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Biomedical subjects

Gary M Franklin

Publications and source records attributed to Gary M Franklin.

At least 19 recordsLinked to original sources
PubMed2006

Lumbar fusion outcomes in Washington State workers' compensation.

STUDY DESIGN: Retrospective population-based cohort study. OBJECTIVE: To evaluate the influence of lumbar intervertebral fusion devices on clinical and disability outcomes among Washington State compensated workers with chronic back pain. SUMMARY OF BACKGROUND DATA: The efficacy of lumbar fusion for chronic low back pain remains controversial. Recent randomized controlled trials have shown results of fusion to be equivalent to those of structured exercise and cognitive intervention. Lumbar fusion rates, however, continue to increase nationally, fueled, in part, by introduction of new fusion devices, including intervertebral cages in 1996. It is not known whether these newer devices have improved outcomes, and particularly in compensated workers. METHODS: In this population-based retrospective cohort study, we identified Washington State injured workers who underwent lumbar fusion between 1994 and 2001 from Washington State Workers' Compensation system administrative database. All the data for this study were obtained from either the claims or medical bill payment databases. Multiple logistic regression analyses were used to examine the association between the surgical technique (interbody cages and/or instrumentation) and the risk of disability, reoperation, and complications following lumbar fusion. RESULTS: Among the 1,950 eligible subjects, fusions with cages increased from 3.6% in 1996 to 58.1% in 2001. Overall disability rate at 2 years after fusion was 63.9%, reoperation rate 22.1%, and rate for other complications 11.8%. Use of cages or instrumentation was associated with increased complication risk compared with bone-only fusions without improving disability or reoperation rates. Legal, work-related, and psychologic factors predicted worse disability. Discography and multilevel fusions predicted greater reoperation risk. Degenerative disc disease and concurrent decompression procedures predicted lower reoperation risk. CONCLUSIONS: Use of intervertebral fusion devices rose rapidly after their introduction in 1996. This increased use was associated with an increased complication risk without improving disability or reoperation rates.

Cohort Studies↗
PubMed2006

Calcium channel blockers and beta-blockers in relation to Parkinson's disease.

We investigated the risk of Parkinson's disease (PD) associated with calcium channel blockers (CCBs) and beta-blockers in a population-based case-control study of 206 men and women between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 controls without PD or other neurodegenerative disorders who were frequency matched on age, sex, duration of GHC enrollment and clinic. The adjusted odds ratio associated with ever use was 0.85 (95% confidence interval [CI]: 0.43, 1.66) for CCBs, and 1.20 (95% CI: 0.71, 2.03) for beta-blockers. We observed no association with PD risk for either class of medication in terms of duration, dose, number of prescriptions or pattern of use. The weakness of these associations and the absence of additional influence of dose or duration of use argue against any causal interpretation.

Adrenergic beta-Antagonists↗
PubMed2006

5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study.

The dopamine transporter gene (SLC6A3) is a candidate gene for Parkinson's disease (PD) on the basis of its critical role in dopaminergic neurotransmission. Previously, we identified 22 SNPs in the 5' region of SLC6A3, which segregate as eight haplotypes that differ in transcriptional activity when transfected in rat dopamine-producing cells. In the present work from a case-control study size of 293 cases and 395 controls, we employed a cladistic approach to examine gene-disease association. First, we found strong evidence of balancing selection in this region, as determined by a Tajima's D statistic of 2.97 (P<0.001). Second, we found that the eight haplotypes fit into two main clades and that diplotypes of these clades were marginally associated with PD. Then, after we classified cases and controls by the number of risk alleles, accounting for the well-known 3' region VNTR polymorphism, we found that having two or more risk alleles resulted in a modest but significant increase in PD risk [odds ratio=1.58; 95% confidence interval (CI): 1.03-2.40]. Finally, we detected a significant interaction between occupational pesticide exposure in men and the number of risk alleles. Among pesticide-exposed subjects, the odds ratio for having two or more risk alleles was 5.66 (95% CI: 1.73-18.53). Thus, allelic variants in SLC6A3, which affect gene expression, are associated with PD in this population and may interact with occupational pesticide exposure to increase PD risk.

3' Flanking Region↗
PubMed2006

Nonsteroidal anti-inflammatory drugs and risk of Parkinson's disease.

Inflammation and oxidative stress have been implicated as pathogenic mechanisms in Parkinson's disease (PD). Evidence from in vitro and animal studies suggests a possible protective role of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin. We investigated the risk of PD associated with use of aspirin and nonaspirin NSAIDs in a population-based case-control study among enrollees of Group Health Cooperative, a health maintenance organization in the Seattle area. Subjects included 206 cases between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 randomly selected controls frequency-matched by age, sex, duration of enrollment, and clinic. We obtained information on participants' age, smoking, and medical history from interview. Exposure to NSAIDs was ascertained from an automated pharmacy database. Medications filled within 5 years of the interview were excluded. After adjusting for age, sex, smoking, duration of enrollment, and clinic, the risk of PD among individuals who received nonaspirin NSAIDs between 1977 and 1992 was 0.90 (95% CI: 0.59-1.35) and 1.67 (95% CI: 0.60-4.60) between 1993 and 2002. Use of ibuprofen was not associated with PD (OR: 0.89; 95% CI: 0.60-1.32). The risk of PD associated with aspirin or aspirin-containing medications was 0.74 (95% CI: 0.49-1.12). We observed no trend in risk according to number of fills for these drugs. Our results provide only limited support for the hypothesis that use of aspirin may reduce the risk of this disease, and no indication of protection from other NSAIDs.

Adult↗
PubMed2005

Diabetes, smoking, and other medical conditions in relation to Parkinson's disease risk.

Associations of Parkinson's disease (PD) with diabetes mellitus (DM) and other medical conditions were investigated in a case-control study of 352 newly diagnosed PD case and 484 control subjects. Men with DM had a significantly lower risk of PD, than men without DM (odds ratio (OR) = 0.52, 95% confidence interval (CI) = 0.28, 0.97), whereas the association in women was weaker (OR = 0.80, 95% CI = 0.35, 1.83). PD risk was reduced among male and female smokers, with and without diabetes. However, among diabetics, the PD risk was especially reduced in non-smoking men (OR = 0.09, 95% CI = 0.02, 0.44). Other medical conditions showed no strong relations with PD.

Adult↗
PubMed2005

Opioid dosing trends and mortality in Washington State workers' compensation, 1996-2002.

BACKGROUND: The use of opioids for chronic non-cancer pain has increased in the United States since state laws were relaxed in the late 1990s. These policy changes occurred despite scanty scientific evidence that chronic use of opioids was safe and effective. METHODS: We examined opiate prescriptions and dosing patterns (from computerized databases, 1996 to 2002), and accidental poisoning deaths attributable to opioid use (from death certificates, 1995 to 2002), in the Washington State workers' compensation system. RESULTS: Opioid prescriptions increased only modestly between 1996 and 2002. However, prescriptions for the most potent opioids (Schedule II), as a percentage of all scheduled opioid prescriptions (II, III, and IV), increased from 19.3% in 1996 to 37.2% in 2002. Among long-acting opioids, the average daily morphine equivalent dose increased by 50%, to 132 mg/day. Thirty-two deaths were definitely or probably related to accidental overdose of opioids. The majority of deaths involved men (84%) and smokers (69%). CONCLUSIONS: The reasons for escalating doses of the most potent opioids are unknown, but it is possible that tolerance or opioid-induced abnormal pain sensitivity may be occurring in some workers who use opioids for chronic pain. Opioid-related deaths in this population may be preventable through use of prudent guidelines regarding opioid use for chronic pain.

Accidents↗
PubMed2005

Work-related carpal tunnel syndrome in Washington State workers' compensation: temporal trends, clinical practices, and disability.

BACKGROUND: Work-related carpal tunnel syndrome (CTS) is a leading cause of disability. There is a need for information about temporal trends, clinical practices, and treatment outcomes. METHODS: A population based, retrospective cohort study of Washington State workers' compensation claims for CTS was initiated focusing on claims filed during 1990-1994, followed through 2000 (n = 16,710). RESULTS: Half of the claims were filed for conditions other than CTS, but were eventually identified to be or include CTS. The first CTS diagnosis occurred more than 3 months after claim filing in 20% of claims. The longer that the CTS diagnosis occurred after claim filing, the more likely that CTS was accompanied by other problems, and disability tended to be longer. CONCLUSIONS: Making an accurate diagnosis of CTS and initiating appropriate actions earlier than might otherwise occur could reduce the disability and costs in a large fraction of claims that are ultimately determined to involve CTS.

Carpal Tunnel Syndrome↗
PubMed2005

Compliance with electrodiagnostic guidelines for patients undergoing carpal tunnel release.

OBJECTIVE: To describe how clinical practice in those who underwent carpal tunnel release (CTR) matched the American Association of Electrodiagnostic Medicine (AAEM) 1993 practice parameters for electrodiagnostic evaluation of carpal tunnel syndrome (CTS). DESIGN: Cohort study using 1998-1999 Medicare billing data. SETTING: Washington State. PARTICIPANTS: State Medicare beneficiaries who underwent CTR in 1999 (N=1567) Interventions Not applicable. MAIN OUTCOME MEASURES: Compliance with the AAEM practice parameters. RESULTS: Of the 1567 [corrected] receiving surgery, 324 [corrected] (20.7%) did not have any electrodiagnostic testing before surgery. One hundred seventy-one (10.9%) had testing performed that did not lead to the diagnosis of CTS. One thousand seventy-two (68.4%) patients were diagnosed with CTS through electrodiagnostic testing; 155 (9.9%) had less than 2 sensory nerves studied, 114 (7.3%) had less than 2 motor nerves studied, and 65 (4.2%) of the studies met neither the standard (sensory nerve testing) nor guideline (motor nerve testing). In a multivariate analysis, neurologists were more likely than physiatrists not to meet the AAEM standards (adjusted relative risk [adj RR]=1.61; 95% confidence interval [CI], 1.13-2.31) and patients living in rural areas were more likely to have no or inadequate testing (adj RR=1.6; 95% CI, 1.3-1.9). CONCLUSIONS: Over one third of Medicare patients undergoing CTR in Washington State in 1999 may have had an inappropriate electrodiagnostic workup before the surgery. Policymakers should consider mandating an appropriate electrodiagnostic test before approving CTR.

Aged↗
PubMed2005

Dopamine transporter (SLC6A3) 5' region haplotypes significantly affect transcriptional activity in vitro but are not associated with Parkinson's disease.

The dopamine transporter (DAT) plays a critical role in dopaminergic neurotransmission and is also the major site of action for some drugs of abuse. The coding region of the DAT gene, SLC6A3, is well conserved, but non-coding regions are more variable, most notably a variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region, which has been studied in a number of dopamine-related neurological disorders, including Parkinson's disease (PD). We aimed to characterize variation in the 5' region of SLC6A3 because little is known about the extent of variation in this region and potential consequences of such variation on gene expression. We identified multiple single nucleotide polymorphisms (SNPs) covering approximately 5000 bp 5' of exon 1 through the start of exon 2 (+2106). These SNPs segregated as eight haplotypes, six of which were common. These haplotypes differed significantly in activity in a reporter gene activity assay. However, we did not observe associations between common SNPs or haplotypes and PD in a case-control study of 261 incident cases and 376 age- and gender-matched unrelated controls. By contrast, we did observe a modest association of the 3' VNTR 9-repeat allele with PD (odds ratio=1.45; 95% confidence interval=1.04-2.03). This association was limited to subjects 60 years of age and greater versus those less than 60 years of age. We conclude that although DAT 5' region SNPs haplotypes significantly alter in vitro transcriptional activity, they are not related to PD risk. In addition, our findings provide further evidence supporting an association of PD with the VNTR polymorphism.

3' Untranslated Regions↗
PubMed2004

No associations between Parkinson's disease and polymorphisms of the quinone oxidoreductase (NQO1, NQO2) genes.

Reactive oxygen species derived from dopamine metabolism can induce oxidative stress and thus may contribute to Parkinson's disease (PD) pathogenesis. The quinone oxidoreductases, nicotinamide adenine dinucleotide (phosphate) (NAD[P]H): quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) detoxify quinones and quinonoid compounds. We investigated associations of genetic polymorphisms of NQO1 (C609T) and NQO2 (I/D, 29 base pairs) with PD in a population-based case-control study of 190 idiopathic PD cases and 305 unrelated controls matched on age and sex. No associations were detected for either gene variant or for any allele combinations.

Aged↗
PubMed2004

DNA sequence analysis of monoamine oxidase B gene coding and promoter regions in Parkinson's disease cases and unrelated controls.

The allele G of the intron 13 G/A polymorphism of the monoamine oxidase B gene (MAO-B) has been associated with Parkinson's disease (PD) in several studies. Apart from a potential direct effect on splicing processes, the association of this intronic polymorphism with PD is due possibly to linkage disequilibrium with other mutations in the coding or promoter regions of the gene. We addressed this latter hypothesis by determining the DNA sequence of the entire MAO-B coding region comprising 15 exons and partial intronic sequences flanking each exon, in 33 cases with idiopathic PD and 38 unrelated controls. The promoter region of MAO-B gene up to base -1,369 from ATG (start point of mRNA translation) was also sequenced to identify variants with potential functional effects on gene transcription. In the promoter region, a new polymorphism consisting of a C to T single base change was detected in position -1,114 from ATG, with an allelic frequency of 3.5%, but it was not associated with PD risk. No commonly occurring (>10%) polymorphisms were found in the exons or the intronic sequences flanking the exons, although several rare variants were detected in the coding and promoter regions.

Aged↗
PubMed2004

Multidisciplinary pain center outcomes in Washington State Workers' Compensation.

We conducted this study to evaluate the clinical and disability status of injured workers 4.6 years after undergoing multidisciplinary pain center evaluation, comparing subjects who received treatment to subjects who were evaluated only. Three hundred injured workers were selected for a telephone survey; 150 had received pain center treatment and 150 had been evaluated but not treated. The survey included the SF-12, and questions about subjects' pain intensity and current work status. A workers' compensation database indicated the disability status of subjects. The response rate was 50%. In multivariate analyses, treated and evaluated-only subjects did not differ significantly in disability status, pain intensity, SF-12 scores, or current work status. At 4.6 years follow up, there was no evidence that pain center treatment affects either disability status or clinical status of injured workers.

Accidents, Occupational↗
PubMed2004

A communitywide intervention to improve outcomes and reduce disability among injured workers in Washington State.

One pressing challenge facing the U.S. health care system is the development of effective policies and clinical management strategies to address deficiencies in health care quality. In collaboration with researchers at the University of Washington, the Washington State Department of Labor and Industries has created a communitywide delivery system intervention to improve health outcomes and reduce disability among injured workers. This intervention is currently being tested in two sites in western and eastern Washington. So far, it appears to be possible to engage physicians and health care institutions in quality improvement initiatives and to form effective public-private partnerships for this purpose. Furthermore, collaborating with university researchers may help enhance the scientific rigor of the quality improvement initiative and create more opportunities for a successful evaluation.

Accidents, Occupational↗
PubMed2004

Policy-relevant research: when does it matter?

Evidence-based medicine is most meaningful to policy makers when research questions are clearly informed by strategic health policy questions. In Washington State workers' compensation, key structural characteristics allow for the conduct of effective policy-relevant research. These include clear authority and a stable funding stream, a formal relationship between a policy agency and a University, development of appropriate research capacity, development of research questions related to strategic goals, and a robust data source. The research conducted relies on computerized medical bills and work disability records, medical records, structured telephone surveys to collect data on pain, functional status, quality of life, and computerized data on employment status. The types of policy-relevant research include identification of factors leading to preventable disability, outcomes research of specific procedures, technology assessment, and "real-time" research that addresses rapidly emerging questions. Health policy changes implemented from research have been substantial in Washington State workers' compensation, including: 1) noncoverage or partial coverage decisions for emerging technologies not proven to be of value to injured workers, 2) formal treatment guidelines and utilization review criteria for invasive, expensive, or marginally effective procedures, 3) disability prevention efforts, and 4) relatively rapid changes in policy as emerging patterns suggest harmful outcomes from existing treatments (e.g., schedule II opioids). Key structural characteristics must be in place to conduct policy-relevant research effectively. The workers' compensation system in Washington State is a single-payer system with other unique properties that have allowed the emergence of these structural characteristics and the conduct of research linked to the strategic goals of policy makers.

Adult↗
PubMed2003

Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson's disease.

Oxidative stress is widely thought to contribute significantly to the pathogenesis Parkinson's disease (PD). Given the role of glutathione S-transferases (GSTs) in the conjugation of electrophiles and protection against reactive oxygen species, genes encoding the GSTs have been considered candidates for association studies of PD. We tested for associations between genotypes of GSTM1(homozygous deletion vs. non-deleted), GSTT1(homozygous deletion vs. non-deleted), and GSTP1 (Ile104Val and Ala113Val) and PD in a case-control study of 214 idiopathic PD cases and 330 age- and gender-matched, unrelated controls of Caucasian ethnicity. No significant associations with any of the GST genotypes were observed. However, there was a marginally significant difference in the distribution of GSTP1 104 genotypes between cases and controls (P=0.07), with an excess of Ile104Val heterozygotes found among cases (odds ratio (OR)=1.43; 95% Confidence Interval (CI): 0.98-2.08). This difference in the genotype distribution was strongest among smokers (OR for heterozygote=1.92; 95% CI: 1.12-3.29) versus non-smokers and among males (OR for heterozygote=1.99; 95% CI: 1.24-3.19) versus females. The distribution of GSTP1 Ile104Val and Ala113Val haplotypes did not differ between cases and controls. Taken together, these results suggest a potentially minor role of GSTP1 in PD, but do not give evidence for associations with either GSTM1 or GSTT1.

Adult↗