A pilot randomised double blind controlled trial of the efficacy of purified fatty acids for the treatment of women with endometriosis-associated pain (PurFECT):study protocol

Abstract Background Endometriosis affects 6–10% of women and is associated with debilitating pelvic pain. It costs the UK > £2.8 billion per year in loss of productivity. Endometriosis can be managed by surgical excision or medically by ovarian suppression. However, ~ 75% symptoms recur after surgery and available medical treatments have undesirable side effects and are contraceptive. Omega-3 purified fatty acids (PUFA) have been shown in animal models to reduce factors that are thought to lead to endometriosis-associated pain, have minimal side effects, and no effects on fertility. This paper presents a protocol for a two-arm, pilot parallel randomised controlled trial (RCT) which aims to inform the planning of a future multicentre trial to evaluate the efficacy of Omega-3 PUFA in the management of endometriosis-associated pain in women. Methods The study will recruit women with endometriosis over a 12-month period in the National Health Service (NHS) Lothian, UK, and randomise them to 8 weeks of treatment with Omega-3 PUFA or comparator (olive oil). The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness/acceptability to participants of the proposed methods of recruitment/randomisation/treatments/questionnaires, to inform the sample size calculation and to refine the research methodology for a future large randomised controlled trial. Response to treatment will be monitored by pain scores and questionnaires assessing physical and emotional function compared at baseline and 8 weeks. Discussion We recognise that there may be potential difficulties in mounting a large randomised controlled trial for endometriosis to assess Omega-3 PUFA because they are a dietary supplement readily available over the counter and already used by women with endometriosis. We have therefore designed this pilot study to assess practical feasibility and following the ‘Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials’ recommendations for the design of chronic pain trials. Trial registration ISRCTN4420234

Laparoscopic treatment of isolated superficial peritoneal endometriosis for managing chronic pelvic pain in women:study protocol for a randomised controlled feasibility trial (ESPriT1)

Background: Endometriosis (where endometrial-like tissue is found outside the uterus) affects ~ 176 million women worldwide and can lead to debilitating pelvic pain. Three subtypes of endometriosis exist, with ~ 80% of women having superficial peritoneal endometriosis (SPE). Endometriosis is diagnosed by laparoscopy and, if SPE is found, gynaecologists usually remove it surgically. However, many women get limited pain relief from surgical removal of SPE. We plan to undertake a future large trial where women who have only SPE found at initial laparoscopy are randomly allocated to have surgical removal (excision or ablation) of SPE, or not. Ultimately, we want to determine whether surgical removal improves overall symptoms and quality of life, or whether surgery is of no benefit, exacerbates symptoms, or even causes harm. The primary objective of this feasibility study is to determine what proportion of women with suspected SPE undergoing diagnostic laparoscopy will agree to randomisation. The secondary objectives are to determine if there are differences in key prognostic parameters between eligible women that agree to be randomised and those that decline; how many women having laparoscopy for investigation of chronic pelvic pain are eligible for the trial; the range of treatment effects and variability in outcomes and the most acceptable methods of recruitment, randomisation and assessment tools. Methods: We will recruit up to 90 women with suspected SPE undergoing diagnostic laparoscopy over a 9-month recruitment period in four Scottish hospitals and randomise them 1:1 to either diagnostic laparoscopy alone (with a sham port to achieve blinding of the allocation) or surgical removal of endometriosis. Baseline characteristics, e.g. age, index of social deprivation, ethnicity, and intensity/duration of pain will be collected. Participants will be followed up by online questionnaires assessing pain, physical and emotional function at baseline, 3 months, 6 months and 12 months. Discussion: Recruitment to a randomised controlled trial to assess the effectiveness of surgery for endometriosis may be challenging because of preconceived ideas about treatment success amongst patients and clinicians. We have designed this study to assess feasibility of recruitment and to inform the design of our future definitive trial. Trial registration: ClincicalTrials.gov, NCT04081532 Status: Recruiting

The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390]

BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age ≥ 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN

Functional status of masticatory system, excutive function and episodic memory in older persons.

Findings from human experimental studies suggest that mastication positively influences cognitive function. The participants in those studies were relatively young. The goal of this study was to examine the relationship between the functional status of the masticatory system, episodic memory, and executive functions in elderly people. The participants, elderly people living independently at home, were divided into two groups. One group had a full complement of natural teeth (n = 19) and the other group had full dentures (n = 19). The functional status of the masticatory system was assessed by measuring mandibular excursions (i.e. the distances over which the mandible can move in the open, lateral, and forward directions), bite force, number of occluding pairs and complaints of the masticatory system (facial pain, headaches/migraine). Executive functions and episodic memory were assessed by neuropsychological tests. Backward regression analysis showed that only in the group of elderly people with full dentures, 22% of executive functions were predicted by complaints of the masticatory system and 19.4% of episodic memory was predicted by masticatory performance (composed of mandibular excursions and bite force). The conclusion of this study is that only in older persons with full dentures the relationship between mastication, episodic memory, and executive function becomes evident when the functional status of the masticatory system decreases

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

Level of arterial ligation in total mesorectal excision (TME): an anatomical study

Introduction: High-tie ligation is a common practice in rectal cancer surgery. However, it compromises perfusion of the proximal limb of the anastomosis. This anatomical study was designed to assess the value of low-tie ligation in order to obtain a tension-free anastomosis. Materials and methods: Consecutive high- and low-tie resections were performed on 15 formalin-fixed specimens, with or without splenic flexure mobilization. If the proximal colon limb could reach the superior aspect of the symphysis pubis with more than 3 cm, the limb would be long enough for a tension-free colorectal anastomosis. Results: In 80% of cases, it was not necessary to perform high-tie ligation as sufficient length was gained with low-tie ligation. The descending branch of the left colic artery was the limiting factor in the other 20% of cases. Resecting half the sigmoid resulted in four times as many tension-free anastomoses after low-tie resection. Conclusion: In the majority of cases, it was not necessary to perform high-tie ligation in order to create a tension-free anastomosis. Low-tie ligation was applicable in 80% of cases and might prevent anastomotic leakage due to insufficient blood supply of the proximal colon limb

Predictors of pain intensity and persistence in a prospective Italian cohort of patients with herpes zoster: relevance of smoking, trauma and antiviral therapy

Herpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors

Acupuncture for the treatment of severe acute pain in Herpes Zoster: results of a nested, open-label, randomized trial in the VZV Pain Study

<p>Abstract</p> <p>Background</p> <p>Data on the potential efficacy of acupuncture (AC) in controlling intense or very intense pain in patients with Herpes Zoster (HZ) has not been so far adequately assessed in comparison with standard pharmacological treatment (ST) by a controlled trial design.</p> <p>Methods</p> <p>Within the VZV Pescara study, pain was assessed in HZ patients on a Visual Analogue Scale (VAS) and by the McGill Pain Questionnaire (MPQ) both at the beginning and at the end of treatment. Response rates, mean changes in pain intensity, differences in total pain burden with an area-under-the-curve (AUC) method over a 1-year follow-up and differences in the incidence of Post-Herpetic Neuralgia (PHN) were evaluated.</p> <p>Results</p> <p>One hundred and two patients were randomized to receive either AC (n = 52) or ST (n = 50) for 4 weeks. Groups were comparable regarding age, sex, pain intensity at presentation and missed antiviral prescription. Both interventions were largely effective. No significant differences were observed in response rates (81.6% vs 89.2%, p = 0.8), mean reduction of VAS (4.1 +/- 2.3 vs 4.9 +/- 1.9, p = 0.12) and MPQ scores (1.3 +/- 0.9 vs 1.3 +/- 0.9, p = 0.9), incidence of PHN after 3 months (48.4% vs 46.8%, p = 0.5), and mean AUC during follow-up (199 +/- 136 vs 173 +/- 141, p = 0.4). No serious treatment-related adverse event was observed in both groups.</p> <p>Conclusions</p> <p>This controlled and randomized trial provides the first evidence of a potential role of AC for the treatment of acute herpetic pain.</p> <p>Trial registration</p> <p>ChiCTR-TRC-10001146.</p

Interventions for families affected by HIV

Family-based interventions are efficacious for human immunodeficiency virus (HIV) detection, prevention, and care, but they are not broadly diffused. Understanding intervention adaptation and translation processes can support evidence-based intervention (EBI) diffusion processes. This paper provides a narrative review of a series of EBI for families affected by HIV (FAH) that were adapted across five randomized controlled trials in the US, Thailand, and South Africa over 15 years. The FAH interventions targeted parents living with HIV and their children or caregiver supports. Parents with HIV were primarily mothers infected through sexual transmission. The EBIs for FAH are reviewed with attention to commonalities and variations in risk environments and intervention features. Frameworks for common and robust intervention functions, principles, practice elements, and delivery processes are utilized to highlight commonalities and adaptations for each location, time period, and intervention delivery settings. Health care, housing, food, and financial security vary dramatically in each risk environment. Yet, all FAH face common health, mental health, transmission, and relationship challenges. The EBIs efficaciously addressed these common challenges and were adapted across contexts with fidelity to robust intervention principles, processes, factors, and practices. Intervention adaptation teams have a series of structural decision points: mainstreaming HIV with other local health priorities or not; selecting an optimal delivery site (clinics, homes, community centers); and how to translate intervention protocols to local contexts and cultures. Replication of interventions with fidelity must occur at the level of standardized functions and robust principles, processes, and practices, not manualized protocols. Adopting a continuous quality improvement paradigm will enhance rapid and global diffusion of EBI for FAH