Can cost utility evaluations inform decision making about interventions for low back pain?

Background contextLow back pain (LBP) is associated with high health-care utilization and lost productivity. Numerous interventions are routinely used, although few are supported by strong evidence. Cost utility analyses (CUAs) may be helpful to inform decision makers.PurposeTo conduct a systematic review of CUAs of interventions for LBP.Study designSystematic review.MethodsA search strategy combining medical subject headings and free text related to LBP and health economic evaluations was executed in MEDLINE. Cost utility analyses combined with randomized controlled trials for LBP were included. Studies that were published before 1998, non-English, decision analyses, and duplicate reports were excluded. Search results were evaluated by two reviewers, who extracted data independently related to clinical study design, economic study design, direct cost components, utility results, cost results, and CUA results.ResultsThe search produced 319 citations, and of these 15 met eligibility criteria. Most were from the United Kingdom (n=8), published in the past 3 years (n=12), studied chronic LBP or radiculopathy (n=13), and had a follow-up >12 months (n=13). Combined, there were 33 study groups who received a mean 2.1 interventions, most commonly education (n=17), exercise therapy (n=13), spinal manipulation therapy (n=7), surgery (n=7), and usual care from a general practitioner (n=7). Mean baseline utility was 0.57, improving to 0.67 at follow-up; the mean difference in utility improvement between study groups was 0.04. Based on available data and converted to US dollars, the cost per quality-adjusted life year ranged from $304 to $579,527, with a median of $13,015.ConclusionsFew CUAs were identified for LBP, and there was heterogeneity in the interventions compared, direct cost components measured, indirect costs, other methods, and results. Reporting quality was mixed. Currently published CUAs do not provide sufficient information to assist decision makers. Future CUAs should attempt to measure all known direct cost components relevant to LBP, estimate indirect costs such as lost productivity, have a follow-up period sufficient to capture meaningful changes, and clearly report methods and results to facilitate interpretation and comparison.     

Co-occurrence of major depression or suicide attempt with migraine with aura and risk for unprovoked seizure

We hypothesized and found that the co-occurrence of migraine with aura (MA) with major depression (MD) or with suicide attempt (SA) increases the risk for developing unprovoked seizure more than these conditions alone. Number of conditions showed a linear relationship to seizure risk. This may reflect a new condition cluster defined by MA, MD, SA and unprovoked seizures. Identifying the biological underpinnings this cluster may affect clinical diagnosis and treatment.     

The role of titration schedule of topiramate for the development of depression in patients with epilepsy

Purpose:   To determine whether a fast titration schedule of topiramate (TPM) has different effects on the occurrence of depression, in relation to other risk factors for TPM-induced depression, including history of depression (HxDEP), febrile seizures (FS), and hippocampal sclerosis (HS).
Methods:   Using data from a large case registry of patients prescribed TPM, two models were constructed: Model 1 examined the independent effect of rapid TPM titration after separate adjustment for FS, HxDEP, and HS. Model 2 examined effect of the cooccurrence of rapid titration on the development of depression with each of these risk factors.
Results:   A total of 423 patients were included (51.8% females), mean age (SD) 35.5 (11.8) years, mean duration of epilepsy of 22.2 (11.5) years. Forty-four patients (10.4%) developed depression during TPM therapy. A rapid TPM titration was associated with 5-fold increased risk of depression that increased to 12.7-fold in the presence of both FS and rapid TPM titration, 23.3-fold in the presence of both HxDEP and rapid TPM titration, and 7.6-fold in the presence of both HS and rapid TPM titration schedule.
Conclusions:   Our study suggests that a rapid titration schedule is associated with an increased risk of developing depression during TPM therapy. HxDEP and FS are major contraindications to the use of a rapid titration, with a 23.3-fold and 12.7 fold increased risk, respectively.     

Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure

Purpose:   To compare mortality and subsequent unprovoked seizure risk in a population-based study of acute symptomatic seizure and first unprovoked seizure due to static brain lesions.
Methods:   We ascertained all first episodes of acute symptomatic seizure and unprovoked seizure due to central nervous system (CNS) infection, stroke, and traumatic brain injury (TBI). Subjects were residents of Rochester, Minnesota, identified through the Rochester Epidemiology Project's records-linkage system between 1/1/55 and 12/31/84. Information was collected on age, gender, seizure type, etiology, status epilepticus (SE), 30-day and 10-year mortality, and subsequent episodes of unprovoked seizure.
Results:   Two hundred sixty-two individuals experienced a first acute symptomatic seizure and 148 individuals experienced a first unprovoked seizure, all due to static brain lesions. Individuals with a first acute symptomatic seizure were 8.9 times more likely to die within 30 days compared to those with a first unprovoked seizure [95% confidence intervals (CI) = 3.5–22.5] after adjustment for age, gender, and SE. Among 30-day survivors, the risk of 10-year mortality did not differ. Over the 10-year period, individuals with a first acute symptomatic seizure were 80% less likely to experience a subsequent unprovoked seizure compared with individuals with a first unprovoked seizure [adjusted rate ratio (RR) = 0.2, 95% CI = 0.2–0.4].
Discussion:   The prognosis of first acute symptomatic seizures differs from that of first unprovoked seizure when the etiology is stroke, TBI, and CNS infection. Acute symptomatic seizures have a higher early mortality and a lower risk for subsequent unprovoked seizure. These differences argue against the inclusion of acute symptomatic seizures as epilepsy.     

Underlying cause of death in incident unprovoked seizures in the urban community of Northern Manhattan, New York City

We determined underlying cause-specific mortality for incident unprovoked seizures from Northern Manhattan, New York City. We calculated the case fatality, proportionate mortality, and the underlying cause-specific standardized mortality ratios (SMRs), with U.S. death rates as the standard. Thirty-two deaths were observed between 2003 and 2007 among 209 participants. Case fatality was significantly lower for idiopathic/cryptogenic seizures versus symptomatic seizures. About 31.3% of the deaths were attributed to malignant neoplasms, 25.0% to diseases of the heart, 15.6% to influenza and pneumonia, 3.1% to cerebrovascular diseases, and 25.0% to other causes. Significant SMRs were observed for all causes (SMR = 1.6), influenza and pneumonia (SMR = 7.1), and malignant neoplasms (SMR = 2.9). Younger cases (<65 years) had increased SMRs for all causes, malignant neoplasms, and other causes. Older cases (≥65 years) had increased SMRs for influenza and pneumonia. Underlying cause of death paralleled the underlying cause of seizure in patients with symptomatic etiologies.     

Status epilepticus without an underlying cause and risk of death: a population-based study

OBJECTIVE: To determine the independent effect of status epilepticus (SE) on risk of death. DESIGN: Retrospective cohort study. The increased risk of death after SE has been largely ascribed to the underlying medical condition. It is unknown whether SE itself affects risk of death. We address this question by studying idiopathic/cryptogenic SE. SETTING: Population-based study. PARTICIPANTS: We identified all incident idiopathic/cryptogenic unprovoked seizures in the population of Rochester, Minnesota, from January 1, 1955, through December 31, 1984, and observed them until death, loss to follow-up, or the end of the study. MAIN OUTCOME MEASURES: We compared the risk of death in those with a brief unprovoked seizure (<30 minutes) with risk of death in those with an unprovoked seizure of 30 minutes or longer (SE), using Kaplan-Meier and Cox proportional hazards regression. The standardized mortality ratio was also determined. RESULTS: We ascertained 291 people with a first brief unprovoked seizure and 16 with SE. There were 27 deaths among people with seizure and 5 deaths (all aged > 65 years) among people with SE. Compared with people with seizure, the adjusted relative risk for death in those with SE was 2.4 (95% confidence interval [CI], 0.9-6.3) over 10 years. It was increased 5-fold (relative risk, 5.1; 95% CI, 1.6-15.7) among those older than 65 years and 6-fold among those with SE who later developed epilepsy (relative risk, 6.3; 95% CI, 1.5-26.0). Compared with the general population, the standardized mortality ratio was 2.6 (95% CI, 0.8-5.3) for SE and 1.2 (95% CI, 0.8-1.6) for a first seizure of short duration. CONCLUSION: Idiopathic/cryptogenic SE was associated with an increased risk of death among elderly persons and those who later developed epilepsy.     

Multiple primary malignancies in patients with Merkel cell carcinoma1

Background Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumour, the incidence of which is increasing. Second malignancies have been reported to occur with high incidence in these patients. Objectives We report the rate and nature of multiple malignancies in patients with MCC treated over a 10 year period in Addenbrooke’s Hospital in Cambridge, United Kingdom, as well as the temporal relationship of these additional malignancies to the diagnosis of MCC. Results The 27 patients had an approximately equal sex incidence with a median age at diagnosis of 79 years. Seventy percent (n=19) of patients had a second primary malignant tumour; and 7 of these patients had two or more tumours in addition to the MCC. Eighteen patients had additional cutaneous malignancies: melanoma, squamous cell carcinoma and basal cell carcinoma, and 8 patients presented non‐cutaneous malignancy including colorectal, haematological and breast tumours. Of the 28 additional tumours in our patients, half were diagnosed prior to presentation of MCC, 32% within 6 months of diagnosis, and 18% between 6 months and 3 years after diagnosis. Possible reasons for the high rate of additional tumours in this population are discussed. Conclusions Our figures reflect a higher incidence of multiple malignancies in those with Merkel cell tumour than has previously been reported. This has important implications for the care and surveillance of these patients.