Due to the cross-sectional nature, it was not possible to ascertain the vaccination status of calves in the study with certainty, instead we relied on the in-person survey reported vaccination protocols, although respondents were asked to answer the questions with respect to the current cohort of calves on their premises during the visit. If calves were older than the age of vaccination stated in the questionnaire they were considered vaccinated. However, the true vaccination status and time since vaccination may have been different for an unknown number of calves. No associations between reported vaccination status and BRD were found when calves at least 7 d older than age of vaccination were considered vaccinated to account for time to initiate an immune response. Our findings correlated with a randomized clinical trial by Windeyer et al. of 2,874 heifer calves on 19 commercials dairy farms in Minnesota and Ontario, in which they found no difference in risk of BRD between calves vaccinated at 2 or 5 wk of age or both with a commercial multi-valent modified live vaccine against the common respiratory viruses compared with a placebo control group. Those authors cited interference by maternal antibodies, unresponsiveness of the neonatal immune system, timing of immunity relative to pathogen exposure, disease caused by pathogens other than the viruses in the vaccine, or herd immunity as possible explanations for their findings. The vaccination of dams may only be effective in preventing calfhood BRD in combination with adequate transfer of passive immunity. Many factors can affect the efficiency of transfer of passive immunity, from the amount, quality,cannabis grow facility layout and timing of colostrum fed to the storage time and temperature . It is possible that any positive effect of dam vaccination may have been diluted by other variables affecting transfer of passive immunity.
In a longitudinal study following over 11,300 preweaned calves on 5 dairies in California and associating management factors to BRD in the calves, vaccinating dams with either a killed or a modified live vaccine reduced the risk of disease in calves. . The longitudinal study design combined with close follow-up of management practices by verifying changes every 1 to 4 mo in a few dairies may have been the reason that study found these associations, whereas in the present study they were not apparent. The complexity of factors involving vaccination of neonatal calves combined with the present study design make it difficult to extend recommendations based on our findings.Although the benefits of colostrum on calf health have been previously reported , we found no association between volume, source, quality, or storage conditions of colostrum and BRD in the study herds. Windeyer et al. reported serum total protein levels ≥5.7 g/dL during the first week of life as well as supplementation with an antibody product at birth to be negatively associated with BRD, but the predictive value positive was low when using serum total protein levels at the cut point of <5.7 g/dL to predict BRD. In a study by Virtala et al. , low post colostral total serum IgG concentrations ≤1,200 mg/dL was associated with increased risk of BRD in a prospective cohort study of 410 preweaned heifer calves. Diagnostic accuracy of prediction in that study was 54%. Both groups of authors stated that additional factors could play a role in the development of BRD. The current study did not include data on failure of transfer of passive immunity for the study calves. The data on volume of colostrum fed as well as whether colostrum from first-calf heifers was used and if the quality of colostrum was assessed served as proxies for adequate passive transfer. The fact that all colostrum-management variables had to be assessed on a herd-level basis may have masked the effect of colostrum quality fed to individual calves in the study, as it was unknown which calves received colostrum from first-calf heifers or colostrum stored at a certain temperature or for a certain amount of time if there was variability within a dairy.The cross-sectional nature of the study prohibits drawing of causal inferences. Although a longitudinal study design would have allowed us to draw causal inferences, the large number and wide geographic distribution of dairies enrolled did not allow such a study.
However, findings reported here provide the basis for hypothesizing potentially causal factors and promote the design of further studies with longitudinal design to directly examine housing and management factors found to be associated with BRD. Participating dairies were not chosen randomly from all dairies in California, and it could be argued that those willing to invite researchers onto their dairy might differ from those who do not. However, considering the wide geographic distribution of dairies, the inclusion of both organic and conventional operations, and a wide range of herd sizes, as well as representation of Holstein and Jersey breeds, in the sample further ensures that the spectrum of California dairy operations was captured in the current study population.Among PLWH, the average self-reported marijuana use in the past six months ranges between 25% and 56% . The prevalence of daily or nearly daily marijuana use among PLWH is on the rise . The increasing prevalence of marijuana use among PLWH corresponds with recent trends in passage of state laws governing recreational and medical marijuana across the United States. Currently, 33 states and the District of Columbia have passed legislation allowing marijuana for medical or recreational use . PLWH report using marijuana as a self-medicating strategy to manage HIV related symptoms such as nausea, pain, mood problems, and poor appetite . However, data on the potential benefits or adverse health effects of marijuana use in this population are limited . The endocannabinoid system is comprised of two endogenous receptors: cannabinoid receptors 1 and cannabinoid receptors 2 . CBR1 are located primarily in the central nervous system including the brain , while CBR2 are on cells and tissues of the immune system . The primary component in marijuana, delta-9- tetrahydrocannabinol partially binds to and activates CBR1 . Stimulation of CBR1 by THC increases appetite and promotes caloric consumption , suggesting that regular marijuana use may promote weight gain and concomitant higher body mass index , an established risk factor for type 2 diabetes . By contrast, studies have shown that marijuana use is either not associated with BMI/waist circumference or significantly associated with lower BMI and smaller waist circumference . Additionally, prior studies have found lower odds of metabolic syndrome , hyperglycemia , insulin resistance , and mean fasting glucose among current marijuana users compared with nonusers.
One recently published meta-analysis including eight cross sectional studies reported that marijuana use was associated with reduced odds of type 2 diabetes . In addition to cross-sectional findings, at least two longitudinal studies have examined the association of marijuana use with incident type 2 diabetes. Bancks et al. prospectively followed up 2,758 men and women in the Study of Coronary Artery Risk Development in Young Adults , who contributed more than 50,000 person-years of follow-up and found no statistically significant association between marijuana use and incident type 2 diabetes, but found a higher risk of prediabetes in participants with greater lifetime marijuana use compared to never users . Similarly, in their analysis of a population-based cohort of men and women in Sweden, Danielsson et al. found no statistical relationship between marijuana use and incident type 2 diabetes. Majority of prior studies of the association between marijuana use and type 2 diabetes have been cross-sectional,indoor grow shelves and existing longitudinal studies have employed few measurement occasions of cannabis use or long follow-up measurement intervals and few follow-ups of participants. As such, prospective analysis of data with multiple, short-term spacing of marijuana measurement over a long-term period of participant follow-up, better documents changes in marijuana use in relation to incident type 2 diabetes. In addition, a prospective analysis of this type can better explore potential reverse associations between marijuana use and incident type 2 diabetes, i.e., pre–type 2 diabetes symptoms resulting in an individual potentially ceasing or reducing marijuana use during the follow-up period. In addition, prior studies have not adequately addressed the role of other confounders on the relationship between marijuana use and type 2 diabetes. For instance, marijuana use is positively associated with tobacco smoking and illicit drug use such as cocaine, heroin, methamphetamine, and other stimulants . Tobacco smoking and stimulant use have been associated with suppression of appetite and lower body weight . Further, to our knowledge, no longitudinal analysis has addressed this question despite the high prevalence of marijuana use and two-fold higher prevalence of type 2 diabetes among PLWH compared with the prevalence in the general population of adults . The objective of this analysis is to determine whether self-reported frequency of marijuana use is associated with incident type 2 diabetes in women and men living with and at risk for HIV.
We aimed to address this question by examining the potential role of reverse causality on the relationship between self-reported marijuana use and type 2 diabetes using prospectively collected data from two large, long-term cohort studies of women and men living with and at risk for HIV with long-term follow-up. Given what is known about the mechanisms relating marijuana use to stimulation of appetite and increased caloric intake, we hypothesized that marijuana use will be associated with increased risk of type 2 diabetes. The Multicenter AIDS Cohort study and Women’s Interagency HIV Study are wellestablished, ongoing, prospective multicenter cohorts of men who have sex with men and women living with or at risk for HIV in the United States, respectively. Eligibility criteria and follow-up procedures for the MACS and WIHS have been previously described. Participants in the MACS were recruited at four centers: Baltimore, Maryland/Washington, DC; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Participants in the WIHS were recruited from ten sites in Brooklyn, New York; the Bronx/Manhattan, New York; Washington, DC; Chicago, Illinois; San Francisco, California; Los Angeles, California; Chapel Hill, North Carolina; Atlanta, Georgia; Birmingham, Alabama/Jackson, Mississippi; and Miami, Florida. The MACS enrolled men who have sex with men across three waves: 4,954 in 1984–1985, 668 in 1987– 1991, and 1350 in 2001–2003 . The WIHS enrolled women across 4 waves: 2623 in 1994–1995, 1,143 in 2000–2001, 371 in 2011–2012, and 845 in 2013–2015 . Data in both cohorts are collected using structured interviews and standardized physical and laboratory assessments, with study visits typically occurring every six months. HIV status was assessed by enzyme-linked immunosorbent assay with confirmatory testing at baseline for HIV-positive participants. The study questionnaires used in the MACS are available at www.aidscohortstudy.org and in the WIHS at https:// statepi.jhsph.edu/wihs/wordpress/. The institutional review boards at the respective study centers approved the MACS and WIHS study protocols, and all participants provided written informed consent. For both cohorts, the index visit was defined as the first visit at which fasting blood glucose data were available and we included HIV-positive participants with confirmatory testing at baseline and HIV-negative participants. For the WIHS, we included participants who were active beginning from October 2000 to September 2017. Fasting glucose was measured at each follow-up visit beginning from October 2000 through March 2003 and then annually thereafter. Hemoglobin A1C was measured beginning from October 2000, annually through March 2006, suspended from April 2006 through October 2010 and then measured annually thereafter. Of the 4,099 active WIHS participants in October 2000, we excluded those with prevalent type 2 diabetes at the index visit , those with less than 3 follow-up visits and those who seroconverted during the follow-up period , leaving a final analysis sample of 3,578. For the MACS, we included participants who were active beginning from April 1999 to September 2017. Fasting glucose and Hemoglobin A1C was measured in the MACS biannually during the study follow-up period. Of the 3,570 active MACS participants in April 1999, we excluded those with prevalent type 2 diabetes at the index visit , those with less than 3 follow-up visits and those who seroconverted during the follow-up period , leaving a final analysis sample of 2,682. 90 mm Hg, or diagnosed with hypertension and use of medications. Family history of diabetes, alcohol use, smoking status, and illicit drug use were self-reported at every visit.