Shorts

briefed by Jule Klotter

Antipyretic Use and Flu

Taking aspirin or other antipyretics to reduce fever during flu has become standard advice, yet available research indicates that reducing fever is counterproductive. “The febrile response, of which fever is only one component, is a complex response involving activation of immunological, endocrinological and other physiological systems. The response is generally beneficial,” Lisa A. Greisman and Philip A. Mackowiak write in a 2002 review article. The presence of fever boosts leukocyte, macrophage, and T lymphocyte activity – infection-fighting elements of the immune system. Animal and human studies indicate that allowing a fever to run its course without antipyretics is the best medicine in many instances, including colds and flu. Antipyretic use (aspirin, acetaminophen, and ibuprofen) increased nasal symptoms in adults with colds and also extended the duration of rhinovirus shedding (Graham MH et al. J Infect Dis. 1990; 162:1277–1282). In addition to interfering with immune response, antipyretic drugs have adverse effects, as Greisman and Mackowiak point out. Acetaminophen, for example, damages the liver.

Antipyretic treatment for influenza increases mortality in animals, according to a 2010 review and meta-analysis led by Sally Eyers. Eyers and her New Zealand colleagues found no human randomized, placebo-controlled trials that looked at antipyretic treatment for influenza and mortality. They point out that most influenza A viral strains stop replicating at 38 to 41 °C (100.4–105.8 °F). Using antipyretics to lower body temperature to 33 to 37 °C (91.4–98.6 °F), the temperatures at which influenza viruses replicate in the upper respiratory tract, may prolong illness. Antipyretic use may also be contributing to mortality. “We suggest that randomized placebo-controlled trials of antipyretic use in human influenza infection are urgently required,” Eyers and colleagues write, “and that these are sufficiently powered to investigate a potential effect on mortality.”

Eyers S, Weatherall M, Shirtcliffe P, Perrin K, Beasley R. The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis. J R Soc Med. 2010: 103:403–411. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC2951171. Accessed September 6, 2014.

Greisman LA, Mackowiak PA. Fever: beneficial and detrimental effects of antipyretics. Current Opinion in Infectious Diseases. 2002;15 :241–245. Available at http://www.ufrgs.br/fisiologiacelular/site/arqs/ENSINO/artigos%20em%20PDF/Fever%20-%20beneficial%20and%20detrimental%20effects%20of%20antipyretics.pdf.

Accessed September 6, 2014.

Commensal Bacteria and Inflammation

The type of commensal bacteria living in the gut affects CD4+ T cell differentiation in the lamina propria (connective tissue below the epithelium of the intestine’s mucous membrane). Clostridium, for example, induces naïve CD4+ T cells to become Treg cells. Tregs secrete cytokines that regulate immune response. On the other hand, segmented filamentous bacterium (SFB) stimulates the production of Th17 cells, whose cytokines control infection. An abundance of Th17 cells provides more protection against infection than an abundance of Tregs; but a preponderance of Th17 cells also brings a greater risk of chronic autoimmune inflammation, as Dr. Andrew W. Campbell explains in a 2014 review article. Diet, medications, smoking, alcohol, gut motility and transit time, mucosal blood flow, and renal clearance all affect the composition of gut microbiota – which, in turn, affects T cell composition.

Campbell considers gut dysbiosis, along with environmental factors and genetics, to be a major factor in the development of autoimmunity. “There are still questions that remain to be answered: does the immune system shape the gut microbiota or vice-versa? This complex and dynamic symbiosis needs further elucidation and may help in determining the outcome of autoimmune diseases in patients,” he writes.

Campbell AW. Autoimmunity and the Gut. Autoimmune Dis. 2014. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036413. Accessed October 6, 2014.

Eye Exercises

A 2013 Canadian PLOS ONE study, led by Paula Di Noto, investigated the effect of a single session of eye exercise on visual attention and visual memory. Di Noto and colleagues hypothesized that even a short period of eye exercise could strengthen neural pathways and thereby improve visual attention. Eye movement and visual attention are controlled by similar brain areas.

Di Noto and colleagues randomized 20 volunteers into two age- and gender-matched groups. All participants completed a 10-minute rapid serial visual presentation (RSVP) task at baseline to assess visual reaction time, accuracy, and memory. RSVP consists of random and rapid (33 msec) computer presentations of either a black (nontarget) or white (target) letter separated by 50 msec without a letter. Participants responded to target letters by pressing a button on a computer keyboard. At one point in the assessment, participants were asked to identify target letters on the keyboard. After baseline assessment, the test group exercised their eyes by “following a white square on a black background through a series of paths” for 18.5 minutes. The control group watched a movie clip on a small screen, which minimized eye movement, for 18.5 minutes. All participants then completed a second RSVP task.

In the posttask RSVP assessment, the eye exercise group showed significant improvement in response accuracy when target letters were separated by just one black letter (as opposed to several black letters in a row). Letter identification in the eye exercise group also improved significantly in posttask RSVP compared with baseline. The control group showed no improvement in response accuracy or letter identification. Reaction time to target letters did not change from pretask assessment in either the eye exercise group or the control. Di Noto and colleagues say, “Theoretically, these results suggest that a common cortical network that mediates cognition, attention, and oculomotor behavior is capable of undergoing very short-term plasticity, which in turn improves subsequent performance on related tasks.”

This study indicates that visual therapy (eye exercise regimes) may be effective for improving visual function and cognition, but many questions remain. Is the RSVP task the best way to assess vision therapy? Which eye exercises provide the most benefit for specific disorders? Could vision therapy become, as the authors propose, “the most effective option for cognitive and eye-related impairments”?

Di Noto P, Uta S, DeSouza JFX. Eye exercises enhance accuracy and letter recognition, but not reaction time, in a modified rapid serial visual presentation task. PLOS ONE. March 2013;8(3). Available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0059244. Accessed September 12, 2014.

Influenza Vaccine Mandate

Over the past few years, health-care personnel have faced increased demands from employers and, in some cases, state or municipal governments to receive flu shots. The belief is that vaccinated health-care personnel will decrease the likelihood of spreading flu to patients who are at risk for developing complications. While some health-care workers willingly receive vaccination, others do not. In many cases, those who do not get vaccinated – whether by choice or for medical reasons – are required to wear surgical masks when caring for patients. Some who have refused to follow the mandate have been fired from their jobs. Mandating flu vaccination raises questions about health-care choice, privacy, and the role of evidence-based medicine.

Dr. Karen Sibert, who works in Los Angeles, California, questions the legality and effectiveness of the mandate. An October 2013 order from the director of the LA County Department of Public Health requires all health-care workers in the county to be vaccinated or to wear a mask while in patient care areas. Sibert points out that the requirement to wear a mask violates privacy and is a HIPAA violation since it publicizes information about workers’ health decisions: those without a mask were vaccinated, and those wearing masks were not.

Moreover, the push for vaccination is based on the assumption that manufacturers have chosen the correct influenza virus for a given year’s vaccine and that the vaccine is highly effective. Yet, vaccine effectiveness varies from year to year. Vaccine effectiveness for H3N2 influenza during the 2012–2013 season was only 45%, according to D. M. Skowronski et al. Siebert points out, “If I should become ill with a strain of influenza that hasn’t been covered by this year’s vaccine, since I’ve been vaccinated I don’t have to wear a mask though I could be quite contagious for at least a day before I develop overt symptoms. … If we are really to be logical and scientific about flu transmission, either we all should wear masks or none of us should bother.”

Evidence for the health-care worker (HCW) mandate is moderate to low, according to two 2013 meta-analyses. The first meta-analysis, performed by CDC researchers, used four randomized controlled trials, which they rated moderate in quality, and four observational trials. (Observational trials provide clues, not confirmation of cause and effect.) The researchers pooled results from the studies and estimated a 29% decline in patient death from all causes with the HCW mandate. They also determined a 42% decline in influenzalike illness. The rate of laboratory-confirmed influenza among patients did not significantly decline. The CDC researchers conclude that “the benefits of HCW vaccination to employees and the patients outweigh possible harms, and the practice can improve patient safety,” according to Lisa Scherring at the University of Minnesota’s Center for Infectious Disease Research and Policy (CIDRAP).

The 2013 Cochrane meta-analysis was more critical. The Cochrane team looked at three of the four randomized controlled trials used in the CDC review. All three studies took place in long-term care facilities, not hospitals where patient stays are considerably shorter. When looking at laboratory-proven influenza or its complications (e.g., lower respiratory tract infection, hospitalization, death), the team “did not identify a benefit of healthcare worker vaccination on these key outcomes. …” Moreover, the Cochrane report criticizes the studies for providing no information on other interventions, such as hand-washing, face masks, quarantine, restricting visitors, antivirals, and asking health-care workers with influenza or influenzalike illness to stay home from work, that may have been used in conjunction with HCW vaccination. In light of the CDC comment that “benefits outweigh possible harms,” I found it interesting that the Cochrane team commented that none of these studies looked at adverse effects of mandated vaccination. The Cochrane report concludes, “This review does not provide reasonable evidence to support the vaccination of healthcare workers to prevent influenza in those aged 60 years or older resident in [long-term care facilities].”

“Despite its attractive façade, employer mandated immunization policies have limited demonstrated efficacy, ignore less invasive (and more effective) alternatives and threaten to permanently undermine the rights of [healthcare workers],” write John F. Tocci and Amy Doherty in an article for the Massachusetts Bar Association Lawyers Journal. “Those rights are embodied in the ebb and flow of a century of immunization case law and the development of the concepts of a constitutional right to privacy and bodily integrity.”

Schnirring L. Analysis finds limited evidence for HCW flu vaccination. September 19, 2013. Available at http://www.cidrap.umn.edu/news-perspective/2013/09/analysis-finds-limited-evidence-hcw-flu-vaccination. Accessed March 19, 2014.

Sibert K. No HIPAA for us in healthcare. December 30, 2013. Available at http://apennedpoint.com/no-hipaa-for-us-in-healthcare/#more-899. Accessed March 26, 2014.

Skowronski, DM, Janjua NZ, DeSerres G, et al. Low 2012-2013 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses. PLoS One. March 25, 2014. Available at www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0092153. Accessed September 25, 2014.

Thomas RE, Jefferson T, Lasserson TJ. Influenza vaccination for healthcare workers who care for people aged 60 or older living in long-term care institutions [abstract]. Cochrane Report. July 22, 2013. Available at www.onlinelibrary.wiley.com/doi/10.1002/14651858.CD005187.pub4/abstract. Accessed September 29, 2014.

Tocci JF, Doherty A. Mandating flu immunization of health care workers: Not the best medicine. Lawyers Journal. Available http://www.massbar.org/publications/lawyers-journal/2013/february/mandating-flu-immunization-of-health-care-workers-not-the-best-medicine. Accessed March 26, 2014.

Myopia Prevention and Light

For decades, genetics and “close work” (i.e., reading and other activities that require the eyes to focus near the face) have drawn the blame for myopia (nearsightedness). While these two factors may play some role, recent evidence points to a more significant instigator: lack of exposure to outdoor light. In myopia, the eyeball lengthens along its axis so that the focal point hits in front of the retina. The more distant an object, the more blurry it appears.

Several Asian countries, including Singapore, Taiwan, and South Korea, are experiencing a “sharp spike in myopia rates” in young people, according to an Environmental Health Perspectives article by Tim Lougheed. Initially, researchers blamed children’s increasingly long hours performing schoolwork. Economic development in these countries requires educated workers. Computer games and entertainment have added to the amount of time children spend using close vision.

The importance of outdoor exposure became clear in a comparison study of children (6–7 years old) of Chinese ethnicity living in Singapore and in Sydney, Australia. “Although the two groups presumably shared a similar genetic predisposition to myopia,” Lougheed writes, “Their measured prevalence of this condition contrasted sharply: 3.3% among those living in Sydney versus 29.1% for those in Singapore.” The Sydney group spent just as much time performing close work as the Singapore group. Unlike the Singapore group, however, the Australian children spent more time outdoors – an average of 14 hours per week compared with Singapore’s 3 hours.

Ian Morgan, an Australian ophthalmology researcher, and colleagues hypothesize that daylight protects the eye from developing myopia. In laboratory experiments, bright light prevented myopia in animals raised in myopia-prone conditions. Light stimulates dopamine release from the retina. Dopamine appears to have a role in regulating eyeball growth.

Clinical trials in Taiwan and in Guangzhou, China, showed a 50% and 25% reduction, respectively, in new cases of myopia when children were made spend more time outdoors. Some Asian countries are now using information campaigns, directed at parents and children, to encourage outdoor time as the way to prevent myopia.

Lougheed T. Myopia: the evidence for environmental factors. Environ Health Perspect. January 2014:122(1);A12–A19. Available at http://ehp.niehs.nih.gov/122-a12. Accessed October 1, 2014.

Triphala and Cataract Prevention

Triphala, a commonly used Ayurvedic herbal formula, is known primarily as a colon tonic and laxative in the US. Among Ayurvedic practitioners in India, however, the formula is an “important and potent” balancer and rejuvenator of life’s three constitutional types (doshas). Triphala consists of Indian gooseberry (Emblica officinalis), chebulic myrobalan (Terminalia chebula), and beleric myrobalan (Terminalia belerica). Its antioxidant, anti-inflammatory, antimicrobial, blood-purifying, and immunomodulating properties have made it useful for a number of conditions including cataracts, according to D. V. Gowda and colleagues. Researchers are just beginning to investigate Triphala’s anticataract properties.

A 2010 Indian study, led by Suresh Kumar Gupta at Delhi Institute of Pharmaceutical Sciences and Research, evaluated Triphala’s ability to prevent selenite-induced cataracts in rats. Sodium selenite produces cataracts with characteristics similar to human cataracts, including increased calcium, protein aggregation, and reduced glutathione. The researchers performed in vitro experiments using rat lenses and in vivo studies with young rats. Four groups of 9-day-old pups (10 per group) received a single sodium selenite injection. One group acted as the control. The other three groups received an intraperitoneal injection of Triphala aqueous extract 4 hours before the selenite at a dose of 25, 50, or 75 mg/kg of body weight. The test mice received additional daily injections of Triphala for the next 5 days. When the pups opened their eyes on day 18 postpartum, researchers looked for cataracts using a slit lamp.

Rats given 25 mg/kg had the best response. Sixty percent of the eyes were clear, 20% had pinpoint opacity, and 20% had nuclear cataracts. The two higher doses had worse results. Only 28% of the eyes in the 50 mg/kg group were clear, and no clear eyes were found in the 100 mg/kg group. (I wonder if a dose lower than 25 mg/kg would have been even more effective.) This dose-response pattern also occurred in the in vitro experiment, which looked at Triphala’s ability to restore depleted glutathione. “Triphala restored [glutathione] levels in a concentration-dependent manner with optimal activity occurring at a dose of 800µg/ml, activity being constant up to 1000µg/ml. With further increase in the drug concentration, a gradual decline in [glutathione] activity was observed,” the authors write.

Instead of injection, a 2011 Indian study, led by K. N. Mahajan, used nasal-gastric administration to test Triphala ghrita on rats. Ghrita is ghee (purified butter oil) made from cow’s milk. The rats were randomized into five groups of five. Group A had a normal diet of standard rat chow pellets. Group B, the test control, ate a mix of powdered rat chow (70%) and galactose (30%). Group C ate the 70-30 mix along with 216 mg of Triphala ghrita in distilled water. Group D received the mix and a 1080 mg dose of Triphala. Group E received the mix and a 2160 mg dose. The rats’ eyes were checked at day 14, 21, and 30 for cataracts, which were graded into four stages.

One hundred percent of the galactose-fed control group had Stage 4 cataracts (covering the entire lens) after 30 days, while all signs of cataract formation were absent in rats eating the standard pellets. Triphala ghrita had a protective effect on the other galactose-fed groups, with Group D (1080 mg) showing the best results. After 30 days, ten% of Group D was cataract free with 60% at Stage 1 (vacuoles of less than 1/3 of lens radius) and 30% at Stage 2 (1/3 to 2/3 of radius from periphery). No rat in this group had progressed to Stage 3 or Stage 4. In comparison, 5% of high-dose Group E was cataract free, with 25% at Stage 1, 40% at Stage 2, and 30% at Stage 3 (vacuoles extend up to 2/3 from periphery). None had progressed to Stage 4. The low-dose Triphala ghrita group contained no cataract-free animals, with fairly even distribution over the four stages.

These studies indicate that Triphala prevents cataract formation in animals. More research is needed to determine the most effective dose for humans. Triphala’s ability to resolve cataracts that have already formed needs to be investigated.

Gowda DV, Muguli G, Rangesh PR, Deshpande RD. Phytochemical and pharmacological actions of Triphala: Ayurvedic formulation – a review. Int J Pharm Sci Rev Res. 2012:15(2):61–65. Available at www.researchgate.net. Accessed October 1, 2014.

Gupta SK, Kalaiselvan V, Srivastava S, Agrawal SS, Saxena R. Evaluation of anticataract potential of Triphala in selenite-induced cataract: In vitro and in vivo studies. J Ayurveda Integr Med. Oct–Dec 2010:1(4):280–286. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC3117320. Accessed on September 10, 2014.

Mahajan KN, Singhai AK, Vadnere GP. Investigation on Anticataract Activity of Triphala Ghrita. E J Chem. 2011:8(3):1438–1443. Available at www.hindawi.com/journals/jchem/2011/571627/abs. Accessed on October 1, 2014.