It is profoundly captivating, beautiful, and haunting to read great writers’ reflections on their own imminent mortality. Christopher Hitchens a few years ago, Oliver Sacks now. As if the mind is raging creatively towards that final moment, the dying of the light. Rest in Peace, Dr. Sacks.
Originally published here: http://www.clinicalcorrelations.org/?p=5899
By Jeffrey Shyu, MD
Faculty Peer Reviewed
Climate change has been linked to a variety of adverse effects on human health, effects that are expected to worsen in the coming decades . For example, a heat wave in August 2003 resulted in nearly 15000 deaths in France, and the anticipated increase in average world temperatures is expected to lead to longer and more frequent heat waves that will disproportionately affect our more vulnerable populations. Infectious disease outbreaks, particularly vector-borne ones such as malaria, are expected to rise with global warming . Wild swings in weather patterns, including large-scale flooding and droughts, will more likely occur. Smog and particulate air pollution, both of which lead to pulmonary disease and increased mortality, are expected to worsen [3, 4]. Agriculture production may be greatly impacted in certain regions of the world, raising the possibility of widespread famine .
Some of these effects are obvious, while others may surprise the reader. NYU nephrologist David Goldfarb has spoken of a possible link between climate change and the rising incidence and prevalence of yet another disorder—kidney stones. Kidney stones, also known as nephrolithiasis, are linked to a number of factors including diet, infection, and hereditary conditions like cystinuria. However, the link between climate change and nephrolithiasis has also been studied, and a literature review turns up a number of articles that touch on this question.
An intriguing report by Brikowski et al. in the Proceedings of the National Academy of Sciences (PNAS)  describes a “kidney stone belt” along the southern United States. Stone disease may be as much as 50 percent more prevalent in southern states when compared to the northwest, and according to the authors, much of this difference is attributed to differences in mean annual temperature (MAT). The authors predict that with global warming, by 2050 we will see a climate-related increase of approximately 2 million lifetime cases of kidney stones in the country, primarily in the south.
What is the mechanism? Kidney stones can form in response to metabolic and environmental factors, including low urine output from decreases in fluid intake or from increases in insensible fluid loss, mainly from sweating. When urine saturates, stone forming salts become concentrated and precipitate. The thought is that higher temperatures make people more prone to low urine output, making them more prone to stone formation.
However, the link between temperature and stone formation is not entirely clear. Some data suggest that the relationship behaves in a nonlinear fashion; that is, stone formation peaks at a certain MAT and then plateaus at higher temperatures (perhaps because people are less active at these higher temperatures). Other data suggest that the correlation is more linear. For their study, the authors employed both linear and nonlinear models using large survey datasets.
In both models, the authors of the PNAS article find that the “kidney stone belt” will grow, with the percentage of people living in high-risk zones increasing from 40 percent to 56 percent by 2050. They also estimate that the cost of treating this increase in kidney stones will cost the United States an additional $1 billion annually, not accounting for inflation.
Fakheri and Goldfarb  reanalyzed some of the data used in the PNAS study. They took the original data used by Brikowski’s non-linear model and graphed the prevalence of kidney stones with MAT, broken down by gender. They were able to show a greater association of kidney stones and increased temperature among both menand women though the effect on men was more marked. The authors speculate that this may be because men are more likely to have occupations that expose them to higher ambient temperatures. However, it has also been suggested that perhaps women are better able to keep up with fluid losses than men, via an unclear mechanism .
However, a cross-sectional survey of American soldiers returning from service in the Middle East, many of whom were likely to have been exposed to high temperatures, actually demonstrated a lower rate of nephrolithiasis (1%) compared to the general population (2-3%). The military emphasizes forced hydration to prevent heat injury, and this may be the reason why a lower rate was seen. They did find an increase of stone disease in people who have a previous history of kidney stones, and also people with a family history of the disease.
Clearly, more evidence is needed. A causal mechanism for temperature and kidney stone formation makes intuitive sense – higher temperatures make people more prone to dehydration and low urine output, encouraging stone formation. However, stone formation is a multifactorial process, and diet plays a large role as well. Diet and obesity have also been shown be strongly linked to stone formation.  However, the southern United States, which tends to get more kidney stones, also has a higher overall rate of obesity compared to the north. This is one obvious potential confounder.
Another suggested mechanism is that increases in sun exposure (specifically UV light) leads to the increased production of 1,25-OH-vitamin D, which in turn increases the absorption of dietary calcium and possibly the excretion of calcium in the kidneys . Another potential confounder certainly, however this mechanism is largely unproven and one would expect people to try to avoid the sun during times of higher temperature.
In addition to obtaining data that control for these confounders, data that show a tighter link between temperature and stone formation would be helpful. Instead of using mean annual temperature, a study that looked at the incidence of stone formation by month, or to average monthly temperature would provide more convincing evidence for an association. However, conducting that study may be complicated by the fact that stones may take months to develop before they become clinically significant. They may start to form in the hot summer days, but patients may not present with symptoms until months later. Clearly, more work is needed to establish a link between climate change and this common and very painful disease.
Dr. Jeffrey Shyu recently completed his preliminary year internal medicine residency at NYU Langone Medical Center
Peer Reviewed by David Goldfarb, Nephrology, NYU Langone Medical Center
Image courtesy of Wikimedia Commons
1. Costello A, Abbas M, Allen A, Ball S. Managing the health effects of climate change. Lancet. 2009 May 16: 373(9676): 1693-1733.http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(09)60935-1
2. Tanser FC, Sharp B, Le Sueur D. Potential effect of climate change on malaria transmission in Africa. Lancet. 2003 Nov 29. 362(9398): 1792-1798. (http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(03)14898-2)
3. Levy JJ, Chemerynski SM, Sarnat JA. Ozone exposure and mortality: an empiric bayes metaregression analysis. Epidemiology. 2005 Jul; 16(4): 458-468.
4. Pope CA, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, Thurston GD. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA. 2002 Mar 6; 287(9): 1132-1141. (http://jama.ama-assn.org/content/287/9/1132.long)
5. Parry ML, Rosenzweig C, Iglesias A, Livermore M, Fischer G. Effects of climate change on global food production under SRES emissions and socio-economic scenarios. Global Environmental Change. 2004 14: 53-67. (http://www.preventionweb.net/files/1090_foodproduction.pdf)
6. Brikowski TH, Lotan Y, Pearle MS. Climate-related increase in the prevalence of urolithiasis in the United States. Proc Natl Acad Sci USA. 2008 Jul 15; 105(28): 9841-6 (http://www.pnas.org/content/105/28/9841.long)
7. Fakheri RJ, Goldfarb DS. Association of nephrolithiasis prevalence rates with ambient temperature in the United States: a re-analysis. Kidney Int. 2009 Oct; 76(7): 798. (http://www.nature.com/ki/journal/v76/n7/full/ki2009274a.html)
8. Parks JH, Barsky R, Coe FL. Gender differences in seasonal variation of urine stone risk factors. J. Urology. 2003 170: 384-388. (http://www.jurology.com/article/S0022-5347(05)63332-0/abstract)
9. Pugliese JM, Baker KC. Epidemiology of nephrolithiasis in personnel returning from Operation Iraqi Freedom. Urology. 2009 Jul; 74(1): 56-60. (http://www.goldjournal.net/article/S0090-4295(09)00127-7/abstract)
10. Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005 Jan 26; 293(4): 455-62. (http://jama.ama-assn.org/content/293/4/455.long)
11. Goldfarb DS. Unpublished correspondence.
The content of this presentation has been published in the Journal of the American College of Radiology.
Originally presented at RSNA 2013.
Jeffrey Shyu, MD
Faculty Peer Reviewed
As the debt ceiling debate continues to rage stateside and as Greece’s financial bailout negotiations take up international headlines, this past week also proved to be a very active and exciting one for medical research.
This edition of Primecuts begins with controversy amongst experts in the spine field. A group of leading researchers submitted a scathing editorial to Spine Journal, blasting industry-sponsored research on recombinant bone morphogenetic protein-2 (rhBMP-2), a bone growth product popular in spinal fusion surgeries . Medtronic, the maker of rhBMP-2 (trade name Infuse), has sponsored trials comparing the product to bone grafts, and according to its critics, the industry-sponsored studies frequently downplayed the risk of complications such as inflammation, osteolysis, cancer, infection, and male sterility. In a literature review published in the same issue, the authors found that the level of adverse events was downplayed 10 to 50-fold, with many of the prior authors having financial ties to the maker of the product . For what it’s worth, Medtronic’s Chairman and CEO Omar Ishrak insists that the product is “safe” . I for one applaud the editors and authors of this Spine Journal issue, and more disclosure and criticism of industry-sponsored research should be had in all fields of medicine.
The value of imaging for cancer screening was another major topic this past week, as two high-profile studies were published demonstrating a mortality benefit in the use of imaging to detect cancer. In Radiology, a three-decade long trial of over 133,000 women in Sweden who were randomized to mammography screeningversus usual care found an absolute long-term benefit to mammography . The study had previously reported a 30% reduction in breast cancer mortality among 40-74 year old women , and study participants were now followed for a longer period of time. In the current study, the number of women needed to screen for a period of 7 years to prevent one breast cancer death ranged from 414 to 519. Moreover, most of the deaths that were prevented would have occurred in the first 10 years of screening. This new study will surely create additional confusion about the benefit of mammography, especially regarding when a woman should start getting the exams, given that the US Preventive Services Task Force recommended in 2009 that mammography screening for most people should begin at age 50 instead of 40 . Unfortunately, this study did not specifically look at the benefit of screening for people between 40 and 50.
Also, the New England Journal of Medicine published the final report came of a study whose results were first announced last year. This study found a 20% relative mortality risk reduction for high-risk subjects when usingchest CT compared to conventional x-ray (p 0.004) . 53,454 people were enrolled in this prospective, multi-center study, and eligible subjects included people between 55 and 74 years of age who had at least 30 pack years of smoking history. Subjects were randomized to three low-dose CTs versus conventional chest x-rays. The survival benefit was attributed to detection of cancers at an earlier stage. However, as one might expect, the rate of positive screening results was substantially higher in the CT group compared to x-ray (24.2% versus 6.9%), and false positives were 96.4% and 94.5%, respectively. Given the increased number of positive results (the vast majority false positive), many subjects underwent further diagnostic workup including further imaging; some had invasive procedures, though adverse events from invasive procedures were rare in both groups. Although the mortality benefit to CT screening is real, many more people are likely to experience the anxiety that comes with a possible (though unlikely) cancer diagnosis if this screening test becomes widely adopted.
Also in the New England Journal, a randomized, multicenter trial with over 4600 patients looked at the timing of starting parenteral nutrition for critically ill patients who cannot obtain sufficient nutrition enterally . Patients either had parenteral nutrition started within 48 hours after ICU admission (early group), or it was not initiated until after day 8 (late group). The researchers found that with late initiation, patients were 6.3% more likely to be discharged alive earlier from the ICU (p = 0.04) and from the hospital (p = 0.04). They also had fewer infections compared to the early group (22.8% versus 26.2%), although death rates in the hospital and at 90 days were similar. Previously, many had thought that early feeding (enteral or parenteral) was desirable. The authors also speculate that the increased risk of complications may be due to early parenteral nutrition causing delayed autophagy and inadequate clearance of microorganisms and cell damage.
Finally, in non-human medical news, for the second time in history a disease has been eradicated from the face of the earth [9, 10]. The first was smallpox, which most of our readers surely know about. This one is rinderpest, which is (was) a relative of measles and an ancient scourge of cattle and other cloven-hoofed animals, killing as much as 95% of afflicted creatures. Despite being noninfectious to humans, given our reliance on domesticated organisms, the virus has had a role in bringing down Rome and starting revolutions in France and Russia. But with vaccines, new diagnostic tests, and aggressive outreach to faraway lands, veterinarians have now conquered the “cattle plague”. This event should give us human doctors some optimism for eradicating our own ancient adversaries like polio or measles, although given the skepticism that some people hold towards vaccines these days, we may still have a long road ahead of us.
Dr. Jeffrey Shyu recently completed his preliminary year internal medicine residencyat NYU Langone Medical Center
Peer reviewed by Neil Shapiro, MD, Editor-In-Chief, Clinical Correlations
Image courtesy of Wikimedia Commons
1. Carragee EJ, Ghanayem AJ, Weiner BK, Rothman DJ, Bono CM. A challenge to integrity in spine publications: years of living dangerously with the promotion of bone growth factors. The Spine Journal 2011; 11: 463-468.http://www.spine.org/Pages/ConsumerHealth/NewsAndPublicRelations/NewsReleases/2011/pressrelease1_062811.aspx
2. Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. The Spine Journal 2011; 11: 471-491. http://www.spine.org/Pages/ConsumerHealth/NewsAndPublicRelations/NewsReleases/2011/pressrelease1_062811.aspx
3. Medtronic CEO Omar Ishrak statement on rhBMP-2 articles in Spine Journal. July 28, 2011.http://wwwp.medtronic.com/Newsroom/NewsReleaseDetails.do?itemId=1309287256363&lang=en_US
4. Tabár L, Vitak B, Chen TH, Yen AM, Cohen A, Tot T, Chiu SY, Chen SL, Fann JC, Rosell J, Fohlin H, Smith RA, Duffy SW. Swedish Two-County Trial: impact of mammographic screening on breast cancer mortality during 3 decades. Radiology 2011. Published online before print June 28, 2011.http://radiology.rsna.org/content/early/2011/06/15/radiol.11110469.abstract
5. Tabár L, Gad A, Holmberg LH, Ljungquist U, Kopparberg County Project Group, Fagerberg CJG, Baldetorp L, Gröntoft O, Lundström B, Mànson JC, Östergötland County Project Group, Eklund G, Day NE, Pettersson F. Reduction in mortality from breast cancer after mass screening with mammography: randomized trial from the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare. The Lancet 1985: 325 (8433). 829-832. http://www.sciencedirect.com/science/article/pii/S0140673685922044
6. US Preventive Services Task Force: Screening for breast cancer. 2009 recommendations.http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca.htm
7. The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. New England Journal of Medicine 2011. Published online ahead of print June 29, 2011. http://www.nejm.org/doi/full/10.1056/NEJMoa1102873?query=featured_homehttp://www.nejm.org/doi/full/10.1056/NEJMoa1104621
8. Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut SV, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G. Early versus late parenteral nutrition in critically ill adults. New England Journal of Medicine 2011. Published online ahead of print June 29, 2011.http://www.nejm.org/doi/pdf/10.1056/NEJMoa1102662
9. “Rinderpest, scourge of cattle, is vanquished”. Donald J. McNeil Jr. New York Times, June 27, 2011.http://http://www.nytimes.com/2011/06/28/health/28rinderpest.html
10. Declaration of global freedom from rinderpest and implementation of follow-up measures to maintain world freedom from rinderpest. Draft resolution, Thirty-seventh session of the Food and Agriculture Organization of the United Nations. Rome, June 25 – July 2 2011. http://www.fao.org/docrep/meeting/022/mb363e.pdf
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