Joseph C. Gardiner

Phenobarbital compared with phenytoin for the treatment of neonatal seizures.

BACKGROUND Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly. METHODS From 1990 to 1995, we studied 59 neonates with seizures that were confirmed by electroencephalography. The neonates were randomly assigned to receive either phenobarbital or phenytoin intravenously, at doses sufficient to achieve free plasma concentrations of 25 microg per milliliter for phenobarbital and 3 microg per milliliter for phenytoin. Neonates whose seizures were not controlled by the assigned drug were then treated with both drugs. Seizure control was assessed by electroencephalographic criteria. RESULTS Seizures were controlled in 13 of the 30 neonates assigned to receive phenobarbital (43 percent) and 13 of the 29 neonates assigned to receive phenytoin (45 percent; P=1.00). When combined treatment is considered, seizure control was achieved in 17 (57 percent) of the neonates assigned to receive phenobarbital first and 18 (62 percent) of those assigned to receive phenytoin first (P=0.67). The severity of the seizures was a stronger predictor of the success of treatment than was the assigned agent. Neonates with mild seizures or with seizures that were decreasing in severity before treatment were more likely to have their seizures end, regardless of the treatment assignment. CONCLUSIONS Phenobarbital and phenytoin are equally but incompletely effective as anticonvulsants in neonates. With either drug given alone, the seizures were controlled in fewer than half of the neonates.

How Much Work-related Injury and Illness is Missed By the Current National Surveillance System?

Objective: We sought to estimate the undercount in the existing national surveillance system of occupational injuries and illnesses. Methods: Adhering to the strict confidentiality rules of the U.S. Bureau of Labor Statistics, we matched the companies and individuals who reported work-related injuries and illnesses to the Bureau in 1999, 2000, and 2001 in Michigan with companies and individuals reported in four other Michigan data bases, workers’ compensation, OSHA Annual Survey, OSHA Integrated Management Information System, and the Occupational Disease Report. We performed capture–recapture analysis to estimate the number of cases missed by the combined systems. Results: We calculated that the current national surveillance system did not include 61% and with capture–recapture analysis up to 68% of the work-related injuries and illnesses that occurred annually in Michigan. This was true for injuries alone, 60% and 67%, and illnesses alone 66% and 69%, respectively. Conclusions: The current national system for work-related injuries and illnesses markedly underestimates the magnitude of these conditions. A more comprehensive system, such as the one developed for traumatic workplace fatalities, that is not solely dependent on employer based data sources is needed to better guide decision-making and evaluation of public health programs to reduce work-related conditions.

Fixed effects, random effects and GEE: What are the differences?

For analyses of longitudinal repeated-measures data, statistical methods include the random effects model, fixed effects model and the method of generalized estimating equations. We examine the assumptions that underlie these approaches to assessing covariate effects on the mean of a continuous, dichotomous or count outcome. Access to statistical software to implement these models has led to widespread application in numerous disciplines. However, careful consideration should be paid to their critical assumptions to ascertain which model might be appropriate in a given setting. To illustrate similarities and differences that might exist in empirical results, we use a study that assessed depressive symptoms in low-income pregnant women using a structured instrument with up to five assessments that spanned the pre-natal and post-natal periods. Understanding the conceptual differences between the methods is important in their proper application even though empirically they might not differ substantively. The choice of model in specific applications would depend on the relevant questions being addressed, which in turn informs the type of design and data collection that would be relevant.

Primary Care Clinicians Treat Patients with Medically Unexplained Symptoms: A Randomized Controlled Trial

AbstractOBJECTIVE: There is no proven primary care treatment for patients with medically unexplained symptoms (MUS). We hypothesized that a long-term, multidimensional intervention by primary care providers would improve MUS patients’ mental health. DESIGN: Clinical trial. SETTING: HMO in Lansing, MI. PARTICIPANTS: Patients from 18 to 65 years old with 2 consecutive years of high utilization were identified as having MUS by a reliable chart rating procedure; 206 subjects were randomized and 200 completed the study. INTERVENTION: From May 2000 to January 2003, 4 primary care clinicians deployed a 12-month intervention consisting of cognitive-behavioral, pharmacological, and other treatment modalities. A behaviorally defined patient-centered method was used by clinicians to facilitate this treatment and the provider-patient relationship. MAIN OUTCOME MEASURE: The primary endpoint was an improvement from baseline to 12 months of 4 or more points on the Mental Component Summary of the SF-36. RESULTS: Two hundred patients averaged 13.6 visits for the year preceding study. The average age was 47.7 years and 79.1% were females. Using intent to treat, 48 treatment and 34 control patients improved (odds ratio [OR]=1.92, 95% confidence interval [CI]: 1.08 to 3.40; P=.02). The relative benefit (relative “risk” for improving) was 1.47 (CI: 1.05 to 2.07), and the number needed to treat was 6.4 (95% CI: 0.89 to 11.89). The following baseline measures predicted improvement: severe mental dysfunction (P<.001), severe body pain (P=.039), nonsevere physical dysfunction (P=.003), and at least 16 years of education (P=.022); c-statistic=0.75. CONCLUSION: The first multidimensional intervention by primary care clinicians led to clinically significant improvement in MUS patients.

Exploration of DSM-IV criteria in primary care patients with medically unexplained symptoms.

Objectives: Investigators and clinicians almost always rely on Diagnostic and Statistical Manual of Mental Disorder, 4th edition’s (DSM-IV) somatoform disorders (and its derivative diagnoses) to characterize and identify patients with medically unexplained symptoms (MUS). Our objective was to evaluate this use by determining the prevalence of DSM-IV somatoform and nonsomatoform disorders in patients with MUS proven by a gold standard chart review. Methods: In a community-based staff model HMO, we identified subjects for a clinical trial using a systematic and reliable chart rating procedure among high-utilizing MUS patients. Only baseline data are reported here. The World Health Organization Composite International Diagnostic Interview provided full and abridged DSM-IV diagnoses. Patients with full or abridged DSM-IV somatoform diagnoses were labeled “DSM somatoform-positive,” whereas those without them were labeled “DSM somatoform-negative.” Results: Two hundred six MUS patients averaged 13.6 visits in the year preceding study, 79.1% were females, and the average age was 47.7 years. We found that 124 patients (60.2%) had a nonsomatoform (“psychiatric”) DSM-IV diagnosis of any type; 36 (17.5%) had 2 full nonsomatoform diagnoses, and 41 (19.9%) had >2; 92 (44.7%) had some full anxiety diagnosis and 94 (45.6%) had either full depression or minor depression diagnoses. However, only 9 of 206 (4.4%) had any full DSM-IV somatoform diagnosis, and only 39 (18.9%) had abridged somatization disorder. Thus, 48 (23.3%) were “DSM somatoform-positive” and 158 (76.7%) were “DSM somatoform-negative.” The latter exhibited less anxiety, depression, mental dysfunction, and psychosomatic symptoms (all p <.001) and less physical dysfunction (p = .011). Correlates of this DSM somatoform-negative status were female gender (p = .007), less severe mental (p = .007), and physical dysfunction (p = .004), a decreased proportion of MUS (p <.10), and less psychiatric comorbidity (p <.10); c-statistic = 0.77. Conclusion: We concluded that depression and anxiety characterized MUS patients better than the somatoform disorders. Our data suggested radically revising the somatoform disorders for DSM-V by incorporating a new, very large group of now-overlooked DSM somatoform-negative patients who were typically women with less severe dysfunction. HMO = health maintenance organization DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition DSM-V = planned for approximately 2010, the Diagnostic and Statistical Manual of Mental Disorders, 5th edition MUS = medically unexplained symptoms ECA = epidemiologic catchment area SD = somatization disorder SF-36 = Short-Form 36 MCS = Mental Component Summary of the SF-36 PCS = Physical Component Summary of the SF-36 SSAS = Spielberger State Anxiety Scale CES-D = Center for Epidemiological Studies Depression inventory PSC = Psychosomatic Symptom Checklist WHO-CIDI = World Health Organization Composite International Diagnostic Interview.

The association of serum nonesterified fatty acids and cholesterol, management and feeding practices with peripartum disease in dairy cows

A prospective study was conducted to determine the relationship of serum nonesterified fatty acids (NEFA) and cholesterol concentrations and herd management practices to the occurrence of metritis, mastitis and retained placenta in Holstein cows in Michigan. Serum samples were collected once prepartum and once postpartum from 257 cows. Animals were under observation for disease occurrence from the date of calving until 3 months postpartum. Metabolic variables used were (1) prepartum only; (2) postpartum only; (3) the NEFA/cholesterol ratio for both pre- and postpartum samples. Management variables included maternity management, feed management, and factors such as season and parity. Multivariable logistic models with random-effect terms to account for the herd effect were used for data analysis. Results showed that: (1) metabolic events associated with energy insufficiency-increased fat mobilization and serum lipoprotein metabolism-were related to increased risk of metritis and retained placenta; (2) higher energy consumption during the last weeks of the dry period might reduce disease risk at parturition; (3) serum NEFA and cholesterol concentrations have potential as indicators of disease risk in dairy cows.

Treating Patients with Medically Unexplained Symptoms in Primary Care

BACKGROUND: There are no proven, comprehensive treatments in primary care for patients with medically unexplained symptoms (MUS) even though these patients have high levels of psychosocial distress, medical disability, costs, and utilization. Despite extensive care, these common patients often become worse.OBJECTIVE: We sought to identify an effective, research-based treatment that can be conducted by primary care personnel.DESIGN: We used our own experiences and files, consulted with experts, and conducted an extensive review of the literature to identify two things: 1) effective treatments from randomized controlled trials for MUS patients in primary care and in specialty settings; and 2) any type of treatment study in a related area that might inform primary care treatment, for example, depression, provider-patient relationship.MAIN RESULTS: We developed a multidimensional treatment plan by integrating several areas of the literature: collaborative/stepped care, cognitive-behavioral treatment, and the provider-patient relationship. The treatment is designed for primary care personnel (physicians, physician assistants, nurse practitioners) and deployed intensively at the outset; visit intervals are progressively increased as stability and improvement occur.CONCLUSION: Providing a comprehensive treatment plan for chronic, high-utilizing MUS patients removes one barrier to treating this common problem effectively in primary care by primary care personnel.

Cancer, medicaid enrollment, and survival disparities

The current article examined survival for adults < 65 years old diagnosed with breast, colorectal, or lung carcinoma who were either Medicaid insured at the time of diagnosis, Medicaid insured after diagnosis, or non‐Medicaid insured.

The effect of subclinical Mycobacterium paratuberculosis infection on days open in Michigan, USA, dairy cows

A prospective cohort study design was used to evaluate the impact of subclinical Mycobacterium paratuberculosis infection on days open in a sample of Michigan dairy herds with a history of cows positive for M. paratuberculosis diagnosed by fecal culture. Participating herds were tested and productivity and reproduction records were monitored for 18 months. All cows > or = 24 months old were tested for M. paratuberculosis infection using the ELISA and radiometric fecal-culture (RFC) techniques. Test-negative cows were re-tested at the conclusion of the monitoring period. Multivariable regression models were used. Using both tests in parallel, the overall sample apparent prevalence for M. paratuberculosis infection was 41.8% (223/533 animals tested). Adjusting for diagnostic sensitivity and specificity, this resulted in a calculated sample true prevalence of 59.9%. ELISA-positive cows (on average) had a 28-day increase in days open when compared to ELISA-negative cows (p=0.02). The diagnostic method used to define a case altered the apparent association between paratuberculosis test status and days open. Fecal culture was a less-effective diagnostic tool for use in herds with a high prevalence of infected animals. The increase in days open in the ELISA-positive cows was an indication that perhaps reduced estrus expression or an increased post-partum anestrous period occurred in the subclinically infected ELISA-positive animals. This might have been due to a negative energy balance associated with M. paratuberculosis infection.

Applying Propensity Score Methods in Medical Research: Pitfalls and Prospects

The authors review experimental and nonexperimental causal inference methods, focusing on assumptions for the validity of instrumental variables and propensity score (PS) methods. They provide guidance in four areas for the analysis and reporting of PS methods in medical research and selectively evaluate mainstream medical journal articles from 2000 to 2005 in the four areas, namely, examination of balance, overlapping support description, use of estimated PS for evaluation of treatment effect, and sensitivity analyses. In spite of the many pitfalls, when appropriately evaluated and applied, PS methods can be powerful tools in assessing average treatment effects in observational studies. Appropriate PS applications can create experimental conditions using observational data when randomized controlled trials are not feasible and, thus, lead researchers to an efficient estimator of the average treatment effect.