, goals, and preferences. Consensus emerged on the key role that therapeutic alliance and patient empowerment play throughout the course of treatment. Reduction in symptoms in the acute phase along with good efficacy and tolerability in the maintenance phase emerged as essential features of a therapy that can favor achievement of long-term outcomes. Long-acting injectable (LAI) antipsychotics enhance adherence to treatment compared to oral formulations and have been shown to be effective in the maintenance phase. Currently available LAIs are characterized by a delayed onset of action and require a loading dose or oral supplementation to achieve therapeutic concentrations. Risperidone ISM® is a novel LAI antipsychotic with fast and sustained release of antipsychotic, reaching therapeutic plasma levels within a few hours after administration without oral supplementation or loading doses. Risperidone ISM® has been shown to rapidly control symptoms in patients with an acute exacerbation of schizophrenia and to be effective and well tolerated as maintenance treatment irrespective of the severity of initial symptoms. It thus represents a valuable and novel therapeutic option in management of schizophrenia.

More Than Just an Entertainment Show: Identification of Medical Clowns' Communication Skills and Therapeutic Goals.

Medical clowns (MCs) are trained professionals who aim to change the hospital environment through humor. Previous studies focused on their positive impact and began identifying their various skills in specific situations. When placed in pediatrics, MCs face various challenges, including approaching frustrated adolescents who are unwilling to cooperate with their care, dealing with their anxious parents, and communicating in a team in the presence of other health professionals. Research that systematically describes MCs' skills and therapeutic goals in meeting these challenges is limited. This article describes a qualitative, immersion/crystallization study, triangulating between 26 video-recorded simulations and 12 in-depth-semi-structured interviews with MCs. Through an iterative consensus-building process we identified 40 different skills, not limited to humor and entertainment. Four main therapeutic goals emerged: building a relationship, dealing with emotions, enhancing a sense of control, caring, and encouragement, and motivating treatment adherence. Mapping MCs' skills and goals enhances the understanding of MCs' role and actions to illustrate their unique caring practices. This clarification may help other healthcare professionals to recognize their practices and the benefits in involving them in care. Furthermore, other health professionals may apply some of the identified skills when faced with these challenges themselves.

Knowledge of the Therapeutic Goals of Diabetes Care among Patients with Type 2 Diabetes at a Tertiary Hospital in Ethiopia.

Background: A comprehensive cardiovascular risk control reduces diabetes-associated complications but achieving the triplet goals (blood glucose, blood pressure (BP), and low-density lipoprotein (LDL-C)) remains a clinical challenge. Patients' knowledge of these diabetes therapeutic goals has been shown to improve glycemic control. However, this is not well studied in Ethiopia. Methods: A cross-sectional study was conducted from March to June 2020 in Tikur Anbessa Specialized Hospital among randomly selected 419 patients with type 2 diabetes. Data was collected using a pretested, structured questionnaire. A multivariable binary logistic regression was fitted to identify determinants of knowledge. Results: The mean age (±SD) of study participants was 57.4 (±10.8) years and the median duration (IQR) of diabetes was 12 (7, 20) years. A quarter of them achieved fasting glycemic control, a fifth of them attained the A1c goal and only 3% achieved the triple targets. Patients who reported knowing their target goals for BP, fasting blood sugar (FBS), A1C, and LDL-C were 79.5, 77.3, 11.7, and 7.2% respectively. The factors associated with knowledge of the therapeutic goals were longer diabetes duration, increased household income, age, being divorced as compared to married, having no formal education, and primary education. Conclusion: The majority of participants knew their BP and FBS targets while only a minority understood their A1c and LDL-C targets. It highlighted the need for the provision of patient-centered diabetes education to improve knowledge of the therapeutic targets.

Evolving Short- and Long-Term Goals of Management of Inflammatory Bowel Diseases: Getting It Right, Making It Last.

Short- and long-term treatment targets in inflammatory bowel diseases (IBDs) evolved during the last decade, shifting from symptom control to endoscopic healing and patient-centered parameters. The STRIDE-II consensus placed these targets on a timeline from initiating treatment and introduced additional targets, normalization of serum and fecal biomarkers, restoration of quality of life, prevention of disability, and, in children, restoration of growth. Transmural healing in Crohn's disease and histologic healing in ulcerative colitis currently serve as adjunct measures to gauge remission depth. However, whether early treatment according to a treat-to-target paradigm affects the natural course of IBD remains unclear, leading to the need for prospective disease-modification trials. The SPIRIT consensus defined the targets for these trials to assess the long-term impact of early treatment on quality of life, disability, disease complications, risk of neoplastic lesions, and mortality. As further data emerge about the risk-benefit balance of aiming toward deeper healing, the targets in treating IBDs may continue to shift.

Disease clearance in ulcerative colitis: Setting the therapeutic goals for future in the treatment of ulcerative colitis.

Ulcerative colitis, one of the phenotypic patterns of inflammatory bowel disease, should be considered a progressive disease with an increased risk of complications if intestinal inflammation is not adequately controlled. The advent of new lines of treatment for this condition has changed and expanded the therapeutic goals to modify its natural history and evolution. The concept of "disease clearance" in ulcerative colitis aims to achieve clinical and biological remission as well as mucosal healing (endoscopic, histological, and in future molecular) in these patients. This review provides the available data on each of the goals of disease clearance in ulcerative colitis to be considered for application in clinical practice in the coming years.

Nursing workload. Calculation of cardiovascular risk and therapeutic objectives. / Carga de enfermedad. Cálculo del riesgo cardiovascular y objetivos terapéuticos.

Therapeutic intervention should be determined by the risk of developing atheromatous cardiovascular disease (CVD). The higher the risk, the more intense the action should be. This is the reason for the stratification of patient risk. In primary prevention, the two main guidelines used, the American Heart Association and the American College of Cardiology (ACC/AHA) use the Pooled cohort equations (PCE) and the guidelines of the European societies use the SCORE tables. The PCE calculates the risk of fatal and non-fatal CVD, and the SCORE calculates risk of fatal CVD only. In young people, it is useful to consider the lifetime risk calculation. The Spanish Society of Arteriosclerosis (SEA) recommends the SCORE system in Spain. SCORE and PCE calculate the risk for people up to 70 and 75 years of age. Prediction and potentials are available for 80 years of age and above, with the data available being much more scarce. Risk stratification in secondary prevention may be useful to identify the subgroup of patients who may benefit from more intensive treatment. Imaging tests, especially coronary calcium scans and vascular ultrasound, can help to better the profile risk. European guidelines identify LDL cholesterol as a therapeutic target. They recommend initiating treatment with statins, and increasing dose and potency until targets are achieved, and then to treatment with potent statins at a maximum tolerated dose, and ezetimibe if targets are not achieved. As a third step, PCSK9 inhibitors are indicated. They set very ambitious targets, as low as 40 mg/dL in those subjects with recurrences before two years of CVD despite high-intensity statin therapy, and below 55 mg/dL for all very high-risk subjects.

Functional Communication Profiles of Children and Youth with Autism: A Roadmap to Therapeutic and Educational Interventions.

BACKGROUND: Autism spectrum disorder (ASD) entails varied developmental pathways along the entire lifespan, demanding early and ongoing diverse and responsive interventions to children's needs. This study examined in situ education and development attained by children and youth with ASD in a school with a therapeutic and educational curriculum. OBJECTIVES: (1) Construct individual communication profiles in educational and developmental aspects. (2) Examine for associations between variables. (3) Demonstrate the clinical and educational utility of including cognitive-linguistic integrative variables. (4) Showcase how the profiles guide interventions tailored to students' individual needs. METHODS: Functional communication profiles (FCPs) of 21 students, aged 5.0-16.8 years, mostly from bilingual middle-high socioeconomic status families, were constructed with input from their educational and therapeutic staff. Students' performance was examined with an array of instruments and tasks, including person and clock drawings, false belief, and bouba-kiki metaphor screens. Qualitative and quantitative analyses were performed to uncover associations, weaknesses, and strengths. RESULTS: The profiles revealed associations between cognitive, linguistic, social, and educational abilities, indicating that some abilities from different domains tend to co-occur. CONCLUSIONS: Including cognitive linguistic integrative variables was a novelty that revealed additional aspects of the children's abilities. Staff feedback confirmed the utility of FCPs in providing "a roadmap" to needed individual and common curriculum adjustments.

Do NSAIDs Take Us Away From Treatment Goals in Axial Spondyloarthritis: A Story About Dysbiosis or Just a Matter of Bias?

Non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of treatment for spondyloarthritides (SpA), a group of entities with common clinical and pathophysiological aspects, but also with differential features. Although NSAIDs provide significant symptomatic relief, especially for joint pain and morning stiffness, their role in achieving and maintaining the treatment goals advocated by the treat to target strategy in SpA is not entirely clear. These agents can induce changes in the composition of the intestinal microbiota, also favoring an alteration of the barrier function in the gut epithelium. All of this, favored by a pre-disposing genetic background, could activate a specific type of aberrant immune response in the gut lamina propria, also known as type-3 immunity. This article offers a perspective on how NSAIDs, despite their undeniable value in the short-term SpA treatment, could hinder the achievement of medium and long-term treatment goals by compromising the barrier function of the gut mucosa and potentially altering the composition of the gut microbiota.

To whom recommend intensive treatment for hypertension?

Arterial hypertension is the main identifiable cardiovascular risk factor, and although the benefit of blood pressure reduction is universally acknowledged, the scientific community has long been divided over the therapeutic blood pressure targets to be reached, also considering the estimated overall cardiovascular risk and the presence of individual risk factors and associated comorbidities. During the last few years, numerous clinical studies and meta-analyses, in particular, the SPRINT study, have been published, demonstrating the advantages of an intensive antihypertensive treatment, over a target blood pressure value (<140/90 mmHg), in the reduction of major cardiovascular events, myocardial infarction, stroke, heart failure, and all-causes cardiovascular mortality. Stemming from these results the major International Guidelines revisited the therapeutic objectives, recommending blood pressure value <130/80 mmHg for the vast majority of hypertensive patients until the age of 65 and suggesting a reduction of the target also in the elderly. Numerous studies and meta-analyses demonstrated that the reduction of the risk of coronary or cerebral events, and of all-causes cardiovascular mortality, is independent from the baseline value of blood pressure and the individual estimated risk. It has been also demonstrated that an early institution of antihypertensive treatment is associated with a faster realization of the recommended targets, and consequent significant benefits in terms of reduction of the incidence of myocardial infarction, heart failure, and major cardiovascular events, particularly when blood pressure control is achieved during the first 6 months of treatment, and even better during first 3 months. Other studies outlined that combination therapy with two or more drugs, mainly in a single pill configuration, are superior in reaching the recommended therapeutic targets. This is the reason why this strategy is strongly supported by the European Society of Cardiology/European Society of Hypertension (ESC/ESH) 2018 Guidelines, specifically the use of renin-angiotensin-aldosterone system inhibitors [angiotensin-converting enzyme (ACE) inhibitors and Sartans], in combination with calcium antagonist and/or thiazide diuretics, with the option to add antagonist of mineralcorticoid receptors, when an adequate blood pressure control has not been reached, or other classes of drugs, such as beta-blockers, when specific clinical indications are present, first and foremost ischaemic cardiomyopathy or heart failure. The newly proposed therapeutic goals are particularly important in high-risk patients, such as patients with previous cardiovascular events, diabetes mellitus, renal insufficiency, and patients older than 65 years of age.

Combination therapy in the treatment of hypertension.

Hypertension is a major preventable risk factor for atherosclerosis and ischemic heart disease. Although modern and effective antihypertensive drugs are available, most patients remain with a suboptimal blood pressure control. Most hypertensive patients will need a combination of antihypertensive agents to achieve the therapeutic goals - recent guidelines recommend initiating treatment with two drugs in those patients with a systolic blood pressure >20 mmHg and/or a diastolic blood pressure >10 mmHg above the goals, and in those patients with high cardiovascular risk. In addition, approximately 25% of patients will require three antihypertensive agents to achieve the therapeutic targets. In this review, we analyse the latest information available regarding the treatment of hypertension with combination therapy.

Risk Factor Profiles Achieved with Medical Therapy in Prevalent Patients with Pulmonary Arterial and Distal Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: The latest pulmonary hypertension (PH) guidelines define therapeutic goals in terms of symptoms, exercise capacity, and haemodynamics for patients with pulmonary arterial hypertension (PAH) and recommend advanced combined medical therapy. For inoperable or post-surgical residual distal chronic thromboembolic PH (CTEPH) medical treatment is similarly advised. OBJECTIVES: We analysed whether risk factor goals are achieved and combination therapy is used in prevalent patients with PAH or distal CTEPH. METHODS: PAH or distal CTEPH patients who were seen at the University Hospital Zurich during the last year were analysed in terms of demography, clinical data, medication, and therapeutic goals. Achievement of therapeutic goals was defined as New York Heart Association (NYHA) class ≤II, N-terminal pro-brain natriuretic peptide (NTpro-BNP) < 300 ng/L, and 6-min walking distance (6MWD) > 440 m. RESULTS: A total of 108 PAH patients (age 59 ± 18 years, 62% female, 64% idiopathic, 36% associated) and 38 distal CTEPH patients (age 69 ± 14 years, 55% female) were included. They had been diagnosed on average 66 ± 48 months (±SD) previously. The percentage of PAH/CTEPH patients with NYHA ≤II was 52/53, respectfully, the percentage of those with NTproBNP < 300 ng/L was 61/52, and with 6MWD > 440 m 63/50. Overall, 33/31% fulfilled 3 and 29/35% fulfilled 2 of these goals. Regarding therapy, 43% of PAH patients were on double and 10% on triple combination therapy, whereas 16% of distal CTEPH patients were on double and 3% on triple combination therapy. CONCLUSIONS: In this real-life cohort of prevalent patients with PAH or distal CTEPH, targeted drug therapy resulted in an achievement of ≥2/3 predefined therapeutic goals in 2/3 of patients. Patients with PAH were more likely to receive combination therapy compared to CTEPH patients.

The relationship between patients' knowledge of diabetes therapeutic goals and self-management behaviour, including adherence.

Background The Middle East region has one the highest prevalence rates of diabetes in the world. Little is known about the determinants of adherence and the role of knowledge in diabetes self-management within these populations. Objective To investigate the relationship between patients knowledge of diabetes therapeutic targets with adherence to self-care measures in a sample of patients with type 2 diabetes in Kuwait. Setting Primary care chronic care clinics within the Ministry of Health of Kuwait. Methods A cross sectional survey was carried out with 238 patients from six clinics. A multistage stratified clustered sampling method was used to first randomly select the clinics and the patients. MAIN OUTCOME MEASURE: Self-reported adherence to three behaviours: medication taking, diet and physical activity. Results Respondents were able to correctly report a mean (SD) of 1.6 (1.3) out of 5 of the pre-specified treatment targets. Optimal adherence to physical activity, diet and medications was reported in 25, 33 and 47 % of the study cohort, respectively. A structural equation model analysis showed better knowledge of therapeutic goals and own current levels translated into better adherence to medications, diet and physical activity. Conclusion Knowledge of therapeutic goals and own recent levels is associated with adherence to medications, diet, or physical activity in this Kuwaiti cohort of patients with diabetes. Low adherence to self-care management and poor overall knowledge of diabetes is a big challenge to successful diabetes care in Kuwait.

Imiglucerase in the management of Gaucher disease type 1: an evidence-based review of its place in therapy.

INTRODUCTION: Gaucher disease is the first lysosomal disease to benefit from enzyme replacement therapy, thus serving as model for numerous other lysosomal diseases. Alglucerase was the first glucocerebrosidase purified from placental extracts, and this was then replaced by imiglucerase - a Chinese hamster ovary cell-derived glucocerebrosidase. AIM: The aim was to review the evidence underlying the use of imiglucerase in Gaucher disease type 1. EVIDENCE REVIEW: Data from clinical trials and Gaucher Registries were analyzed. CONCLUSION: Imiglucerase has been prescribed and found to have an excellent efficacy and safety profile. We report herein the evidence-based data published for 26 years justifying the use of imiglucerase.

Patients with type 1 Gaucher disease in Spain: A cross-sectional evaluation of health status.

A multicentre, cross-sectional epidemiological survey was conducted to describe the health status of patients with type 1 Gaucher disease (GD1) in Spain. Patient data were collected retrospectively from clinical records. Therapeutic goals for seven clinical parameters were chosen as primary outcome measures. 108 GD1 patients (mean age 44.8 years; 53% male) were recruited from 28 hospitals. Ninety-five patients (88%) were receiving treatment for GD1. Hemoglobin concentration was the therapeutic goal with the highest level of achievement, being met by 105 of 108 patients (97%), followed by the goals for liver volume (86/98 patients; 88%), spleen volume (67/77 patients; 87%) and platelet count (81/108 patients; 75%). The goal for bone mineral density (BMD) was met by 48 of 75 patients (64%), and the goal for quality of life was met by 65 of 103 patients (63%). Bone pain was the parameter with the lowest level of achievement (goal met by 50/94 patients; 53%). The clinical information most often missing from patient records was the BMD Z-score (missing for 31% of patients). These data suggest that most Spanish GD1 patients have good control over hematological and visceral parameters, but there is a need to improve monitoring and treatment of GD-related bone disease.

New drugs and patient-centred end-points in old age: setting the wheels in motion.

Older patients with various degrees of frailty and disability, a key population target of pharmacological interventions in acute and chronic disease states, are virtually neglected in pre-marketing studies assessing the efficacy and safety of investigational drugs. Moreover, aggressively pursuing established therapeutic targets in old age, e.g. blood pressure, serum glucose or cholesterol concentrations, is not necessarily associated with the beneficial effects, and the acceptable safety, reported in younger patient cohorts. Measures of self-reported health and functional status might represent additional, more meaningful, therapeutic end-points in the older population, particularly in patients with significant frailty and relatively short life expectancy, e.g. in the presence of cancer and/or neurodegenerative disease conditions. Strategies enhancing early knowledge about key pharmacological characteristics of investigational drugs targeting older adults are discussed, together with the rationale for incorporating non-traditional, patient-centred, end-points in this ever-increasing group.

Current Status of Management in Type 2 Diabetes Mellitus at General Hospitals in South Korea.

BACKGROUND: In Korea, the prevalence, complications, and mortality rate of diabetes are rapidly increasing. However, investigations on the actual condition of diabetes management are very limited due to lack of nation-wide research or multicenter study. Hence, we have minutely inquired the current status of diabetes management and achievement of glucose target goal in general hospital offering education program. That way, we are able to furnish data for policy making of diabetes education and draw up guideline which may allow us to reduce the morbidity and mortality of diabetes. METHODS: The subjects consisted of 2,610 patients with type 2 diabetes who visited the 13 general hospital in Seoul or Gyeonggi region from March 19 to May 29, 2013. General characteristics, associated diseases, complications, and management status were investigated. RESULTS: The mean age was 61.0±11.6 years, body mass index was 25.0±3.3 kg/m(2), and family history of diabetes was 50.5%. The mean duration of diabetes was 10.7±7.9 years and 53% received education about diabetes. The prevalence of hypertension and dyslipidemia were 59.2% and 65.5%, respectively, and 18.3% of the subjects were accompanied by liver disease. Diabetic retinopathy appeared in 31.6%, nephropathy in 28.1%, and neuropathy in 19.9% of the subjects. The mean glycosylated hemoglobin (HbA1c) level was 7.3%±1.3% and the achieving rate based on Korean Diabetes Association guideline (HbA1c <6.5%) was 24.8%, blood pressure (130/80 mm Hg or less) was 49.4%, and low density lipoprotein cholesterol (<100 mg/dL) was 63.6%. The reaching rate to the target level in four parameters (blood glucose, blood pressure, lipids, and body weight) was 7.8%. CONCLUSION: The blood glucose control rate was lower than other parameters, and the implementation rate of diabetes education was only 53%. Thus more appropriate glucose control and systematic diabetes education are imperative.