Neurotropin® relieves oxaliplatin-induced neuropathy via Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system

Aims

Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic peripheral neuropathies. We previously reported that repeated administration of neurotropin prevents oxaliplatin-induced mechanical allodynia by inhibiting axonal degeneration in rats. In the present study, we investigated the analgesic effect of a single administration of neurotropin on oxaliplatin-induced neuropathy in rats.

Main methods

Oxaliplatin (4 mg/kg) was administered intraperitoneally twice a week for 4 weeks. Cold hyperalgesia was assessed using the acetone test and mechanical allodynia was evaluated using the von Frey test.

Key findings

Repeated injection of oxaliplatin induced cold hyperalgesia on day 5 and mechanical allodynia on day 28. A single administration of neurotropin transiently relieved both pain behaviors. The analgesic effect of neurotropin was inhibited by pretreatment with 5-HT_1A, 5-HT₂, 5-HT₃, and α2 receptor antagonists and by monoamine depletion. Moreover, the analgesic effect of neurotropin was abolished by intrathecal injection of pertussis toxin, a G_i protein inhibitor.

Significance

These results suggest that neurotropin is effective in relieving oxaliplatin-induced neuropathy, and that G_i protein-coupled receptors in the monoaminergic descending pain inhibitory system may be involved in the analgesic effect of neurotropin. Neurotropin may have clinical potential for the treatment of oxaliplatin-induced neuropathies.     

Do we protect or discriminate? Representation of senior adults in clinical trials

Aim

The analysis of barriers responsible for low recruitment of older patients in clinical trials and presentation of possible solutions are the subject of this review.

Background

Europe''s population is ageing, and the group of people who more frequently develop neoplasms increases. Oncologists are confronted with a new challenge – how to treat cancer in this group of patients, especially considering the lack of Evidence Based Medicine (EBM) guidelines for treatment of cancer in the elderly population.

Materials and methods

Medline search and analysis of studies published between 1999 and 2012, containing key words: senior adults, cancer, elderly in clinical trials.

Results

Detailed analysis of relevant studies demonstrated that senior adults are underrepresented in clinical trials. Moreover, there is a lack of trials exclusively designed for this heterogeneous group of patients. The analysis of reasons for low recruitment of older patients in clinical trials revealed barriers dependent on patient''s and physician''s attitudes as well as institutional and logistic problems.

Conclusions

It is necessary to widen the scale of trials of all phases in the group of seniors with appropriate assessment of toxicity. This will allow a proper stratification and obtaining representative groups for statistical analysis and credible trial results. Another priority is the design of trials dedicated exclusively to the elderly.     

Adaptación y validación de la versión española de la escala de evaluación de dolor en personas con demencia avanzada: PAINAD-Sp

Introduction

Pain in elderly people is considered a major concern in nursing home facilities affecting between 49% and 83% of the residents. Progression of Alzheimer's Disease causes more communication difficulties in patients with advanced dementia and therefore more problems to understand even the most simple pain evaluation scales. Identification and implementation of appropriate pain management strategies depends on an adequate pain assessment.

Material and methods

The main objective of the study was to validate the Spanish version of the PAINAD Scale (PAINAD-Sp) and to assess its applicability in Spanish Geriatric Nursing Homes. The 20 patients diagnosed with severe dementia from a Geriatric Centre in Spain were observed by five observers with different professional profiles for 5 minutes to each participant, and PAINAD-Sp Scale was administered simultaneously to a Visual Analogical Scale-VAS. Three different observational conditions were established: resting condition, during presumably pleasant activity and during presumable painful activity.

Results

Cronbach's alpha ranged between 0.467 and 0.827 (average 0.692), and rose if Breathing item was deleted. Inter-rater reliability ranged between 0.587 and 0.956. Correlation between PAINAD-Sp Scale total measures and VAS was statistically significant (P<.05) in all measures and ranged from 0.517 to 0.868.

Conclusions

Findings in the study showed that the scale is useful to measure pain in non communicative patients suffering from dementia. The scale maintains good levels of reliability for different healthcare professionals even when they have little training.     

Características y manejo del cáncer de mama primario en pacientes octogenarias: estudio retrospectivo

Background

The number of elderly patients with breast cancer is increasing, and a large proportion of these older patients do not receive conventional treatment. Clinical and biological characteristics of tumours at this age and survival according to local or systemic therapy were analysed.

Material and method

A total of 96 consecutive early breast cancer patients over 80 years of age diagnosed in our Unit between January 2002 and September 2008 were retrospectively investigated. Of them, 54 underwent surgery with or without adjuvant hormonal treatment, and 42 received primary hormonal therapy.

Results

Tumours of patients 80 years old or older had more favourable biological characteristics, including expression of steroid receptors, and absence of c-erb B2 expression. Overall survival was 50 months for the group subjected to surgery, and 44 months for the group who did not undergo surgery. The survival free of local recurrence in the surgery group was 44 months, whereas it was 18 months in the non-surgery group.

Conclusion

In a cohort of patients aged 80 years and older, survival was similar in those who received hormonal or surgical therapy, although the former had a shorter period of progression-free survival or local recurrence.     

Detección de disfagia en mayores institucionalizados

Objective

To determine the prevalence of dysphagia in a population of institutionalised elderly people, and the effectiveness of a clinical method for its detection.

Methodology

A prospective study was conducted on a random sample of elderly residents. A clinical evaluation along with an assessment with different volumes and viscosities (MECVV) were used. Specific care and follow up was arranged following this assessment.

Results

Forty residents were studied. The prevalence of unrecognised dysphagia was 42.5%. Following assessment by the MECVV, the prevalence rose from 22.5% to 65% (P=.012). Dysphagia detected by MECVV was related to nutritional risk, as measured by the Mini-Nutritional Assessment (MNA) (P=.007), and to the diagnosis of dementia (P=.028).

Conclusions

The diagnosis of dysphagia in this sample of institutionalised elderly people increases when applying a clinical method for detection, reaching a prevalence similar to other studies.     

Calcium electroporation in three cell lines: a comparison of bleomycin and calcium,calcium compounds,and pulsing conditions

Background

Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium electroporation and electrochemotherapy.

Methods

The effects of calcium electroporation and bleomycin electroporation (alone or in combination) were compared in three different cell lines (DC-3F, transformed Chinese hamster lung fibroblast; K-562, human leukemia; and murine Lewis Lung Carcinoma). Furthermore, the effects of electrical pulsing parameters and calcium compound on treatment efficacy were determined.

Results

Electroporation with either calcium or bleomycin significantly reduced cell survival (p < 0.0001), without evidence of a synergistic effect. Cellular death following calcium or bleomycin treatment occurred at similar applied voltages, suggesting that similar parameters should be applied. At equimolar concentrations, calcium chloride and calcium glubionate resulted in comparable decreases in cell viability.

Conclusions

Calcium electroporation and bleomycin electroporation significantly reduce cell survival at similar applied voltage parameters. The effect of calcium electroporation is independent of calcium compound.

General significance

This study strongly supports the use of calcium electroporation as a potential cancer therapy and the results may aid in future clinical trials.     

Evidence for the involvement of descending pain-inhibitory mechanisms in the attenuation of cancer pain by carvacrol aided through a docking study

Aims

The present study evaluated the carvacrol (CARV) effect on hyperalgesia and nociception induced by sarcoma 180 (S180) in mice.

Main methods

Carvacrol treatment (12.5–50 mg/kg s.c.) once daily for 15 days was started 24 h after injection of the sarcoma cells in the hind paw (s.c.). Mice were evaluated for mechanical sensitivity (von Frey), spontaneous and palpation-induced nociception, limb use and tumor growth on alternate days. CARV effects on the central nervous system were evaluated through immunofluorescence for Fos protein. Molecular docking studies also were performed to evaluate intermolecular interactions of the carvacrol and muscimol, as ligands of interleukin-10 and GABA_A receptors.

Key findings

CARV was able to significantly reduce mechanical hyperalgesia and spontaneous and palpation-induced nociception, improve use paw, decrease the number of positively marked neurons in lumbar spinal cord and activate periaqueductal gray, nucleus raphe magnus and locus coeruleus. CARV also caused significant decreased tumor growth. Docking studies showed favorable interaction overlay of the CARV with IL-10 and GABA_A.

Significance

Together, these results demonstrated that CARV may be an interesting option for the development of new analgesic drugs for the management of cancer pain.     

La neurólisis del nervio mediano en el paciente anciano: evaluación a largo plazo

Purpose

Carpal tunnel release by opening the flexor retinaculum is considered a satisfactory treatment. However, several factors, like ageing, may influence postoperative results. We present the long term outcomes in elderly patients.

Methods

This is an historical prospective long term study of 52 patients who received surgical treatment of carpal tunnel syndrome when they were 65 or older. We have carried out a clinical-functional (with the Levine questionnaire), electromyographic and dynamometric valuation of the patients studied, up to ten years from the surgery.

Results

The results of Levine's questionnaire, revealed favourable data for a mean follow-up of 10.35 years, with a mean improvement in the clinical score of 1.93 points (95% confidence interval [CI]: 1.72-2.17) and in the functional score of 0.83 points (95% CI: 0.68-0.99). Similarly, the electromyographic values showed a significant improvement compared to preoperative ones (mean difference of sensory velocity of 8.43 m/s, 95% CI: 8.17-11.63; mean difference of motor latency of 1.65 ms, 95% CI: 1.24-2.25). The data on grip strength did not reach statistical significance.

Conclusions

In elderly patients, complete section of the carpal transverse ligament, allows maintaining favourable differences in most of the parameters studied, ten years after surgery, making the surgical treatment a recommendable option.     

The Efficacy of Acupuncture in Post-Operative Pain Management: A Systematic Review and Meta-Analysis

Background

Postoperative pain resulting from surgical trauma is a significant challenge for healthcare providers. Opioid analgesics are commonly used to treat postoperative pain; however, these drugs are associated with a number of undesirable side effects.

Objective

This systematic review and meta-analysis evaluated the effectiveness of acupuncture and acupuncture-related techniques in treating postoperative pain.

Data Source

MEDLINE, Cochrane Library, and EMBASE databases were searched until Sep 30, 2014.

Study Eligibility Criteria

Randomized controlled trials of adult subjects (≥ 18 years) who had undergone surgery and who had received acupuncture, electroacupuncture, or acupoint electrical stimulation for managing acute post-operative pain were included.

Results

We found that patients treated with acupuncture or related techniques had less pain and used less opioid analgesics on Day 1 after surgery compared with those treated with control (P < 0.001). Sensitivity analysis using the leave-one-out approach indicated the findings are reliable and are not dependent on any one study. In addition, no publication bias was detected. Subgroup analysis indicated that conventional acupuncture and transcutaneous electric acupoint stimulation (TEAS) were associated with less postoperative pain one day following surgery than control treatment, while electroacupuncture was similar to control (P = 0.116). TEAS was associated with significantly greater reduction in opioid analgesic use on Day 1 post surgery than control (P < 0.001); however conventional acupuncture and electroacupuncture showed no benefit in reducing opioid analgesic use compared with control (P ≥ 0.142).

Conclusion

Our findings indicate that certain modes of acupuncture improved postoperative pain on the first day after surgery and reduced opioid use. Our findings support the use of acupuncture as adjuvant therapy in treating postoperative pain.     

La participación de personas con demencia en las reuniones del plan de atención individualizada: impacto en el bienestar y la calidad del cuidado

Introduction

An individualised intervention plan (IIP) offers a new paradigm in the care of the elderly with dementia, with the aim of increasing their quality of life through personalisation, respect for their freedom, and their participation in the decisions that affect their lives.

Objective

To evaluate the impact of the residential home patient with dementia and their quality of care when they take part in the interdisciplinary meeting in which their care plan is decided.

Material and methods

A total of 52 elderly patients with dementia took part in the study. They were distributed into two groups, one experimental (37 residents) and another control (15 residents). The Dementia Care Mapping (DCM) tool was used to assess the well-being and quality of care of the residents. This tool was used twice, before and after the intervention.

Results

The well-being of the resident, evaluated using the DCM, was similar before and after the intervention in the experimental group. No differences were observed either on comparing the control and experimental groups. However, some indicators of carer behaviour were different before and after the intervention, and when the control and experimental group were compared.

Conclusion

The inclusion of elderly persons with dementia in their IIP meeting had a positive effect in the interaction of the staff with the residents, but not on the well-being of the resident.     

Prevalencia de síntomas neuropsiquiátricos en pacientes institucionalizados con diagnóstico de demencia y factores asociados: estudio transversal multicéntrico

Objective

The aim was to estimate the prevalence and severity of neuropsychiatric symptoms in patients with dementia in nursing homes, assessing their association with certain factors that may influence their occurrence.

Material and methods

A cross-sectional study was carried out, and included all elderly patients diagnosed with degenerative, vascular, or mixed dementia, stage 4 to 7 on the Global Deterioration Scale of Reisberg (GDS), and residents in 6 nursing homes in the province of Ourense (Spain). A sample size of 120 individuals was determined to be necessary. The assessment of symptoms was performed using the Neuropsychiatric Inventory-Nursing Home test. The influence of the determined factors was investigated using logistic and linear regression analysis, and subsequently corrected for possible confounding factors.

Results

A total of 212 cases were included, with a mean age of 85.7 (SD = 6.7) years. The prevalence of neuropsychiatric symptoms was 84.4%. The most common symptom was apathy, followed by agitation and delirium, and the least frequent were euphoria and hallucinations. The symptom that produced most occupational disruption was agitation. Multivariate analysis showed that a higher score on the NPI-NH was associated with a higher score on the Global Deterioration Scale of Reisberg, the use of neuroleptics, cholinesterase inhibitors, and memantine.

Conclusions

In nursing home patients, prevalence of neuropsychiatric symptoms was high, and associated with the severity of dementia (GDS), the use of neuroleptics, cholinesterase inhibitors, and memantine.     

Effects of intrathecal opioids combined with low-dose naloxone on motilin and its receptor in a rat model of postoperative pain

Aims

To investigate the effects of intrathecal morphine and fentanyl combined with low-dose naloxone on the expression of motilin and its receptor in a rat model of postoperative pain.

Main methods

An intrathecal catheter was implanted, and saline, opioids (morphine and fentanyl) and naloxone were intrathecally administered 7 days later. An incisional pain model was established to induce pain behaviors in rats by unilateral plantar incision. Thermal hyperalgesia and mechanical allodynia were measured by using a radiant heat and electronic Von Frey filament, respectively. The expression of motilin in the hippocampus, stomach, duodenum, and plasma was determined by ELISA; and the expression of motilin receptor in the hippocampus was detected by Western blot assay.

Key findings

Motilin and its receptor were detected in the hippocampus. Acute incisional pain increased the motilin expression in the hippocampus and duodenum, while decreasing its expression in the gastric body and plasma. Postoperative analgesia with morphine + fentanyl upregulated the expression of motilin in the hippocampus; however, motilin was downregulated in peripheral sites. Naloxone at 1 ng/kg restored motilin to baseline levels. Acute pain, morphine + fentanyl, and naloxone all induced the expression of motilin receptor in the hippocampus.

Significance

Acute pain, postoperative analgesia with opioids, and naloxone significantly impacted the expression of hippocampal and peripheral motilin. Variation trends in all sites were not identical. Intrathecal injection of low-dose naloxone upregulated paw withdrawal thermal latency and enhanced the analgesic effects of opioids. The findings presented here provide a new basis for central and peripheral regulations in GI motility, clinical postoperative analgesia, and management of analgesic complications.     

Planificación anticipada de decisiones en las enfermedades crónicas avanzadas

Introduction

Advanced care planning (ACP) helps in make decisions on the health problems of people who have lost the capacity for informed consent. It has proven particularly useful in addressing the end of life. The aim of this study was to determine the prevalence of ACP in patients with severe chronic diseases.

Material and methods

Review of medical records of patients with dementia, amyotrophic lateral sclerosis, Parkinson's disease, chronic obstructive pulmonary disease or interstitial lung disease, heart failure, chronic kidney disease on dialysis and cancer, all in advanced stages. We collected data on living wills or registered prior decisions by the physician according to clinical planned.

Results

A total of 135 patients were studied. There was a record of ACP in 22 patients (16.3%). In most of them it was planned not to start any vital treatment in the event of high risk of imminent death and lacking the ability to make decisions. Only two patients were had a legal living will.

Conclusion

The registration of ACP is relatively low, and this can affect decision-making in accordance with the personal values of patients when they do not have the capacity to exercise informed consent.     

Descripción de los resultados y costes de una intervención preventiva a nivel respiratorio en el anciano institucionalizado: ensayo controlado aleatorizado

Introduction

The institutionalized elderly with functional impairment show a greater decline in respiratory muscle (RM) function. The aims of the study are to evaluate outcomes and costs of RM training using Pranayama in institutionalized elderly people with functional impairment.

Material and methods

A randomized controlled trial was conducted on institutionalized elderly people with walking limitation (n = 54). The intervention consisted of 6 weeks of Pranayama RM training (5 times/week). The outcomes were measured at 4 time points, and were related to RM function: the maximum respiratory pressures and the maximum voluntary ventilation. Perceived satisfaction in the experimental group (EG) was assessed by means of an ad hoc questionnaire. Direct and indirect costs were estimated from the social perspective.

Results

The GE showed a significant improvement related with strength (maximum respiratory pressures) and endurance (maximum voluntary ventilation) of RM. Moreover, 92% of the EG reported a high satisfaction. The total social costs, direct and indirect, amounted to €21,678.

Conclusions

This evaluation reveals that RM function improvement is significant, that intervention is well tolerated and appreciated by patients, and the intervention costs are moderate.     

Percutaneous ultrasonography and computed tomography guided pancreatic cryoablation: Feasibility and safety assessment

Objective

To assess the safety and feasibility of percutaneous cryoablation on pancreatic cancer via ultrasonography (US) and computed tomography (CT) guidance.

Materials and methods

This retrospective review was approved by the institutional review board and of informed consent. Thirty-two patients (18 men and 14 women; median age 62; age range, 30–77 years) with pancreatic cancer (stage II/III/IV, 3/11/18) treated with percutaneous US and CT guided cryoablations between February 2009 and February 2010 were eligible for this review. Thirteen tumors in pancreatic head and 19 in pancreatic body and/or tail measuring 2–11 cm (mean, 5.2 cm ± 8 [standard deviation]) were ablated with 49 procedures in total. Feasibility was analyzed by enhanced CT 1–3 months post procedure and safety was assessed by clinical signs, symptoms and laboratory results.

Results

Neither procedural death nor serious complications occurred. Fifteen tumors (46.9%) smaller than 5 cm were successfully ablated by one session of cryoablation. Twenty-seven patients experienced a ?50% reduction in pain score, 22 experienced a 50% decrease in analgesic consumption and 16 experienced a ?20 increase in Karnofsky Performance Status (KPS) Score. Partial response (PR) and stable disease (SD) turned up in 9 and 21 patients, respectively, lesions in whom were identified controlled by none enhancement on enhanced CT. Mean and median survival was 15.9 and 12.6 months, respectively. The 6-, 12- and 24-month survival rates were 82.8%, 54.7% and 27.3%, respectively.

Conclusion

US and CT guided percutaneous cryoablation is a safe and promising local treatment for pancreatic cancer.     

Efectividad de una intervención educativa sobre hipertensión arterial dirigida a pacientes hipertensos de edad avanzada

Introduction

Hypertension is the most prevalent cardiovascular risk factor among people over the age 60. The aim of this study is to assess the effectiveness of an educational intervention tool, and its reliability.

Material and methods

Experimental study, prospective, randomised, parallel-group in a sample of 120 patients, 62 in the intervention group and 58 in the control group. The intervention group received a written and oral educational program on hypertension and cardiovascular risk; the control group did not receive any intervention.

Results

At the end of the intervention there was an increase in the percentage of correct responses, with statistically significant differences compared to the control group, as regards knowledge of hypertension, risk factors associated with the risks of having high blood pressure and control medication.

Conclusion

The implementation of an educational intervention on hypertension and cardiovascular risk associated with the same care activity is capable of increasing the level of knowledge by elderly hypertensive patients admitted to hospital.     

Upper gastrointestinal haemorrhage in patients over 80 years-old

Objectives

To evaluate the patient characteristics, outcome, and prognosis of upper gastrointestinal haemorrhage in the elderly.

Material and methods

A prospective study was conducted on 103 patients aged 80 years and over, admitted to a Gastrointestinal Bleeding Unit after an episode of upper gastrointestinal bleeding. We analysed the personal history, the characteristics of the bleeding event, and whether an urgent diagnostic or therapeutic endoscopy was performed, in order to identify clinical data and endoscopic findings that may have an influence on the outcome of the haemorrhage.

Results

The major cause of the haemorrhage was peptic ulcer in 65.1%, and 60.2% of patients were on chronic treatment with non-steroidal anti-inflammatory drugs. An urgent diagnostic endoscopy was performed in all of them, identifying the source of bleeding in 94.2%, and treatment was carried out on 28.2%. The likelihood of rebleeding was 8%, and 4.9% of patients underwent emergency surgery, with an overall mortality rate of 5.8%.

Conclusions

The performance of urgent endoscopy and the application of endoscopic haemostasis are safe and effective in stopping upper gastrointestinal bleeding in the elderly. This has significantly reduced the need for emergency surgery, improving the survival of the bleeding elderly patient and preventing recurrent bleeding.     

El déficit de vitamina B12 y ácido fólico en la población mayor de 65 años: estudio descriptivo

Introduction

The aim of this study is to establish the prevalence of vitamin B12 and folic acid deficiency in the population of 65 years and over in semi-urban and rural area, as well as investigating the risk factors, and the determining factors of this deficiency in this population and its relationship with the prevalence of concomitant cardiovascular and cognitive diseases.

Materials and methods

A cross-sectrionall study conducted in the Geriatrics Outpatients in the period between 2008 and 2010. Demographic, clinical and laboratory were collected at 3 different times.A bivariate analysis was performed with lack of vitamin B12 and folic acid, as the outcome variables.

Results

Vitamin B12 defieciency was found in 16.5% of the sample, and no folic acid deficiency. A strong association was found with vitamin B12 deficiency and cardiac and cerebrovascular diseases, vascular risk factors and drugs administered in prevention of cardiac events and ischaemic stroke.

Conclusions

There was a higher prevalence of vitamin B12 deficiency in the elderly population in the catchment area of Medina del Campo compared to that found in the literature, but not so with the isolated deficiency of folic acid.     

Paget’s disease of the nipple treated successfully with cryosurgery: A series of cases report

Introduction

Paget’s disease of the nipple is a rare form of breast malignancy. Underlying breast cancer, either in situ or invasive accompanies lesions of the nipple in most of the cases. The connection between both entities and their exact origin remains unclear. Nevertheless, underlying ductal breast cancer is often confined to the central, subareolar part of the breast. Radical mastectomy, although successful, seems to be too mutilating treatment in the era of breast sparing surgery. Studies describing breast conserving surgery performed without adjuvant treatment are rare and the patients not numerous. Due to low incidence of the disease, there are no randomised trials conducted which could show the optimal method of treatment.

Materials and methods

We performed cryosurgery of the affected nipple-areola complex (NAC) in treatment of six patients with Paget’s disease of the nipple who presented general contraindications or lack of consent for surgery.

Results

With a follow up ranging from 60 to 121 months (average 94) we obtained very good results in terms of disease specific survival: there were two cases of recurrent disease, confined to the scar and treated successfully with cryosurgery again; four patients are alive without disease. Death was not related to cancer in the remained two cases.

Conclusions

Cryotherapy is successful form of treatment of localised Paget’s disease of the nipple – especially in face of contraindications for surgery or lack of patient’s agreement for operational treatment.