ABSTRACT
Background: Most existing research in chronic edema (CO) care takes place in high-income countries and is both clinically and medically focused, although often accorded low prestige and status. A myriad of challenges define the problems and important gaps in understanding and translating what we know into sustainable practice. Less considered, however, are the consequences and socioeconomic significance of this "knowledge gap" in an increasingly globalized world. This article seeks to address this lacuna by suggesting a political economy approach across three different income settings, the United Kingdom (high), Kerala in India (middle), and Uganda (low), to learn from international practice and understand the contribution of local (community-specific) health traditions. Methods and Result: We used a comparative case study approach. In the three case studies we demonstrate how particular thinking, sets of power relationships, and resource distributions influence and structure the provision of CO management more generally. We demonstrate how these intertwined and often invisible processes reflect a market-led biomedical hierarchization that focuses on high-interventionist, high-cost approaches that are then imposed on lower income settings. At the same time, low-cost but evidence-based local knowledge innovation in wound and CO care from low- or middle-income countries is neither recognized nor valued. Conclusion: We conclude that unpacking these dynamics is a necessary route to providing a more equitable health delivery accessible for the many rather than the few.
Subject(s)
Edema , Long-Term Care , Humans , India , United KingdomABSTRACT
Treatment of patients with lymphedema focuses on reducing limb volume with more recent recognition of the importance of qualityof- life issues. Perhaps due to the incidence of filariasis-related lymphedema compared to breast cancer-related lymphedema in the western world, the Institute of Applied Dermatology (IAD) in Kerala, India has developed a low-cost and culturally acceptable treatment with quality-of-life focus that works well in that area. Worldwide, there is also recognition of chronic edema as a potential co-morbidity and the recent advances in genetic analysis continue to shed light on lymphedema development that may be important in filariasisrelated lymphedema. Although improvement in treatment outcomes by surgical means has been shown, there is often conventional treatment mixed in the therapy and no randomized controls of any therapy exist. In addition, these techniques require supermicrosurgical skill not available in many areas of the world. The WHO has documented the need in filariasis for both universal health care and innovative care for chronic conditions. The IAD has addressed these issues with its integrative model of treatment with patient quality-of-life at the forefront to incorporate traditional practice to involve the patient more fully in family and community support for an additional therapeutic tool.
Subject(s)
Developing Countries , Community Support , Elephantiasis, Filarial/epidemiology , Humans , Lymphedema/prevention & control , MorbidityABSTRACT
BACKGROUND: Pediatric use of pneumococcal conjugate vaccines (PCV) has been associated with significant decrease in disease burden. However, disease caused by non-vaccine serotypes has increased. Safety and immunogenicity of 15-valent PCV (PCV15) containing serotypes included in 13-valent PCV (PCV13) plus serotypes 22F and 33F were evaluated in infants (NCT01215188). METHODS: Infants received adjuvanted PCV15, nonadjuvanted PCV15, or PCV13 at 2, 4, 6, and 12-15â¯months of age. Safety was monitored for 14â¯days after each dose. Serotype-specific IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured at postdose-3, predose-4, and postdose-4. RESULTS: Safety profiles were comparable across vaccination groups. At postdose-3, both PCV15 formulations were non-inferior to PCV13 for 10 of 13 shared serotypes but failed non-inferiority for 3 serotypes (6A, 6B, and 19A) based on proportion of subjects achieving IgG GMC ≥0.35⯵g/mL. Adjuvanted PCV15 and nonadjuvanted PCV15 were non-inferior to PCV13 for 11 and 8 shared serotypes, respectively, based on postdose 3 comparisons of GMC ratios. PCV15 induced higher antibodies to serotypes 3, 22F, and 33F than PCV13. CONCLUSIONS: PCV15 displayed acceptable safety profile and induced IgG and OPA to all 15 vaccine serotypes at levels comparable to PCV13 for 10 of 13 shared serotypes. Study identification: V114-003. CLINICALTRIALS.GOV identifier: NCT01215188.
Subject(s)
Pneumococcal Vaccines/adverse effects , Pneumococcal Vaccines/immunology , Vaccines, Conjugate/adverse effects , Vaccines, Conjugate/immunology , Female , Humans , Infant , Male , Pneumococcal Vaccines/therapeutic use , Serogroup , Vaccines, Conjugate/therapeutic useABSTRACT
BACKGROUND: Innovation in the treatment of lower extremity lymphedema has received low priority from the governments and pharmaceutical industry. Advancing lymphedema is irreversible and initiates fibrosis in the dermis, reactive changes in the epidermis and subcutis. Most medical treatments offered for lymphedema are either too demanding with a less than satisfactory response or patients have low concordance due to complex schedules. A priority setting partnership (PSP) was established to decide on the future priorities in lymphedema research. METHODS: A table of abstracts following a literature search was published in workshop website. Stake holders were requested to upload their priorities. Their questions were listed, randomized, and sent to lymphologists for ranking. High ranked ten research priorities, obtained through median score, were presented in final prioritization work shop attended by invited stake holders. A free medical camp was organized during workshop to understand patients' priorities. RESULTS: One hundred research priorities were selected from priorities uploaded to website. Ten priorities were short listed through a peer review process involving 12 lymphologists, for final discussion. They were related to simplification of integrative treatment for lymphedema, cellular changes in lymphedema and mechanisms of its reversal, eliminating bacterial entry lesions to reduce cellulitis episodes, exploring evidence for therapies in traditional medicine, improving patient concordance to compression therapy, epidemiology of lymphatic filariasis (LF), and economic benefit of integrative treatments of lymphedema. CONCLUSION: A robust research priority setting process, organized as described in James Lind Alliance guidebook, identified seven priority areas to achieve effective morbidity control of lymphedema including LF. All stake holders including Department of Health Research, Government of India, participated in the PSP.
ABSTRACT
INTRODUCTION: Vaqas and Ryan (2003) advocated yoga and breathing exercises for lymphedema. Narahari et al. (2007) developed an integrative medicine protocol for lower-limb lymphedema using yoga. Studies have hypothesized that yoga plays a similar role as that of central manual lymph drainage of Foldi's technique. This study explains how we have used yoga and breathing as a self-care intervention for breast cancer-related lymphedema (BCRL). METHODS: The study outcome was to create a yoga protocol for BCRL. Selection of yoga was based on the actions of muscles on joints, anatomical areas associated with different groups of lymph nodes, stretching of skin, and method of breathing in each yoga. The protocol was piloted in eight BCRL patients, observed its difficulties by interacting with patients. A literature search was conducted in PubMed and Cochrane library to identify the yoga protocols for BCRL. RESULTS: Twenty yoga and 5 breathing exercises were adopted. They have slow, methodical joint movements which helped patients to tolerate pain. Breathing was long and diaphragmatic. Flexion of joints was coordinated with exhalation and extension with inhalation. Alternate yoga was introduced to facilitate patients to perform complex movements. Yoga's joint movements, initial positions, and mode of breathing were compared to two other protocols. The volume reduced from 2.4 to 1.2 L in eight patients after continuous practice of yoga and compression at home for 3 months. There was improvement in the range of movement and intensity of pain. DISCUSSION: Yoga exercises were selected on the basis of their role in chest expansion, maximizing range of movements: flexion of large muscles, maximum stretch of skin, and thus part-by-part lymph drainage from center and periphery. This protocol addressed functional, volume, and movement issues of BCRL and was found to be superior to other BCRL yoga protocols. However, this protocol needs to be tested in centers routinely managing BCRL.
ABSTRACT
A comprehensive analysis is performed to evaluate the effect of weight, height and body mass index (BMI) of occupants on side impact injuries at different body regions. The accident dataset for this study is based on the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) for accident year 2000-08. The mean BMI values for driver and front passenger are estimated from all types of crashes using NASS database, which clearly indicates that mean BMI has been increasing over the years in the USA. To study the effect of BMI in side impact injuries, BMI was split into three groups namely (1) thin (BMI<21), (2) normal (BMI 24-27), (3) obese (BMI>30). For more clear identification of the effect of BMI in side impact injuries, a minimum gap of three BMI is set in between each adjacent BMI groups. Car model years from MY1995-1999 to MY2000-2008 are chosen in order to identify the degree of influence of older and newer generation of cars in side impact injuries. Impact locations particularly side-front (F), side-center (P) and side-distributed (Y) are chosen for this analysis. Direction of force (DOF) considered for both near side and far side occupants are 8 o'clock, 9 o'clock, 10 o'clock and 2 o'clock, 3 o'clock and 4 o'clock respectively. Age <60 years is also one of the constraints imposed on data selection to minimize the effect of bone strength on the occurrence of occupant injuries. AIS2+ and AIS3+ injury risk in all body regions have been plotted for the selected three BMI groups of occupant, delta-V 0-60kmph, two sets (old and new) of car model years. The analysis is carried with three approaches: (a) injury risk percentage based on simple graphical method with respect to a single variable, (b) injury distribution method where the injuries are marked on the respective anatomical locations and (c) logistic regression, a statistical method, considers all the related variables together. Lower extremity injury risk appears to be high for thin BMI group. It is found that BMI does not have much influence on head injuries but it is influenced more by the height of the occupant. Results of logistic analysis suggest that BMI, height and weight may have significant contribution towards side impact injuries across different body regions.
Subject(s)
Abbreviated Injury Scale , Accidents, Traffic/statistics & numerical data , Body Height , Body Weight , Obesity/epidemiology , Thinness/epidemiology , Wounds and Injuries/epidemiology , Abdominal Injuries/classification , Abdominal Injuries/epidemiology , Adult , Age Factors , Air Bags , Body Mass Index , Craniocerebral Trauma/classification , Craniocerebral Trauma/epidemiology , Databases, Factual , Female , Humans , Leg Injuries/classification , Leg Injuries/epidemiology , Logistic Models , Male , Middle Aged , Thoracic Injuries/classification , Thoracic Injuries/epidemiology , United States/epidemiology , Wounds and Injuries/classification , Young AdultABSTRACT
Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit with a multifactorial pathogenesis. Topical and oral antibiotics are a mainstay treatment for inflammatory acne lesions and are widely utilized for all levels of disease severity. Over the past forty years, a gradual increase in antibacterial-resistant strains of Propionibacterium acnes has changed the way practitioners use antibiotics to manage acne. Updated recommendations call for avoiding antibiotic monotherapy and prescribing it in combination with benzoyl peroxide or retinoids. In addition to reducing the risk of developing bacterial resistance, antibiotics prescribed in combination formulations with benzoyl peroxide or retinoids are more efficacious than monotherapy, provide fast therapeutic results, and are associated with greater patient adherence due to the simplification of treatment regimens. Newer management strategies include limiting antibiotic use to the initial 3-6 months of treatment and then switching to topical retinoids for maintenance therapy.
Subject(s)
Acne Vulgaris/drug therapy , Anti-Bacterial Agents/therapeutic use , Acne Vulgaris/microbiology , Humans , Practice Guidelines as TopicABSTRACT
This article demonstrates how the intracellular compartmentalization of the S. cerevisiae host cell can be exploited to impart selectivity during the primary purification of lipid-envelope virus-like particles (VLPs). The hepatitis B surface antigen (HBsAg) was used as the VLP model in this study. Expressed HBsAg remain localized on the endoplasmic reticulum and the recovery process involves treating cell homogenate with a detergent for HBsAg liberation. In our proposed strategy, a centrifugation step is introduced immediately following cell disruption but prior to the addition of detergent to allow the elimination of bulk cytosolic contaminants in the supernatant, achieving approximately 70% reduction of contaminating yeast proteins, lipids, and nucleic acids. Recovery and subsequent treatment of the solids fraction with detergent then releases the HBsAg into a significantly enriched product stream with a yield of approximately 80%. The selectivity of this approach is further enhanced by operating under moderate homogenization pressure conditions ( approximately 400 bar). Observed improvements in the recovery of active HBsAg and reduction of contaminating host lipids were attributed to the low-shear conditions experienced by the HBsAg product and reduced cell fragmentation, which led to lower coextraction of lipids during the detergent step. As a result of the cleaner process stream, the level of product capture during the loading stage of a downstream hydrophobic interaction chromatography stage increased by two-fold leading to a concomitant increase in the chromatography step yield. The lower level of exposure to contaminants is also expected to improve column integrity and lifespan.
Subject(s)
Cell Compartmentation , Hepatitis B Surface Antigens/isolation & purification , Intracellular Space/metabolism , Saccharomyces cerevisiae/virology , Viral Envelope Proteins/isolation & purification , Viral Envelope Proteins/metabolism , Cells, Cultured , Chemical Fractionation , Detergents/chemistry , Endoplasmic Reticulum/metabolism , Hepatitis B Surface Antigens/analysis , Hepatitis B Surface Antigens/metabolism , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/metabolism , Viral Envelope Proteins/geneticsABSTRACT
Virus-like particles (VLPs) are expressed intracellularly in Saccharomyces cerevisiae and the recovery process involves the use of a detergent, which facilitates the release of VLP from host cell components. The detergent-mediated liberation of VLPs is a critical step in primary recovery and is responsible for setting the backdrop for subsequent purification in terms of product yield and characteristics of the process stream. In this paper the use of Triton X-100 detergent for the recovery of lipid envelope VLPs, using the hepatitis B surface antigen (HBsAg) as the VLP model, was investigated. To develop a framework that can be adopted in process design for future generation VLP vaccine candidates, the impact of Triton X-100 was characterized via different response factors: (i) recovery and activity of the HBsAg; (ii) level of protein and lipid contamination from the host cell; and (iii) indirect impact on the performance of an ultrafiltration step following primary recovery. Our studies identified that an increase in detergent concentration favors recovery of HBsAg only to a specific threshold, 0.5% v/v Triton X-100. Further increase in detergent results in delipidation of HBsAg leading to loss in antigenic activity. The level of contamination due to host protein and lipid co-liberation is in proportion with the amount of detergent employed. Greater membrane resistance during ultrafiltration was observed for samples generated using higher concentrations of detergent due to the increase in membrane fouling by the contaminants. Based on this study, Triton X-100 concentrations in the range of 0.2-0.5% v/v appears to be most suitable for recovery of native HBsAg. Choosing between 0.2-0.5% v/v would involve identifying a suitable tradeoff between desired product yield and the level of contamination that can be tolerated by downstream operations.
Subject(s)
Detergents/chemistry , Hepatitis B Vaccines/isolation & purification , Hepatitis B/metabolism , Octoxynol/chemistry , Saccharomyces cerevisiae/chemistry , Saccharomyces cerevisiae/virology , Virion/isolation & purification , Chemical Fractionation/methods , Emulsions/isolation & purification , Lipoproteins/isolation & purification , Lipoproteins/therapeutic use , Ultrafiltration/methodsABSTRACT
The Global Alliance for the Elimination of Lymphatic Filariasis (GAELF) has recommended exploring local health traditions of skin care and a low cost treatment paradigm for rural communities has been proposed by Vaqas and Ryan. Our case study incorporates these promising treatments for use in treating filariasis in rural communities. Patients having lymphedema of one or both lower limbs (skin: normal, thickened or with trophic/warty changes) received treatment components from ayurveda, yoga and biomedicine simultaneously: including soap wash, phanta soaking, Indian manual lymph drainage (IMLD), pre- and post-IMLD yoga exercises, and compression using bandages for 194 days, along with diet restrictions and oral herbal medicines indicated for "elephantiasis" in Ayurveda. Entry points when infected were treated with biomedical drugs. The study was conducted in the reverse pharmacology design. 112 patients and 149 lower limbs completed 194 days of treatment during 2003-2006. Significant improvements were observed in the limb circumference measurements and the frequency of acute dermatolymphangioadenitis, use of preventive antibiotics, and reduction in the number of entry points were also improved. The objective to obtain significant benefit for a common problem using locally available, sustainable and affordable means has been achieved. It has not been our purpose to show that the regimen employed is better than another but the results do pose the question--"Are there components of Ayurvedic medicine that deserve further study?" It is important to understand that the regimen has been delivered mostly at home and that participants we have treated, representing a population suffering from a common problem, have not had access to effective conservative therapy that is culturally acceptable, safe, and efficacious.
Subject(s)
Elephantiasis, Filarial/therapy , Rural Population , Analysis of Variance , Bandages , Drainage , Elephantiasis, Filarial/epidemiology , Feeding Behavior , Female , Follow-Up Studies , Hot Temperature , Humans , India/epidemiology , Lower Extremity/pathology , Middle Aged , Patient Compliance , Rural Population/statistics & numerical data , Severity of Illness Index , Skin Care , Soaps , Stockings, Compression , Time Factors , Treatment Outcome , YogaABSTRACT
A series of copolymers of 2-hydroxyethyl methacrylate (HEMA)/glycidyl methacrylate (GMA) and ethylene dimethacrylate (EGDM) were synthesized by frontal polymerization (FP). This study was conducted to investigate the effect of crosslink density, type and concentration of initiator, the use of a complex initiator system, porogen, and diluent on the most relevant parameters of FP, such as sustainability of the front, temperature profile, front velocity, and yield. The products were also characterized for intruded pore volume, pore-size distribution, epoxy-functionality number, and surface morphology. Higher crosslink densities (CLDs) and initiator concentration produced higher front velocities, whereas no trend in front temperature was noted. A complex initiation system was effective in stabilizing and increasing the polymerization yield. Relative to suspension polymerization (SP), FP products synthesized without a solvent were microporous, whereas micro-to-macroporous products were obtained in the presence of a solvent (for HEMA-EGDM polymers). We also present, explain, and discuss the exotic patterns observed under a microscope. We observed two basic types of spatial patterns, namely, planar and nonplanar patterns. The type of planar pattern observed under scanning electron microscopy (SEM) has a spatial impulse that appears as a loop followed by regular periodic motion in the radial and axial directions. This behavior gives rise to a repeating pattern that is a few microns thick. Also, nonplanar patterns, namely, layered concentric rings and winding staircase patterns, were observed under SEM.
ABSTRACT
Antibody purification seems to be safely ensconced in a platform, now well-established by way of multiple commercialized antibody processes. However, natural evolution compels us to peer into the future. This is driven not only by a large, projected increase in the number of antibody therapies, but also by dramatic improvements in upstream productivity, and process economics. Although disruptive technologies have yet escaped downstream processes, evolution of the so-called platform is already evident in antibody processes in late-stage development. Here we perform a wide survey of technologies that are competing to be part of that platform, and provide our [inherently dangerous] assessment of those that have the most promise.
Subject(s)
Antibodies/isolation & purification , Protein Engineering/methods , Antibodies/chemistry , Centrifugation/methods , Centrifugation/trends , Chromatography, Affinity/methods , Chromatography, Affinity/trends , Forecasting , Ligands , Protein Engineering/trendsABSTRACT
Robust design of a dead end filtration step and the resulting performance at manufacturing scale relies on laboratory data collected with small filter units. During process development it is important to characterize and understand the filter fouling mechanisms of the process streams so that an accurate assessment can be made of the filter area required at manufacturing scale. Successful scale-up also requires integration of the lab-scale filtration data with an understanding of flow characteristics in the full-scale filtration equipment. A case study is presented on the development and scale-up of a depth filtration step used in a 2nd generation polysaccharide vaccine manufacturing process. The effect of operating parameters on filter performance was experimentally characterized for a diverse set of process streams. Filter capacity was significantly reduced when operating at low fluxes, caused by both low filtration pressure and high stream viscosity. The effect of flux on filter capacity could be explained for a variety of diverse streams by a single mechanistic model of filter fouling. To complement the laboratory filtration data, the fluid flow and distribution characteristics in manufacturing-scale filtration equipment were carefully evaluated. This analysis identified the need for additional scale-up factors to account for non-uniform filter area usage in large-scale filter housings. This understanding proved critical to the final equipment design and depth filtration step definition, resulting in robust process performance at manufacturing scale.
Subject(s)
Biological Products/isolation & purification , Microfluidics/methods , Models, Theoretical , Ultrafiltration/instrumentation , Ultrafiltration/methods , Computer Simulation , Equipment Failure , Equipment Failure Analysis , Pilot Projects , PorosityABSTRACT
Chromatography is undoubtedly the workhorse of downstream processes, affording high resolution for bioseparations. At the same time, it has the notoriety of being the single largest cost center in downstream processing and of being a low-throughput operation. Consequently, 'chromatography alternatives' are an attractive proposition, even if only a reduction in the extent of use of packed beds can be realized. This paper reviews the current state of unit operations posing as chromatography alternatives--including membrane filtration, aqueous two-phase extraction, three-phase partitioning, precipitation, crystallization, monoliths and membrane chromatography--and their potential to do the unthinkable.