Adaptive innovations to provide services to children with developmental disabilities during the COVID-19 pandemic.

Children with developmental disabilities are experiencing significant challenges to service access due to suspension of in-person assessments during the current COVID-19 pandemic. Telehealth is rapidly becoming the new service delivery model, which presents a unique opportunity for innovation in care that could be beneficial in the post-pandemic period. For example, using a combination of in-home video and telehealth options could form the first step in developmental assessment, allowing children to receive the necessary supports without delay. Recent telehealth funding is welcome but additional Medicare items for joint consultations including general practitioners (GPs), and paediatric, mental health and allied health professionals is critical.

The changing face of family medicine in the COVID and post-COVID era.

This article describes the prospective changes and the fundamental values of the relationships between family doctors, patients and community according to an ethical-social concept of medicine. New aspects of the organization of the activity and of the roles of family doctors are reported in order to build hypotheses pointing to a modern and efficient management of patients in the coming the post-COVID era.

Diabetes Mellitus and Cardiovascular Disease.

Cardiovascular disease remains a leading cause of morbidity and mortality in people with types 1 or 2 diabetes mellitus. Although beneficial roles for strict control of hyperglycemia have been suggested, such a strategy is not without liabilities. Specifically, the risk of hypoglycemia and its consequences remain an omnipresent threat with such approaches. The advent of the CVOT (Cardiovascular Outcomes Trials) for new antidiabetes mellitus treatments has uncovered unexpected benefits of cardiovascular protection in some of the new classes of agents, such as the GLP-1 RAs (glucagon-like peptide-1 receptor agonists) and the SGLT-2 (sodium-glucose cotransporter-2) inhibitors. Further, state-of-the-art approaches, such as antibodies to PCKSK9 (proprotein convertase subtilisin-kexin type 9); RNA therapeutics; agents targeting distinct components of the immune/inflammatory response; and novel small molecules that block the actions of RAGE (receptor for advanced glycation end products) signaling, also hold potential as new therapies for diabetes mellitus and cardiovascular disease. Finally, interventions such as weight loss, through bariatric surgery, may hold promise for benefit in diabetes and cardiovascular disease. In this Brief Review, some of the novel approaches and emerging targets for the treatment of diabetes mellitus and cardiovascular disease are discussed. Ultimately, identification of the optimal timing and combinations of such interventions, especially in the context of personalized approaches, together with emerging disease-modifying agents, holds great promise to reduce the burden that diabetes poses to the cardiovascular system.

Current therapies under investigation for COVID-19: potential COVID-19 treatments.

In response to the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), researchers are expeditiously searching for antiviral treatments able to alleviate the symptoms of infection, which can be life-threatening. Here, we provide a general overview of what is currently known about the structure and characteristic features of SARS-CoV-2, some of which could potentially be exploited for the purposes of antiviral therapy and vaccine development. This minireview also covers selected and noteworthy antiviral agents/supportive therapy out of hundreds of drugs that are being repurposed or tested as potential treatments for COVID-19, the disease caused by SARS-CoV-2.

Introducing 'Health Vulnerability'. Towards a Human Right Claim for Innovative Orphan Drugs?

Although several European law instruments specifically promote the development of orphan medicines, rare disease patients still suffer from an excessive lack of access to orphan drugs. In order to base a claim for equity of access to research benefits, health vulnerability is introduced as a human rights-based public health concept. It represents a potentially valuable and powerful means in European law for rare disease patients to claim for an improved public action to develop innovative orphan drugs, including through the use of novel data-driven technologies such as computer modelling and simulation, as they have the potential to palliate some of the obstacles in the current development process of orphan medicines. The human rights-based approach would be all the more valuable, as it would simultaneously draw attention on privacy aspects of vulnerability for orphan disease patients, especially regarding increased risks stemming from the processing of highly sensitive health data.

Addressing critical needs in the fight to end tuberculosis with innovative tools and strategies.

This month in PLOS Medicine we launched a Special Issue on New Tools and Strategies for Tuberculosis Diagnosis, Care, and Elimination. In this issue's Editorial, the Guest Editors Claudia Denkinger, Richard Chaisson, and Mark Hatherill highlight some of the research that will publish and how these studies focusing on discovery, clinical trials and implementation research collectively add to the prospects for reaching the EndTB targets of the WHO by 2035.

Pruritus secondary to primary biliary cholangitis: a review of the pathophysiology and management with phototherapy.

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune hepatobiliary disorder characterized by destruction of liver bile ducts leading to intrahepatic cholestasis. It causes intractable pruritus for which ultraviolet (UV)B phototherapy is an experimental treatment when alternative therapies fail. The pathophysiology of cholestatic itch and the mechanism of action of narrowband UVB in this condition remains poorly understood. OBJECTIVES: To summarize the current literature and propose testable hypotheses for the mechanism of action of phototherapy in attenuating itch. METHODS: A focused PubMed search for articles relating to the pathogenesis of itch in cholestatic disease was performed. A total of 3855 articles were screened and 50 were found suitable for literature review. Evidence from this literature review was combined with author expertise in the area. RESULTS: Formulated hypotheses focus on the role of bile salts, autotaxin and specific receptors including G-protein-coupled bile acid receptor, Gpbar1 (also known as TGR5) and the nuclear transcription factor farnesoid X receptor. CONCLUSIONS: Several testable mechanisms through which phototherapy may exert its effects are discussed in this review. The next steps are to carry out an objective assessment of the efficacy of phototherapy in cholestatic pruritus, gain further knowledge on the underlying pathways, and subsequently trial its use against current licensed therapies. Such studies could lead to increased mechanistic understanding, identification of novel therapeutic targets and the potential to refine phototherapy protocols, leading to improved control of itch and quality of life in patients with PBC. What's already known about this topic? Primary biliary cholangitis (PBC) is frequently associated with intractable pruritus for which current treatment options are often unsuccessful. Phototherapy is used as an experimental treatment for PBC-associated pruritus when alternative better-studied treatments fail. What does this study add? This study reviews the current literature on the pathophysiology and management of cholestatic pruritus, an area which remains poorly understood. We propose testable hypotheses of the mechanisms behind the attenuation of cholestatic pruritus with phototherapy.

Innovations in efforts to expand treatment for opioid use disorder.

Fewer than 20% of Americans with opioid use disorder receive empirically-supported treatment. There is a critical need for innovative approaches to support expansion of evidence-based opioid treatment, particularly in rural geographic areas so impacted by the current opioid public health crisis. Doing so will require more diverse pathways into treatment, novel pharmacological tools, improved integration and efficiency among treatment modalities, and harm reduction when treatment is not available. In this invited commentary, we review exciting recent efforts to accomplish these aims as well as offer additional considerations for future clinical and research efforts to increase the availability of treatment for opioid use disorder.

The nexus of opioids, pain, and addiction: Challenges and solutions.

Pain and addiction are complex disorders with many commonalities. Beneficial outcomes for both disorders can be achieved through similar principles such as individualized medication selection and dosing, comprehensive multi-modal therapies, and judicious modification of treatment as indicated by the patient's status. This is implicit in the term "medication assisted treatment" (MAT) for opioid use disorders (OUD), and is equally important in pain management; however, for many OUD and pain patients, medication is central to the treatment plan and should neither be denied nor withdrawn if critical to patient well-being. Most patients prescribed opioids for pain do not develop OUD, and most people with OUD do not develop it as a result of appropriately prescribed opioids. Nonetheless, concerns about undertreatment of pain in the late 20th century likely contributed to inappropriate prescribing of opioids. This, coupled with a shortfall in OUD treatment capacity and the unfettered flood of inexpensive heroin and fentanyl, behavioral economics and other factors facilitated the 21st century opioid epidemic. Presently, injudicious reductions in opioid prescriptions for pain are contributing to increased suffering and suicides by pain patients as well as worsening disparities in pain management for ethnic minority and low-income people. Many of these people are turning to illicit opioids, and no evidence shows that the reduction in opioid prescriptions is reducing OUD or overdose deaths. Comprehensive, science-based policies that increase access to addiction treatment for all in need and better serve people with pain are vital to addressing both pain and addiction.

Charlie Gard and the weight of parental rights to seek experimental treatment.

The case of Charlie Gard, an infant with a genetic illness whose parents sought experimental treatment in the USA, brought important debates about the moral status of parents and children to the public eye. After setting out the facts of the case, this article considers some of these debates through the lens of parental rights. Parental rights are most commonly based on the promotion of a child's welfare; however, in Charlie's case, promotion of Charlie's welfare cannot explain every fact of the case. Indeed, some seem most logically to extend from intrinsic parental rights, that is, parental rights that exist independent of welfare promotion. I observe that a strong claim for intrinsic parental rights can be built on arguments for genetic propriety and children's limited personhood. Critique of these arguments suggests the scope of parental rights remains limited: property rights entail proper use; non-personhood includes only a small cohort of very young or seriously intellectually disabled children and the uniqueness of parental genetic connection is limited. Moreover, there are cogent arguments about parents' competence to make judgements, and public interest arguments against allowing access to experimental treatment. Nevertheless, while arguments based on propriety may raise concerns about the attitude involved in envisioning children as property, I conclude that these arguments do appear to offer a prima facie case for a parental right to seek experimental treatment in certain limited circumstances.

Ethical implications of medical crowdfunding: the case of Charlie Gard.

Patients are increasingly turning to medical crowdfunding as a way to cover their healthcare costs. In the case of Charlie Gard, an infant born with encephalomyopathic mitochondrial DNA depletion syndrome, crowdfunding was used to finance experimental nucleoside therapy. Although this treatment was not provided in the end, we will argue that the success of the Gard family's crowdfunding campaign reveals a number of potential ethical concerns. First, this case shows that crowdfunding can change the way in which communal healthcare resources are allocated. Second, within the UK's National Health Service, healthcare is ostensibly not a market resource; thus, permitting crowdfunding introduces market norms that could commodify healthcare. Third, pressures inherent to receiving funds from external parties may threaten the ability of patients-cum-recipients to voluntarily consent to treatment. We conclude that while crowdfunding itself is not unethical, its use can have unforeseen consequences that may influence conceptions of healthcare and how it is delivered.

Can Congress Get 'Right to Try' Right?

A federal bill would expand access to experimental treatments to seriously ill patients, but critics say the right to try would take away FDA oversight and create a "Wild West." Proponents counter that the FDA's current process can be onerous for people with just a few months to live. Meanwhile, most states' right-to-try laws have gone unused.

First Newborn Baby to Receive Experimental Therapies Survives Ebola Virus Disease.

A neonate born to an Ebola virus-positive woman was diagnosed with Ebola virus infection on her first day of life. The patient was treated with monoclonal antibodies (ZMapp), a buffy coat transfusion from an Ebola survivor, and the broad-spectrum antiviral GS-5734. On day 20, a venous blood specimen tested negative for Ebola virus by quantitative reverse-transcription polymerase chain reaction. The patient was discharged in good health on day 33 of life. Further follow-up consultations showed age-appropriate weight gain and neurodevelopment at the age of 12 months. This patient is the first neonate documented to have survived congenital infection with Ebola virus.

Backs against the wall: novel and existing strategies used during the 2014-2015 Ebola virus outbreak.

The 2014-2015 outbreak of Ebola virus (EBOV), originating from Guinea, is now responsible for the infection of >20,000 people in 9 countries. Whereas past filovirus outbreaks in sub-Saharan Africa have been rapidly brought under control with comparably few cases, this outbreak has been particularly resistant to containment efforts. Both the general population and primary health care workers have been affected by this outbreak, with hundreds of doctors and nurses being infected in the line of duty. In the absence of approved therapeutics, several caregivers have turned to investigational new drugs as well as experimental therapies in an effort to save lives. This review aims to summarize the candidates currently under consideration for postexposure use in infected patients during the largest EBOV outbreak in history.

Experimental subjects and partial truth telling during technological change in radiotherapy.

BACKGROUND: Cone Beam Computed Tomography (CBCT), the focus of a number of radiotherapy fundraising campaigns in the mid-2000s, was introduced accompanied by a fanfare of newness and discourses of 'hope', 'inspiring clinical confidence' and 'accuracy'. The CBCT system, used in the delivery of Radiotherapy treatment, was incorporated into strategic planning priorities across the United Kingdom based on a rationale of self-evidence. During this time, the way in which the new system was discussed with patients was variable. RESEARCH OBJECTIVES: The purpose of this study was to uncover how experimental practices were embedded and enacted during the use of a new technological system, specifically relating to how patients were enrolled during introductory phases of technology adoption. Research design and context: Drawing on ethnographic work and interviews with staff members in one hospital, the study examines staff discussions prior to the introduction of the Cone-Beam CT imaging system in radiotherapy. It considers how staff views were at odds with practices that occurred during the 'experimental' stages of use and how these were shared with patients. Ethical considerations: Approval was obtained from the Local National Health Service Research Ethics Committee and National Health Service Main Research Ethics Committee (REC 07/Q1308/16) for the interview and ethnographic stages, respectively. All names have been changed and participants signed a consent form. FINDINGS: Staff reported a lack of evidence, absence of proof and perturbing doubts with the X-ray volumetric imaging. Both patients' and practitioners' partial understanding about the risks and benefits of the system created incommensurable ideas regarding its use and what the patients' role was during these introductory stages. CONCLUSION: Maintaining partial truth telling renders patients' experiences of new treatment at odds with 'experimental' practice. This has wide-reaching implications for practice.

Should acute myeloid leukemia patients with actionable targets be offered investigational treatment after failing one cycle of standard induction therapy?

PURPOSE OF REVIEW: Therapeutic failure in acute myeloid leukemia remains common. It may be advantageous to identify patients with suboptimal treatment responses early as they may benefit from timely care strategy changes. Here, responses portending failure of standard induction therapy are reviewed and therapeutic options examined, including use of investigational, targeted agents for suitable patients. RECENT FINDINGS: Patients entering complete remission without minimal residual disease early, that is, with one cycle of standard induction chemotherapy, have a lower relapse risk and live longer than other similarly-treated patients, supporting the proposition of early complete remission without minimal residual disease as a criterion for induction therapy success. Investigational small molecule drugs are appealing for patients who fail standard therapies, but complete remission rates as a single agent are typically modest. SUMMARY: The relative value of different treatment strategies if a first standard induction therapy cycle fails to produce complete remission is unknown. However, retreatment with the same therapy often leads to complete remission and provides a benchmark against which other approaches should be compared. Addition of investigational small molecule drugs to standard reinduction therapy in patients with actionable targets could offer an attractive therapeutic strategy in this situation that might improve outcomes and facilitate clinical drug testing.

Footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in patients with diabetes: a systematic review.

BACKGROUND: Footwear and offloading techniques are commonly used in clinical practice for preventing and healing of foot ulcers in persons with diabetes. The goal of this systematic review is to assess the medical scientific literature on this topic to better inform clinical practice about effective treatment. METHODS: We searched the medical scientific literature indexed in PubMed, EMBASE, CINAHL, and the Cochrane database for original research studies published since 1 May 2006 related to four groups of interventions: (1) casting; (2) footwear; (3) surgical offloading; and (4) other offloading interventions. Primary outcomes were ulcer prevention, ulcer healing, and pressure reduction. We reviewed both controlled and non-controlled studies. Controlled studies were assessed for methodological quality, and extracted key data was presented in evidence and risk of bias tables. Uncontrolled studies were assessed and summarized on a narrative basis. Outcomes are presented and discussed in conjunction with data from our previous systematic review covering the literature from before 1 May 2006. RESULTS: We included two systematic reviews and meta-analyses, 32 randomized controlled trials, 15 other controlled studies, and another 127 non-controlled studies. Several randomized controlled trials with low risk of bias show the efficacy of therapeutic footwear that demonstrates to relief plantar pressure and is worn by the patient, in the prevention of plantar foot ulcer recurrence. Two meta-analyses show non-removable offloading to be more effective than removable offloading for healing plantar neuropathic forefoot ulcers. Due to the limited number of controlled studies, clear evidence on the efficacy of surgical offloading and felted foam is not yet available. Interestingly, surgical offloading seems more effective in preventing than in healing ulcers. A number of controlled and uncontrolled studies show that plantar pressure can be reduced by several conservative and surgical approaches. CONCLUSIONS: Sufficient evidence of good quality supports the use of non-removable offloading to heal plantar neuropathic forefoot ulcers and therapeutic footwear with demonstrated pressure relief that is worn by the patient to prevent plantar foot ulcer recurrence. The evidence base to support the use of other offloading interventions is still limited and of variable quality. The evidence for the use of interventions to prevent a first foot ulcer or heal ischemic, infected, non-plantar, or proximal foot ulcers is practically non-existent. High-quality controlled studies are needed in these areas.

Surgical treatment of the Charcot foot.

With the increased number of diabetics worldwide and the increased incidence of morbid obesity in more prosperous cultures, there has become an increased awareness of Charcot arthropathy of the foot and ankle. Outcome studies would suggest that patients with deformity associated with Charcot Foot arthropathy have impaired health related quality of life. This awareness has led reconstructive-minded foot and ankle surgeons to develop surgical strategies to treat these acquired deformities. This article outlines the current clinical approach to this disabling medical condition.

Innovative strategies to improve diabetes outcomes in disadvantaged populations.

Diabetes disproportionately affects disadvantaged populations. Eighty percent of deaths directly caused by diabetes occurred in low- and middle-income countries. In high-income countries, there are marked disparities in diabetes control among racial/ethnic minorities and those with low socio-economic status. Innovative, effective and cost-effective strategies are needed to improve diabetes outcomes in these populations. Technological advances, peer educators and community health workers have expanded methodologies to reach, educate and monitor individuals with diabetes. In the present manuscript we review the outcomes of these strategies, and describe the barriers to and facilitators of these approaches for improving diabetes outcomes.

An Advisory Committee for the Regulation of Innovation in Gynaecologic Practice: Development and Implementation.

The fundamental precepts that underpin the delivery of all medical care are safety and efficacy. Although these precepts, in theory, are accepted without challenge, in many settings where clinical care is delivered, there is a lack of formal oversight necessary to ensure their implementation in practice. Even though most medical specialties have national bodies that provide guidelines for good medical practice, and hospital accreditation makes reference to dissemination of such guidelines, there is usually not a mechanism to monitor medical uptake and adherence to good practice in the day-to-day delivery of care. Most hospitals require approval by an institutional review board before research protocols can be undertaken, but regional health authorities and hospitals do not usually have formal processes in place to regulate the adoption of new technologies into clinical practice. Recognizing the lack of a formal process at the hospital level to guide and regulate the introduction of new technologies or procedures, we set out to establish an oversight process to fill this gap. A committee was established to oversee innovation in the Gynaecology Division of our hospital. We describe here the establishment of this committee, the tools the committee used, and the processes used for the committee to do its work. We conclude that formal, local oversight of medical innovation is indispensible for ensuring the high standards of medical practice necessary to optimize patient safety.