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To examine how countries differ in attitudes to adverse drug reactions by examining published scientific papers.We searched Ovid EMBASE for publications indexed by the category′therapeutic agents′, and the subcategory′adverse effects′, by country for 43 countries.We counted 1 810 202 papers world-wide regarding therapeutic agents during 14 years, of which 195 154 (10.8%) were included in the adverse effects subcategory. There were substantial differences between countries, not explained by population, economic variation, overall publication rate on therapeutic agents, or the presence of large indigenous pharmaceutical companies.Many local cultural factors influence the ratio of papers on adverse reactions to all drug effects, so it may be difficult to improve their recognition and reporting by international efforts. [ABSTRACT FROM AUTHOR]

Comments on two research on pharmacologic therapy for prehypertension and therapeutic inertia as a barrier to blood pressure control. Blood pressure values of prehypertension; Results of the Trial of Preventing Hypertension that began in 1999; Definition of therapeutic inertia.

The article comments on the study "Prevention of Cardiovascular Events With an Antihypertensive Regimen of Amlodipine Adding Perindopril as Required Versus Atenolol Adding Bendroflumethiazide as Required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm: A Multicentre Randomised Controlled Trial," by B. Dahlof, P. S. Sever, N. R. Poulter and colleagues. It explains that the trial suggests that atenolol is not an acceptable therapy for the treatment hypertension. Further, it suggests that a strategy using a calcium channel blockers is more effective than the β-blocker atenolol. It argues that the trial was not a trial of combination agent therapy and should not be interpreted as such. It also states the blood pressure in the trial was poorly controlled.

Discusses several research on hypertension. Comments regarding the use of atenolol as a drug for hypertension; Cardiovascular benefits that can be derived from angiotensin-converting enzyme inhibit therapy by low-risk patients with coronary artery disease and preserved left ventricular function; Information on protection against fracture offered by beta blockers.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies. [ABSTRACT FROM AUTHOR]

Background: The novel proteasome inhibitor carfilzomib alone or in combination with other agents is already one of the standard therapies for relapsed and/or refractory multiple myeloma (MM) patients and produces impressive response rates in newly diagnosed MM as well. However, carfilzomib-related cardiovascular adverse events (CVAEs) - including hypertension (all grades: 12.2%; grade ≥3: 4.3%), heart failure (all grades: 4.1%; grade ≥3: 2.5%) and ischemic heart disease (all grades: 1.8%; grade ≥3: 0.8%) - may lead to treatment suspensions. At present, there are neither prospective studies nor expert consensus on the prevention, monitoring and treatment of CVAEs in myeloma patients treated with carfilzomib.Methods: An expert panel of the European Myeloma Network in collaboration with the Italian Society of Arterial Hypertension and with the endorsement of the European Hematology Association aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome and the risk-benefit ratio of diagnostic and therapeutic tools, thereby achieving myeloma response with novel combination approaches whilst preventing CVAEs.Results: Patients scheduled to receive carfilzomib need a careful cardiovascular evaluation before treatment and an accurate follow-up during treatment.Conclusions: A detailed clinical assessment before starting carfilzomib treatment is essential to identify patients at risk for CVAEs, and accurate monitoring of blood pressure and of early signs and symptoms suggestive of cardiac dysfunction remains pivotal to safely administer carfilzomib without treatment interruptions or dose reductions. [ABSTRACT FROM AUTHOR]

Background: miRNA‐based strategies have recently emerged as a promising therapeutic approach in several neurodegenerative diseases. Unregulated cation influx is implicated in several cellular mechanisms underlying neural cell death during ischemia. The brain constitutively active isoform of transient receptor potential melastatin 7 (TRPM7) represents a glutamate excitotoxicity‐independent pathway that significantly contributes to the pathological Ca2+ overload during ischemia. Aims: In the light of these premises, inhibition of TRPM7 may be a reasonable strategy to reduce ischemic injury. Since TRPM7 is a putative target of miRNA135a, the aim of the present paper was to evaluate the role played by miRNA135a in cerebral ischemia. Therefore, the specific objectives of the present paper were: (1) to evaluate miR135a expression in temporoparietal cortex of ischemic rats; (2) to investigate the effect of the intracerebroventricular (icv) infusion of miR135a on ischemic damage and neurological functions; and (3) to verify whether miR135a effects may be mediated by an alteration of TRPM7 expression. Methods: miR135a expression was evaluated by RT‐ PCR and FISH assay in temporoparietal cortex of ischemic rats. Ischemic volume and neurological functions were determined in rats subjected to transient middle cerebral artery occlusion (tMCAo) after miR135a intracerebroventricular perfusion. Target analysis was performed by Western blot. Results: Our results demonstrated that, in brain cortex, 72 h after ischemia, miR135a expression increased, while TRPM7 expression was parallelly downregulated. Interestingly, miR135a icv perfusion strongly ameliorated the ischemic damage and improved neurological functions, and downregulated TRPM7 protein levels. Conclusions: The early prevention of TRPM7 activation is protective during brain ischemia. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease occurring in adults. In the last decade, the results of a number of clinical trials based on the updated disease classification have been published. The registration of pirfenidone and nintedanib, the first two pharmacological treatment options approved for IPF, marks a new chapter in the management of patients with this disease. Other nonpharmacological treatments such as lung transplantation, rehabilitation and palliation have also been shown to be beneficial for these patients. In this review, past and present management is discussed based on a comprehensive literature search. A treatment algorithm is presented based on available evidence and our overall clinical experience. In addition, unmet needs with regard to treatment are highlighted and discussed. We describe the development of various treatment options for IPF from the first consensus to recent guidelines based on evidence from large-scale, multinational, randomized clinical trials, which have led to registration of the first drugs for IPF. [ABSTRACT FROM AUTHOR]

Trixacarus caviae is a sarcoptic mange mite infesting guinea pigs. Infestation in immunosuppressed animals produces severe dermatological problems, including alopecia, intense pruritus, hyperkeratosis and non‐dermatological issues (e.g., seizures). Treatment options are limited and include topical application of macrocyclic lactones or amitraz or injectable administration of ivermectin or doramectin. Considering the severity of the disease and the challenging treatment, the present paper aimed to determine the efficacy of oral afoxolaner in a severe case of infestation with T. caviae in a pet guinea pig. One female guinea pig was referred to the New Companion Animal Clinic due to severe dermatological problems. A clinical evaluation was done, and skin scrapings were collected and examined under the microscope. Small mites were detected and morphologically identified as T. caviae. The animal was treated with a single oral dose of 2.50 mg/kg afoxolaner, and the lesions, presence/absence of mites and intensity of pruritus were evaluated periodically until 2 months post‐treatment. A week after the medication, the lesions were milder, but pruritus was still present and was attributed to the healing process. Further examinations showed significant improvement with the complete remission of clinical signs and no mites at the microscopic examination after 4 weeks. Afoxolaner was safe and effective in this guinea pig for the treatment of T. caviae mange with no repetition needed. [ABSTRACT FROM AUTHOR]

Severe acute malnutrition (SAM) remains a major global public health problem. SAM cases are treated using ready‐to‐use therapeutic food (RUTF) at a dosage of ∼200 kcal/kg/day per the standard treatment protocol (STD). Emerging evidence on simplifications to the standard protocol, which among other adaptations, includes reducing the daily RUTF dosage, indicates that it is effective and safe for treating children with SAM. In response to a foreseen stock shortage of RUTF, the government of Afghanistan endorsed the temporary use of a modified treatment protocol in which the daily RUTF dosage was prescribed at 1000 kcal/day (irrespective of body weight) until the child achieved moderate acute malnutrition status (weight‐for‐height z‐score ≥ −3 or mid‐upper arm circumference [MUAC] ≥ 115 mm), at which point 500 kcal/day was prescribed until cured (modified treatment protocol [MTP]). In this paper, we report the results of this nonweight‐based daily RUTF dosage experience. Data of 2042 children with SAM, treated using either the STD protocol (n = 269) or the MTP protocol (n = 1773) from August 2019 to March 2021 in five provinces, were analyzed. The per‐protocol analyses confirmed noninferiority of MTP protocol when compared to STD protocol for recovery rate [93.3% vs. 90.2%; ∆ (95% confidence interval, CI) = 3.1 (−0.9; 7.2) %] and length‐of‐stay [82.6 vs. 75.6 days; ∆ (95% CI) = 6.9 (3.3; 10.5) days], considering the margin of noninferiority of −10% and +14 days, respectively. Weight gain velocity was smaller in the MTP protocol group than in the STD protocol group [3.7 (1.7) vs. 5.2 (2.9) g/kg/day; ∆ (95% CI) = −1.5 (−1.8, −1.2); p < 0.001]. The STD group had a significantly higher mean than the MTP group for absolute MUAC gain [∆ (95% CI) = 1.7 (1.0; 2.3) mm; p < 0.001] and the MUAC velocity [∆ (95% CI) = 0.29 (0.20; 0.37) mm/week; p < 0.001]. Our results confirm the noninferiority of a nonweight‐based daily dosage and support the endorsement of this modification as an alternative to the standard protocol in resource‐constrained contexts. Key messages: More evidence supporting the use of the nonweight‐based daily ready‐to‐use therapeutic food (RUTF) dosage for treating uncomplicated severe acute malnutrition (SAM), in specific contexts, is needed.Our real‐world prospective nonrandomized study showed that the fixed nonweight‐based daily RUTF dosage protocol is as effective as the standard weight‐based protocol for treating uncomplicated SAM in children <5 in the Afghanistan context.Our findings support the reflection of a nonweight‐based daily RUTF dosage in resource‐constrained contexts in national and global policies and guidelines to improve coverage of all children in need of treatment. [ABSTRACT FROM AUTHOR]

Decellularized matrices derived from diseased tissues/organs have evolved in the most recent years, providing novel research perspectives for understanding disease occurrence and progression and providing accurate pseudo models for developing new disease treatments. Although decellularized matrix maintaining the native composition, ultrastructure, and biomechanical characteristics of extracellular matrix (ECM), alongside intact and perfusable vascular compartments, facilitates the construction of bioengineered organ explants in vitro and promotes angiogenesis and tissue/organ regeneration in vivo, the availability of healthy tissues and organs for the preparation of decellularized ECM materials is limited. In this paper, we review the research advancements in decellularized diseased matrices. Considering that current research focuses on the matrices derived from cancers and fibrotic organs (mainly fibrotic kidney, lungs, and liver), the pathological characterizations and the applications of these diseased matrices are mainly discussed. Additionally, a contrastive analysis between the decellularized diseased matrices and decellularized healthy matrices, along with the development in vitro 3D models, is discussed in this paper. And last, we have provided the challenges and future directions in this review. Deep and comprehensive research on decellularized diseased tissues and organs will promote in‐depth exploration of source materials in tissue engineering field, thus providing new ideas for clinical transformation. [ABSTRACT FROM AUTHOR]

Background and Aim: The traditional drug delivery approach involves systemic administration of a drug that could be nonspecific in targeting, low on efficacy, and with severe side‐effects. To address such challenges, the field of smart drug delivery has emerged aiming at designing and developing delivery systems that can target specific cells, tissues, and organs and have minimal off‐target side‐effects. Methods: A literature search was done to collate papers and reports about the currently available various strategies for smart nano‐inspired drug delivery. The databases searched were PubMed, Scopus, and Google Scholar. Based on selection criteria, the most pertinent and recent items were included. Results: Smart drug delivery is a cutting‐edge revolutionary intervention in modern medicines to ensure effective and safe administration of therapeutics to target sites. These hold great promise for targeted and controlled delivery of therapeutic agents to improve the efficacy with reduced side‐effects as compared to the conventional drug delivery approaches. Current smart drug delivery approaches include nanoparticles, liposomes, micelles, and hydrogels, each with its own advantages and limitations. The success of these delivery systems lies in engineering and designing them, and optimizing their pharmacokinetics and pharmacodynamics properties. Conclusion: Development of drug delivery systems that can get beyond various physiological and clinical barriers, as observed in conventionally administered chemotherapeutics, has been possible through recent advancements. Using multifunctional targeting methodologies, smart drug delivery tries to localize therapy to the target location, reduces cytotoxicity, and improves the therapeutic index. Rapid advancements in research and development in smart drug delivery provide wider and more promising avenues to guarantee a better healthcare system, improve patient outcomes, and achieve higher levels of effective medical interventions like personalized medicine. [ABSTRACT FROM AUTHOR]

Aims: Understanding how much healthcare professionals (HCPs) know about medication can help in devising strategies to improve rational medication use. This study aimed to synthesize information on the level of medication knowledge of HCPs in Africa. Method: We performed a systematic literature study in Embase and PubMed. We included original studies quantifying HCPs' medication knowledge, published between 2012 and 2016. We extracted disease focus, country, number and type of HCPs included and all medication‐related knowledge questions and scored the quality of papers. The outcome measure was the percentage of HCPs who correctly answered medication knowledge questions. Results: We identified 64 studies from 12 African countries, comprising 13 911 HCPs, mostly nurses/midwifes and physicians. We extracted 306 medication‐related knowledge questions, and only 52% (SD 28) of HCPs correctly answered them. Knowledge questions were mainly about medication prescribed for communicable diseases (70%), followed by non‐communicable diseases (11%), and family planning/gynaecology (10%). Most papers concluded that there was a considerable medication knowledge gap among HCPs. Conclusion: We found a low level of medication knowledge across different disease areas, countries and HCPs. This underlines the continuous need to strengthen the undergraduate and postgraduate education in (clinical) pharmacology and therapeutics in Africa. [ABSTRACT FROM AUTHOR]

Treatment of Epilepsy with Electrical Status Epilepticus During Slow-Wave Sleep and Factors Related to the Response to Treatment.Purpose:To elucidate the effect of treatment of epilepsy with electrical status epilepticus during slow sleep (ESES) and factors related to the response to treatment.Methods:We studied 26 patients with ESES who were admitted to Okayama University Hospital (age range, 2y0m to 9y7m). Patients were treated with one or more of the following therapies: (a) high-dose valproate (VPA) therapy (plasma level,>100μg/ml), (b) a combination therapy of VPA and ethosuximide (ESM), (c) a short cycle of high-dose diazepam (DZP; 0.54–1 mg/kg/day, orally or intrarectally for 6–14 days), and (d) synthetic adrenocorticotropic hormone (ACTH) therapy (Cortrosyn-Z; 0.01–0.036 mg/kg/day, intramuscularly, for 11–43 days). Basically, we started treatment with high-dose VPA therapy. When this failed or yielded adverse side effects, we tried the combination therapy of VPA and ESM. When both were unsuccessful, we tried a short cycle of high-dose DZP or synthetic ACTH therapy. All patients were followed up for≥2 years. We also investigated response patterns to treatments and mental outcome in each patient.Results:Treatment effects: Regarding the initial effects, treatment was defined as effective when continuous spike–waves during slow-wave sleep (CSWSs) were suppressed (≥1 month with markedly decreased or no diffuse spike-waves during slow-wave sleep). In terms of initial effect, high-dose VPA was effective in 12 (50%) of 24 trials; combination therapy with VPA and ESM in six (43%) of 14 trials; a short cycle of high-dose DZP, in six (75%) of eight trials; and synthetic ACTH, in three (43%) of seven trials. However, CSWSs recurred within 1 year of treatment in two patients treated with high-dose VPA, in four treated with a short cycle of high-dose DZP, and in all three treated with synthetic ACTH. Response patterns and mental outcomes: Subjects were divided into two groups: 15 patients with favorable EEG response to the initial treatment maintained throughout the clinical course (group A), and 11 patients with no favorable EEG response to the initial treatment, or deterioration after an initial favorable response (group B). All patients except one in group A were treated with high-dose VPA or the combination therapy of VPA and ESM or both. All patients except two in group B were treated with a short cycle of high-dose DZP or synthetic ACTH after the failure of high-dose VPA or both or the combination therapy of VPA and ESM or both. Comparing these two groups, ages at onset of ESES were significantly lower in group B (p= 0.0009). Organic brain lesions such as brain malformations were seen more often in group B. Mental deterioration after the onset of ESES was observed significantly more often in group B (p= 0.037). Regarding mental outcome, patients with normal mentality or slight mental retardation predominated in group A, whereas those with severe mental retardation were found only in group B.Conclusions:Remission of ESES was achieved in approximately half of the patients treated with high-dose VPA therapy or combination therapy with VPA and ESM or both. Even when these treatments were ineffective, a short cycle of high-dose DZP or synthetic ACTH therapy was effective in most cases. However, the effects of the latter two treatments were only temporary. Group B was characterized by early-onset patients associated with organic brain lesions. These patients responded poorly to treatment and consequently had mental deterioration and poor mental outcomes. Thus response to ESES treatment may be related to the underlying organic brain lesion(s). To prevent poor mental outcome, we believe that it is critical to achieve remission as early as possible by using intensive treatment. An Investigation of Growth and Growth Disorders in School-Aged Patients with Post-West Syndrome.Purpose:To contribute to improved quality of life (QOL) for school-aged children with epilepsy, we investigated growth and growth disorders in patients with the post-West syndrome, who may be at greater risk for short stature.Methods:The 26 school-aged epilepsy patients with post-West syndrome (p-WS) were studied after informed consent was obtained from the parents. The patients consisted of seven who had cryptogenic WS[M/F= 3:4; mean age, 8 years; without cerebral palsy and nutritional problem (six of seven cases, 85.7%)] and 19 who had symptomatic WS[M/F= 11:8; mean age, 8.3 years; with cerebral palsy and required tube feeding (10 of 19 cases, 52.6%)]. The cross-sectional height SD score (HSDS), ratio of bone age to chronologic age (BA/CA), serum insulin-like growth factor (IGF-1) and other biochemical markers (serum ALP, Ca, IP, total protein and total albumin) were measured. The differences between the p-WS patients, divided into cryptogenic WS and symptomatic WS, and age-matched children with epilepsy were compared. The correlation between growth disorders and some clinical factors was investigated.Results:(a) The mean HSDS and the rate of short stature (HSDS≤−2.0 SD) in the p-WS patients were−1.89 SD (−5.94 to+0.63 SD) and 11 of 26 cases (42.3%), respectively. Obvious growth retardation without bone maturational delay (BA/CA: 0.88) was noticed in the p-WS patients compared with 56 age-matched epilepsy patients we reported previously (mean HSDS,−0.75 SD; HSDS≤−2.0 SD; 10 of 56 cases, 17.9%). Especially the symptomatic WS group showed markedly shorter stature (mean HSDS,−2.34 SD) and lower serum IGF-1 and ALP levels (mean, 110 ng/ml and 465 IU/L, respectively) compared with the cryptogenic WS group, who showed growth similar to that of age-matched epilepsy controls. (b) Markedly short stature (HSDS≤−2.0 SD) and abnormally low serum IGF-1 levels (≤−2.0 SD) were observed most frequently in the patients with cerebral palsy and feeding problems (eight of 11 cases, 72.7%, and five of 11 cases, 45.5%, respectively), followed by patients with prenatal etiology and those with poor seizure prognosis. However, the therapeutic regimens and the EEG findings showed no correlation with the growth disorders (3). Severely short stature (HSDS≤−3 SD, six of 26 cases, 23.1%) was noticed exclusively in the symptomatic WS group with cerebral palsy and feeding difficulties, as a result of an almost bedridden state and malnutrition.Conclusions:We have great concerns about the QOL of school-aged children with epilepsy and previously reported their growth and growth disorders as a part of the studies to improve their QOL. In this study, we investigated the growth in p-WS patients who may be at greater risk for short stature. Marked growth retardation was observed in the p-WS patients, especially in those with symptomatic WS, compared with age-matched controls and cryptogenic WS. Definite short stature (HSDS≤−2 SD) and low IGF-1 levels were observed mostly in patients with the complications of cerebral palsy requiring tube feeding, regardless of their EEGs and therapeutic regimens. It is particularly noteworthy that markedly short stature (HSDS≤−3 SD, six of 26, 23.1%) was observed exclusively in the symptomatic WS cases with cerebral palsy and feeding difficulties. The growth disorders may be a result of severe motor disturbances, leading to an almost bedridden state, and low IGF-1 levels may be due to malnutrition. Few reports exist of growth disorders in school-aged epilepsy patients, especially in the p-WS patients. As a base for comprehensive medicine for children with epilepsy to improve QOL, further accumulation of findings on growth and growth disorders is required. Long-Term Prognosis of Infantile Spasms (ISs): Late Relapses of Other Seizures After the Last IS.Purpose:The timing of discontinuation of drug treatment should vary with individual epileptic syndromes. Epilepsies with early onset probably deserve protracted periods of treatment (>5 years) because they are usually severe. In such cases, late relapses of other seizures are not uncommon, whereas precise studies are not known. In this study, we analyzed the long-term prognosis of infantile spasms (ISs) with special reference to late relapses.Methods:Between1969 to 2001, 52 children with ISs were treated at our facilities. Among them, 35 patients (19 boys and 16 girls) who had been followed up for>5 years were analyzed in this study. The follow-up period ranged from 5 to 33 years, with an average of 15.3 years. Adrenocorticotropic hormone (ACTH) therapy was used in 26 cases. Patients were divided into three groups according to the seizure status after the last IS; group I (G-I), eight seizure-free cases after the last IS; group II (G-II), eight cases with a seizure-free period of>5 years; and group III (G-III): 19 cases who continued to have seizures or relapsed within 5 years.Results:The classification of ISs and the mental status of 35 patients were analyzed in each group. Although the ratio of cryptogenic to symptomatic cases was the same in G-I (4:4) and G-II (4:4), G-III included many symptomatic cases (3:16). Mental status was assessed by the ratio of normal mentality/mild delay/moderate delay/severe delay. It was better in G-I (2:4:2:0) than in G-II (1:2:5:0), whereas G-III had many cases with severe mental delay (0:1:5:13). Next, we analyzed the forms of other seizures after the last IS in each group. The most common form of other seizures was partial seizures in G-II (seven of eight cases), often with secondary generalization (five of seven cases), and Lennox–Gastaut syndrome in G-III (nine of 19 cases). Then late relapses of other seizures were analyzed in G-II that had eight patients with seizure-free periods for>5 years (>10 years for five of eight patients, and 5–10 years for the remaining three). Ages at relapses after the last IS ranged from 5 years 11 months to 19 years 2 month, with an average of 11 years 11 months). The drug-free period of these eight cases ranged from 0 to 7 years, with an average of 2 years 6 months. Four patients were drug free for several years. For late relapses, focal paroxysmal discharges were found in the EEGs of seven patients. Focal discharges were most commonly found in the temporal region (five cases), followed by the frontal (one case) and the occipital region (one case). The prognosis of other seizures after a long seizure-free period was good in six cases, whereas in the other two patients, seizures were refractory to treatment. Refractory cases include cryptogenic as well as symptomatic cases.Discussion:Among 35 patients with ISs followed up for>5 years, eight (23%) cases had late relapses>5 years after the last IS. Five of eight cases had seizure-free periods of>10 years, and four cases had drug-free periods of several years. Four of eight cases were cryptogenic. From these observations, long-term follow-up is necessary, even in cryptogenic cases that have been seizure free and drug free for long periods. Other seizures that occurred after long seizure-free periods were mostly partial seizures with secondary generalization. These seizures, however, were fortunately not so therapy resistant. [ABSTRACT FROM AUTHOR]

If Parkinson's disease patients only present motorically when 50% of their dopamine cells are lost, then the condition must have been slowly evolving over 25 to 50 years. Thereafter, the pathology progresses at the rate of 1% to 2% of dopamine cells per year even though the pathological species was there from day zero- given the cells were placed into the brains of patients with moderately advanced PD. I would say this paper has fundamentally challenged the long-held view that the pathogenesis of PD is primarily a cell-autonomous process - although even at the time it was published this was being challenged both for PD and other proteinopathies of the brain. [Extracted from the article]

Progression‐free survival (PFS) is an important clinical metric for comparing and evaluating similar treatments for the same disease within oncology. After the completion of a clinical trial, a descriptive analysis of the patients' PFS is often performed post hoc using the Kaplan–Meier estimator. However, to perform predictions, more sophisticated quantitative methods are needed. Tumor growth inhibition models are commonly used to describe and predict the dynamics of preclinical and clinical tumor size data. Moreover, frameworks also exist for describing the probability of different types of events, such as tumor metastasis or patient dropout. Combining these two types of models into a so‐called joint model enables model‐based prediction of PFS. In this paper, we have constructed a joint model from clinical data comparing the efficacy of FOLFOX against FOLFOX + panitumumab in patients with metastatic colorectal cancer. The nonlinear mixed effects framework was used to quantify interindividual variability (IIV). The model describes tumor size and PFS data well, and showed good predictive capabilities using truncated as well as external data. A machine‐learning guided analysis was performed to reduce unexplained IIV by incorporating patient covariates. The model‐based approach illustrated in this paper could be useful to help design clinical trials or to determine new promising drug candidates for combination therapy trials. [ABSTRACT FROM AUTHOR]

Background: People with motor neuron disease (pwMND) are routinely offered gastrostomy feeding tube placement and (non‐invasive and invasive) ventilation to manage the functional decline associated with the disease. This study aimed to synthesise the findings from the qualitative literature to understand how individual, clinical team and organisational factors influence pwMND decisions about these interventions. Methods: The study design was guided by the enhancing transparency in reporting the synthesis of qualitative research (ENTREC) statement. The search of five bibliography databases and an extensive supplementary search strategy identified 27 papers that included qualitative accounts of pwMND, caregivers and healthcare professionals' (HCPs) experiences of making decisions about gastrostomy and ventilation. The findings from each study were included in a thematic synthesis. Findings: Making decisions about interventions is an emotional rather than simply a functional issue for pwMND. The interventions can signal an end to normality, and increasing dependence, where pwMND consider the balance between quality of life and extending survival. Interactions with multiple HCPs and caregivers can influence the process of decision‐making and the decisions made. These interactions contribute to the autonomy pwMND are able to exert during decision‐making. HCPs can both promote and threaten pwMND perceived agency over decisions through how they approach discussions about these interventions. Though there is uncertainty over the timing of interventions, pwMND who agree to interventions report reaching a tipping point where they accept the need for change. Conclusion: Discussion of gastrostomy and ventilation options generate an emotional response in pwMND. Decisions are the consequence of interactions with multiple external agents, including HCPs treading a complex ethical path when trying to improve health outcomes while respecting pwMND right to autonomy. Future decision support interventions that address the emotional response and seek to support autonomy have the potential to enable pwMND to make informed and timely decisions about gastrostomy placement and ventilation. Patient or Public Contribution: The lead author collaborated with several patient and participant involvement (PPI) groups with regards to the conceptualisation and design of this project. Decisions that have been influenced by discussions with multiple PPI panels include widening the scope of decisions about ventilation in addition to gastrostomy placement and the perceptions of all stakeholders involved (i.e., pwMND, caregivers and HCPs). [ABSTRACT FROM AUTHOR]

The article discusses the research study on the treatment options for ovarian cancer patients with ascites and suggests the development of a consensus guidelines for treating ascites.

The aptness of machine learning (ML) to learn from large datasets, discover trends, and make predictions has demonstrated its potential to metamorphose the medical field. Medical data analysis with ML algorithms can improve patient outcomes in terms of both treatment and diagnosis. This paper investigates the numerous possibilities of ML in the medical industries, including radiology, pathology, genomics, and clinical decision‐making. It also goes over the benefits and drawbacks of ML in various sectors as well as the limitations that come with its application. It illustrates the potential advantages of ML, such as better accuracy and efficiency in diagnosis and individualized treatment programs, through a review of previous studies. Lastly, it provides perspectives on prospective advancements and prospects for the discipline. This study also intends to investigate the applications of deep learning (DL) in the medical field. DL algorithms have performed exceptionally satisfactorily in several healthcare‐related fields. The main conclusions of the study are summarized, and their ramifications for the healthcare sector are discussed in this paper's conclusion. This paper intends to contribute to a greater understanding of the prevailing state of the discipline and the possibility for future developments by emphasizing the prospects of these methodologies to alter medical study and clinical practice. [ABSTRACT FROM AUTHOR]

Alzheimer's disease, often known as dementia, is a severe neurodegenerative disorder that causes irreversible memory loss by destroying brain cells. People die because there is no specific treatment for this disease. Alzheimer's is most common among seniors 65 years and older. However, the progress of this disease can be reduced if it can be diagnosed earlier. Recently, artificial intelligence has instilled hope in the diagnosis of Alzheimer's disease by performing sophisticated analyses on extensive patient datasets, enabling the identification of subtle patterns that may elude human experts. Researchers have investigated various deep learning and machine learning models to diagnose this disease at an early stage using image datasets. In this paper, a new Deep learning (DL) methodology is proposed, where MRI images are fed into the model after applying various pre‐processing techniques. The proposed Alzheimer's disease detection approach adopts transfer learning for multi‐class classification using brain MRIs. The MRI Images are classified into four categories: mild dementia (MD), moderate dementia (MOD), very mild dementia (VMD), and non‐dementia (ND). The model is implemented and extensive performance analysis is performed. The finding shows that the model obtains 97.31% accuracy. The model outperforms the state‐of‐the‐art models in terms of accuracy, precision, recall, and F‐score. [ABSTRACT FROM AUTHOR]

The article offers research news briefs for various topics including material science, biotechnology and drug discovery as of January 2015. It discusses synthesis of genetically modified (GM) bacteria that can convert glucose into methyl ketones for applications in fragrances and renewable blending agents for diesel fuels by the US Department of Energy's Joint BioEnergy Institute; and development of therapy for binge drinking, published in the periodical "Alcoholism & Drug Dependence."

Early-infantile Krabbe disease (EIKD) is an autosomal recessive, progressive, neurodegenerative disorder that usually leads to death in infancy. A study published in 2005 indicated that hematopoietic stem-cell transplantation (HSCT) was effective in the treatment for EIKD when used before the onset of symptoms. This finding suggested that newborn screening for EIKD, which would allow earlier diagnosis, might lead to earlier treatment and better outcomes. In 2006, New York was the first state to implement newborn screening for Krabbe disease; however, the results were not as good as proponents had hoped. In this paper, we present the history of efforts to diagnose and treat EIKD. Based on our findings, we question the efficacy of newborn screening for Krabbe disease. We present two arguments. First, testing itself is too imprecise. Even with the most rigorous testing standards, such as those used in New York, many of the children who are identified as being 'at risk' for EIKD remain asymptomatic. It is unclear if they will remain asymptomatic forever and, thus, whether the tests should be considered 'false positives', or whether they will eventually develop the disease. Second, we question the efficacy of early HSCT. We recommend placing a moratorium on mandatory newborn screening for EIKD. WHAT THIS PAPER ADDS: Current tests to identify which children are likely to develop Krabbe diseased are inadequate. Many children identified as being 'at risk' for early infantile Krabbe disease remain asymptomatic. Psychosine appears to be more specific than low galactosylceramidase levels for diagnosing early infantile Krabbe disease. [ABSTRACT FROM AUTHOR]

Summary: Background: Metabolic dysfunction‐associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Its prevalence is increasing with the epidemic of obesity and metabolic syndrome. MASLD progression into metabolic dysfunction‐associated steatohepatitis (MASH) and advanced fibrosis may lead to decompensated cirrhosis and development of liver‐related events, hepatocellular carcinoma and death. Monitoring disease progression is critical in decreasing morbidity, mortality, need for transplant and economic burden. Assessing for treatment response once FDA‐approved medications are available is still an unmet clinical need. Aims: To explore the most up‐to‐date literature on testing used for monitoring disease progression and treatment response Methods: We searched PubMed from inception to 15 August 2023, using the following MeSH terms: 'MASLD', 'Metabolic dysfunction‐associated steatotic liver disease', 'MASH', 'metabolic dysfunction‐associated steatohepatitis', 'Non‐Alcoholic Fatty Liver Disease', 'NAFLD', 'non‐alcoholic steatohepatitis', 'NASH', 'Biomarkers', 'clinical trial'. Articles were also identified through searches of the authors' files. The final reference list was generated based on originality and relevance to this review's broad scope, considering only papers published in English. Results: We have cited 101 references in this review detailing methods to monitor MASLD disease progression and treatment response. Conclusion: Various biomarkers can be used in different care settings to monitor disease progression. Further research is needed to validate noninvasive tests more effectively. [ABSTRACT FROM AUTHOR]

Accumulating evidence during the last two decades has addressed the potential anti‐inflammatory properties of berberine (BBR), a bioactive alkaloid compound isolated from Coptidis rhizoma, in controlling or treating several inflammatory diseases. Periodontitis is one of the most common chronic and serious inflammatory diseases, in which uncontrolled and unabated host immune responses against periodontopathic pathogens play critical and crucial roles in the disease pathogenesis. Hence, regulating inflammatory responses in periodontitis has a valuable approach and holds promise in treating periodontitis. For the first time, this paper reviews the evidence from in vitro and in vivo experimental models to explore the anti‐inflammatory effects of BBR in periodontitis and exhibits that BBR has the high potency to exert anti‐inflammatory effects by reducing expression and secretion of pro‐inflammatory mediators including TNF‐α, IL‐1β, IL‐17, RANKL, MMP‐2, MMP‐9 and MCP‐1. The BBR‐mediated anti‐inflammatory actions could translate into the inhibition of the periodontal tissues and alveolar bone destruction and the control of the disease in vivo. As the second aim of this paper, we also paid attention to the therapeutic potential of BBR in treating human diseases regarding its anti‐inflammatory properties. [ABSTRACT FROM AUTHOR]

Introduction: Substance use is an important risk factor for HIV, with both concentrated in certain vulnerable and marginalized populations. Although their management differs, there may be opportunities to integrate services for substance use and HIV. In this paper we systematically review evidence from studies that sought to integrate care for people living with HIV and substance use problems. Methods: Studies were included if they evaluated service integration for substance use and HIV. We searched multiple databases from inception until October 2015. Articles were screened independently by two reviewers and assessed for risk of bias. Results and discussion: 11,057 records were identified, with 7616 after removal of duplicates. After screening titles and abstracts, 51 met the inclusion criteria. Integration models were categorized by location (HIV, substance use and other facilities), level of integration from mirco (integrated care delivered to individuals) to macro (system level integrations) and degree of integration from least (screening and counselling only) to most (care for HIV, substance use and/or other illnesses at the same facility). Most reported descriptive or cohort studies; in four randomized control trials integrated activities improved patient outcomes. There is potential for integrating services at all facility types, including mobile health services. While services offering screening only can achieve synergies, there are benefits from delivering integrated treatment for HIV and substance use, including ease of referral to other mental health and social services. Conclusions: Our review used a wide range of databases and conference archives to increase representation of papers from low- and middle-income countries. Limitations include the overrepresentation of studies from the United States, and the descriptive nature of the majority of papers. The evidence reviewed shows that greater integration offers important benefits in both patient and service outcomes but further research and outcome reporting is needed to better understand innovative and holistic care models at the complex intersection of substance use and HIV services. [ABSTRACT FROM AUTHOR]

Rett syndrome (RTT) is an X‐linked neurogenetic disorder caused by mutations of the MECP2 (methyl‐CpG‐binding protein 2) gene. Over two decades of work established MeCP2 as a protein with pivotal roles in the regulation of the epigenome, neuronal physiology, synaptic maintenance, and behaviour. Given the genetic aetiology of RTT and the proof of concept of its reversal in a mouse model, considerable efforts have been made to design therapeutic approaches to re‐express MeCP2. By being at the forefront of the development of innovative gene therapies, research on RTT is of paramount importance for the treatment of monogenic neurological diseases. Here we discuss the recent advances and challenges of promising genetic strategies for the treatment of RTT including gene replacement therapies, gene/RNA editing strategies, and reactivation of the silenced X chromosome. What this paper adds: Recent advances shed light on the promises of gene replacement therapy with new vectors designed to control the levels of MeCP2 expression.New developments in DNA/RNA editing approaches or reactivation of the silenced X chromosome open the possibility to re‐express the native MeCP2 locus at endogenous levels.Current strategies still face limitations in transduction efficiency and future work is needed to improve brain delivery. [ABSTRACT FROM AUTHOR]

Aim: To evaluate early dystonic features in children and adolescents with SGCE‐myoclonus–dystonia. Method: In this cross‐sectional study, 49 patients (26 females and 23 males) with SGCE‐myoclonus–dystonia (aged 15y 2mo, SD 12y) with childhood‐onset (2y 10mo, SD 1y 10mo) dystonia were examined using a standardized video recorded protocol. Dystonia was rated using the Writer's Cramp and Gait Dystonia Rating Scales. Disability and impairment for handwriting and walking were also rated. Results: Dystonia was present at rest (n=1), posture (n=12), and during specific motor tasks (n=45) such as writing (n=35), walking (n=23), and running (n=20). Most children reported disability while performing these tasks. Early dystonic patterns were identified for writer's cramp and gait dystonia, the latter named the 'circular shaking leg', 'dragging leg', and 'hobby‐horse gait' patterns. Sensory tricks were used by five and eight children to improve dystonia and myoclonus during writing and walking respectively. The rating scales accurately measured the severity of action dystonia and correlated with self‐reported disability. Interpretation: Children with SGCE‐myoclonus–dystonia show recognizable dystonic patterns and sensory tricks that may lead to an early diagnosis and timely therapeutic approach. Isolated writer's cramp is a key feature in childhood and should prompt SCGE analysis. The proposed action dystonia scales could be used to monitor disease course and response to treatment. What this paper adds: Most children with SGCE‐myoclonus–dystonia got writer's cramp and had walking and running dystonia.Writer's cramp was a key feature and should prompt SGCE genetic investigation.'Circular shaking leg', 'dragging leg', and 'hobby‐horse gait' were recognized as early gait patterns.Children used sensory tricks to improve myoclonus and dystonia, suggesting common pathophysiological mechanisms.Action dystonia rating scales are valid tools to assess severity in children. [ABSTRACT FROM AUTHOR]

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Background: As part of a multifaceted approach to patient and public involvement and engagement (PPIE), alongside traditional methods, a closed Facebook group was established to facilitate PPIE feedback on various aspects of a project that used video‐recording to examine risk communication in NHS Health Checks between June 2017 and July 2019. Objective: To explore the process and impact of conducting PPIE through a closed Facebook group and to identify the associated benefits and challenges. Methods: Supported by reflections and information from project meetings used to document how this engagement informed the project, we describe the creation and maintenance of the Facebook Group and how feedback from the group members was obtained. Facebook data were used to investigate levels and types of engagement in the closed Facebook group. We reflect on the challenges of using this method of engaging the public in health research. Results: A total of 289 people joined the 'Risk Communication of Cardiovascular disease in NHS Health Checks' PPIE closed Facebook group. They provided feedback, which was used to inform aspects of the study, including participant‐facing documents, recruitment, camera position and how the methodology being used (video‐recorded Health Checks and follow‐up interviews) would be received by the public. Discussion: Using a closed Facebook group to facilitate PPIE offered a flexible approach for both researchers and participants, enabled a more inclusive method to PPIE (compared with traditional methods) and allowed rapid feedback. Challenges included maintaining the group, which was more labour intensive than anticipated and managing members' expectations. Suggestions for best practice include clear communication about the purpose of the group, assigning a group co‐ordinator to be the main point of contact for the group, and a research team who can dedicate the time necessary to maintain the group. Conclusion: The use of a closed Facebook group can facilitate effective PPIE. Its flexibility can be beneficial for researchers, patients and public who wish to engage in the research process. Dedicated time for sustained group engagement is important. Patient or Public Contribution: Patient representatives were engaged with the development of the research described in this paper and a patient representative reviewed the manuscript. [ABSTRACT FROM AUTHOR]

Haemophilia is a congenital disorder with bleeding episodes as its primary symptom. These episodes can result in negative outcomes including joint damage, loss of active days due to hospitalization and reduced quality of life. Effective treatment, however, can improve the outcome. Registries have been used as a valuable source of information regarding the monitoring of treatment and outcome. The two main aims of this exploratory study were to establish which haemophilia registries publish peer-reviewed outcome assessment research and then to extract, classify and report the treatment outcomes and their extent of use in the retrieved registries. Using relevant keywords, we searched PubMed and Web of Science databases for publications during the period 1990-2015. Retrieved references were screened in a stepwise process. Eligible papers were original full articles on haemophilia outcomes that used data from a computerized patient database. Descriptive results were summarized. Of 2352 references reviewed, 25 full texts were eligible for inclusion in the study. These papers were published by 11 registries ranging from local to international in coverage. It is still relatively rare for registries to produce peer-reviewed publications about outcomes, and most that currently do produce such papers are located in Europe and North America. More information is available on traditional outcomes such as comorbidities and arthropathy than on health-related quality of life or the social and developmental impact of haemophilia on patients. Inhibitors, HIV and viral hepatitis are amongst the most commonly reported comorbidities. Research has focused more on factor consumption and less on hospitalization or time lost at school or work due to haemophilia. Haemophilia registries, especially those at the national level, are valuable resources for the delivery of effective health care to patients. Validated outcome measurement instruments are essential for the production of reliable and accurate evidence. Finally, such evidence should be communicated to physicians, patients, the public and health policymakers. [ABSTRACT FROM AUTHOR]

Many countries have adopted new triage recommendations for use in the event that intensive care beds become scarce during the COVID‐19 pandemic. In addition to establishing the exact criteria regarding whether treatment for a newly arriving patient shows a sufficient likelihood of success, it is also necessary to ask whether patients already undergoing treatment whose prospects are low should be moved into palliative care if new patients with better prospects arrive. This question has led to divergent ethical guidelines. This paper explores the distinction between withholding and withdrawing medical treatment during times of scarcity. As a first central point, the paper argues that a revival of the ethical distinction between doing and allowing would have a revisionary impact on cases of voluntary treatment withdrawal. A second systematic focus lies in the concern that withdrawal due to scarcity might be considered a physical transgression and therefore more problematic than not treating someone in the first place. In light of the persistent disagreement, especially concerning the second issue, the paper concludes with two pragmatic proposals for how to handle the ethical uncertainty: (1) triage protocols should explicitly require that intensive care attempts are designed as time‐limited trials based on specified treatment goals, and this intent should be documented very clearly at the beginning of each treatment; and (2) lower survival prospects can be accepted for treatments that have already begun, compared with the respective triage rules for the initial access of patients to intensive care. [ABSTRACT FROM AUTHOR]

There is increasing national and international interest in overprescribing and polypharmacy, and the burden that the inappropriate use of multiple medicines can place on individual patients and on society as a whole. This paper explores the challenges faced by prescribers and pharmacists wishing to reduce polypharmacy, including the uncertainties about the risks and benefits of continuing or stopping individual drugs. We discuss the factors influencing us to prescribe—which may lead to overprescribing—including the increasing number of guidelines, perceived patient pressure and advertising. We offer a critical appraisal of the tools currently available to clinicians and pharmacists aiming to rationalise medicines, and finally a systems‐wide approach to improving overprescribing and problematic polypharmacy. [ABSTRACT FROM AUTHOR]

Comprehensive reviews of the clinical characteristics and pathogenesis of Aicardi-Goutières syndrome (AGS), particularly its contextualization within a putative type I interferonopathy framework, already exist. However, recent reports of attempts at treatment suggest that an assessment of the field from a therapeutic perspective is warranted at this time. Here, we briefly summarize the neurological phenotypes associated with mutations in the seven genes so far associated with AGS, rehearse current knowledge of the pathology as it relates to possible treatment approaches, critically appraise the potential utility of therapies, and discuss the challenges in assessing clinical efficacy. WHAT THIS PAPER ADDS: Progress in understanding AGS disease pathogenesis has led to the first attempts at targeted treatment. Further rational therapies are expected to become available in the short- to medium-term. [ABSTRACT FROM AUTHOR]

Most rare diseases have no approved treatments available, and doctors often prescribe existing drugs for "off‐label" use in the sense that a drug is prescribed for a medical condition that is different from the original condition approved by regulatory authorities. To develop approved treatments for rare diseases quickly without starting from scratch, governments have introduced different subsidy programs to entice pharmaceutical companies to exert extra efforts to "convert" certain drugs from off‐label to "on‐label" use. However, the impact of this subsidized conversion strategy on patient welfare remains unclear because both efficacy and price can change once a drug is converted from off‐label to on‐label use. This paper represents an initial attempt to investigate the effectiveness of different types of government subsidies (e.g., offer subsidies to manufacturers, patients, or both) for improving patient welfare through the drug conversion strategy. We present a three‐stage Stackelberg game‐theoretic model that captures the interactions among the government, manufacturer, and patients, and determine whether it is optimal to subsidize the manufacturer, patients, or both. We identify requisite (market and subsidy) conditions for a manufacturer to convert a drug from off‐label to on‐label use. We also determine the optimal extra development effort to convert an off‐label drug, and the optimal unit selling price for the on‐label drug after conversion. Contrary to the generally held public opinions, our analysis reveals that subsidizing pharmaceutical manufacturers is more effective than subsidizing patients. This result implies that subsidies offered to manufacturers would incentivize higher conversion efforts, and subsequently increase the expected patient welfare. Furthermore, we show that this result continues to hold even when the patients are risk‐averse or on‐label market size is uncertain. Our numerical analysis on the drugs Aralen, Humira, Revlimid, and Zostex reveals that government subsidies are necessary for enticing conversion from off‐label to on‐label use. [ABSTRACT FROM AUTHOR]

COVID-19, ataxia, myoclonus, SARS CoV-2 References 1 Godani M, Beronio A, Lanza G. Post-COVID-19 myoclonus-ataxia syndrome responsive to intravenous immunoglobulins. Keywords: COVID-19; SARS CoV-2; ataxia; myoclonus EN COVID-19 SARS CoV-2 ataxia myoclonus 724 725 2 04/18/23 20230401 NES 230401 We have read with interest the case report on post-COVID-19 myoclonus-ataxia syndrome responsive to intravenous immunoglobulins (IVIG).[1] In recent months, post COVID-19 motor complications have been described in several papers. [Extracted from the article]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 46 issue‐toc‐levels 0 issue‐pricelist‐year 2016 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2016 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2016 article‐registration‐date‐month 9 article‐registration‐date‐day 17 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2016_Article_121.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> Background: We conducted a clinical study that tested the effect of suppressive treatment with the botanical product Gene‐Eden‐VIR/Novirin on genital herpes. Our previous paper showed that the treatment decreased the number of genital herpes outbreaks without any side effects. It also showed that the clinical effects of Gene‐Eden‐VIR/Novirin are mostly better than those reported in the studies that tested acyclovir, valacyclovir, and famciclovir. The current paper reports the effect of suppressive treatment with Gene‐Eden‐VIR/Novirin on the duration of outbreaks, in severe and mild genital herpes cases. Methods: The framework was a retrospective chart review. The population included 137 participants. The treatment was 1–4 capsules per day. The duration of treatment was 2–48 months. The study included three controls: baseline, no‐treatment, and dose–response. Results: The treatment decreased the duration of outbreaks in 87 % of participants and decreased the mean duration of outbreaks from 8.77 days and 6.7 days in the control groups to 2.87 days in the treatment group (P < 0.001, both groups). All participants reported no adverse experiences. Conclusions: This paper shows that suppressive treatment with Gene‐Eden‐VIR/Novirin decreased the duration of genital herpes outbreaks, in both severe and mild cases, without any side effects. Based on the results reported in this and our previous paper, we recommend suppressive treatment with Gene‐Eden‐VIR/Novirin as a natural alternative to both suppressive and episodic treatments with current drugs, in both severe and mild genital herpes cases. Trial registration ClinicalTrials.gov NCT02715752 Registered 17 March 2016 Retrospectively Registered [ABSTRACT FROM AUTHOR]

Objective: To systematically review literature reporting interventions for weight change following paediatric acquired brain injury (ABI).Method: A systematic search of the literature was conducted using advanced search techniques. The retrieval identified 1562 papers, of which 30 were relevant. The total number of paediatric participants was 759.Results: There is a paucity of higher quality evidence to support the use of weight change interventions following paediatric ABI. Substantial variation in screening, outcome measures, intervention, and reporting were demonstrated. Some support was found for the use of hypothalamic-sparing surgery as a method to prevent obesity following craniopharyngioma resection.Interpretation: There is a need for further study in this area to inform clinical and research practice; recommendations are given. [ABSTRACT FROM AUTHOR]

With the rising popularity of field experiments in economics, re‐randomization schemes have emerged as tools to induce balance in observable variables across treatment groups. However, re‐randomization is not fully understood and the methodologies to estimate its effects on the distribution of parameters are still under‐developed. This paper helps to close that gap by suggesting an asymptotically normal re‐randomization scheme and bootstrapping procedure to carry inference under a wide range of estimators and re‐randomization schemes. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Devroey et al. (2011) Online monitoring of flu in Belgium. Influenza and Other Respiratory Viruses 5(5), 351-356. Background The diagnosis and treatment of patients with the A(H1N1) pandemic flu caused some serious burden for general practitioners (GPs) in the summer and autumn of 2009. Objective The aim of this study was to track the incidence of influenza and influenza-like illness (ILI) in Belgium and to describe the characteristics of the affected patients. Methods In July 2009, the Belgian online influenza surveillance system (BOISS) was set up to monitor the spread of influenza and ILI. Registrations were made by 93 GPs from all 10 Belgian provinces who participated at least 1 week during the first 12 months of the registration. Only patients who met the WHO criteria for flu were recorded. Results In total, 1254 patients (53% men) with influenza or ILI were included. Mainly younger persons were affected: 43% was under the age of 20 years. A risk factor for influenza-related complications was determined in 19% of cases, mainly patients with chronic respiratory problems. A treatment with oseltamivir or zanamivir was prescribed in 13%, and 3% of the patients was admitted to a hospital. The time of the peak incidence (44th week) and the magnitude (623 cases per week per 100 000 inhabitants) corresponded with the figures of the existing paper-based registration network. The small sample size and possible reporting biases may have influenced the findings of the study. Conclusions The BOISS provides a good alternative to conduct surveillance activities for influenza and ILI in Belgium. It provides complementary information regarding ILI compared to the existing data capturing. [ABSTRACT FROM AUTHOR]

There is a long history of removing oneself from ‘society’ in order to recuperate or repair. This paper considers a yoga and massage retreat in Southern Spain, and what opportunities this retreat experience might offer for recuperation and the creation of healthy bodies. The paper positions ‘nature’ as an active participant, and as ‘enrolled’ in the experiences of the retreat as a ‘therapeutic landscape’, and questions how and what particular aspects of yoga practice (in intimate relation with place) give rise to therapeutic experiences. [ABSTRACT FROM AUTHOR]

What is already known about this subject • The reviews already published on population pharmacokinetic/pharmacodynamic (PK/PD) analyses have focused on theory and have presented some clinical applications, evaluated validation practices in limited circumstances, defined the interest and sometimes the complexity of this approach in drug development or proposed a list of relevant articles. • None of them has exhaustively evaluated published analyses and more precisely the model-building steps. • In view of the statistical complexity of population PK/PD methodology, more attention is required to how models are built and how they are reported in the literature. What this study adds • With a strict methodology and by establishing a standardized tool, this survey provides an exhaustive, objective and up-to-date review of model-building practices. • It reveals deficiencies in information reporting in most articles and the genuine need for guidance in publishing. • An initial, minimal list of items is suggested, which can be used by authors and reviewers in pharmacology journals. • The value of published peer-reviewed papers could be greatly improved if authors were to address the suggested list of items systematically. Aims A descriptive survey of published population pharmacokinetic and/or pharmacodynamic (PK/PD) analyses from 2002 to 2004 was conducted and an evaluation made of how model building was performed and reported. Methods We selected 324 articles in Pubmed using defined keywords. A data abstraction form (DAF) was then built comprising two parts: general characteristics including article identification, context of the analysis, description of clinical studies from which the data arose, and model building, including description of the processes of modelling. The papers were examined by two readers, who extracted the relevant information and transmitted it directly to a MySQL database, from which descriptive statistical analysis was performed. Results Most published papers concerned patients with severe pathology and therapeutic classes suffering from narrow therapeutic index and/or high PK/PD variability. Most of the time, modelling was performed for descriptive purposes, with rich rather than sparse data and using NONMEM software. PK and PD models were rarely complex (one or two compartments for PK; Emax for PD models). Covariate testing was frequently performed and essentially based on the likelihood ratio test. Based on a minimal list of items that should systematically be found in a population PK–PD analysis, it was found that only 39% and 8.5% of the PK and PD analyses, respectively, published from 2002 to 2004 provided sufficient detail to support the model-building methodology. Conclusions This survey allowed an efficient description of recent published population analyses, but also revealed deficiencies in reporting information on model building. [ABSTRACT FROM AUTHOR]

We conducted a sero-epidemiological study of kala-azar in two endemic communities (Kasaini and Gidhaniya) situated in the Terai (plain) of eastern Nepal. Direct agglutination test (DAT) was used as a serological test for screening. Capillary blood samples were collected by filter paper method from 601 (96%) people of a total population of 628 in Kasaini and from 482 (94%) people of 515 in Gidhaniya. Positive DAT titres (1 :2000) were found in 66 (6.09%) of 1083 sera tested. The male–female sero-prevalence ratio was 1.44:1 and the age group of 15 years and above was most affected. Among the bone marrow aspirates collected from 66 DAT seropositive cases, only 19 were positive for Leishmania donovani (LD bodies). Of the 47 DAT seropositive but LD bodies’ negative cases, three were clinically active cases of kala-azar. Another nine developed clinical symptoms of kala-azar during 6 months follow-up and 23 were cases that had received prior treatment for kala-azar (within 1 year). The results of this study show the potential of the DAT on filter paper as a screening test for the surveillance of kala-azar at a community level. [ABSTRACT FROM AUTHOR]

Introduction Between September 2012 and December 2015, a series of national and regional consultations, aimed at resolving a persistent dynamic of conflict between law enforcement agencies (LEAs) and civil society organizations (CSOs) working on issues of access to HIV services in high-priority countries for people who use drugs have been organized by the HIV/AIDS Section of the United Nations Office on Drugs and Crime, the Joint United Nations Programme on HIV/AIDS, the Law Enforcement and HIV Network (LEAHN) and other international organizations. The aim of these consultations has been to understand, at a national and regional level, the key points of tension between police and CSOs and how to overcome these tensions to enhance access to and uptake of services by key populations, including people who inject drugs, sex workers, men who have sex with men and transgenders. This commentary briefly describes the methods, process, content and key outcomes of these consultations held across diverse number of countries and regions, including Africa, South East Asia, South Asia, Central Asia, Eastern Europe and Latin America. Discussion While the context varies, this paper highlights that there are commonalities that drive a persistent dynamic of conflict and therefore also common methods for resolution of conflict and forging partnerships. Both policing and CSOs have key sectoral responsibilities and reform agendas to implement to ensure that as an individual agency they are able to meet their obligations as partners in the HIV response. Using the key outcomes of discussions and recommendations from these consultations and drawing on existing literature, the objective of this paper is to present a preliminary model that roadmaps the critical path from resolution of conflict to partnership between LEAs and CSOs. Conclusions This paper seeks to highlight that critical resources are required to support ongoing development and harnessing of partnerships between LEAs and CSOs and argues that these resources should not just come from global HIV funding mechanisms but should be part of a more mainstreamed security sector reform agenda that understands the mutual benefits that programming for human rights-based policing reform would have on HIV, development and security. [ABSTRACT FROM AUTHOR]

An introduction to various articles within the issue which focus on incentives for physicians is presented.

Objectives Treatment guidelines for acute pulmonary embolism (PE) recommend risk stratifying patients to assess PE severity, as those at higher risk should be considered for therapy in addition to standard anticoagulation to prevent right ventricular (RV) failure, which can cause hemodynamic collapse. The hypothesis was that 12-lead electrocardiography (ECG) can aid in this determination. The objective of this study was to measure the prognostic value of specific ECG findings (the Daniel score, which includes heart rate > 100 beats/min, presence of the S1Q3T3 pattern, incomplete and complete right bundle branch block [RBBB], and T-wave inversion in leads V1-V4, plus ST elevation in lead aVR and atrial fibrillation suggestive of RV strain from acute pulmonary hypertension), in patients with acute PE. Methods Studies were identified by a structured search of MEDLINE, PubMed, EMBASE, the Cochrane library, Google Scholar, Scopus, and bibliographies in October 2014. Case reports, non-English papers, and those that lacked either patient outcomes or ECG findings were excluded. Papers with evidence of a predefined reference standard for PE and the results of 12-lead ECG, stratified by outcome (hemodynamic collapse, defined as circulatory shock requiring vasopressors or mechanical ventilation, or in hospital or death within 30 days) were included. Papers were assessed for selection and publication bias. The authors also assessed heterogeneity (I2) and calculated the odds ratios (OR) for each ECG sign from the random effects model if I2 > 24% and fixed effects if I2 < 25%. Funnel plots were used to examine for publication bias. Results Forty-five full-length studies of 8,209 patients were analyzed. The most frequent ECG signs found in patients with acute PE were tachycardia (38%), T-wave inversion in lead V1 (38%), and ST elevation in lead aVR (36%). Ten studies with 3,007 patients were included for full analysis. Six ECG findings (heart rate > 100 beats/min, S1Q3T3, complete RBBB, inverted T waves in V1-V4, ST elevation in aVR, and atrial fibrillation) had likelihood and ORs with lower-limit 95% confidence intervals above unity, suggesting them to be significant predictors of hemodynamic collapse and 30-day mortality. OR data showed no evidence of publication bias, but the proportions of patients with hemodynamic collapse or death and S1Q3T3 and RBBB tended to be higher in smaller studies. Patients who were outcome-negative had a significantly lower mean ± SD Daniel score (2.6 ± 1.5) than patients with hemodynamic collapse (5.9 ± 3.9; p = 0.039, ANOVA with Dunnett's post hoc), but not patients with all-cause 30-day mortality (4.9 ± 3.3; p = 0.12). Conclusions This systematic review and meta-analysis revealed 10 studies, including 3,007 patients with acute PE, that demonstrate that six findings of RV strain on 12-lead ECG (heart rate > 100 beats/min, S1Q3T3, complete RBBB, inverted T waves in V1-V4, ST elevation in aVR, and atrial fibrillation) are associated with increased risk of circulatory shock and death. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra‐ or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular‐targeted therapies, targeted radionuclide therapies and epigenetic modification‐based therapies. These topics are trending headlines and their combination with cell‐based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced. [ABSTRACT FROM AUTHOR]

Background Carious affected dentine ( CAD) represents a very common substrate in adhesive dentistry. Despite its ability to interact with adhesive systems, the intrinsic character of CAD leads to lower bonding compared with sound dentine, regardless of the adhesive systems used. This low bonding may be more susceptible to leakage and hydrolysis of the interface by matrix metalloproteinases ( MMPs). This systematic review aimed to determine current knowledge of CAD bonding, together with bond strength and MMP inhibitors' ability to prevent hybrid layer instability. Methods MEDLINE/Pubmed, Scopus and The Cochrane Library databases were electronically searched for articles published from 1 January 1960 to 31 August 2014. Two reviewers independently screened and included papers according to predefined selection criteria. Results The electronic searches identified 320 studies. After title, abstract and full-text examinations, 139 articles met the inclusion criteria. Data highlighted that a poor resin saturation of the already demineralized collagen matrix in CAD is strictly related to nanoleakage in interdiffusion and is the basis of the progressive decrease in strength with hydrolysis by MMPs. The use of mild self-etching systems seems to be the more accredited method to establish bonding in CAD. Inhibitors of MMPs may ensure better performance of CAD bonding, allowing undisturbed remineralization of the affected matrix. Conclusions CAD bonding needs further understanding and improvement, particularly to enhance the strength and durability of the hybrid layer. [ABSTRACT FROM AUTHOR]

The aim of this article was to identify the literature that examined and explored physical and psychological morbidity and patient and family caregiver resilience following acute wound development and/or wound blistering post orthopaedic surgery. A systematic review of the literature using the databases MEDLINE, CINAHL and EMBASE was undertaken. The papers were examined using title and abstract for relevance to the primary and secondary outcomes. The primary outcome of interest was family caregiver resilience following acute wound development and/or wound blistering post orthopaedic surgery. The search yielded 275 records after removing any duplicates; eight studies were considered eligible and were reviewed as full text. Following full review, none of the studies was included in this article. To conclude, there were no papers that investigated or examined the concept of resilience in relation to the management of acute post-surgical orthopaedic wounds. Four of the papers identified, following the review process, did discuss quality of life outcomes and how these may be improved following wound development; most papers focused on the management of chronic wounds. It is apparent from the review that there is no evidence currently available that explores patient and family caregiver resilience following acute wound development and/or wound blistering post orthopaedic surgery. [ABSTRACT FROM AUTHOR]

Figures from the Editor's selected issue highlights will be displayed each month in the journal image carousel on the BJCP homepage http://bpspubs.onlinelibrary.wiley.com/hub/journal/10.1111/(ISSN)1365-2125/ We live in a most interesting time. Some of us will be at the forefront of patient care, either treating patients, providing drugs or perhaps directing laboratory development and implementation of new diagnostic tests. The next study, from Switzerland, models the pharmacokinetics and pharmacodynamics of Cenerimod in healthy subjects and patients with systemic lupus erythematosus (http://onlinelibrary.wiley.com/doi/10.1111/bcp.14182/full). [Extracted from the article]

Introduction: Female sex workers (FSWs) are at high-risk for HIV acquisition in South Africa, where the advent of new HIV prevention and treatment interventions represent the potential to significantly impact the epidemic. This paper focuses on aspects of PrEP acceptability as a new intervention within the context of a larger service delivery programme including the simultaneous rollout of early ART. This paper explores PrEP acceptability among the FGD participants as future potential users. Methods: FGDs were conducted in two clinic-based sites in Johannesburg and Pretoria. They aimed to explore community-level, multi-dimensional acceptability of PrEP within the context of imminent implementation alongside early ART in the TAPS Demonstration Project. Sex worker peer educators recruited participants from varying sex work locales. Facilitation was in English with adaptation by facilitators into local languages as needed. Transcripts were translated and transcribed into English. Thematic analysis was used to analyse the data. Results: Four FGDs were conducted in each site for a total of eight FDGs and 69 participants. Demographics were largely similar across the sites. Overall, there was strong acceptability of PrEP among participants and positive anticipation for the imminent delivery of PrEP in the local sex worker clinics. Themes arising from the discussions exploring aspects of PrEP acceptability included: awareness and understanding of PrEP; PrEP motivations including choice, control, and vulnerability, managing PrEP risks and worries; and, de-stigmatizing and empowering PrEP delivery. Participant discussions and recommendations highlighted the importance of developing clear education and messaging to accurately convey the concept of PrEP, and intervention integration into supportive and tailored services. Conclusions: Through the course of these FGDs, PrEP became a positive and highly anticipated prevention option among the FSWs participants who endorsed implementation in their communities. Effective integration of PrEP into existing services will include comprehensive health programming where ART is also available, appropriate messaging, and support. [ABSTRACT FROM AUTHOR]