Trends in opioid use following balloon kyphoplasty or vertebroplasty for the treatment of vertebral compression fractures.

This retrospective analysis of insurance claims evaluated real-world trends in prescription fills among patients treated with balloon kyphoplasty (N = 6,656) or vertebroplasty (N = 2,189) following diagnosis of vertebral compression fracture. Among those with evidence of opioid use, nearly half of patients discontinued or reduced prescription fills relative to pre-operative levels. INTRODUCTION: Vertebral compression fractures (VCF) are associated with debilitating pain, spinal misalignment, increased mortality, and increased healthcare-resource utilization in elderly patients. This study evaluated the effect of balloon kyphoplasty (BKP) or vertebroplasty (VP) on post-procedure opioid prescription fills and payer costs in patients with VCF. METHODS: This was a retrospective analysis of a large, nationally representative insurance-claims database. Clinical characteristics, opioid prescription patterns, and payer costs for subjects who underwent either BKP or VP to treat VCF were evaluated beginning 6 months prior to surgery through 7-month follow-up that included a 30-day, postoperative medication washout. Patient demographics, changes in opioid utilization, and payer costs were analyzed. RESULTS: A total of 8,845 patients met eligibility criteria (75.3% BKP and 24.7% VP) with a mean of age 77 and 74% female. Among the 75% of patients who used opioids, 48.7% of patients discontinued opioid medication and 8.4% reduced prescription fills versus preoperative baseline. Patients who reduced or discontinued prescriptions exhibited a decrease in all-cause payer costs relative to pre-intervention levels, which was a significantly greater change relative to patients with no change, increase, or new start of opioids. CONCLUSIONS: Interventional treatment for VCF was associated with decreased or discontinued opioid prescription fills and reduced payer costs in follow-up in a significant proportion of the study population. Reduction of opioid-based harms may represent a previously unrecognized benefit of vertebral augmentation for VCF, especially in this elderly and medically fragile population.

Cost-effectiveness of balloon kyphoplasty and vertebroplasty versus conservative medical management in the USA.

The cost-effectiveness of surgical versus conservative medical management of vertebral compression fractures in the US was analyzed in the context of inpatient versus outpatient treatment. Surgical intervention (balloon kyphoplasty and vertebroplasty) was found to be cost-effective relative to conservative medical management at a US willingness-to-pay threshold. INTRODUCTION: To date, only one published study has evaluated the cost-effectiveness (C/E) of balloon kyphoplasty (BKP) or vertebroplasty (VP) in US Medicare patients with osteoporotic vertebral compression fractures. This study further evaluates the C/E of surgical treatment vs. conservative medical management (CMM), expanding on prior modeling by accounting for quality-adjusted life-years gained. METHODS: A Markov microsimulation model of 1000 patients was constructed. Cost data were based on an analysis of Medicare claims payments, with propensity-score matching performed for BKP and VP vs. controls (CMM). Mortality inputs were based on US life tables, modified to account for age at initial fracture, presence of subsequent fracture(s), and relative risk of mortality by treatment. Separate incremental cost-effectiveness ratios (ICERs) were calculated for BKP and VP in inpatient and outpatient surgical treatment locations to account for individual clinical profiles presenting to each. RESULTS: The discounted ICER for inpatient BKP vs. CMM was $43,455 per QALY gained; for outpatient BKP vs. CMM, $10,922; for inpatient VP vs. CMM, $39,774; and for outpatient VP vs. CMM, $12,293. Probabilistic sensitivity analysis confirmed that both BKP and VP would be considered C/E vs. CMM at a US willingness-to-pay (WTP) threshold of $50,000/QALY in 80% and 100% of 500 model simulations, respectively. The most sensitive parameters included quality of life estimates and hazard ratios for mortality. CONCLUSION: While VP and BKP are more expensive treatment options than CMM in the short term, model results suggest interventional treatment is cost-effective, among patients eligible for surgery, at a US WTP threshold. This conclusion supports those from economic analyses conducted in EU-member countries.

Properties of cyclopean motion perception.

This study investigated the ability of human observers to discriminate the direction of laterally-moving cyclopean stimuli, in order to assess some of the properties of stereoscopic mechanisms that mediate the perception of cyclopean motion (motion existing at levels of binocular integration). The stimuli were moving grating patterns created from dynamic random-dot stereograms. Experiment 1 showed that duration thresholds for discrimination decrease with velocity; they are not governed by temporal frequency nor a constant spatial displacement. Experiment 2 revealed that discrimination thresholds increase with disparity magnitude, for both the crossed and uncrossed disparity directions equally. Experiment 3 showed that the rate of temporal variation at and above which direction discrimination fails (cyclopean upper limit of temporal resolution) is 8 Hz. Our results indicate that a mechanism for motion perception exists at binocular-integration levels of the visual system, which supports a model of motion perception that posits the existence of first-order and second-order processes.

Mitochondrial DNA variation in Nicobarese Islanders.

The aboriginal populations living in the Nicobar Islands are hypothesized to be descendants of people who were part of early human dispersals into Southeast Asia. However, analyses of ethnographic histories, languages, morphometric data, and protein polymorphisms have not yet resolved which worldwide populations are most closely related to the Nicobarese. Thus, to explore the origins and affinities of the Nicobar Islanders, we analyzed mitochondrial DNA (mtDNA) hypervariable region 1 sequence data from 33 Nicobarese Islanders and compared their mtDNA haplotypes to those of neighboring East Asians, mainland and island Southeast Asians, Indians, Australian aborigines, Pacific Islanders, and Africans. Unique Nicobarese mtDNA haplotypes, including five Nicobarese mtDNA haplotypes linked to the COII/tRNA(Lys) 9-bp deletion, are most closely related to mtDNA haplotypes from mainland Southeast Asian Mon-Kmer-speaking populations (e.g., Cambodians). Thus, the dispersal of southern Chinese into mainland Southeast Asia may have included a westward expansion and colonization of the islands of the Andaman Sea.

The distribution of human genetic diversity: a comparison of mitochondrial, autosomal, and Y-chromosome data.

We report a comparison of worldwide genetic variation among 255 individuals by using autosomal, mitochondrial, and Y-chromosome polymorphisms. Variation is assessed by use of 30 autosomal restriction-site polymorphisms (RSPs), 60 autosomal short-tandem-repeat polymorphisms (STRPs), 13 Alu-insertion polymorphisms and one LINE-1 element, 611 bp of mitochondrial control-region sequence, and 10 Y-chromosome polymorphisms. Analysis of these data reveals substantial congruity among this diverse array of genetic systems. With the exception of the autosomal RSPs, in which an ascertainment bias exists, all systems show greater gene diversity in Africans than in either Europeans or Asians. Africans also have the largest total number of alleles, as well as the largest number of unique alleles, for most systems. GST values are 11%-18% for the autosomal systems and are two to three times higher for the mtDNA sequence and Y-chromosome RSPs. This difference is expected because of the lower effective population size of mtDNA and Y chromosomes. A lower value is seen for Y-chromosome STRs, reflecting a relative lack of continental population structure, as a result of rapid mutation and genetic drift. Africa has higher GST values than does either Europe or Asia for all systems except the Y-chromosome STRs and Alus. All systems except the Y-chromosome STRs show less variation between populations within continents than between continents. These results are reassuring in their consistency and offer broad support for an African origin of modern human populations.

Patterns of ancestral human diversity: an analysis of Alu-insertion and restriction-site polymorphisms.

We have analyzed 35 widely distributed, polymorphic Alu loci in 715 individuals from 31 world populations. The average frequency of Alu insertions (the derived state) is lowest in Africa (.42) but is higher and similar in India (.55), Europe (.56), and Asia (.57). A comparison with 30 restriction-site polymorphisms (RSPs) for which the ancestral state has been determined shows that the frequency of derived RSP alleles is also lower in Africa (.35) than it is in Asia (.45) and in Europe (.46). Neighbor-joining networks based on Alu insertions or RSPs are rooted in Africa and show African populations as separate from other populations, with high statistical support. Correlations between genetic distances based on Alu and nuclear RSPs, short tandem-repeat polymorphisms, and mtDNA, in the same individuals, are high and significant. For the 35 loci, Alu gene diversity and the diversity attributable to population subdivision is highest in Africa but is lower and similar in Europe and Asia. The distribution of ancestral alleles is consistent with an origin of early modern human populations in sub-Saharan Africa, the isolation and preservation of ancestral alleles within Africa, and an expansion out of Africa into Eurasia. This expansion is characterized by increasing frequencies of Alu inserts and by derived RSP alleles with reduced genetic diversity in non-African populations.

Genetic evidence on the origins of Indian caste populations.

The origins and affinities of the approximately 1 billion people living on the subcontinent of India have long been contested. This is owing, in part, to the many different waves of immigrants that have influenced the genetic structure of India. In the most recent of these waves, Indo-European-speaking people from West Eurasia entered India from the Northwest and diffused throughout the subcontinent. They purportedly admixed with or displaced indigenous Dravidic-speaking populations. Subsequently they may have established the Hindu caste system and placed themselves primarily in castes of higher rank. To explore the impact of West Eurasians on contemporary Indian caste populations, we compared mtDNA (400 bp of hypervariable region 1 and 14 restriction site polymorphisms) and Y-chromosome (20 biallelic polymorphisms and 5 short tandem repeats) variation in approximately 265 males from eight castes of different rank to approximately 750 Africans, Asians, Europeans, and other Indians. For maternally inherited mtDNA, each caste is most similar to Asians. However, 20%-30% of Indian mtDNA haplotypes belong to West Eurasian haplogroups, and the frequency of these haplotypes is proportional to caste rank, the highest frequency of West Eurasian haplotypes being found in the upper castes. In contrast, for paternally inherited Y-chromosome variation each caste is more similar to Europeans than to Asians. Moreover, the affinity to Europeans is proportionate to caste rank, the upper castes being most similar to Europeans, particularly East Europeans. These findings are consistent with greater West Eurasian male admixture with castes of higher rank. Nevertheless, the mitochondrial genome and the Y chromosome each represents only a single haploid locus and is more susceptible to large stochastic variation, bottlenecks, and selective sweeps. Thus, to increase the power of our analysis, we assayed 40 independent, biparentally inherited autosomal loci (1 LINE-1 and 39 Alu elements) in all of the caste and continental populations (approximately 600 individuals). Analysis of these data demonstrated that the upper castes have a higher affinity to Europeans than to Asians, and the upper castes are significantly more similar to Europeans than are the lower castes. Collectively, all five datasets show a trend toward upper castes being more similar to Europeans, whereas lower castes are more similar to Asians. We conclude that Indian castes are most likely to be of proto-Asian origin with West Eurasian admixture resulting in rank-related and sex-specific differences in the genetic affinities of castes to Asians and Europeans.