The advent of highly active antiretroviral therapy (HAART), which constitutes HIV protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors, has dramatically reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infection in resource-rich countries. However, this disease still kills several million people each year. Though the reason for therapeutic failure is multi-factorial, an important concern is the treatment and control of HIV within the central nervous system (CNS). Due to the restricted entry of anti-HIV drugs, the brain is thought to form a viral sanctuary site. This not only results in virological resistance, but also is often associated with the development of complications such as HIV-associated dementia. The CNS delivery of anti-HIV drugs is limited by the blood–brain and blood–CSF interfaces due to a combination of restricted paracellular movement, powerful metabolic enzymes and numerous transporters including members of the ATP binding cassette (ABC) and solute carrier (SLC) superfamilies. A better appreciation of the transporters present at the brain barriers will prove a valuable milestone in understanding the limited brain penetration of anti-HIV drugs in HIV and also aid the development of new anti-HIV drugs and drug combinations, with enhanced efficacy in the CNS. This review aims to summarise current knowledge on the transport of anti-HIV drugs across the blood–brain barrier and the choroid plexus, as well as provide recommendations for future research.
The decremental pattern of more complex interventions used demonstrates that the algorithm can provide a logical management pathway to reduce blood transfusions, hysterectomies, admissions to intensive care units, and maternal deaths.
Introduction Inguinoscrotal hernias are the commonest form of abdominal wall hernia, but for them to contain stomach is extremely rare. The management of these hernias can be very challenging owing to their acute nature of presentation and distortion of anatomy. Our aim was to systematically review the literature for all reported cases of inguinoscrotal hernias containing stomach. In turn we analysed patient demographics, site of hernia, presentation and treatment. Outcomes were reviewed where available. Method We conducted a systematic search of the PUBMED, Embase and Medline databases with a combination of keywords: Hernia AND (inguin* OR scrot*) AND (gastric OR gastro*). An author's own case has also been included. Results There were 20 case reports included in the review, plus the author’s own case. They ranged in publication date from 1942 to 2020. Mean age at presentation was 71 years (range 49 to 87). All cases were male. In total, 62% (n = 13) of cases presented with combined symptoms of abdominal pain and vomiting, 48% (n = 10) presented with gastric outlet obstruction (GOO) and 48% (n = 10) presented with gastric perforation. All successfully treated cases with gastric perforation required a midline laparotomy approach, whereas 56% (n = 5) of patients in the GOO group were successfully treated conservatively. There were three deaths reported in this review, all in the gastric perforation group. Conclusion Stomach as a content of inguinoscrotal hernias is extremely rare. These hernias predominantly present acutely in the form of GOO or gastric perforation. All patients with gastric perforation will require a midline laparotomy. Patients with GOO can be successfully managed either surgically or in selective cases with conservative management.
The study aims to conduct a systematic review to characterise the spread and use of the concept of ‘disruptive innovation’ within the healthcare sector. We aim to categorise references to the concept over time, across geographical regions and across prespecified healthcare domains. From this, we further aim to critique and challenge the sector-specific use of the concept. PubMed, Medline, Embase, Global Health, PsycINFO, Maternity and Infant Care, and Health Management Information Consortium were searched from inception to August 2019 for references pertaining to disruptive innovations within the healthcare industry. The heterogeneity of the articles precluded a meta-analysis, and neither quality scoring of articles nor risk of bias analyses were required. 245 articles that detailed perceived disruptive innovations within the health sector were identified. The disruptive innovations were categorised into seven domains: basic science (19.2%), device (12.2%), diagnostics (4.9%), digital health (21.6%), education (5.3%), processes (17.6%) and technique (19.2%). The term has been used with increasing frequency annually and is predominantly cited in North American (78.4%) and European (15.2%) articles. The five most cited disruptive innovations in healthcare are ‘omics’ technologies, mobile health applications, telemedicine, health informatics and retail clinics. The concept ‘disruptive innovation’ has diffused into the healthcare industry. However, its use remains inconsistent and the recognition of disruption is obscured by other types of innovation. The current definition does not accommodate for prospective scouting of disruptive innovations, a likely hindrance to policy makers. Redefining disruptive innovation within the healthcare sector is therefore crucial for prospectively identifying cost-effective innovations.
Many systemic pharmacological agents have been investigated as adjuncts to venous ulcer healing; however, pentoxifylline (400 mg, three times a day) is currently the only drug that has promising evidence to support its use. Other compounds are in early stage research.
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