Abraar Karan

Toxicologic implications of cutaneous barriers: a molecular, cellular, and anatomical overview

The skin barrier is a complex system of chemical, biological and physical processes that together regulate the admission and expulsion of foreign agents in contact with the skin. The eggresive movement of the stratum corneum (SC) is often a measure of its integrity, and transepidermal water loss has typically been a gold standard. However, the skin barrier has several barrier systems, such as ion flux, O2, CO2 and pH, which can give an informative and sometimes more sensitive measure of the SC condition. Furthermore, the penetrative interactions with the barrier have focused around occlusive methods to promote drug delivery, the interactions of topically applied drugs with the barrier and the presence of environmental agents that can harm the barrier. However, the nature of penetrative barrier interactions must also be elucidated on a microscopic level. The variable nature of barrier function is demonstrated when comparing the skin properties of neonates and adults. In addition, new biochemical methods have used keratin metrics to improve diagnostic efficacy and barrier integrity analysis. This review addresses the aforementioned aspects of the skin barriers that require further study to help discern the complexity of this essential organ as it relates to dermatotoxicology and dermatopharmacology. Copyright

The Influence of Poverty and Culture on the Transmission of Parasitic Infections in Rural Nicaraguan Villages

Intestinal parasitic infections cause one of the largest global burdens of disease. To identify possible areas for interventions, a structured questionnaire addressing knowledge, attitude, and practice regarding parasitic infections as well as the less studied role of culture and resource availability was presented to mothers of school-age children in rural communities around San Juan del Sur, Nicaragua. We determined that access to resources influenced knowledge, attitude, and behaviors that may be relevant to transmission of parasitic infections. For example, having access to a clinic and prior knowledge about parasites was positively correlated with the practice of having fencing for animals, having fewer barefoot children, and treating children for parasites. We also found that cultural beliefs may contribute to parasitic transmission. Manifestations of machismo culture and faith in traditional medicines conflicted with healthy practices. We identified significant cultural myths that prevented healthy behaviors, including the beliefs that cutting a childs nails can cause tetanus and that showering after a hot day caused sickness. The use of traditional medicine was positively correlated with the belief in these cultural myths. Our study demonstrates that the traditional knowledge, attitude, and practice model could benefit from including components that examine resource availability and culture.

Microscopically differentiating dermatophytes from sock fibers

BACKGROUND Dermatophytes are responsible for a number of superficial fungal infections that affect millions worldwide. During microscopic observation a potassium hydroxide (KOH) fungal smear, various filamentous materials such as common textile fibers from socks can obfuscate proper discernment of dermatophytes. OBJECTIVE To differentiate dermatophytes from 9 common sock fibers. METHODS Nine different textile fiber samples were microscopically analyzed by using a KOH direct smear test; their defining structural features were compared and contrasted with those of dermatophytes. RESULTS Although there are several similarities, sock fibers tend to have a non-septate, uniform structure which differentiates them from dermatophytes. Sock fibers are also significantly larger than dermatophytes and can be viewed better at lower magnifications. LIMITATIONS There is a lack of sock samples with 100% textile fiber composition. Also, fibers were examined in a clean setting, without the detritus that normally accompanies dermatophytes in a clinical setting. CONCLUSION While textile fibers may be present in KOH preparations, their general appearance typically differs from that of dermatophytes; an observer who is familiar with these distinctions will be able to differentiate between the two.

Evaluation of Adverse Events in Self-Reported Sulfa-Allergic Patients Using Topical Carbonic Anhydrase Inhibitors

PURPOSE To investigate whether a self-reported history of allergy to sulfa-based drugs is a predictor for subsequent adverse reactions to topical carbonic anhydrase inhibitors (CAIs). METHODS A retrospective case-controlled cohort study via chart review was performed on 1,287 patients with a diagnosis of glaucoma. The outcome measure was the development of an adverse reaction (either ocular, systemic, or both) within at least 30 days after receipt of 1 of 4 classes of topical glaucoma medications: CAIs (dorzolamide and brinzolamide), prostaglandin analogues, beta-adrenergic blockers, and alpha2-adrenergic agonists. RESULTS Patients with a self-reported history of sulfa allergy had significantly more ocular adverse reactions after the initiation of any of the topical antiglaucoma medications when compared to those patients with no reported allergies. Patients with a self-reported sulfa allergy and patients who self-reported other, nonsulfa-related allergies had similar rates of adverse reactions to most of the topical medications. The patients reporting a sulfa allergy who used topical CAIs did not have more adverse reactions compared with patients who reported having other, nonsulfa-related allergies who used topical CAIs. Self-reported sulfa-allergic patients had similar rates of adverse reactions to topical CAIs compared with topical prostaglandin analogues. CONCLUSION It may be safe to use a topical CAI in patients who report a history of a sulfa allergy. Patients with medication allergies of any kind may be more likely to develop allergic reactions to other, unrelated drug classes.

Evaluating the socioeconomic and cultural factors associated with pediatric burn injuries in Maputo, Mozambique

BackgroundPediatric burn injuries are one of the leading causes of preventable morbidity and mortality in Sub-Saharan Africa. Research on the complex system of social, economic and cultural factors contributing to burn injuries in this setting is much needed.MethodsWe conducted a prospective questionnaire-based analysis of pediatric burn patients presenting to the Hospital Central de Maputo. A total of 39 patients were included in the study. Interviews were conducted with the children’s caretakers by two trained medical students at the Eduardo Mondlane Medical School in Maputo with the aid of local nursing staff.ResultsMost burns occurred from scald wounds (26/39) particularly from bathwater, followed by fire burns (11/39). Burns occurred more frequently in the afternoon (16/39) and evening (16/39). Over one quarter of burns (9/33) occurred in the absence of a caretaker. One-third (12/36) of participants attempted to treat the burn at home prior to bringing the child into the hospital, and roughly two-thirds (24/37) reported using traditional remedies for burn care. The average household had just 2 rooms for an average of 5 family members. Most burns were second degree (25/37).ConclusionsPrevention efforts in this setting are much needed and can be implemented taking complex cultural and social factors into account. Education regarding regulation of water temperature for baths is important, given the prevalence of scald burns. Moreover, the introduction of low-cost, safer cooking technology can help mitigate inhalation injury and reduce fire burns. Additionally, burn care systems must be integrated with local traditional medical interventions to respect local cultural medicinal practices.

The effect of a visual aid on the comprehension of cataract surgery in a rural, indigent South Indian population

PURPOSE To determine whether a visual aid improves the understanding and retention of information presented during informed consent for rural, indigent patients presenting for cataract surgery. MATERIALS AND METHODS This was a randomized, unmasked, interventional study. We recruited patients who presented to the Hande Surgical Hospital in Chennai, India, for cataract surgery. Patients were randomized into two groups: verbal consent alone (group A) and verbal consent plus a poster (group B). Both groups completed an 11-question true/false quiz immediately before and after informed consent and one day after surgery. RESULTS A total of 60 patients were recruited for the study, with 30 randomly assigned to each group; 23 patients from group A and 17 from group B completed the study. Informed consent improved patient scores in both groups; however, group B had significantly higher mean scores on postoperative day 1 (7.4 vs 8.7, P = 0.005) and significantly greater improvement in mean scores from pre-informed consent to postoperative day 1 (1.3 vs 3.6, P = 0.002). CONCLUSIONS Informed consent improves patient understanding of cataract surgery. Using a visual aid during informed consent for cataract surgery improves understanding and retention of information more than verbal consent alone in a rural South Indian population.

Ebola and the need for restructuring pharmaceutical incentives.

The Ebola outbreak in West Africa has claimed the lives of over 9000 people largely due to a combination of poor health care infrastructure in affected countries, traditional beliefs and cultural practices, including the consumption of bushmeat and certain burial rituals that have amplified transmission, and the lack of therapeutic interventions such as medications and vaccinations [1,2]. Ebola virus was discovered in 1976, and since then there have been over 30 outbreaks, the majority occurring in Sub-Saharan Africa, yet development of medications has been negligible [3]. Moreover, while the current epidemic has spurred a new race to develop Ebola vaccines and treatment regimens, the current patent system makes it unlikely that people in the most afflicted nations will have access to such vaccines or medications when they are brought to market without the assistance of development aid initiatives from the United Nations (UN), World Health Organization, the GAVI Alliance and other multinational global entities. While there have been just a handful of deaths outside of Africa, the vast majority of fatalities from Ebola virus have been in low-income African countries. This is largely because wealthy nations have been able to mount strong public health responses through providing effective medical care to stabilize patients, enforcing strict isolation protocols to prevent further transmission, and accessing experimental therapies for use in their populations, including ZMapp and TKM-Ebola [4]. Several other drugs and vaccines are also under rapid development, most notably ChAd3, which was recently highlighted in the New England Journal of Medicine as having immunogenicity in humans [5]. According to a February 2015 press release from the UN and WHO, large-scale research trials have now begun in Liberia, with Sierra Leone and Guinea to follow soon [6]. But when these drugs are fully approved for international distribution, will they be affordable for all? Given the current global drug-patenting paradigm with its 20-year delay on generic competition, patent holders can set drug prices as high as they please, effectively making their drugs inaccessible to poor populations. Moreover, with a limited supply of Ebola medications even in the near future, wealthy nations will likely stockpile the drugs and vaccines as was done with Tamiflu in 2009 [7], preventing poorer nations from accessing therapy to treat those who are currently infected. There is no financial or political mechanism to ensure that drugs and vaccines are available and affordable for the people of Guinea, Liberia, Sierra Leone and other poor nations at high risk of Ebola epidemics. As of December 2014, the GAVI Alliance has made a commitment of US

The effect of multimedia interventions on the informed consent process for cataract surgery in rural South India.

300 million to purchase Ebola vaccines for those in affected countries, but this is only an ad hoc solution as opposed to a fundamental restructuring of the system [8]. Photo: Courtesy of Alasdair Campbell, personal collection The affordable provision of treatment for people in West Africa is not only an ethical imperative, but also the best strategy to keep Ebola from spreading to other continents on a larger scale. Ultimately, the international community must intervene to ensure that future Ebola medications are sold at a tiered price to developing countries that are most heavily afflicted. But it remains unclear if this can or will happen. While making Ebola medications accessible to all will be the challenge going forward, we should also ask why no therapy for this high-fatality virus was brought to market since its discovery 40 years ago. The reason lies in the way our pharmaceutical innovation system is structured. Four years ago, scientists at the National Institute of Allergy and Infectious Disease developed an Ebola vaccine that was able to prevent animal transmission, but no pharmaceutical company was interested in taking it to trial in human subjects [9]. While there are programmes, such as the USAID Emerging Pandemic Threats programme, to detect potential pandemic illness, there is little financial promise for major pharmaceutical companies to invest in vaccines or drugs for these potential threats until they are a threat to countries that have consumers who can afford them [10]. Had there been significant Ebola outbreaks in affluent nations rather than in Sub-Saharan Africa in the past few decades, we would likely have an arsenal of medications in stock today. While pharmaceutical companies continue to profit from sales of non-essential medicines, and neglect investments in medicines that are needed mainly by the poor, the global community ends up paying as result. Current estimates by the World Bank put the cost of the Ebola outbreak at upwards of US

Global general pediatric surgery partnership: The UCLA–Mozambique experience

32.6 billion by the end of 2015 – vastly more than what it would have cost to develop effective therapies to stop the epidemic in its tracks [11]. Ultimately, the approach to controlling developing pandemic diseases is multifold. Strengthening health systems, as discussed by Boozary et al., will be important for controlling the spread of disease [12]. However, without access to medications, strong health systems can only do so much to prevent transmission and provide effective care. To cure patients and suppress further transmission, an effective complement to the current pharmaceutical drug development system is urgently needed (Table 1). Table 1 Mechanisms to incentivize drug development for Ebola and other diseases of the poor As described in detail in The Lancet by Banerjee et al., the Health Impact Fund (HIF) can play this role and help overcome the current inefficiencies and inequities of the patent system [13]. The HIF would give pharmaceutical innovators the option of registering any new medicine, thereby agreeing to provide it at cost anywhere it is needed. In exchange, the firm is rewarded based on the drug’s actual health impact, in essence its success in reducing morbidity and mortality. The HIF would pay out a fixed amount of money each year, divided among the registered medicines according to their respective health impact. The HIF would be most attractive for products that are expected to have a large global health impact but relatively low profitability under conventional monopoly pricing. If most countries agreed to contribute around 0.01% of their GNI, the HIF could get started with annual reward pools of US

The potential for political leadership in HIV/AIDS communication campaigns in Sub-Saharan Africa

6 billion. Ebola is no isolated case. Several hundred new infectious diseases have emerged in the last century, mostly in low-income regions, and under present rules global market forces have proven insufficient to promote innovation. By rewarding health impact regardless of the patient’s socioeconomic status, the HIF would provide strong incentives to study such diseases, to develop remedies against them and to promote optimal use of treatments even in the poorest regions [14]. The HIF would answer a moral imperative—to respect and protect the health and lives of the poor—as well as a prudential one—to be smart and proactive in our perennial battle against disease.