Article

Fluoroquinolones form drug-topoisomerase-DNA complexes that rapidly block transcription and replication. Crystallographic and biochemical studies showthat quinolone binding involves a water/metalion bridge between the quinolone C3-C4 keto-acid and amino acids in helix-4 of the target proteins, GyrA(gyrase) and ParC (topoisomerase IV). A recent cross-linking study revealed a second drug-binding modeinwhichtheotherendofthequinolone, the C7 ring system, interacts with GyrA. We report that addition of a dinitrophenyl (DNP) moiety to the C7 end of ciprofloxacin (Cip-DNP) reduced protection due to resistance substitutions in Escherichia coli GyrA helix-4, consistent with the existence of a second drug-binding mode not evident in X-ray structures of drug-topoisomerase-DNA complexes. Several other C7 aryl fluoroquinolones behaved in a similar manner with particular GyrA mutants. Treatment of E. coli cultures with Cip-DNP selectively enriched an uncommon variant, GyrA-A119E, a change that may impede binding of the dinitrophenyl group at or near the GyrA-GyrA interface. Collectively the data support the existence of a secondary quinolone-binding mode in which the quinolone C7 ring system interacts with GyrA; the data also identify C7 aryl derivatives as a new way to obtain fluoroquinolones that overcome existing GyrA-mediated quinolone resistance.

Objective: To assess the feasibility of recruiting sciatica patients and to evaluate their compliance in preparation for a full-scale randomized clinical trial. We also aimed to determine the responsiveness of key outcome measures.

Methods: Thirty-two subjects were randomly assigned to spinal manipulation (n=11), epidural steroid injections (n=11), or self-care education (n=10). No between-group comparisons were planned because of the small sample size.

Results: At week 12 (the end of the treatment phase), the outcome measures indicating the most improvement/change were the Oswestry disability score (mean, 22.9; SD, 19.9; effect size [ES], 1.8), leg pain severity (mean, 2.9; SD, 1.7; ES, 1.7), and if the symptoms were bothersome (mean, 25.2; SD, 16.0; ES, 1.6). Twenty-four patients were either “very satisfied” or “completely satisfied,” and 22 of 32 patients reported 75% or 100% improvement. After 52 weeks, the outcome measure showing the most improvement/change was leg pain severity (mean, 2.3; SD, 2.6; ES, 1.35), followed by the Oswestry disability score (mean, 15.6; SD, 20; ES, 1.2) and if symptoms were bothersome (mean, 18.1; SD, 22.6; ES, 1.1). Eighteen patients were either “very satisfied” or “completely satisfied,” and 15 of 32 patients reported 75% or 100% improvement.

Conclusions: The results of this pilot study suggest that it is feasible to recruit subacute and chronic sciatica patients and to obtain their compliance for a full-scale randomized clinical.

Background: Low back pain (LBP) and neck pain (NP) are common conditions in old age, leading to impaired functional ability and decreased independence. Manual and exercise therapies are common and effective therapies for the general LBP and NP populations. However, these treatments have not been adequately researched in older LBP and NP sufferers.

The primary aim of these studies is to assess the relative clinical effectiveness of 1) manual treatment plus home exercise, 2) supervised rehabilitative exercise plus home exercise, and 3) home exercise alone, in terms of patient-rated pain, for senior LBP and NP patients. Secondary aims are to compare the three treatment approaches in regards to patient-rated disability, general health status, satisfaction, improvement and medication use, as well as objective outcomes of spinal motion, trunk strength and endurance, and functional ability. Cost-effectiveness and cost-utility will also be assessed. Finally, using qualitative methods, older LBP and NP patient's perceptions of treatment will be explored and described.

Methods/Design: This paper describes the design of two multi-methods clinical studies focusing on elderly patients with non-acute LBP and NP. Each study includes a randomized clinical trial (RCT), a cost-effectiveness study alongside the RCT, and a qualitative study. Four hundred and eighty participants (240 per study), ages 65 and older, will be recruited and randomized to one of three, 12-week treatment programs. Patient-rated outcome measures are collected via self-report questionnaires at baseline and at 4, 12, 26, and 52 weeks post-randomization. Objective outcomes are assessed by examiners masked to treatment assignment at baseline and 12 weeks. Health care cost data is collected through standardized clinician forms, monthly phone interviews, and self-report questionnaires throughout the study. Qualitative interviews using a semi-structured format are conducted at the end of the 12 week treatment period.

Discussion: To our knowledge, these are the first randomized clinical trials to comprehensively address clinical effectiveness, cost-effectiveness, and patients' perceptions of commonly used treatments for elderly LBP and NP sufferers.

Content on integrative healthcare and complementary and alternative medicine is being taught in hundreds of educational programs across the country. Nursing, medical, osteopathic, chiropractic, acupuncture, naturopathic, and other programs are finding creative and innovative ways to include these approaches in new models of education and practice. This column spotlights such innovations in integrative healthcare and CAM education and presents readers with specific educational interventions they can adapt into new or ongoing educational efforts at their institution or programs. We invite readers to submit brief descriptions of efforts in their institutions that reflect the creativity, diversity, and interdisciplinary nature of the field. 

A complex legacy of racism in the United States continues to create health inequities among people of color. Systemic biases in education, employment, housing, healthcare, access to food, accumulation of wealth, and the legal system contribute to poorer health among communities of color. These social determinants of health are driving factors behind the “weathering hypothesis”, where chronic exposure to discrimination and disadvantage lead to accelerated decline in health outcomes, particularly among Black individuals. Black Americans experience greater rates of disease in nearly every major indicator of physical health as compared to other racial and ethnic groups in the United States. Infant mortality among African Americans is twice the national average, and the life expectancy for Black men and women is consistently shorter than their White counterparts.  While this report focuses primarily on Black communities and other persons of color, we acknowledge many groups similarly face discrimination based on gender identity, sexual orientation, social class, and ability.

Introduction. Acute pain is a common ailment in the U.S. often treated with opioids. This technical brief maps the current evidence on pain treatments for select acute pain conditions (postdischarge postoperative pain, musculoskeletal pain, acute migraine, dental pain, renal colic, and acute pain associated with sickle cell disease).

 Methods. We conducted Key Informant discussions to develop the context around the acute pain conditions, settings, and current clinical practice. We then conducted a systematic literature search to identify recent systematic reviews of sufficient quality that evaluated pain treatments for select acute pain conditions. We screened results and extracted relevant data into evidence tables. We subsequently searched for original research published after systematic review search dates. 

Results. Key Informant discussions identified important issues regarding common acute pain conditions and treatments. Certain acute pain conditions have not received sufficient attention in rigorous comprehensive systematic review; for most types of acute pain, pain etiology is critical to selecting appropriate treatment; the value of acute pain assessments in guiding treatment decisions is unclear; and regional and health system level policies play a large role in treatment decisions. Our search for systematic reviews for pain treatments for priority acute pain conditions identified 1226 potentially relevant references, of which 527 underwent full text review. After supplemental searching and full text review, 110 systematic reviews met basic eligibility criteria. Most acute pain conditions had systematic reviews that met eligibility criteria, but few reviews were sufficiently rigorous and comprehensive. Few eligible reviews focused on specific settings except emergency departments for several acute pain conditions. Eligible reviews rarely addressed specific subpopulations such as racial and ethnic groups, rural residents, pregnant women, individuals with comorbidities, or those with a history of substance use disorder, overdose, or mental illness. Comparisons addressed by many systematic reviews often included opioids. 

Discussion. Our discussions with Key Informants and review of the literature show that additional original research and up-do-date comprehensive systematic reviews would help inform treatment decisions for a wide variety of acute pain conditions.

Objective. To summarize evidence on: (1) the accuracy of brief cognitive tests for identifying clinical Alzheimer’s-type dementia (CATD) in individuals with suspected cognitive impairment; (2) the accuracy of biomarkers for identifying Alzheimer’s disease (AD) in individuals with dementia; and (3) the benefits and harms of prescription drugs and supplements for cognition, function, and behavioral and psychological symptoms of dementia (BPSD) in patients with CATD. 

Objective: The purpose of this cross-sectional study was to compare functional limitations and comorbidity prevalence between older adult users and nonusers of chiropractic and osteopathic (DC/DO) manipulation to inform provider training.

Methods: We conducted a secondary analysis of the 2012 National Health Interview Survey data. Adults age 65 or older who responded to the survey were included. Descriptive statistics are reported for adults who used DC/DO manipulation (vs nonusers) regarding function, comorbidities, musculoskeletal complaints, and medical services. Weighted percentages were derived using SAS and compared with χ2 tests.

Results: The DC/DO users were more often female, overweight or obese, and of white race than nonusers. More DC/DO users reported arthritis (55.3% vs 47.0%, <0.01) or asthma (15.0% vs 10.0%, P < .01) than nonusers; hypertension (61.9% vs 55.5%, P = .02) and diabetes (20.3% vs 15.7%, P = .02) were more prevalent in nonusers; and other comorbidities were comparable. The DC/DO users reported more joint pain/stiffness (55.7% vs 44.8%), chronic pain (19.8% vs 14.2%), low back pain (27.8% vs 18.4%), low back with leg pain (18.8% vs 10.6%), and neck pain (24.2% vs 13.1%) than nonusers (all P < .01). Functional limitations affected two-thirds overall, but DC/DO users reported more difficulties stooping and bending; other limitations were comparable. One in 9 reported activities of daily living or instrumental activities of daily living limitations; nonusers were more affected. Surgery was more common among DC/DO users (26.1% vs 19.3%, <0.01); emergency room visits were comparable.

Conclusion: Differences existed between older adult manipulation users and nonusers, especially surgical utilization, musculoskeletal complaints, and comorbidities; functional differences were modest. Our findings highlight areas for provider training and awareness regarding comorbidity burden and management needs in older patients who may simultaneously use manipulation and medical care for musculoskeletal complaints.

Objectives: Transgender individuals commonly experience barriers to quality health care and may suffer from unique musculoskeletal complaints. Although these needs are often inadequately addressed within the health care system, they could be attended to by the chiropractic community. This narrative review describes best practices for delivering culturally sensitive care to transgender patients within the context of chiropractic offices.

Methods: A literature search generated peer-reviewed material on culturally competent care of the transgender community. Google Scholar and trans-health RSS feeds on social media were also searched to find relevant gray literature. Information pertinent to a chiropractic practice was identified and summarized.

Results: Contemporary definitions of transgender, gender identity, and sexual orientation provide a framework for culturally sensitive language and clinic culture. Small changes in record keeping and office procedures can contribute to a more inclusive environment for transgender patients and improve a chiropractor's ability to collect important health history information. Special considerations during a musculoskeletal examination may be necessary to properly account for medical and nonmedical practices transgender patients may use to express their gender. Chiropractors should be aware of health care and social and advocacy resources for transgender individuals and recommend them to patients who may need additional support.

Conclusions: Small yet intentional modifications within the health care encounter can enable chiropractors to improve the health and well-being of transgender individuals and communities.

Spinal manipulative therapy (SMT) and exercise have demonstrated effectiveness for neck pain (NP). Adverse events (AE) reporting in trials, particularly among elderly participants, is inconsistent and challenges informed clinical decision making.

This paper provides a detailed report of AE experienced by elderly participants in a randomized comparative effectiveness trial of SMT and exercise for chronic NP.

AE data, consistent with CONSORT recommendations, were collected on elderly participants who received 12 weeks of SMT with home exercise, supervised plus home exercise, or home exercise alone. Standardized questions were asked at each treatment; participants were additionally encouraged to report AE as they occurred. Qualitative interviews documented participants' experiences with AE. Descriptive statistics and content analysis were used to categorize and report these data.

Compliance was high among the 241 randomized participants. Non-serious AE were reported by 130/194 participants. AE were reported by three times as many participants in supervised plus home exercise, and nearly twice as many as in SMT with home exercise, as in home exercise alone. The majority of AE were musculoskeletal in nature; several participants associated AE with specific exercises. One incapacitating AE occurred when a participant fell during supervised exercise session and fractured their arm. One serious adverse event of unknown relationship occurred to an individual who died from an aneurysm while at home. Eight serious, non-related AE also occurred.

Musculoskeletal AE were common among elderly participants receiving SMT and exercise interventions for NP. As such, they should be expected and discussed when developing care plans.