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Coronavirus disease 2019 (COVID-19) first emerged in China in November 2019. Most governments have responded to the COVID-19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID-19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID-19 era (group activities, telemedicine, outpatients treatment, alcohol-related liver disease and liver transplantation, collecting samples); (d) AUD and SARS-CoV-2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID-19 disease will need implementation. Thus, the COVID-19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in-depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment. [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]

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]

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: 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]

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]

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]

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.

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]

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]

LINKED CONTENT: This article is linked to Yoon et al paper. To view this article, visit https://doi.org/10.1111/apt.17909 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Hong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17819 and https://doi.org/10.1111/apt.17937 [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]

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]

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]

LINKED CONTENT: This article is linked to Wu et al papers. To view these articles, visit https://doi.org/10.1111/apt.17667 and https://doi.org/10.1111/apt.17679 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Wu et al papers. To view these articles, visit https://doi.org/10.1111/apt.17667 and https://doi.org/10.1111/apt.17685 [ABSTRACT FROM AUTHOR]

Analyzes a study on the significance of the progestin called drospirenone in reducing blood pressure when combined with estradiol in postmenopausal women with stage 1 hypertension. Information on drospirenone; Benefits of postmenopausal hormone therapy; Methods used in the study and its results.

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]

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]

Background: As the mainstream treatment of axillary osmidrosis, surgical treatment is still limited by various complications, such as paresthesia, scars, local infection, hematoma, flap necrosis, and long recovery time. In this study, we tried to adopt the improved mini‐incision surgery for osmidrosis treatment. Objectives: The paper aims to evaluate the clinical effectiveness and safety of the improved mini‐incision surgery for axillary osmidrosis treatment. Patients/Methods: Clinical series of patients underwent improved mini‐incision surgery were retrospectively reviewed. Dates of complications, including paresthesia, scars, infection, hematoma, skin necrosis, and recurrence were analyzed. Results: Among 61 cases, 58 cases had a preoperative osmidrosis score of 3 and 3 cases had a preoperative score of 2; while 13 cases had a postoperative osmidrosis score of 0, 43 cases had a postoperative score of 1 and 5 cases had a postoperative score of 2, significantly lower than that before (p < 0.001). A total of 12 axillae complications occurred, 2 axillae (1.6%) had paresthesia; 5 axillae (4.1%) had hematoma; 2 axillae (1.6%) had local flap necrosis due to hematoma; and 3 axillae (2.4%) had hypertrophic scars. Conclusions: The results showed that the improved mini‐incision surgery was safe and effective for osmidrosis treatment. [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]

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.

LINKED CONTENT: This article is linked to Sharma et al papers. To view these articles, visit https://doi.org/10.1111/apt.16369 and https://doi.org/10.1111/apt.16910 [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]

Aim: To describe existing evidence on non-pharmacological interventions to manage sleep disturbance in children with neurodisabilities.Method: We systematically reviewed non-pharmacological interventions aimed at improving non-respiratory sleep disturbance in children with neurodisability. Sixteen databases, grey literature, and reference lists of included papers were searched up to February 2017. Two researchers (B.B., C.M., G.S., A.S., A.P.) undertook screening, data extraction, and quality appraisal.Results: Twenty-five studies were included: 11 randomized controlled trials and 14 before-and-after studies. All studies were at high or unclear risk of bias. Parent-directed interventions were categorized as comprehensive tailored interventions (n=9), comprehensive non-tailored interventions (n=8), and non-comprehensive interventions (n=2). Six 'other' non-pharmacological interventions were included. Seventy-one child and parent sleep-related outcomes were measured across the included studies. We report the two most commonly measured outcomes: the Child Sleep Habits Questionnaire and sleep onset latency. Five studies reported significant improvements on at least one of these outcomes.Interpretation: Various types of non-pharmacological intervention for managing sleep disturbance have been evaluated. Clinical heterogeneity and poor study quality meant we could not draw definitive conclusions on the effectiveness of these interventions. Current clinical guidance recommends parent-directed interventions as the first approach to managing sleep disturbance; prioritizing research in this area is recommended.What This Paper Adds: Existing evidence on non-pharmacological interventions to manage sleep disturbance in children with neurodisabilities is predominately of poor quality. Most included studies evaluated parent-directed interventions of varying content and intensity. There was very little consistency between studies in the outcome measures used. There is some evidence that parent-directed interventions may improve child outcomes. [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]

Diagnostic medical imaging plays an imperative role in clinical assessment and treatment of medical abnormalities. The fusion of multimodal medical images merges complementary information present in the multi-source images and provides a better interpretation with improved diagnostic accuracy. This paper presents a CT–MR neurological image fusion method using an optimised biologically inspired neural network in nonsubsampled shearlet (NSST) domain. NSST decomposed coefficients are utilised to activate the optimised neural model using particle swarm optimisation method and to generate the firing maps. Low and high-frequency NSST subbands get fused using max-rule based on firing maps. In the optimisation process, a fitness function is evaluated based on spatial frequency and edge index of the resultant fused image. To analyse the fusion performance, extensive experiments are conducted on the different CT–MR neurological image dataset. Objective performance is evaluated based on different metrics to highlight the clarity, contrast, correlation, visual quality, complementary information, salient information, and edge information present in the fused images. Experimental results show that the proposed method is able to provide better-fused images and outperforms other existing methods in both visual and quantitative assessments. [ABSTRACT FROM AUTHOR]

Background: Based on subjective experience, patients can identify research priorities important for health services research. A systematic method for priority setting has been developed by the James Lind Alliance. Objective: This article reviews the literature on the research priorities of patients, caregivers and health‐care professionals and presents the prioritized research themes and prioritization methods used. Search strategy: Three electronic databases were searched on 22 May 2018. The search was not limited to any time period or language. Inclusion criteria: The included studies reported the identification and prioritization of research priorities involving patients, relatives and caregivers. Each included paper addressed a specific ICD‐coded health problem, and at least one‐third of the sample involved in the prioritization process was affected by the health problem. Data extraction and synthesis: The 10 top‐ranked research priorities were included in the thematic analysis. With an inductive approach, a system of identified themes and subthemes was developed from the research priorities. Each research priority was assigned to one research theme. Main results: The priority lists of 34 publications involving 331 research priorities were included. Nine main themes represent the content of the research priorities. The most frequently represented main themes are 'Treatment', 'Patients' and 'Health condition'. The distribution of the research priorities varied depending on the health conditions and prioritization methods. Discussion and conclusions: This review provides a comprehensive overview of the overarching research themes in research priorities of affected individuals. The results can guide future patient‐oriented research. [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]

LINKED CONTENT This article is linked to the Rössle et al papers. To view these articles, visit https://doi.org/10.1111/apt.15811 and https://doi.org/10.1111/apt.15930 [ABSTRACT FROM AUTHOR]

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]

Introduction: In 2004, the US government began to utilize the Food and Drug Administration's (USFDA) tentative approval process (tFDA) as a basis to determine which HIV drugs are appropriate to be purchased and used in resource-constrained settings. This process permits products that are not approved for marketing in the US, including medicines with active patents or marketing restrictions in the US, to be purchased and distributed in resource-constrained settings. Although the tFDA was originally intended to support the United States' President's Emergency Plan for AIDS Relief (PEPFAR), the USFDA list has become a cornerstone of international HIV programmes that support procurement of ARVs, such as the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Our objective in this article is to help the global HIV policy makers and implementers of HIV programmes better understand the benefits and limitations of the tFDA by providing an in-depth review of the relevant legal and regulatory processes. Discussion: USFDA's dedicated tFDA process for ARVs used by the PEPFAR programme has a wide impact globally; however, the implementation and the regulatory processes governing the programme have not been thoroughly described in the medical literature. This paper seeks to help stakeholders better understand the legal and regulatory aspects associated with review of ARVs under the tFDA by describing the following: (1) the tFDA and its importance to global ARV procurement; (2) the regulatory pathways for applications under tFDA for the PEPFAR programme, including modifications to applications, review timelines and costs; (3) the role of US patents, US marketing exclusivity rights, and the Medicines Patents Pool in tFDA; and (4) an overview of how applications for PEPFAR programme are processed through the USFDA. We also provide a case study of a new ARV, tenofovir alafenamide fumarate (TAF), not yet reviewed by USFDA for PEPFAR use. Conclusions: In this paper, we describe the importance and implementation of USFDA's tentative approval process to review ARVs for resource-constrained settings. We also highlight the impact of patents and exclusivities on review of HIV drugs under tFDA and illustrate the concepts using a new HIV drug as an example. [ABSTRACT FROM AUTHOR]

Objectives: Aspirin‐exacerbated respiratory disease (AERD) is a chronic respiratory condition characterized by a triad of symptoms: asthma, chronic rhinosinusitis with nasal polyposis, and a respiratory reaction to aspirin and other cyclooxygenase‐1 inhibitors, also known as nonsteroidal anti‐inflammatory drugs. The objective of this review is to provide otolaryngologists with an overview of the pathophysiology, diagnosis, and treatment of this under‐recognized condition. Data sources and methods: Foundational papers on AERD were reviewed, focusing on the clinical otolaryngology and allergy/immunology literature and other high impact journals or trials. Results: AERD results from increased production of pro‐inflammatory leukotrienes and a decrease in production of anti‐inflammatory prostaglandins associated with the dysregulation of multiple enzymes influencing eicosanoid metabolism. Diagnosis hinges on a high index of suspicion, careful history, and confirmatory testing for all three elements. Treatments include endoscopic sinus surgery; topical, inhaled, or oral corticosteroids; aspirin desensitization; leukotriene modifying drugs; and the new class of biologics such as dupilumab. Conclusion: AERD is an under‐recognized disease associated with substantial patient‐reported morbidity. We expect rapid progress in the pathophysiological understanding of this disease and available treatments in the coming decades. Level of evidence: 5 [ABSTRACT FROM AUTHOR]

Glomerular diseases are leading causes of end‐stage renal disease in children. Tacrolimus is frequently used off‐label in the treatment of glomerular diseases. The effectiveness, safety and pharmacokinetic data of tacrolimus in the treatment of glomerular diseases in children are reviewed in this paper to provide evidence to support its rational use in clinical practice. The remission rates in previously published studies were different. In 19 clinical trials on children with nephrotic syndrome, the overall remission rate was 52.6‐97.6%. In four clinical trials on children with lupus nephritis, the overall remission rate was 81.8‐89.5%. In a pilot study with paediatric Henoch‐Schönlein purpura nephritis patients, the overall remission rate was 100.0%. Infection, nephrotoxicity, gastrointestinal symptoms and hypertension are the most common adverse events. Body weight, age, CYP3A5 genotype, cystatin‐C and daily dose of tacrolimus may have significant effects on the pharmacokinetics of tacrolimus in children with glomerular disease. More prospective controlled trials with long follow‐up are needed to demonstrate definitely the effectiveness, safety and pharmacokinetics of tacrolimus in children with glomerular diseases. [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]

Background and objective: End‐stage renal disease (ESRD) affects a multitude of aspects in the patient's daily life, often entailing their own involvement in various aspects of the treatment. Although patient participation is a core health‐care value, what the concept signifies is not yet fully known. The purpose of this paper is to conceptualize patient participation in dialysis care, depicting patients' and health‐care professionals' perspectives. Design: This explorative study employed qualitative interviews and content analysis. Setting and participants: Seven focus group discussions engaging 42 key informants were performed, including patients, staff and managers with experience of dialysis care. Results: In dialysis care, patient participation connotes a sharing of information and knowledge, the learning of and planning of care, including partaking in shared decisions with regards to treatment and management, and being involved in the management of one's own health‐care treatment and/or self‐care activities. Although these attributes were illustrated by all stakeholders, their significance varied: patients suggested that their preferences regarding primary aspects of participation vary, while staff considered patients' performance of dialysis to be the ultimate form of participation. Further, while patients considered multiple ways to execute participation, staff suggested that aspects such as sharing information were a route to, rather than actual, involvement. Conclusions: Without a common understanding to denote the idea of patient participation, staff and patients are exposed to a potential deficit in terms of facilitating patient participation in everyday encounters of dialysis treatment. Further studies and means to serve a mutual understanding are needed. [ABSTRACT FROM AUTHOR]

Summary: Introduction: The incidence rate of psoriasis vulgaris (PSV) coexisting with Juvenile dermatomyositis (JDM) is low. Through our thorough literature search, we found that PSV arising on JDM with superficial fungal infection of facial skin is rarely reported. So, we hereby, report a case of combination of the above three diseases. Meanwhile, we also reviewed the previous literatures aiming at the related basis, clinical manifestation, diagnosis, and treatment of the diseases. Interestingly, of all cases, this case is the only one in which the symptom of muscle weakness preceded the appearance of rash. Case Presentation: A 21‐year‐old man diagnosed with JDM 6 years ago came to our inpatient department due to the appearance of new rash. Skin examination showed some sharply demarcated scaly plaques over the head, neck, torso, and bilateral upper limbs with pruritus and scaling. Histological examination and typical clinical manifestation confirmed the diagnosis of PSV for his new rash. Family history was negative for JDM and PSV. The clear erythema located on his face revealed the existence of superficial fungal infection with the help of fungal fluorescence microscopy. He had marked improvement of his symptoms with the treatment given at our department. In the past 3 months, the patient has been on regular follow‐up at our outpatient department, and his condition is stable at present. Discussion: This paper presents a case of PSV arising on JDM coexisting with superficial fungal infection on the face hoping that this will help clinicians in the better diagnosis of the diseases during literature search. [ABSTRACT FROM AUTHOR]

Epidemiological studies, animal models, and case-control studies indicate maternal immune activation may be an important factor involved in disease expression of autism spectrum disorder (ASD), Tourette syndrome, and obsessive-compulsive disorder (OCD). We report eight children (mean age 6y 6mo [range 4-15y]; six males and two females) referred over a 2-year period with at least one of these neurodevelopmental disorders plus a maternal history of thyroid autoimmunity. Seven of eight children presented with an abrupt onset of neuropsychiatric symptoms (OCD [n=6], tics [n=5], and/or psychosis [n=1]), associated with an autistic or global regression. Four children had a pre-existing diagnosis of ASD. Six presentations were preceded by infection, and symptoms followed a relapsing-remitting course in seven children. All children responded to immunomodulatory treatment as indicated by a reduction in psychiatric symptoms, and seven children were also managed with conventional treatment with additional improvement. We propose that maternal autoimmunity can activate fetal microglia or alter transcription of neurodevelopmental vulnerability and/or immune genes in utero, and is an environmental factor that increases the expression and severity of neurodevelopmental problems, and susceptibility to deteriorations after infectious or stress stimuli. WHAT THIS PAPER ADDS: Maternal thyroid autoimmunity may represent a risk factor for neuropsychiatric disorders in offspring. Atypical neuropsychiatric features in these children may be due to maternal immune activation in utero. [ABSTRACT FROM AUTHOR]

Summary: Background: Direct‐acting anti‐viral therapy (DAA) has transformed hepatitis C virus (HCV) care, particularly in patients with decompensated cirrhosis. However, their impact on hepatocellular carcinoma (HCC) remains unclear. Aim: To use a national registry of patients with advanced liver disease to explore the relationship between DAA therapy and HCC. Methods: All patients with de novo HCC post DAA therapy were frequency matched with patients who did not develop HCC. Demographic, clinical and laboratory data were obtained. Cross‐sectional imaging and multidisciplinary team reports were reviewed for dates of HCC diagnosis and HCC progression. Patients were categorised by treatment outcome and time of HCC development. Data were examined by multivariable analysis and Kaplan‐Meier estimation. Results: Eighty patients with HCC were compared with 165 patients without HCC, treated between June 2014 and September 2015. Mean follow‐up from start of DAA therapy was 32.4 months. Twenty‐eight patients were diagnosed with early HCC (within 6 months of therapy) and 52 presented late. Baseline nonmalignant lesions (HR: 1.99), thrombocytopaenia (HR: 1.59) and diabetes (HR: 1.68) increased likelihood of HCC. Response to therapy was reduced in patients who developed liver cancer (SVR in patients with HCC = 54/80 (68%), SVR in patients without HCC = 143/165 (87%), P < 0.001, OR: 3.13, 95% CI: 1.64‐5.99). We found no difference between tumour size, progression or survival between viraemic and nonviraemic patients. Conclusion: There is no alteration in prognosis or cancer progression following HCC development after HCV treatment. However, baseline nonmalignant liver lesions, diabetes and thrombocytopaenia increase the risk of HCC, and HCC is associated with a decreased SVR rate. Linked Content This article is linked to Hollande and Pol paper. To view this article, visit https://doi.org/10.1111/apt.15328. [ABSTRACT FROM AUTHOR]

Down syndrome disintegrative disorder (DSDD) is an increasingly identified condition characterized by cognitive decline, autistic characteristics, insomnia, catatonia, and psychosis in adolescents and young adults with Down syndrome. Previously we reported a higher rate of autoimmune thyroid disease in these patients compared with unaffected individuals with Down syndrome. We therefore hypothesized DSDD may in some cases be immune-mediated. Here we report four cases of DSDD treated with immunotherapy. Families were interviewed retrospectively for symptoms of cognitive decline, autism, catatonia, psychosis, and insomnia before and after treatment, using established scales where possible. Medical records were reviewed for evaluations and treatment. All four patients received intravenous immunoglobulin with or without additional immunotherapy. Significant improvements were seen in catatonia, insomnia, autistic features, cognition, and psychosis. In this small case series of patients with autoimmunity, core symptoms of DSDD improved significantly after immunotherapy. This supports the hypothesis that, in some patients, DSDD is immune-mediated. Immunotherapy should be considered in the treatment of DSDD, particularly in patients with a history of autoimmunity. WHAT THIS PAPER ADDS: Immunotherapy may improve symptoms of catatonia, insomnia, autism severity, cognitive decline, and psychosis in Down syndrome disintegrative disorder. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Cho et al papers. To view these articles, visit https://doi.org/10.1111/apt.17255 [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]

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]

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]

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]

Vascular endothelial growth factor inhibitors (anti‐VEGF) have consistently demonstrated efficacy and safety and changed both the aim and perspectives of diabetic macular edema (DME) treatment. Hence, the present and future role of focal/grid laser photocoagulation in DME treatment has been subjected to some debate. However, extensive insight into technical advances in novel laser systems, treatment protocols of anti‐VEGF trials and the functional impact of modern focal/grid photocoagulation is needed to evaluate the present and future role of photocoagulation in DME treatment. Across a wide range of clinical trials laser therapy was required as adjunctive/rescue treatment in approximately 20–50% of patients receiving anti‐VEGF monotherapy for centre involving DME. Further, a lower retreatment rate and a more stable reduction in retinal thickness have been demonstrated in more studies. However, lacking information on the laser systems used, their technical specifications and protocols of application often complicates direct comparison of results in anti‐VEGF trials. Hence, this paper aimed to provide an overview of the currently available data relevant to the potential role of focal/grid laser photocoagulation in DME treatment including a thorough overview of the current most commonly used laser systems. Results with subthreshold diode micropulse laser photocoagulation are intriguing and may offer a valuable option as adjunctive therapy to anti‐VEGF treatment. However, more well‐designed studies on combination therapy are warranted to determine the full potential of modern retinal photocoagulation systems. In conclusion, current data suggest that focal/grid laser therapy should still be an option for consideration as adjunctive therapy in many patients. [ABSTRACT FROM AUTHOR]