Public involvement in participatory research: the experiences of peer interviewers from Roma, Gypsy and Traveller communities.

BACKGROUND: A vital component of research is patient and public involvement (PPI). The challenges of PPI increase when conducting cross-cultural research into sensitive subjects with marginalised ethnic minority groups. AIM: To present the authors' reflections on conducting peer interviews with members of Roma, Gypsy and Traveller communities. DISCUSSION: The authors provide examples of reflections on collecting data from a participatory research project that explored Gypsies, Roma and Travellers' experiences of cancer in their communities. They derived the reflections from audio-recorded, post-interview debriefs with co-researchers from the same ethnic backgrounds as interviewees ('peer researchers'). The main challenges for the peer researchers were cultural, linguistic and pragmatic, all fundamentally related to exploring a sensitive health topic through the lens of ethnicity. CONCLUSION: Peer researchers recognised their role in building bridges between participants and the research team. They did this by establishing a relationship of trust, minimising distress, representing the views of their communities and obtaining data to meet the aims of the project. Peer researchers perform multiple roles to assist in cross-cultural data collection in participatory research. IMPLICATIONS FOR PRACTICE: This article highlights underexplored aspects of peer researchers' work that have implications for the planning and conduct of cross-cultural research with marginalised groups.

Cancer diagnosis, treatment and care: A qualitative study of the experiences and health service use of Roma, Gypsies and Travellers.

BACKGROUND: Early diagnosis and treatment are key to reducing deaths from cancer, but people from Black and Minority Ethnic (BME) groups are more likely to encounter delays in entering the cancer care system. Roma, Gypsies and Travellers are ethnic minorities who experience extreme health inequalities. OBJECTIVE: To explore the experiences of cancer diagnosis, treatment and care among people who self-identify as Roma or Gypsies and Travellers. METHODS: A participatory qualitative approach was taken. Peer researchers conducted semi-structured interviews (n = 37) and one focus group (n = 4) with community members in Wales and England, UK. RESULTS: Cancer fatalism is declining, but Roma, Gypsies and Travellers experience barriers to cancer healthcare at service user, service provider and organisational levels. Communication was problematic for all groups, and Roma participants reported lack of access to interpreters within primary care. Clear communication and trusting relationships with health professionals are highly valued and most frequently found in tertiary care. CONCLUSION: This study suggests that Roma, Gypsies and Travellers are motivated to access health care for cancer diagnosis and treatment, but barriers experienced in primary care can prevent or delay access to diagnostic and treatment services. Organisational changes, plus increased cultural competence among health professionals, have the potential to reduce inequalities in early detection of cancer.

Knowledge and experience of cancer prevention and screening among Gypsies, Roma and Travellers: a participatory qualitative study.

BACKGROUND: The incidence of cancer is increasing worldwide, which has led to greater public health focus on primary prevention. Ethnic minorities have lower awareness of cancer risk factors and services, and are at greater risk of cancer mortality. While Gypsies, Roma and Travellers have poor health outcomes even in comparison with other ethnic minorities, little is known about how they view and enact primary prevention. This study takes a participatory approach to explore knowledge and experience of cancer prevention and screening in these communities. METHODS: Peer researchers conducted interviews (n = 37) and a focus group (n = 4) with a purposive sample of community members in Wales and South-West England. Participants self-identified as Roma (from Slovakia and Romania) or as Gypsies, Travellers or Showpeople (here described as Gypsy/Travellers). A third of the sample were Roma, and a quarter male, with ages ranging from 18 to 77 years. Data were collected from October 2018 to March 2019. RESULTS: Women and men knew that lifestyle factors, such as healthy diet, stopping smoking, drinking less alcohol and using sun protection, contribute to cancer risk reduction. However, there was a widespread lack of confidence in the effectiveness of these measures, particularly in relation to smoking. Traditional cultural beliefs were shared by Roma and Gypsy/Travellers, but did not necessarily affect the behaviour of individuals. Most women participated in cervical and breast screening but few Gypsy/Traveller men would engage with bowel screening, which conflicted with community ideals of stoical masculinity. Roma participants described language barriers to screening, with confusion about differences in timing and eligibility between the UK and Slovakian programmes; this led some to access screening abroad. CONCLUSION: This study provides new knowledge about how Gypsies, Roma and Travellers keep healthy and prevent disease, giving insights into similarities and differences between ages, sexes and communities. These culturally distinct and high-need ethnic minorities have specific needs in relation to cancer prevention and screening, which merit targeted and acceptable health promotion to reduce health inequalities.

Best Practice for Delivering Small-Volume Intermittent Intravenous Infusions.

This study investigated the delivery of small-volume intermittent intravenous (IV) infusions. Laboratory protocol evaluated potential medication loss among 6 administration methods using 50- and 100-mL solutions. Significant variations existed in calculated medication loss depending on administration method and volume. Up to 35% of medication may not be administered due to residual volume, with the greatest percentage associated with 50-mL solutions. Results suggest that intermittent IV infusions should only be delivered as a secondary infusion through a primary infusion administration set with a continuous infusion or an infusion that can flush the administration set at the completion of the secondary infusion.

Long-term quality of life improvement for chronic intractable back and leg pain patients using spinal cord stimulation: 12-month results from the SENZA-RCT.

PURPOSE: Chronic axial low-back pain is a debilitating disorder that impacts all aspects of an afflicted individual's life. Effective, durable treatments have historically been elusive. Interventional therapies, such as spinal cord stimulation (SCS), have shown limited efficacy at best. Recently, a novel treatment, 10 kHz SCS, has demonstrated superior pain relief compared with traditional SCS in a randomized controlled trial (RCT). In this manuscript, we report on the long-term improvements in quality of life (QoL) outcomes for subjects enrolled in this study. METHODS: A prospective, multicenter, randomized controlled trial (SENZA-RCT) was conducted. Patients with both chronic back and leg pain were enrolled and randomized (1:1) into 10 kHz SCS or traditional SCS treatment groups. A total of 171 subjects received a permanent SCS device implant. QoL and functionality measures were collected up to 12 months. The device remote control utilization, which is an indication of patient interaction with the device for adjustments, was collected at 24-month post-implantation. RESULTS: At 12 months, a higher proportion of 10 kHz SCS subjects had marked improvement of their disability (Oswestry Disability Index) to a "moderate" or "minimal" impact on their daily function versus the control group. The subjects also reported better improvement in the Global Assessment of Functioning, Clinician Global Impression of Change, Pittsburgh Sleep Quality Index, and short-form McGill Pain Questionnaire, compared to traditional SCS subjects. The 10 kHz SCS subjects also reported far higher rates of both driving and sleeping with their device turned on, as well as reduced reliance on their programmers to adjust therapy settings. CONCLUSIONS: In addition to superior pain relief, 10 kHz SCS provides long-term improvements in quality of life and functionality for subjects with chronic low-back and leg pain. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01609972).

Paresthesia-Independence: An Assessment of Technical Factors Related to 10 kHz Paresthesia-Free Spinal Cord Stimulation.

BACKGROUND: Spinal cord stimulation (SCS) has been successfully used to treat chronic intractable pain for over 40 years. Successful clinical application of SCS is presumed to be generally dependent on maximizing paresthesia-pain overlap; critical to achieving this is positioning of the stimulation field at the physiologic midline. Recently, the necessity of paresthesia for achieving effective relief in SCS has been challenged by the introduction of 10 kHz paresthesia-free stimulation. In a large, prospective, randomized controlled pivotal trial, HF10 therapy was demonstrated to be statistically and clinically superior to paresthesia-based SCS in the treatment of severe chronic low back and leg pain. HF10 therapy, unlike traditional paresthesia-based SCS, requires no paresthesia to be experienced by the patient, nor does it require paresthesia mapping at any point during lead implant or post-operative programming. OBJECTIVES: To determine if pain relief was related to technical factors of paresthesia, we measured and analyzed the paresthesia responses of patients successfully using HF10 therapy. STUDY DESIGN: Prospective, multicenter, non-randomized, non-controlled interventional study. SETTING: Outpatient pain clinic at 10 centers across the US and Italy. METHODS: Patients with both back and leg pain already implanted with an HF10 therapy device for up to 24 months were included in this multicenter study. Patients provided pain scores prior to and after using HF10 therapy. Each patient's most efficacious HF10 therapy stimulation program was temporarily modified to a low frequency (LF; 60 Hz), wide pulse width (~470 mus), paresthesia-generating program. On a human body diagram, patients drew the locations of their chronic intractable pain and, with the modified program activated, all regions where they experienced LF paresthesia. Paresthesia and pain drawings were then analyzed to estimate the correlation of pain relief outcomes to overlap of pain by paresthesia, and the mediolateral distribution of paresthesia (as a surrogate of physiologic midline lead positioning). RESULTS: A total of 61 patients participated across 11 centers. Twenty-eight men and 33 women with a mean age of 56 ± 12 years of age participated in the study. The average duration of implantable pulse generator (IPG) implant was 19 ± 9 months. The average predominant pain score, as measured on a 0 - 10 visual analog scale (VAS), prior to HF10 therapy was 7.8 ± 1.3 and at time of testing was 2.5 ± 2.1, yielding an average pain relief of 70 ± 24%. For all patients, the mean paresthesia coverage of pain was 21 ± 28%, with 43% of patients having zero paresthesia coverage of pain. Analysis revealed no correlation between percentage of LF paresthesia overlap of predominant pain and HF10 therapy efficacy (P = 0.56). Exact mediolateral positioning of the stimulation electrodes was not found to be a statistically significant predictor of pain relief outcomes. LIMITATIONS: Non-randomized/non-controlled study design; short-term evaluation; certain technical factors not investigated. CONCLUSION: Both paresthesia concordance with pain and precise midline positioning of the stimulation contacts appear to be inconsequential technical factors for successful HF10 therapy application. These results suggest that HF10 therapy is not only paresthesia-free, but may be paresthesia-independent.

Comparison of 10-kHz High-Frequency and Traditional Low-Frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: 24-Month Results From a Multicenter, Randomized, Controlled Pivotal Trial.

BACKGROUND: Pain relief with spinal cord stimulation (SCS) has focused historically on paresthesias overlapping chronically painful areas. A higher level evidence supports the use of SCS in treating leg pain than supports back pain, as it is difficult to achieve adequate paresthesia coverage, and then pain relief, in the low back region. In comparison, 10-kHz high-frequency (HF10 therapy) SCS therapy does not rely on intraoperative paresthesia mapping and remains paresthesia-free during therapy. OBJECTIVE: To compare long-term results of HF10 therapy and traditional low-frequency SCS. METHODS: A pragmatic randomized, controlled, pivotal trial with 24-month follow-up was conducted across 11 comprehensive pain treatment centers. Subjects had Visual Analog Scale scores of ≥5.0/10.0 cm for both back and leg pain, and were assigned randomly (1:1) to receive HF10 therapy or low-frequency SCS. The primary end point was a responder rate, defined as ≥50% back pain reduction from baseline at 3 months with a secondary end point at 12 months (previously reported). In this article, 24-month secondary results are presented. Non-inferiority was first assessed, and if demonstrated the results were tested for superiority. RESULTS: In the study, 198 subjects were randomized (101 HF10 therapy, 97 traditional SCS). One hundred seventy-one subjects (90 HF10 therapy, 81 traditional SCS) successfully completed a short-term trial and were implanted. Subjects averaged 54.9 ± 12.9 years old, 13.6 ± 11.3 years since diagnosis, 86.6% had back surgery, 88.3% were taking opioid analgesics. At 3 months, 84.5% of implanted HF10 therapy subjects were responders for back pain and 83.1% for leg pain, and 43.8% of traditional SCS subjects were responders for back pain and 55.5% for leg pain (P < .001 for both back and leg pain comparisons, non-inferiority and superiority). At 24 months, more subjects were responders to HF10 therapy than traditional SCS (back pain: 76.5% vs 49.3%; 27.2% difference, 95% CI, 10.1%-41.8%; P < .001 for non-inferiority and superiority; leg pain: 72.9% vs 49.3%; 23.6% difference, 95% CI, 5.9%-38.6%; P < .001 for non-inferiority and P = .003 for superiority). Also at 24 months, back pain decreased to a greater degree with HF10 therapy (66.9% ± 31.8%) than traditional SCS (41.1% ± 36.8%, P < .001 for non-inferiority and superiority). Leg pain also decreased to a greater degree with HF10 therapy (65.1% ± 36.0%) than traditional SCS (46.0% ± 40.4%, P < .001 for non-inferiority and P = .002 for superiority). CONCLUSION: This study demonstrates long-term superiority of HF10 therapy compared with traditional SCS in treating both back and leg pain. The advantages of HF10 therapy are anticipated to impact the management of chronic pain patients substantially. ABBREVIATIONS: IPG, implantable pulse generatorMCID, minimal clinically important differencePI, permanent implantODI, Oswestry Disability IndexSCS, spinal cord stimulationVAS, Visual Analog Scale.

Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial.

BACKGROUND: Current treatments for chronic pain have limited effectiveness and commonly known side effects. Given the prevalence and burden of intractable pain, additional therapeutic approaches are desired. Spinal cord stimulation (SCS) delivered at 10 kHz (as in HF10 therapy) may provide pain relief without the paresthesias typical of traditional low-frequency SCS. The objective of this randomized, parallel-arm, noninferiority study was to compare long-term safety and efficacy of SCS therapies in patients with back and leg pain. METHODS: A total of 198 subjects with both back and leg pain were randomized in a 1:1 ratio to a treatment group across 10 comprehensive pain treatment centers. Of these, 171 passed a temporary trial and were implanted with an SCS system. Responders (the primary outcome) were defined as having 50% or greater back pain reduction with no stimulation-related neurological deficit. RESULTS: At 3 months, 84.5% of implanted HF10 therapy subjects were responders for back pain and 83.1% for leg pain, and 43.8% of traditional SCS subjects were responders for back pain and 55.5% for leg pain (P < 0.001 for both back and leg pain comparisons). The relative ratio for responders was 1.9 (95% CI, 1.4 to 2.5) for back pain and 1.5 (95% CI, 1.2 to 1.9) for leg pain. The superiority of HF10 therapy over traditional SCS for leg and back pain was sustained through 12 months (P < 0.001). HF10 therapy subjects did not experience paresthesias. CONCLUSION: HF10 therapy promises to substantially impact the management of back and leg pain with broad applicability to patients, physicians, and payers.

Novel spinal cord stimulation parameters in patients with predominant back pain.

OBJECTIVES: To examine the feasibility of novel high-frequency spinal cord stimulation therapy in a cohort of patients with chronic predominant back pain during a four day, percutaneous trial. DESIGN: Prospective, multicenter open label pilot trial. SETTING AND PATIENTS: Twenty-four patients with back pain greater than leg pain who were candidates for spinal cord stimulation were trialed at five U.S. centers. INTERVENTIONS: Patients completed a percutaneous trial with a commercially available spinal cord stimulator. The implanted leads were then connected to the novel external stimulation device and patients were trialed for an additional four days. OUTCOME MEASURES: Pain intensity ratings, subjective descriptions, and patients' preference. RESULTS: There was significant improvement from baseline in overall pain scores (8.68 to 2.03, [p < 0.001]) and back pain scores (8.12 to 1.88, [p < 0.001]) with the investigational stimulation. The investigational stimulation was preferred to the commercially available systems in 21 of 24 patients (88%). CONCLUSIONS: Patients with predominant back pain reported a substantial reduction in overall pain and back pain when trialed with high-frequency spinal cord stimulation therapy.

Residual DNA analysis in biologics development: review of measurement and quantitation technologies and future directions.

Residual DNA (rDNA) is comprised of deoxyribonucleic acid (DNA) fragments and longer length molecules originating from the host organism that may be present in samples from recombinant biological processes. Although similar in basic structural base pair units, rDNA may exist in different sizes and physical forms. Interest in measuring rDNA in recombinant products is based primarily on demonstration of effective purification during manufacturing, but also on some hypothetical concerns that, in rare cases, depending on the host expression system, some DNA sequences may be potentially infectious or oncogenic (e.g., HIV virus and the Ras oncogene, respectively). Recent studies suggest that a sequence known as long interspersed nucleotide element-1 (LINE-1), widely distributed in the mammalian genome, is active as a retrotransposon that can be transcribed to RNA, reverse-transcribed into DNA and inserts into a new site in genome. This integration process could potentially disrupt critical gene functions or induce tumorigenesis in mammals. Genomic DNA from microbial sources, on the other hand, could add to risk of immunogenicity to the target recombinant protein being expressed, due to the high CpG content and unmethylated DNA sequence. For these and other reasons, it is necessary for manufacturers to show clearance of DNA throughout production processes and to confirm low levels in the final drug substance using an appropriately specific and quantitative analytical method. The heterogeneity of potential rDNA sequences that might be makes the testing of all potential analytes challenging. The most common methodology for rDNA quantitation used currently is real-time polymerase chain reaction (RT-PCR), a robust and proven technology. Like most rDNA quantitation methods, the specificity of RT-PCR is limited by the sequences to which the primers are directed. To address this, primase-based whole genome amplification is introduced herein. This paper will review the recent advancement in rDNA quantitation and recent findings regarding potential risks of immunogenicity, infectivity, and oncogenicity of rDNA.

The measurement of regional cerebral blood flow during glossolalia: a preliminary SPECT study.

Glossolalia (or "speaking in tongues") is an unusual mental state that has great personal and religious meaning. Glossolalia is experienced as a normal and expected behavior in religious prayer groups in which the individual appears to be speaking in an incomprehensible language. This is the first functional neuroimaging study to demonstrate changes in cerebral activity during glossolalia. The frontal lobes, parietal lobes, and left caudate were most affected.

Effect of incongruence of acute myocardial infarction symptoms on the decision to seek treatment in a rural population.

People are advised to obtain immediate treatment for acute myocardial infarction (AMI), yet a delay occurs between the onset of symptoms and the decision to seek treatment. The objective of the study was to determine the extent of incongruence between expected and actual symptoms of AMI, effect of incongruence on decision time to seek treatment, and predictive effect of selected variables on decision time in a rural population. Ninety-eight rural patients receiving inpatient treatment for AMI at 2 hospitals in the Northeast of the United States from August 2001 through October 2002 completed the Morgan Incongruency of Heart Attack Symptoms Index and the Response to Symptoms Questionnaire. The median decision time was 93 minutes. There were differences between men and women regarding the symptoms that were expected to occur and that actually occurred. The extent to which symptoms interfered with the ability to carry out normal activities, degree of anxiety, and type of insurance coverage explained 23% of the variance in decision time. Although the expected symptoms did not match the actual symptoms, this incongruence did not affect decision time.

Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients.

Patients with controlled background pain associated with cancer frequently also experience episodes of moderate to severe intensity breakthrough pain. Opioid pharmacotherapy, particularly with oral morphine, remains the cornerstone for the management of cancer pain. Nasal administration of opioids provides a mechanism for more rapid drug absorption and more rapid onset of pain relief compared with oral dosing. This non-randomized, open-label, uncontrolled investigation evaluated the pharmacokinetics, safety and efficacy of a single 40 mg dose of nasal morphine gluconate, administered to cancer patients in response to an episode of breakthrough pain. Single dose nasal morphine gluconate administered to 11 patients was associated with effective plasma morphine concentrations (mean C(max) 64 ng/ml; range 33.8-121 ng/ml) and low plasma morphine metabolites (morphine-6-glucuronide mean C(max) 114 ng/ml; range 46-189 ng/ml; morphine-3-glucuronide mean C(max) 572 ng/ml; range 257-990 ng/ml). Side effects were minor and limited to nasal irritation. Patients reported rapid onset of pain relief (perceptible pain relief achieved in 10/11 patients, time to onset 2.4+/-2.1 min; and meaningful pain relief, achieved in five patients, 6.8+/-7.3 min to onset, mean t(max) 0.36 h). Pain intensity scores were significantly reduced at all times after dosing; pain relief scores were unchanged. Patient satisfaction ratings were high. These results show that nasal morphine has rapid absorption and apparent onset of effect. Additional multi-dose, dose-ranging and placebo-controlled studies of nasal morphine for cancer pain are warranted.