Telemedicine as a Means to an End, Not an End in Itself

Telemedicine (TM)—the management of disease at a distance—has potential usefulness for patients with advanced respiratory disease. Underscoring this potential is the dramatic expansion of its applications in clinical medicine. However, since clinical studies testing this intervention often provide heterogeneous results, its role in the medical management of respiratory disorders remains inconclusive. A major problem in establishing TM’s effectiveness is that it is not a single intervention; rather, it includes a number of divergent diagnostic and therapeutic modalities—and each must be tested separately. Reflecting the discord between the need for further documentation of its approaches and effectiveness and its rapid utilization without this needed information, a major challenge is the lack of international guidelines for its integration, regulation, operational plans, and guidance for professionals. Tailored TM, with increased flexibility to address differing healthcare contexts, has the potential to improve access to and quality of services while reducing costs and direct input by health professionals. We should view TM as a tool to aid healthcare professionals in managing their patients with respiratory diseases rather than as a stand-alone substitute to traditional medical care. As such, TM is a means rather than an end.

A Computational Framework to Identify Metabolic Engineering Strategies for the Co-Production of Metabolites

Microbial production of chemicals is a more sustainable alternative to traditional chemical processes. However, the shift to bioprocess is usually accompanied by a drop in economic feasibility. Co-production of more than one chemical can improve the economy of bioprocesses, enhance carbon utilization and also ensure better exploitation of resources. While a number of tools exist for in silico metabolic engineering, there is a dearth of computational tools that can co-optimize the production of multiple metabolites. In this work, we propose co-FSEOF (co-production using Flux Scanning based on Enforced Objective Flux), an algorithm designed to identify intervention strategies to co-optimize the production of a set of metabolites. Co-FSEOF can be used to identify all pairs of products that can be co-optimized with ease using a single intervention. Beyond this, it can also identify higher-order intervention strategies for a given set of metabolites. We have employed this tool on the genome-scale metabolic models of Escherichia coli and Saccharomyces cerevisiae, and identified intervention targets that can co-optimize the production of pairs of metabolites under both aerobic and anaerobic conditions. Anaerobic conditions were found to support the co-production of a higher number of metabolites when compared to aerobic conditions in both organisms. The proposed computational framework will enhance the ease of study of metabolite co-production and thereby aid the design of better bioprocesses.

Multimodal Interventions Are More Effective in Improving Core Symptoms in Children With ADHD

Objective: To investigate the effect of sensory integration training combined with EEG biofeedback on core symptoms in children with ADHD.Methods: Fifty-two children with attention-deficit, hyperactive-impulsive and combined ADHD were selected. They were randomly divided into control group, sensory integration training group, EEG biofeedback group, and sensory integration training + EEG biofeedback group, and after 4 months of intervention, concentration time and impulsive- hyperactivity and hyperactivity index scores on the PSQ scale were assessed.Results: Compared with that before the intervention, the attention time was significantly increased (P < 0.01), and the impulsive-hyperactivity and hyperactivity index scores were significantly decreased (P < 0.05, P < 0.01). After the intervention, the attention time was significantly higher than that of the control group (P < 0.05, P < 0.01), the attention time of the multimodal intervention group was significantly higher than that of the single intervention group (P < 0.01), and the impulsive-hyperactivity and hyperactivity index scores were significantly lower than those of the single intervention group (P < 0.05).Conclusion: Multimodal intervention can significantly improve the concentration level of children with ADHD, and significantly improve the behavioral symptoms of impulsive-hyperactivity and hyperactivity. Multimodal interventions were more effective than single interventions in improving core symptoms in children with ADHD. The results of this study provide a reference for related research and practical application.

Reinforcing the Modified Double-Opposing Z-Plasty Approach Using the Pedicled Buccal Fat Flap as an Interpositional Layer for Cleft Palate Repair

Pedicled buccal fat flaps have been adopted in primary Furlow double-opposing Z-plasty palatoplasty to reduce oronasal fistula formation or to attenuate maxillary growth disturbance. We combined both goals in a single intervention. This study describes a series of 33 modified Furlow small double-opposing Z-plasty palatoplasties reinforced with a middle layer of pedicled buccal fat flaps between the oral and nasal layers for full coverage of the dissected palatal surfaces, with rapid mucosalization of lateral relaxing incisions and no dehiscence or fistula formation.

Community interventions for people with complex emotional needs that meet the criteria for personality disorder diagnoses: systematic review of economic evaluations and expert commentary

Background Diagnoses of personality disorder are prevalent among people using community secondary mental health services. Identifying cost-effective community-based interventions is important when working with finite resources. Aims To assess the cost-effectiveness of primary or secondary care community-based interventions for people with complex emotional needs who meet criteria for a diagnosis of personality disorder to inform healthcare policy-making. Method Systematic review (PROSPERO: CRD42020134068) of databases. We included economic evaluations of interventions for adults with complex emotional needs associated with a diagnosis of personality disorder in community mental health settings published before 18 September 2019. Study quality was assessed using the CHEERS statement. Results Eighteen studies were included. The studies mainly evaluated psychotherapeutic interventions. Studies were also identified that evaluated altering the setting in which care was delivered and joint crisis plans. No strong economic evidence to support a single intervention or model of community-based care was identified. Conclusions Robust economic evidence to support a single intervention or model of community-based care for people with complex emotional needs is lacking. The strongest evidence was for dialectical behaviour therapy, with all three identified studies indicating that it is likely to be cost-effective in community settings compared with treatment as usual. More robust evidence is required on the cost-effectiveness of community-based interventions on which decision makers can confidently base guidelines or allocate resources. The evidence should be based on consistent measures of costs and outcomes with sufficient sample sizes to demonstrate impacts on these.

Influenza Vaccination Programs for Healthcare Personnel: Organizational Issues and Beyond

Healthcare personnel (HCP) are a high priority group for influenza vaccination aiming to protect them but also to protect vulnerable patients and healthcare services from healthcare-associated influenza and HCP absenteeism. Multi-component influenza vaccination programs targeting behavioral, organizational, and administrative barriers are critical, if influenza vaccination rates among HCP are to be raised on a sustained basis. Mandatory influenza vaccination policy is the only single intervention that can achieve high and sustainable vaccination rates in HCP in short term. In this article, we provide an overview of issues pertaining to influenza vaccination of HCP, with an emphasis on organizational issues of influenza vaccination programs.

Deuterium-depleted water delayed hormone therapy of prostate cancer

The anticancer effect of deuterium depletion in combination with conventional therapies has been confirmed in phase II double-blind clinical trial with prostate cancer patients. In this study, we describe the case of a patient who was diagnosed with prostate cancer in 2009. He denied the hormone therapy offered, providing an opportunity for following the effect of deuterium depletion as a single intervention. The patient started consuming deuterium-depleted water (DDW) one month after the diagnosis. Already after one month of DDW consumption, his PSA level dropped from 8.7 ng/mL to 6.3 ng/mL and 1.5 years later, an MRI scan could not confirm the presence of the tumor 1 cm in diameter. The 11 years follow-up of the changes in PSA value proved that deuterium depletion controls the growth of prostate cancer. The data also revealed that increasing the length of the break in DDW consumption from 5-6 months to 11 months promoted the progression of the disease as confirmed by an MRI scan. The patient had 13 courses of DDW treatment in 11 years. This study confirms that deuterium depletion is an effective early-stage treatment as a single therapy and delays conventional therapy. Based on previous studies we also conclude that DDW in proper combination with hormone therapy assists in prolonging the development of hormone resistance.

A computational framework to identify metabolic engineering strategies for the co-production of metabolites

ABSTRACTMicrobial production of chemicals is a more sustainable alternative to traditional chemical processes. However, the shift to bioprocess is usually accompanied by a drop in economic feasibility. Co-production of more than one chemical can improve the economy of bioprocesses, enhance carbon utilization and also ensure better exploitation of resources. While a number of tools exist for in silico metabolic engineering, there is a dearth of computational tools that can co-optimize the production of multiple metabolites. In this work, we propose an eXtended version of Flux Scanning based on Enforced Objective Flux (XFSEOF), identify intervention strategies to co-optimize for a set of metabolites. XFSEOF can be used to identify all pairs of products that can be co-optimized with ease, by a single intervention. Beyond this, it can also identify higher-order intervention strategies for a given set of metabolites. We have employed this tool on the genome-scale metabolic models of Escherichia coli and Saccharomyces cerevisiae, and identified intervention targets that can co-optimize the production of pairs of metabolites under both aerobic and anaerobic conditions. Anaerobic conditions were found to support the co-production of a higher number of metabolites when compared to aerobic conditions in both organisms. The proposed computational framework will enhance the ease of study of metabolite co-production and thereby aid the design of better bioprocesses.

Treatment Impact on Patient-Reported Outcomes in Peripheral Neuropathic Pain: Comparing Single Intervention With Topical High-Concentration Capsaicin to Daily Oral Pregabalin

BACKGROUND: Peripheral neuropathic pain (PNP) is a complex, subjective experience affecting both physical and psychological aspects of functioning. Assessing patient-reported outcomes (PROs) beyond pain relief is important and aligns with the recommendations of IMMPACT (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials). Moreover, PRO data are key to clinical decision-making when evaluating treatment options. However, direct comparisons between such options are scarce. High-concentration capsaicin 179 mg (8% w/w) cutaneous patch (HCCP) is applied to the skin at minimum intervals of 90 days under physician supervision; alternative recommended treatments for PNP are mostly orally administered on a daily basis. The ELEVATE study directly compared HCCP with pregabalin and found noninferior efficacy of HCCP to pregabalin in relieving pain after 8 weeks, with a significantly faster onset of action and fewer systemic side effects. OBJECTIVES: The objective of this analysis was to compare PRO outcomes defined as secondary objectives of the ELEVATE study after a single intervention with HCCP to daily oral pregabalin for 8 weeks. STUDY DESIGN: ELEVATE was an open-label, randomized (1:1) multicenter study. SETTING: The study included 92 sites in 22 countries in Europe and Asia. METHODS: Five hundred fifty-nine non-diabetic patients with PNP received a single intervention with HCCP (n = 282; 1-4 patches at baseline) or oral daily pregabalin (n = 277; 150-600 mg, 8 weeks). At baseline (Day 0) and Week 8, patients completed the following PROs in addition to the regular pain assessments: Patient Global Impression of Change (PGIC), Medical Outcomes Study Cognitive Functioning scale (MOS-Cog), Medical Outcomes Study Sleep scale (MOS-Sleep), Treatment Satisfaction Questionnaire for Medication (TSQM), and EuroQol 5-Dimensions 5-levels (EQ-5D-5L) Utility Index (EQ-UI) and Visual Analog Scale (EQ-VAS). RESULTS: At Week 8, 76% and 75.9% of patients on HCCP and pregabalin, respectively, reported to be very much/much/minimally improved on the PGIC. HCCP application was associated with significant improvements from baseline vs. pregabalin in MOS-Cog (mean difference: 4.28 [95% CI: 2.90-5.66]; P < 0.001), EQ-VAS (3.11 [0.30-5.92]; P = 0.030), and TSQM global satisfaction (6.74 [2.29-11.20]; P = 0.029), particularly the side-effects dimension (21.23 [17.55-24.94]; P < 0.0001). No significant differences in improvements were noted for the MOS-Sleep, TSQM convenience, and EQ-UI. LIMITATIONS: The ELEVATE study has an open-label design, with only one comparator (pregabalin); it was limited to 8 weeks. The sample size was determined for the primary endpoint. CONCLUSIONS: A single intervention with HCCP showed benefits vs. daily pregabalin at Week 8 on several PROs. While HCCP has been approved in the United States for PNP treatment in diabetic and PHN patients, these observations provide information on how patients perceive the effects of distinct PNP treatments. They are complementing already existing knowledge on efficacy and safety of different treatment options with data on patient preferences and may help identify the appropriate treatment option in dialogue with the patients and shared decision-making. IRB Approval: At the time of the study, the trial was approved either nationally or at site level. All approvals were granted prior to the initiation of the trial. A list of Ethics Committees that approved the trial is included as a supplemental file. Clinical Trial Registration Number: NCT01713426. KEY WORDS: Capsaicin; comparative study; ELEVATE study; neuropathic pain; pain; pain measurement; patient outcome assessment; pregabalin

Simulating the impact of non-pharmaceutical interventions limiting transmission in COVID-19 epidemics using a membrane computing model

ABSTRACT Epidemics caused by microbial organisms are part of the natural phenomena of increasing biological complexity. The heterogeneity and constant variability of hosts, in terms of age, immunological status, family structure, lifestyle, work activities, social and leisure habits, daily division of time, and other demographic characteristics make it extremely difficult to predict the evolution of epidemics. Such prediction is, however, critical for implementing intervention measures in due time and with appropriate intensity. General conclusions should be precluded, given that local parameters dominate the flow of local epidemics. Membrane computing models allows us to reproduce the objects (viruses, hosts) and their interactions (stochastic but also with defined probabilities) with an unprecedented level of detail. Our LOIMOS model helps reproduce the demographics and social aspects of a hypothetical town of 10,320 inhabitants in an average European country where COVID-19 is imported from the outside. The above-mentioned characteristics of hosts and their lifestyle are minutely considered. For the data in the Hospital and the ICU we took advantage of the observations at the Nursery Intensive Care Unit of the Consortium University General Hospital, Valencia, Spain (included as author). The dynamics of the epidemics are reproduced and include the effects on viral transmission of innate and acquired immunity at various ages. The model predicts the consequences of delaying the adoption of non-pharmaceutical interventions (between 15 and 45 days after the first reported cases) and the effect of those interventions on infection and mortality rates (reducing transmission by 20%, 50%, and 80%) in immunological response groups. The lockdown for the elderly population as a single intervention appears to be effective. This modelling exercise exemplifies the application of membrane computing for designing appropriate multilateral interventions in epidemic situations.