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Scholarly Works (17 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2014)

Objective

To assess whether being able to quit smoking is an early marker of Parkinson disease (PD) onset rather than tobacco being "neuroprotective," we analyzed information about ease of quitting and nicotine substitute use.

Methods

For this case-control study, we identified 1,808 patients with PD diagnosed between 1996 and 2009 from Danish registries, matched 1,876 population controls on sex and year of birth, and collected lifestyle information. We estimated odds ratios and 95% confidence intervals with logistic regression adjusting for matching factors and confounders.

Results

Fewer patients with PD than controls ever established a smoking habit. Among former smokers, those with greater difficulty quitting or using nicotine substitutes were less likely to develop PD, with the risk being lowest among those reporting "extremely difficult to quit" compared with "easy to quit." Nicotine substitute usage was strongly associated with quitting difficulty and duration of smoking, i.e., most strongly among current smokers, followed by former smokers who had used nicotine substitutes, and less strongly among former smokers who never used substitutes.

Conclusions

Our data support the notion that patients with PD are able to quit smoking more easily than controls. These findings are compatible with a decreased responsiveness to nicotine during the prodromal phase of PD. We propose that ease of smoking cessation is an aspect of premanifest PD similar to olfactory dysfunction, REM sleep disorders, or constipation and suggests that the apparent "neuroprotective" effect of smoking observed in epidemiologic studies is due to reverse causation.
    Cover page: Parkinson disease and smoking revisited
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2014)
    OBJECTIVE: To assess whether being able to quit smoking is an early marker of Parkinson disease (PD) onset rather than tobacco being neuroprotective, we analyzed information about ease of quitting and nicotine substitute use. METHODS: For this case-control study, we identified 1,808 patients with PD diagnosed between 1996 and 2009 from Danish registries, matched 1,876 population controls on sex and year of birth, and collected lifestyle information. We estimated odds ratios and 95% confidence intervals with logistic regression adjusting for matching factors and confounders. RESULTS: Fewer patients with PD than controls ever established a smoking habit. Among former smokers, those with greater difficulty quitting or using nicotine substitutes were less likely to develop PD, with the risk being lowest among those reporting extremely difficult to quit compared with easy to quit. Nicotine substitute usage was strongly associated with quitting difficulty and duration of smoking, i.e., most strongly among current smokers, followed by former smokers who had used nicotine substitutes, and less strongly among former smokers who never used substitutes. CONCLUSIONS: Our data support the notion that patients with PD are able to quit smoking more easily than controls. These findings are compatible with a decreased responsiveness to nicotine during the prodromal phase of PD. We propose that ease of smoking cessation is an aspect of premanifest PD similar to olfactory dysfunction, REM sleep disorders, or constipation and suggests that the apparent neuroprotective effect of smoking observed in epidemiologic studies is due to reverse causation.
      Cover page: Parkinson disease and smoking revisited: ease of quitting is an early sign of the disease.
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2015)

      Objective

      To examine the association between head injuries throughout life and the risk for Parkinson disease (PD) in an interview-based case-control study.

      Methods

      We identified 1,705 patients diagnosed with PD at 10 neurologic centers in Denmark in 1996-2009 and verified their diagnoses in medical records. Patients were matched to 1,785 controls randomly selected from the Danish Central Population Register on sex and year of birth. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression.

      Results

      We observed no association between any head injury before first cardinal symptom and PD (OR 1.02; 95% CI 0.88, 1.19). Examination of number of head injuries (1: OR 1.02; 95% CI 0.87, 1.20; ≥2: OR 1.03; 95% CI 0.72, 1.47) or hospitalization for a head injury (OR 0.89; 95% CI 0.70, 1.12) did not show an association with PD. For 954 study subjects with at least one head injury, there was no evidence of an association between loss of consciousness (OR 0.89; 95% CI 0.67, 1.17), duration of loss of consciousness (≤1 minute: OR 0.93; 95% CI 0.58, 1.49; 1-5 minutes: OR 0.74; 95% CI 0.51, 1.08; ≥5 minutes: OR 0.81; 95% CI 0.53, 1.24), or amnesia (OR 1.31; 95% CI 0.88, 1.95) and risk for PD. Application of a lag time of 10 years between head injury and first cardinal symptom resulted in similar risk estimates.

      Conclusions

      The results do not support the hypothesis that head injury increases the risk for PD.
        Cover page: Head injury and risk for Parkinson disease
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2019)
        Cancer patients are at lower risk of developing Parkinson's disease (PD) compared with the general population. One explanation is the negative association between smoking and PD, but PD risk is also lower for cancers not related to smoking. Another explanation is survival bias where death from cancer may act as a competing risk. We conducted a large population-based case-control study in Denmark and investigated whether cancer diagnosis reduced the risk of developing PD even after adjusting for important risk factors including smoking, physical activity, and lifetime oestrogen status. Using probabilistic bias analysis we quantified the influence of survival bias. We estimated negative point estimates (ORs) between cancers and PD for all cancers except skin, female breast, and ill-defined and unspecified 0.85 (95% CI 0.59-1.21); smoking-related cancers 0.75 (95% CI 0.45-1.23); and cancers not related to smoking 0.82 (95% CI 0.49-1.38) that are very similar to those previously reported for a much larger Danish register only based study, even though our confidence intervals include the null. These effect estimates shifted towards the null after accounting for survival bias but most bias-adjusted ORs remained below 1 within the range of priors considered in simulations. Overall, cancer patients have a lower risk of developing PD even after controlling for cancer-related lifestyles factors and correcting for survival bias.
          Cover page: Cancers Preceding Parkinson's Disease after Adjustment for Bias in a Danish Population-Based Case-Control Study.
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2019)
          Cancer patients are at lower risk of developing Parkinsons disease (PD) compared with the general population. One explanation is the negative association between smoking and PD, but PD risk is also lower for cancers not related to smoking. Another explanation is survival bias where death from cancer may act as a competing risk. We conducted a large population-based case-control study in Denmark and investigated whether cancer diagnosis reduced the risk of developing PD even after adjusting for important risk factors including smoking, physical activity, and lifetime oestrogen status. Using probabilistic bias analysis we quantified the influence of survival bias. We estimated negative point estimates (ORs) between cancers and PD for all cancers except skin, female breast, and ill-defined and unspecified 0.85 (95% CI 0.59-1.21); smoking-related cancers 0.75 (95% CI 0.45-1.23); and cancers not related to smoking 0.82 (95% CI 0.49-1.38) that are very similar to those previously reported for a much larger Danish register only based study, even though our confidence intervals include the null. These effect estimates shifted towards the null after accounting for survival bias but most bias-adjusted ORs remained below 1 within the range of priors considered in simulations. Overall, cancer patients have a lower risk of developing PD even after controlling for cancer-related lifestyles factors and correcting for survival bias.
            Cover page: Cancers Preceding Parkinsons Disease after Adjustment for Bias in a Danish Population-Based Case-Control Study.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2023)

            While associations between maternal infections during pregnancy and childhood leukemia in offspring have been extensively studied, the evidence for other types of childhood cancers is limited. Additionally, antibiotic exposure during pregnancy could potentially increase the risk of childhood cancers. Our study investigates associations between maternal infections and antibiotic prescriptions during pregnancy and the risk of childhood cancer in Taiwan. We conducted a population-based cohort study using the Taiwan Maternal and Child Health Database (TMCHD), linked with national health and cancer registries. The study included 2 267 186 mother-child pairs, and the median follow-up time was 7.96 years. Cox proportional hazard models were utilized to estimate effects. Maternal infections during pregnancy were associated with a moderate increase in the risk of childhood hepatoblastoma (adjusted hazard ratio [HR] = 1.34; 95% confidence interval [CI]: 0.90-1.98) and a weaker increase in the risk of childhood acute lymphoblastic leukemia (ALL) (adjusted HR = 1.15; 95% CI: 0.99-1.35). Antibiotic prescriptions during pregnancy were also associated with an elevated risk of childhood ALL (adjusted HR = 1.30; 95% CI: 1.04-1.63), particularly with tetracyclines (adjusted HR = 2.15; 95% CI: 1.34-3.45). Several specific antibiotics were also associated with an increased risk of hepatoblastoma and medulloblastoma. Children exposed in utero to antibiotic prescription or both infections and antibiotics during pregnancy were at higher risk of developing ALL. Our findings suggest that there are associations between maternal infections, antibiotic use during pregnancy and the risk of several childhood cancers in addition to ALL and highlight the importance of further research in this area.

              Cover page: Maternal medically diagnosed infection and antibiotic prescription during pregnancy and risk of childhood cancer: A population-based cohort study in Taiwan, 2004 to 2015.
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2018)

              Objective

              To investigate whether cigarette smoking interacts with genes involved in individual susceptibility to xenobiotics for the risk of Parkinson disease (PD).

              Methods

              Two French population-based case-control studies (513 patients, 1,147 controls) were included as a discovery sample to examine gene-smoking interactions based on 3,179 single nucleotide polymorphisms (SNPs) in 289 genes involved in individual susceptibility to xenobiotics. SNP-by-cigarette smoking interactions were tested in the discovery sample through an empirical Bayes (EB) approach. Nine SNPs were selected for replication in a population-based case-control study from California (410 patients, 845 controls) with standard logistic regression and the EB approach. For SNPs that replicated, we performed pooled analyses including the discovery and replication datasets and computed pooled odds ratios and confidence intervals (CIs) using random-effects meta-analysis.

              Results

              Nine SNPs interacted with smoking in the discovery dataset and were selected for replication. Interactions of smoking with rs4240705 in the RXRA gene and rs1900586 in the SLC17A6 gene were replicated. In pooled analyses (logistic regression), the interactions between smoking and rs4240705-G and rs1900586-G were 1.66 (95% CI 1.28-2.14, p = 1.1 × 10-4, p for heterogeneity = 0.366) and 1.61 (95% CI 1.17-2.21, p = 0.003, p for heterogeneity = 0.616), respectively. For both SNPs, while smoking was significantly less frequent in patients than controls in AA homozygotes, this inverse association disappeared in G allele carriers.

              Conclusions

              We identified and replicated suggestive gene-by-smoking interactions in PD. The inverse association of smoking with PD was less pronounced in carriers of minor alleles of both RXRA-rs4240705 and SLC17A6-rs1900586. These findings may help identify biological pathways involved in the inverse association between smoking and PD.
                Cover page: Smoking and Parkinson disease
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2018)

                Background

                Prenatal exposure to air pollution and smoking increases the risk of pregnancy complications and adverse birth outcomes, but pathophysiologic mechanisms are still debated. Few studies to date have examined the influence of air pollution on uterine vascular resistance and no studies have examined the independent impact of these exposures. We aimed to assess the impact of prenatal exposure to traffic-related air pollution and smoking on uterine vascular resistance.

                Methods

                Our study included 566 pregnant women recruited between 1993 and 1996 in Los Angeles who completed visits at three gestational ages. Information on smoking was collected and uterine vascular resistance was measured at each visit by Doppler ultrasound. We calculated three resistance indices: the resistance index (RI), the pulsatility index (PI), and the systolic/diastolic (S/D) ratio. We estimated exposure to NO2 at the home address of the mother using a land use regression (LUR) model and to NOx using CALINE4 air dispersion modeling. We used generalized linear mixed models to estimate the effects of air pollution and smoking on uterine vascular resistance indices.

                Results

                LUR-derived NO2 and CALINE4-derived NOx exposure increased the risk of high uterine artery resistance in late pregnancy. Smoking during pregnancy also increased the risk of higher uterine resistance and contributed to bilateral notching in mid-pregnancy.

                Conclusion

                Our results suggest that uterine vascular resistance is a mechanism underlying the association between smoking and air pollution, and adverse birth outcomes.
                  Cover page: Prenatal air pollution exposure, smoking, and uterine vascular resistance
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2013)

                  Background

                  Household pesticide use is widespread in the USA. Since the 1970s, organophosphorus chemicals (OPs) have been common active ingredients in these products. Parkinson's disease (PD) has been linked to pesticide exposures but little is known about the contributions of chronic exposures to household pesticides. Here we investigate whether long-term use of household pesticides, especially those containing OPs, increases the odds of PD.

                  Methods

                  In a population-based case-control study, we assessed frequency of household pesticide use for 357 cases and 807 controls, relying on the California Department of Pesticide Regulation product label database to identify ingredients in reported household pesticide products and the Pesticide Action Network pesticide database of chemical ingredients. Using logistic regression we estimated the effects of household pesticide use.

                  Results

                  Frequent use of any household pesticide increased the odds of PD by 47% [odds ratio (OR)=1.47, (95% confidence interval (CI): 1.13, 1.92)]; frequent use of products containing OPs increased the odds of PD more strongly by 71% [OR=1.71, (95% CI: 1.21, 2.41)] and frequent organothiophosphate use almost doubled the odds of PD. Sensitivity analyses showed that estimated effects were independent of other pesticide exposures (ambient and occupational) and the largest odds ratios were estimated for frequent OP users who were carriers of the 192QQ paraoxonase genetic variant related to slower detoxification of OPs.

                  Conclusions

                  We provide evidence that household use of OP pesticides is associated with an increased risk of developing PD.
                    Cover page: Household organophosphorus pesticide use and Parkinson’s disease
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2020)

                    Gestational risk factors such as birth weight, gestational age and parity have been repeatedly found to be related to pediatric cancers, but few reports have emerged from Asian countries. Here we report on demographic and gestational factors in a Taiwanese cohort. Our study included all children born in Taiwan 2004-2014 for whom there was a birth record (n = 2,079,037), of which 1900 children had been diagnosed with cancer prior to age 12. We conducted multivariable hazard regression to examine associations between demographic and gestational factors with cancer. Greater parity (family with 2+ older children) was related to acute myeloid leukemia [Hazard ratio (HR) = 2.15, 95% confidence interval (CI): 1.31, 3.55), central nervous system tumors (HR = 1.67, CI: 1.13, 2.48) and neuroblastoma (HR = 1.67, CI: 1.07, 2.63). Hepatoblastoma cases had a higher risk of low birth weight (<2,500 g; HR = 3.01, CI: 1.85, 4.91), very preterm birth (<33 weeks gestation; HR = 13.71, CI: 7.45, 25.23), plural pregnancies (HR = 2.37, CI: 1.10, 5.14) and both small (HR = 2.13, CI: 1.23, 3.67) and large (HR = 1.83, CI: 1.01, 3.32) for gestational age. Germ cell tumors were more common among children born in rural areas (HR = 1.63, CI: 1.02, 2.60). Despite that Taiwan has lower rates of both high and low birthweight compared to other developed nations, we observed several similar associations to those reported in Western Countries. Further research should examine unique exposures in Taiwan that may be contributing to higher incidence of certain cancer types.

                      Cover page: Gestational risk factors and childhood cancers: A cohort study in Taiwan.
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