Report on the creation of a diabetes register and retinopathy screening outcomes in the Mid-West of Ireland.

BACKGROUND: With concerns that blind registration in Ireland due to diabetic retinopathy is continuing to rise, a structured retinopathy screening service is in the process of being rolled out nationally. AIMS: To report on the validation process for creating a register of diabetics in the Mid-West of Ireland, and findings following retinopathy screening of a representative sample. METHODS: National primary care databases were employed in generating provisional lists of diabetic patients in the Health Service Executive (HSE) Mid-West area. Subsequent engagement with the corresponding general practices over a three year period between 2010 and 2013 facilitated the validation of these lists. A summary of the retinopathy screening outcomes of 1,434 patients and pre-existing screening patterns is reported. RESULTS: The number of patients on the Mid-West diabetes register to date is 11,126. Of the 1,434 patients screened, 288 (20.1 %) had background retinopathy, while 117 (8.2 %) had sight-threatening retinopathy. Seventeen (19.8 %) of the 86 patients identified with maculopathy required treatment with intravitreal injections. Of the 610 patients questioned about previous screening events, 389 (63.8 %) said they had undergone an ocular examination within the previous 12 months. CONCLUSIONS: The HSE Mid-West has over 11,000 patients on its database ready to be screened by the national programme, with the treatment of maculopathy expected to have the largest impact on resources. Although the majority of patients are already undergoing screening in the community in an ad hoc fashion, the rates of sight-threatening retinopathy encountered highlight the timeliness of the full implementation of the national programme.

Daytime patterning of fatigue and its associations with the previous night's discomfort and poor sleep among women with primary Sjögren's syndrome or rheumatoid arthritis.

OBJECTIVES: Fatigue is a prominent symptom in many rheumatic diseases and has a substantial impact on many outcomes. In previous research, fatigue has been linked with poor sleep and discomfort, including joint pain and sicca symptoms. The aim of the present study was to investigate prospectively the daily variations in fatigue and the roles of discomfort and adequacy of sleep the previous night in that fatigue for people with primary Sjögren's syndrome (pSS) or rheumatoid arthritis (RA). METHODS: Thirty-nine women with pSS or RA reported their discomfort and fatigue for 35 days using the Profile of Fatigue and Discomfort. Sleep was monitored with wrist actigraphy, and the quantity and quality of the night's sleep was reported in a diary each morning. RESULTS: The pattern of fatigue did not differ significantly between women with pSS and women with RA. For participants with either condition, both somatic and mental fatigue increased steadily throughout the day. Multi-level regressions indicated that evenings of worse discomfort were followed by poorer reported quantity/quality of sleep and worse sleep efficiency (percentage of time asleep when in bed). In addition, a night of worse discomfort and poor sleep was followed by more severe fatigue compared with the individual's average. CONCLUSIONS: Fatigue management for people with rheumatic disease could include strategies for coping with discomfort at night and difficulties in sleeping. Further research into ameliorating fatigue should include assessments of persistent discomfort or periods of insomnia and identify disease-specific needs that require targeted intervention.

Predictors of fatigue over 1 year among people with rheumatoid arthritis.

Fatigue is a systemic feeling of exhaustion that is a common symptom of many chronic illnesses, including the autoimmune inflammatory disease rheumatoid arthritis (RA). We examined predictors of levels of fatigue among people with RA using Leventhal's Common-Sense Model (CSM), which states that cognitive representations of an illness spur (or halt) people's efforts to cope and thereby influence outcomes of the illness. Our use of the CSM was designed in the light of evidence in the literature specific to fatigue in RA. Current fatigue was reported on a 100 mm visual analogue scale (with anchors "No fatigue" and "Unbearable fatigue") by 114 people (73.7% women) with RA at baseline and 1 year later. Baseline employment status, pain, impact of disability, sleep disruption frequency, depressed mood, perceptions of consequences, arthritis self-efficacy and attempts to cope by praying/hoping were also self-reported. Duration of RA and a haematological measure of systemic inflammation (erythrocyte sedimentation rate; ESR) were obtained from hospital records. Unexpectedly, RA duration did not predict fatigue after 1 year, although lower baseline inflammation did (controlling for baseline fatigue and other disease impact variables). This may be due to sampling flares of RA at baseline. Baseline perceptions that RA has severe consequences and is uncontrollable also predicted greater fatigue after 1 year but this relationship was not mediated by praying/hoping. Targeted psychological care to modify perceptions of severe consequences may therefore improve later fatigue for people with RA even when the condition is longstanding, but the mechanisms of any benefit require further investigation.

Measuring fatigue among women with Sjögren's syndrome or rheumatoid arthritis: a comparison of the Profile of Fatigue (ProF) and the Multidimensional Fatigue Inventory (MFI).

BACKGROUND: Fatigue is common in both Sjögren's syndrome (SS) and rheumatoid arthritis (RA) and can restrict functioning. AIMS: We tested the convergent validity of the Profile of Fatigue (ProF) using the Multidimensional Fatigue Inventory (MFI) in SS and RA. METHODS: The 16-item ProF and the 20-item MFI were completed by 82 White-British women aged 35-79 years (mean 60.4 years). Thirty-four had been diagnosed with SS for a mean of 7.0 years and 48 had been diagnosed with RA for a mean of 14.5 years. The ProF measures four somatic facets of fatigue and two mental facets; the MFI contains one mental and four somatic facets. The structures of the items from both measures were tested by principal component factor analysis using varimax rotation. RESULTS: No significant differences in fatigue were found between the women with SS or RA. Five factors explained a total of 76% of the variance of the MFI; six factors explained 94% of the variance of the ProF. Mental fatigue items from both questionnaires loaded onto separate factors from somatic fatigue items; the two original facets of mental fatigue in the ProF were replicated. The four somatic fatigue facets of the ProF were generally replicated but the somatic facets of the MFI did not replicate as clearly. Equivalent facets correlated well between the two questionnaires (r >or= 0.65). CONCLUSIONS: Both the ProF and the MFI distinguish between somatic and mental fatigue in SS and RA but the ProF appears better at resolving somatic facets of fatigue.

Sleep disruption frequency in rheumatoid arthritis: perceived stress predicts poor outcome over one year.

BACKGROUND: Sleep is an important daily process that can be disrupted by chronic illnesses including rheumatoid arthritis (RA). AIMS: We tested whether demographic, medical and psychological factors act as predictors of change in frequency of sleep disruption associated with RA. METHODS: A cohort of 129 White British people with RA (mean duration of RA 7.19 years; mean age 55.40 years; 75% women) was followed for one year. Self-report questionnaires were employed to record demographic information and assess participants' sleep disruption (on a 4-point frequency scale), morning stiffness (duration), pain and fatigue (visual analogue scales), impact of disability, anxiety, depression, stress, coping, illness perceptions and self-efficacy. Hospital notes were reviewed for duration of RA, antidepressant use and comorbidity. RESULTS: Participants were split into those with sleep disruption that was consistently infrequent or decreasing in frequency (n = 56; 43%) and those with sleep disruption that was consistently frequent or increasing in frequency (n = 73; 57%). Results of a logistic regression demonstrated that greater perceived stress at baseline predicted sleep disruption that was consistently frequent or increasing in frequency over the year. Change in sleep disruption frequency was not predicted by any other assessed variable. Perceived stress at the end of the year was not predicted by change in frequency of sleep disruption. CONCLUSIONS: Self-reported frequency of sleep disruption among people with RA relates to perceived stress. Psychoeducational programmes that help people with RA manage their stress may be a non-pharmacological method of improving sleep quality and therefore merits testing in specific interventional studies.

The value of empathy in dietetic consultations. A pilot study to investigate its effect on satisfaction, autonomy and agreement.

Forty individuals with diabetes and three dietitians completed a questionnaire concerning their consultation. Empathy was examined using the Empathic Communication Coding System (ECCS) (Bylund & Makoul, 2002). The more empathic the professionals' response to emotional opportunities, the more satisfied patients were with their consultations (r = 0.41, d.f. = 15, P = 0.05). There was a nonsignificant trend that the more empathic opportunities that arise during a consultation, the higher the agreement between patient and dietitian on what was discussed (r = 0.28, P = 0.07). The data also suggest that patients reported more autonomy support when they created more empathic opportunities during their consultation (r = -0.29, P = 0.07). This preliminary study suggests that professionals' responses to empathic opportunities may be a useful component of dietetic consultations.

Prospective audit of short-term concurrent ketamine, opioid and anti-inflammatory ('triple-agent') therapy for episodes of acute on chronic pain.

AIM: This prospective audit was undertaken in order to document the analgesic response and adverse effects of concurrent short-term ('burst') triple-agent analgesic (ketamine, an opioid and an anti-inflammatory agent--either steroidal or non-steroidal) administration, for episodes of acute on chronic pain. The clinical hypothesis in this study is that better pain control may be obtained by simultaneous multiple target receptor blockade. METHOD: The response of 18 patients is reported. The pain and analgesic requirement data for the 24 h before starting triple-agent therapy were compared with the last 24 h on the triple-agent therapy. Patients were then classified as responders or non-responders. RESULTS: According to stringent clinical criteria, 12 out of the 18 patients were classified as responders. The response rate was highest for somatic pain (7/9) and appeared to decrease with duration of prior uncontrolled pain. Only four out of the 18 patients reported adverse effects and all of these were minor. CONCLUSIONS: The results suggest that this 'burst' triple-agent approach is safe and effective in an inpatient palliative care population during episodes of poorly controlled acute on chronic pain, and warrants further investigation to ascertain whether it gives superior results compared to the 'gold-standard' WHO ladder approach.

Supraspinal and spinal cord opioid receptors are responsible for antinociception following intrathecal morphine injections.

BACKGROUND AND OBJECTIVE: The clinical practice of spinal morphine administration for pain relief is based on observations in animals that opioid receptors exist in the spinal cord and intrathecal injections of opioids in those species (mostly rats) lead to antinociceptive effects. Clinicians are well aware that administration of spinal opioids is associated with side-effects, such as nausea and respiratory depression, that indicate supraspinal spread of the drug administered. Those observations call into question how much of the observed pain relief is due to action of the drug in the brain. This study investigated the spinal cord actions of morphine given intrathecally to rats in a model that allows investigation of drug-receptor interaction at the spinal cord level. Experiments were performed on male Wistar rats with chronically implanted lumbar subarachnoid catheters. METHODS: Nociceptive thresholds were measured in rats given morphine intrathecally alone and in combination with intrathecal injections of selective opioid receptor antagonists: beta-funaltrexamine (mu), naltrindole (delta) and nor-binaltorphimine (kappa). RESULTS: Intrathecal morphine caused dose-related antinociceptive effects that were reversed totally by naloxone. Intrathecal beta-funaltrexamine and naltrindole did not reverse the effects of intrathecal morphine. However, intrathecal nor-binaltorphimine did reverse the electrical current threshold effects of morphine but not tail flick latency. CONCLUSIONS: Antinociception following intrathecal morphine involves spinal and supraspinal opioid receptors. The tail flick effect described in rat experiments involves actions at opioid receptors in the brain that override any action that may be caused by combination of morphine with mu-opioid receptors in the spinal cord.

Improvement in postoperative pain relief by the addition of midazolam to an intrathecal injection of buprenorphine and bupivacaine.

BACKGROUND AND OBJECTIVE: Intrathecal injections of the benzodiazepine midazolam have been reported to cause antinociception in animals and pain relief in human beings, including the potentiation of opioid analgesia. This study compared the efficacy of the addition of midazolam to a mixture of buprenorphine and bupivacaine used for spinal anaesthesia. METHODS: The study was prospective, randomized, and observer blinded. It involved 60 patients (30 per group), ASA I and II, age 20-40 yr, undergoing minor and intermediate lower abdominal surgery under spinal anaesthesia. Patients were randomized into two groups: the control group received a spinal injection of hyperbaric bupivacaine (15 mg) plus buprenorphine (0.15 mg) and the experimental group received a spinal injection of the same two drugs and doses but supplemented with intrathecal midazolam (2 mg). RESULTS: The duration of postoperative analgesia in the control group was 9.24 +/- 2.57 h (mean +/- SEM), and 21.33 +/- 12.69 h in the midazolam treated group (P < 0.001). Patients treated with intrathecal midazolam had better pain relief judged by visual analogue score on coughing (P = 0.0013) and a nursing mobility score (P < 0.0001). Adverse effects were minor and their incidence was similar in both groups. CONCLUSIONS: We conclude that intrathecal midazolam 2 mg improves the quality and duration of postoperative pain relief afforded by intrathecal buprenorphine and bupivacaine.

Antinociceptive properties of neurosteroids: a comparison of alphadolone and alphaxalone in potentiation of opioid antinociception.

In this study, we investigated the antinociceptive and sedative effects of the opioids fentanyl, morphine, and oxycodone given alone and in combination with two neurosteroids: alphadolone and alphaxalone. An open-field activity monitor and rotarod apparatus were used to define the sedative effects caused by opioid and neurosteroid compounds given alone intraperitoneally to male Wistar rats. Dose-response curves for antinociception were constructed using only nonsedative doses of these drugs. At nonsedating doses, fentanyl, morphine, and oxycodone all caused dose-dependent tail flick latency (TFL) antinociceptive effects. Because neither neurosteroid altered TFL, electrical current was used as the test to determine doses of neurosteroid that caused antinociceptive effects at nonsedative doses. Alphadolone 10 mg/kg intraperitoneally caused significant antinociceptive effects in the electrical test but alphaxalone did not. All three opioid dose-response curves for TFL antinociception were shifted to the left by coadministration of alphadolone even though alphadolone alone had no effect on TFL. Alphaxalone given alone had no antinociceptive effects at nonsedative doses and it had no effect on opioid antinociception. Neither neurosteroid caused sedative effects when combined with opioids. We conclude that coadministration of alphadolone, but not alphaxalone, with morphine, fentanyl, or oxycodone potentiates antinociception and that this effect is not caused by an increase in sedation.

Antinociceptive role of 5-HT1A receptors in rat spinal cord.

BACKGROUND: Intrathecal administration of 5-hydroxytryptamine (5-HT) is antinociceptive to noxious heat and electrical stimuli. The contributions of different receptor subtypes to the antinociceptive effects of 5-HT are controversial. The main reasons for this are the poor receptor subtype selectivity of some agonist drugs and the difficulty of restricting drug action to the spinal cord in some experimental paradigms. This study investigated the roles of different 5-HT receptor subtypes involved in the spinal cord control of the nociception produced by these two nociceptive testing paradigms. METHODS: Tail-flick latency and electric current threshold for nociception were measured in an acute pain model that allowed the study of the antinociceptive effects of intrathecally administered drugs that were due to actions of these drugs at spinal cord receptors. Experiments were performed in male Wistar rats with chronically implanted lumbar subarachnoid catheters. Dose-response curves for spinally mediated antinociceptive effects of agonists selective for 5-HT receptor subtypes were constructed. RESULTS: The 5-HT1 agonist 1-(3-chlorophenyl)-piperazine dihydrochloride caused a dose-dependent antinociceptive effect, measured by both nociceptive tests. However, 8-hydroxy-DPAT (selective 5-HT1A agonist) produced antinociception assessed by electric current but not tail flick. A 5-HT1A-selective antagonist, 4-[3-(benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)-piperazine, reversed the antinociception in the electrical test produced by both of these agonists but the tail-flick latency effects after intrathecal 1-(3-chlorophenyl)-piperazine were not suppressed by this antagonist. CONCLUSIONS: We conclude that 5-HT1A receptors in the spinal cord are involved in the nociceptive mechanisms assessed by noxious electrical stimuli. Other 5-HT1 receptors (non 5-HT1A receptors) are involved in the spinally mediated antinociception assessed by thermal noxious stimuli.

Potentiation by ketamine of fentanyl antinociception. I. An experimental study in rats showing that ketamine administered by non-spinal routes targets spinal cord antinociceptive systems.

BACKGROUND: Ketamine has been found to exert antinociceptive effects in animals and to be analgesic at subanaesthetic doses in humans. This study was designed to investigate the involvement of spinal cord mechanisms in the potentiation of opioid analgesia by parenteral non-spinal administration of ketamine. METHODS: Thresholds for nociception were measured in an acute pain model in rats that allowed identification of antinociceptive effects due to drug action in the spinal cord. Dose-response curves for the antinociceptive effects of ketamine alone and ketamine in conjunction with the mu opioid fentanyl were constructed. RESULTS: Intraperitoneal ketamine up to 3.75 mg kg(-1) caused no sedative or antinociceptive effects and intrathecal ketamine caused dose-dependent, spinally mediated antinociceptive effects. Injections of ketamine doses that caused no antinociceptive effects when given alone (intrathecal 25 microg and intraperitoneal 3.75 mg/kg) significantly increased spinally mediated antinociception produced by intrathecal fentanyl injections when assessed using noxious heat (tail-flick test) but not when assessed by noxious electrical current (electrical current threshold test). CONCLUSIONS: We conclude that ketamine can potentiate the effects of fentanyl by an interaction at the level of the spinal cord even when ketamine is given via a non-spinal route of administration.

Antinociceptive properties of neurosteroids III: experiments with alphadolone given intravenously, intraperitoneally, and intragastrically.

The veterinary neurosteroid anaesthetic Saffan has the same formulation as Althesin now withdrawn from human use and is a mixture of two neurosteroids, alphadolone, and alphaxalone. The molecular structures of these two pregnanes and their properties as i.v. anaesthetics were reported to be similar. Preliminary experiments showed that alphadolone caused powerful antinociceptive effects without sedation when given i.p. In this study, alphadolone was given to rats (weight 100-200 g) i.v., i.p., and intragastrically. I.v. injections of alphadolone (25 mg kg(-1)) caused anaesthesia and sedation, whereas i.p. (0.1-100 mg kg(-1)) and intragastric administration (750 mg kg(-1)) produced no such effects. Intragastric alphadolone caused antinociceptive effects assessed with the electrical current threshold test (response 2.2 x pre-drug control values) without sedation. These effects were reversed at the level of the spinal cord by intrathecally-administered bicuculline (10 pmol). We conclude that a metabolite of alphadolone acetate produced in the liver leads to antinociceptive effects after i.p. and intragastric administration of the parent compound. This antinociception involves spinal cord GABA(A) receptors, even though the drug was administered via a non-spinal route.

Antinociceptive properties of neurosteroids IV: pilot study demonstrating the analgesic effects of alphadolone administered orally to humans.

Fourteen patients scheduled for orthopaedic knee reconstruction surgery were enrolled in a prospective, double-blind, randomized study in which they received alphadolone (25-500 mg, n = 9) or placebo (lactose, n = 5) given orally 1 h after operation. All the subjects received a standardized general anaesthetic and the same type of surgery followed by physiotherapy using a continuous passive movement machine. Morphine was administered intravenously after operation by patient-controlled analgesia. Verbal rating and visual analogue scores assessed pain experiences for 6 h. Orally administered alphadolone up to 500 mg caused no increase in sedation, respiratory depression, nausea or vomiting. The experiences of these side-effects were all rated as none, mild or moderate. Orally administered alphadolone caused statistically significant reductions in morphine use and simultaneous highly significant reductions in pain scores. We conclude that alphadolone is a useful analgesic in humans when given by the oral route.

Spinal and supraspinal components of opioid antinociception in streptozotocin induced diabetic neuropathy in rats.

This study investigated the antinociceptive effect of opioids given via intraperitoneal and intrathecal routes in a diabetes-induced neuropathic pain model in rats. Streptozotocin induced diabetes in 91% of juvenile male Wistar rats at the dose of 150 mg/kg (75 mg/kg intraperitoneal on 2 successive days). When compared with younger weight-matched saline treated rats, the diabetic rats developed hyperalgesia assessed by the paw pressure nociceptive test. Nociceptive thresholds and responses to fentanyl in all nociceptive tests in these younger normal rats were the same as those described previously for older normal rats. Fentanyl (10-100 microg/kg, i.p.) produced a dose-related antinociceptive effect in both neuropathic (n=6-8) and non-neuropathic (n=6-8) rats in electrical current, paw pressure and tail flick nociceptive tests. Higher doses of fentanyl were needed in neuropathic animals to achieve similar antinociceptive effects to those in non-neuropathic animals. Intrathecal injections of fentanyl (0.05-0.5 microg) in non-neuropathic rats, produced a spinally-mediated, dose-related antinociceptive effect assessed by all tests. In contrast, intrathecal administration of fentanyl that confined the drug action to the spinal cord produced little antinociceptive effect in neuropathic rats in all three tests. These experiments suggest that supraspinal mu opioid receptors are responsible for the antinociceptive effect of opioids in this model of neuropathic pain and that spinal cord opioid systems are in some way rendered ineffective for antinociception assessed with noxious heat, electrical and pressure stimuli.

Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery.

Dextromethorphan is a weak N-methyl-d-aspartate (NMDA) receptor antagonist that inhibits spinal cord sensitization in animal models of pain and also inhibits the development of cutaneous secondary hyperalgesia after tissue trauma. Perhaps coadministration of an NMDA antagonist with an opioid would lead to better pain relief, particularly with movement and an opioid-sparing effect. This has been shown for ketamine, but previous studies with dextromethorphan that have used small doses have shown only a modest reduction in morphine requirements with no or minimal changes in the postoperative pain experience. We sought to determine whether a large dose of this drug, just below the maximum tolerated dose, could potentiate morphine analgesia while simultaneously causing a significant improvement in the management of the postoperative pain experience. Sixty-six patients undergoing knee surgery were enrolled in the study. The study design was a prospective, randomized double-blinded comparison with placebo of 200 mg of dextromethorphan given eight hourly. Postoperative pain experiences were assessed by postoperative morphine usage. Visual analog and verbal rating scales were used to assess pain with movement as well as side effects. Dextromethorphan treatment led to a significant but modest reduction in morphine requirements (29.3% P < 0.05) but no reduction in postoperative pain levels. We conclude that increasing orally administered dextromethorphan to near maximum tolerated doses does not provide greater morphine sparing than 20-40 mg given 6-8 hourly as in previous studies. Furthermore we conclude that dextromethorphan does not improve pain scores in a manner expected of a drug with NMDA antagonist properties.