Clinical considerations in Buschke-Ollendorff syndrome

This brief report describes a mother and two daughters with the rare Buschke-Ollendorff syndrome. That the typical dermal connective tissue naevi lesions may become less obvious with time and that the condition is not always so "benign" are important clinical features not well recognised. Incorrect diagnosis may lead to embarkation upon hazardous management.     

Breast cancer angiogenesis — new approaches to therapy via antiangiogenesis,hypoxic activated drugs,and vascular targeting

Summary Several groups have shown that quantitation of tumor angiogenesis by counting blood vessels in primary breast cancer gives an independent assessment of prognosis. Poor prognosis is associated with high blood vessel counts. We have shown that the rate of cell division in endothelial cells is much higher in breast tumours than in normal breast. Breast cancer cell lines and primary human breast tumours express a wide range of vascular growth factors, including VEGF, placenta growth factor, pleiotrophin, TGF1, acidic and basic FGF, and platelet-derived endothelial cell growth factor. Inhibiting angiogenesis by blocking vascular growth factors would be difficult with highly specific agents, but drugs with a broader spectrum of antagonism may be effective. We have developed several suramin analogues which are less toxic than suraminin vivo but more potent in inhibiting angiogenesis, and these have been developed for Phase I. A combination of anti-angiogenesis agents with drugs activated by hypoxia may also be useful, because anti-angiogenesis alone may not kill cells, whereas activation of hypoxic drugs could synergize.New endpoints may be necessary because inhibition of new blood vessel formation may not cause tumour regression. Thus, the endpoint of stable disease and biochemical assessment of inhibition of angiogenesis may be much more important in therapeutic studies and for drug development in the future. The prognostic importance of angiogenesis suggests that this should be a major new therapeutic target.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.     

Selection of endpoints in breast cancer clinical trials: a qualitative study of key trial stakeholders

Clinical trial endpoints are fundamental for evaluating the safety and efficacy of cancer therapies, yet it is not well understood how they are selected or the role of stakeholder groups in deciding endpoints. This study aimed to explore how clinical trial endpoints are selected in breast cancer trials of anti-cancer drugs through semi structured interviews with purposively selected stakeholders involved in breast cancer clinical trials (clinicians, consumers, pharmaceutical company representatives, and members of drug regulatory agencies). Participants were asked to describe the process of selecting trial endpoints. Interviews were transcribed verbatim and analysed using inductive thematic analysis supported by NVivo software. Saturation of the main themes was reached and the final sample included 25 participants from 14 countries (9 clinicians, 7 consumers, 5 members of regulatory agencies, 4 pharmaceutical company representatives). Pharmaceutical companies were almost always identified as the main decision maker. While most consumers and pharmaceutical company representatives felt clinicians and consumers influenced trial design, some clinicians and regulators reported consumers and clinicians had little influence. Factors identified as important considerations in determining trial endpoints included the main goal of the trial, established standardised endpoints, resources, and the investigational agent studied. All pharmaceutical advisors reported that meeting the requirements for regulatory approval was the major factor considered. Clinical trial endpoint selection is largely decided by the pharmaceutical industry, driven by requirements for regulatory approval. Given the limited influence from clinicians and consumers, guidance by regulatory agencies will be important for future inclusion of novel endpoints in clinical trials.     

Exploring the roles and factors influencing community health workers’ performance in managing and referring severe acute malnutrition cases in two subdistricts in South Africa

As primary providers of preventive and curative community case management services in low‐ and middle‐income countries (LMICs), community health workers (CHWs) have emerged as a formalised part of the health system (HS). However, discourses on their practices as formalised cadres of the HS are limited. Therefore, we examined their role in care, referral (to clinics) and rehabilitation of severe acute malnutrition (SAM) cases. Focusing on SAM was essential since it is a global public health problem associated with 30% of all South Africa's (SA's) child deaths in 2015. Guided by a policy analysis framework, a qualitative case study was conducted in two rural subdistricts of North West province. From April to August 2016, data collected from CHW's training manuals and guideline reviews, 20 patient record reviews and 15 in‐depth interviews with four CHW leaders and 11 CHWs. Using thematic content analysis which was guided by the Walt and Gilson policy triangle, data was manually analysed to derive emerging themes on case management and administrative structures. The study found that although CHWs were responsible for identifying, referring, and rehabilitating SAM cases, they neglected curative roles of stabilisation before referral and treatment of uncomplicated cases. Such limitations resulted from restrictive CHW policies, inadequate training, lack of supportive supervision and essential resources. Concurrently, the CHW program was based on weak operational and administrative structures which challenged CHWs practices. Poor curative components and weak operational structures in this context compromised the use of CHWs in LMICs to strengthen primary healthcare. If CHWs are to contribute to Sustainable Development Goal (SDG) 3 by reducing SAM mortality, strategies on community management of acute malnutrition coupled with thorough training, supportive supervision, firm operational structures, adequate resources and providers’ motivation should be adopted by governments.     

Alkali-modified heterogeneous Pd-catalyzed synthesis of acids,amides and esters from aryl halides using formic acid as the CO precursor

To establish an environmentally friendly green chemical process, we minimized and resolved a significant proportion of waste and hazards associated with conventional organic acids and molecular gases, such as carbon monoxide (CO). Herein, we report a facile and milder reaction procedure, using low temperatures/pressures and shorter reaction time for the carboxyl- and carbonylation of diverse arrays of aryl halides over a newly developed cationic Lewis-acid promoted Pd/Co₃O₄ catalyst. Furthermore, the reaction proceeded in the absence of acid co-catalysts, and anhydrides for CO release. Catalyst reusability was achieved via scalable, safer, and practical reactions that provided moderate to high yields, paving the way for developing a novel environmentally benign method for synthesizing carboxylic acids, amides, and esters.

To establish an environmentally friendly green chemical process, we minimized and resolved a significant proportion of waste and hazards associated with conventional organic acids and molecular gases, such as carbon monoxide (CO).     

Functional balance assessment in recreational college-aged individuals with a concussion history

Objectives

Despite evidence for increased musculoskeletal injury after concussion recovery, there is a lack of dynamic balance assessments that could inform management and research into this increased injury risk post-concussion. Our purpose was to identify tandem gait dynamic balance deficits in recreational athletes with a concussion history within the past 18-months compared to matched controls.