Addressing the Challenges of Research With Small Populations

Public health policy relies on accurate data, which are often unavailable for small populations, especially indigenous groups. Yet these groups have some of the worst health disparities in the United States, making it an ethical imperative to explore creative solutions to the problem of insufficient data.We discuss the limits of widely applied methods of data aggregation and propose a mixed-methods approach to data borrowing as a way to augment sample sizes. In this approach, community partners assist in selecting related populations that make suitable “neighbors” to enlarge the data pool.The result will be data that are substantial, accurate, and relevant to the needs of small populations, especially for health-related policy and decision-making at all levels.When President Obama signed US Executive Order 13515, he declared that no community should be invisible.1 Yet for policymakers, the health status of small population groups, especially the indigenous peoples of the United States, remains largely hidden from view. Consistent epidemiological data are needed to inform policy decisions and resource allocation from the community level to the national level. For small population groups, such as American Indians, Alaska Natives, and Native Hawaiians, national reports and public data sets typically fail to provide sufficiently detailed information. Amassing enough accurate data requires innovative solutions, especially because small groups tend to have the largest health disparities. The scarcity of high-quality data means that these groups are often omitted from research agendas—or as the president put it, “Smaller communities in particular can get lost, their needs and concerns buried in a spreadsheet.”1As academics who conduct health research in small populations, we use community-based participatory methods within a theoretical framework that encompasses the social determinants of health. Our experience suggests some useful ways to address the problem of scarce data. One approach is to disaggregate data that lump together dissimilar populations, such as Native Hawaiians and Asian Americans, because aggregation can mask health disparities. Another approach is to augment data on extremely small populations by using statistical methods that borrow data from other groups with pertinent similarities to the population of interest. However, given the pitfalls inherent in data borrowing, we recommend qualitative methods that empower small communities to partner with academic researchers in selecting appropriate “neighbors,” whose adoption will maintain both the relevance and the distinctiveness of the resulting data pool. In the next sections, we describe a collaborative, multiperspective approach with broad application for small groups throughout the United States.     

Complementary and alternative medicine in fibromyalgia and related syndromes

Complementary and alternative medicine (CAM) has gained increasing popularity, particularly among individuals with fibromyalgia syndrome (FMS) for which traditional medicine has generally been ineffective. A systematic review of randomized controlled trials (RCTs) and non-RCTs on CAM studies for FMS was conducted to evaluate the empirical evidence for their effectiveness. Few RCTs achieved high scores on the CONSORT, a standardized evaluation of the quality of methodology reporting. Acupuncture, some herbal and nutritional supplements (magnesium, SAMe) and massage therapy have the best evidence for effectiveness with FMS. Other CAM therapies have either been evaluated in only one RCT with positive results (Chlorella, biofeedback, relaxation), in multiple RCTs with mixed results (magnet therapies), or have positive results from studies with methodological flaws (homeopathy, botanical oils, balneotherapy, anthocyanidins, dietary modifications). Lastly, other CAM therapies have neither well-designed studies nor positive results and are not currently recommended for FMS treatment (chiropractic care).     

The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome

OBJECTIVES: Chronic fatigue syndrome (CFS) has been associated with altered amounts of slow wave sleep, which could reflect reduced delta electroencephalograph (EEG) activity and impaired sleep regulation. To evaluate this hypothesis, we examined the response to a sleep regulatory challenge in CFS. DESIGN: The first of 3 consecutive nights of study served as laboratory adaptation. Baseline sleep was assessed on the second night. On the third night, bedtime was delayed by 4 hours, followed by recovery sleep. Total available sleep time was held constant on all nights. SETTING: A research sleep laboratory. PARTICIPANTS: 13 pairs of monozygotic twins discordant for CFS. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Power spectral analysis quantified slow wave activity (SWA) in the 0.5-3.9 Hz band in successive NREM periods (stage 2, 3, or 4) on each night. To ensure comparability, analyses were restricted to the first 4 NREM periods on each night. Data were coded for NREM period and twin pair. Repeated-measures analysis of variance (ANOVA) contrasted sleep delay effects across NREM periods between twin pairs. A second ANOVA calculated the SWA in each NREM period in recovery sleep relative to baseline SWA. The 2 groups of twins were similar on baseline SWA power. After sleep delay, CFS twins exhibited significantly less SWA power in the first NREM period of recovery sleep and accumulated a smaller percentage of SWA in the first NREM period than their co-twins. CONCLUSIONS: CFS is associated with a blunted SWA response to sleep challenge, suggesting that the basic sleep drive and homeostatic response are impaired.     

Chronic diffuse musculoskeletal pain,fibromyalgia and co-morbid unexplained clinical conditions

This chapter reviews our current knowledge on the presence of overlapping syndromes in one form of chronic diffuse pain, fibromyalgia. Patients with fibromyalgia often present with signs and symptoms of other unexplained clinical conditions, including chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorders, and multiple chemical sensitivities. The high prevalence, impact on function and opportunities for treatment underscore the need for clinicians and researchers to screen routinely for co-morbid unexplained clinical conditions among persons with fibromyalgia. We, therefore, describe a simple approach to screening for such conditions in accordance with published criteria. Interventions should directly address both fibromyalgia symptoms and co-morbid unexplained clinical conditions, as well as the multiple factors that propagate pain, fatigue and limitations in function.     

Environmental,policy, and cultural factors related to physical activity in sedentary American Indian women

Focus group interviews were conducted to explore sociocultural, environmental, and policy-related determinants of physical activity among sedentary American Indian women. Thirty women aged 20 to 50 years (mean = 37.4 +/- 10.6 years) participated. Three sessions were conducted with women aged 20 to 34 years and three with women aged 35 to 50 to evaluate response differences by age. Because no obvious age differences were observed, data were pooled. Barriers to physical activity included inadequate support for household and child care responsibilities and difficulties balancing home-related and societal expectations with physical activity. In addition, women reported little support from their communities and work sites to be physically active. Environmental barriers included lack of safe outdoor areas and accessible walking trails. Weather and stray dogs were also commonly mentioned. Sociocultural barriers included giving family obligations priority above all other things, being expected to eat large portions of high-fat foods, and failing to follow a traditionally active lifestyle. Enablers of physical activity included support from family and coworkers and participation in traditional community events. Suggested intervention approaches included accessible and affordable programs and facilities, community emphasis on physical activity, and programs that incorporated the needs of larger women and of families. Participants emphasized a preference for programs that were compatible with the role expectations of their families and communities, and they expressed the desire for acceptance and encouragement to be physically active from the family, the community, the worksite, and their tribal leaders.     

Crosstalk Between IGF1R and Estrogen Receptor Signaling in Breast Cancer

After the discovery that depriving certain breast tumors of estrogen promoted tumor regression, therapeutic strategies aimed at depriving tumors of this hormone were developed. The tumorigenic properties of estrogen are regulated through the estrogen receptor-α (ER), making understanding the mechanisms that activate this receptor highly relevant. In addition to estrogen activating the ER, other growth factor pathways, such as the insulin-like growth factors (IGFs), can activate the ER. This review will examine the interaction between these two pathways. Estrogen can activate the growth stimulatory properties of the IGF pathway via ER’s genomic and non-genomic functions. Further, blockade of ER function can inhibit IGF-mediated mitogenesis and blocking IGF action can inhibit estrogen stimulation of breast cancer cells. Collectively, these observations suggest that the two growth regulatory pathways are tightly linked and a more thorough understanding of the mechanism of this crosstalk could lead to improved therapeutic strategies in breast cancer.     

Ring artifacts on the barium enema

A specific ring artifact that is occasionally seen on barium enemas is described. The cause, appearance, and means of avoiding this artifact are discussed.     

Porin Loss Impacts the Host Inflammatory Response to Outer Membrane Vesicles of Klebsiella pneumoniae

Antibiotic-resistant strains of Klebsiella pneumoniae often exhibit porin loss. In this study, we investigated how porin loss impacted the composition of secreted outer membrane vesicles as well as their ability to trigger proinflammatory cytokine secretion by macrophages. We hypothesize that porin loss associated with antibiotic resistance will directly impact both the composition of outer membrane vesicles and their interactions with phagocytic cells. Using clonally related clinical isolates of extended-spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae with different patterns of porin expression, we demonstrated that altered expression of OmpK35 and OmpK36 results in broad alterations to the protein profile of secreted vesicles. Additionally, the level of OmpA incorporation was elevated in strains lacking a single porin. Porin loss significantly impacted macrophage inflammatory responses to purified vesicles. Outer membrane vesicles lacking both OmpK35 and OmpK36 elicited significantly lower levels of proinflammatory cytokine secretion than vesicles from strains expressing one or both porins. These data demonstrate that antibiotic resistance-associated porin loss has a broad and significant effect on both the composition of outer membrane vesicles and their interactions with phagocytic cells, which may impact bacterial survival and inflammatory reactions in the host.