Oral Prolonged‐Release Oxycodone/Naloxone for Managing Pain and Opioid‐Induced Constipation: A Review of the Evidence

Background

Opioids provide effective relief from moderate‐to‐severe pain and should be prescribed as part of a multifaceted approach to pain management when other treatments have failed. Fixed‐dose oxycodone/naloxone prolonged‐release tablets (OXN PR) were designed to address the opioid class effect of opioid‐induced constipation (OIC) by combining the analgesic efficacy of oxycodone with the opioid receptor antagonist, naloxone, which has negligible systemic availability when administered orally. This formulation has abuse‐deterrent properties, since systemic exposure to naloxone by parenteral administration would antagonize the euphoric effects of oxycodone.

Methods

A literature search was conducted to assess the evidence base for OXN PR to treat moderate‐to‐severe pain and its impact on bowel function, based on published clinical trials and observational studies.

Results

Extensive data demonstrate that OXN PR provides effective analgesia and clinically relevant improvements in bowel function in patients with OIC and moderate‐to‐severe cancer‐related pain and noncancer pain types such as low back pain, neuropathic pain, and musculoskeletal pain. OXN PR has also been found to improve bowel function in patients with OIC refractory to multiple types of laxatives, and improve Parkinson's disease–related pain. No unanticipated safety concerns have been reported in elderly patients.

Conclusions

Evidence from clinical trials and observational studies confirms that for selected patients OXN PR significantly improves moderate‐to‐severe chronic pain and provides relief from OIC. Treatment should be tailored to individual patients to establish the lowest effective dose. An absence of analgesic ceiling effect was seen across the clinically relevant dose range investigated (≤ 160/80 mg/day).     

Hydralazine-associated Amenorrhea in a Premenopausal Patient With Chronic Kidney Disease: A Case Report and Review of Literature

Purpose

Several antihypertensive medications have been associated with various forms of sexual dysfunction. We present a case report of a premenopausal patient with hydralazine-associated amenorrhea.

A Review of the Efficacy,Safety, and Cost‐Effectiveness of COX‐2 Inhibitors for Africa and the Middle East Region

Abstract: Despite an increasingly sophisticated understanding of pain mechanisms, acute and chronic pain remain undertreated throughout the world. This situation reflects the large gap that exists between evidence and practice in pain management and is typified by inappropriate use of nonsteroidal anti‐inflammatory drugs (NSAIDs). The scientific evidence around these drugs continues to expand at a high rate, yet physicians are often unaware of best practice. To address this gap among physicians in Africa and the Middle East, an Expert Panel meeting was convened with representatives from the region. The principal objective of the meeting was to review the latest guidelines on the management of acute and chronic pain and to review the efficacy, safety, and cost‐effectiveness of cyclooxygenase‐2 (COX‐2) inhibitors in these settings. The main outcome of this review process was a number of consensus statements concerning the definitions of acute and chronic pain, and the efficacy, safety and cost‐effectiveness of traditional nonselective NSAIDs (nsNSAIDs) and selective COX‐2 inhibitors (coxibs). The panel agreed that nsNSAIDs and coxibs are effective analgesics with similar efficacy for acute pain; for chronic musculoskeletal pain, NSAIDs are significantly more effective than either placebo or paracetamol. Coxibs offer important safety advantages over nsNSAIDs, including gastrointestinal safety and preservation of platelet function; notably, the cardiovascular safety of coxibs has been the subject of much recent debate. Furthermore, the panel agreed there is substantial evidence to indicate that cost savings can be achieved by using celecoxib in patients at moderate to high risk of gastrointestinal adverse events, even in countries with moderate healthcare expenditures.     

Presumptive Tricuspid Valve Malfunction Induced by a Pacemaker Lead: A Case Report and Review of the Literature

A 23-year-old woman developed 3 degrees AV block with syncope. Insertion of a permanent pacemaker lead was followed by the onset of a persistent murmur in late systole preceded by single or multiple clicks. The murmur was best heard at the left sternal edge, grade 3-4/6 with two major frequencies (60-250 Hz), increased with inspiration and on assuming the erect posture. It was considered to be tricuspid in origin and related to interference of the tricuspid valve apparatus by the pacemaker lead resulting in tricuspid regurgitation. No tricuspid valve prolapse or flutter was seen on echocardiography. Withdrawal of the pacemaker lead resulted in immediate disappearance of the new auscultatory findings. Review of the literature suggests that the appearance of such a murmur following pacemaker insertion could be associated with later complications in relation to tricuspid valve dysfunction. It is therefore recommended that, under these circumstances, permanent pacemaker leads should be appropriately repositioned.     

The Long‐Term Use of a Low‐Phenylalanine Diet in Late‐Treated Phenylketonuria: A Single Case Report

Background When phenylketonuria (PKU) is not diagnosed and long‐term treatment commenced within the first few weeks of life, permanent brain damage will occur. There is some evidence to show that late diagnosed or untreated people with PKU who have severe challenging behaviours may benefit from a low phenylalanine diet [ Harper & Reid (1987) Journal of Mental Deficiency Research vol. 31, pp. 209–212; Hoskins et al. (1992) Journal of Intellectual Disability Research vol. 36, pp. 183–191; Baumeister & Baumeister (1998) Clinical Neuropharmacology vol. 21, pp. 18–27; Fitzgerald et al. (2000) Journal of Intellectual Disability Research vol. 44, pp. 53–59]. Method In the light of this evidence, a woman with late‐diagnosed PKU was treated with a low‐phenylalanine diet in an attempt to reduce her severe challenging behaviour. Results A reduction in challenging behaviours was observed when phenylalanine levels were maintained within a specific narrow range. Data are reported over a 2‐year period. A dramatic rise in severe challenging behaviour was noticed when her blood phenylalanine levels fell below a certain level. Conclusions This case report suggests that blood phenylalanine levels need to be maintained within a specific range for maximum benefit.     

Medication‐Overuse Headache and Personality: A Controlled Study by Means of the MMPI‐2

(Headache 2010;50:198‐209) Objective.— The main aim of this study involves comparing the personality profiles of patients with medication‐overuse headache (MOH) and episodic headaches, in order to elucidate the role of personality characteristics, according to one of the most widely used and validated personality assessment tool: Minnesota Multiphasic Personality Inventory (MMPI‐2). Background.— Many studies have assessed the personality of headache patients by means of MMPI‐2 only using clinical and content scales. In this study the supplementary scales were also used as they evaluate different aspects of personality, particularly broad personality characteristics, generalized emotional distress and behavioral dyscontrol. Methods.— We recruited 219 subjects (151 women and 68 men) who were grouped in the following categories: MOH group (n = 82); episodic headache group (n = 82; 58 migraine aura; 6 migraine with aura; 6 frequent episodic tension‐type headache; 12 migraine+infrequent episodic tension‐type headache) and 1 group of 55 healthy controls. MMPI‐2 was employed. Data were computed with one‐way anova and post hoc analyses. Results.— Medication‐overuse headache and episodic headache patients (EH) showed a very similar pattern, differentiating each other only in the Hypochondriasis (Hs) (P = .007; MOH: mean 14.18 [SD 5.53]; EH: mean 11.93 [SD 5.88] and Health Concerns [HEA]) (P = .005; MOH: mean 14.06 [SD 5.38]; EH: mean 11.81 [SD 5.59]) scales. Surprisingly, no differences were found between the 3 groups in the scales measuring dependence‐related behavior such as Addiction Potential Scale (Aps) and Addiction Admission Scale (Aas). MOH and episodic headache patients scored significantly higher in the so‐called neurotic scales Hs (P < .0001; MOH: mean 14.18 [SD 5.53]; EH: mean 11.93 [SD 5.88]; Controls: mean 5.91 [SD 3.57]), Depression (D) (P < .0001; MOH: mean 26.44 [SD 7.01]; EH: mean 26.09 [SD 5.85]; Controls: mean 21.47 [SD 4.90]), and Hysteria (Hy) (P < .0001; MOH: mean 27.33 [SD 5.51]; EH: mean 26.81 [SD 5.68]; Controls: mean 21.95 [3.85]) and in many other scales such as Paranoia (Pa), Psychasthenia (Pt), Schizophrenia (Sc) while they scored significantly lower on Ego Strength (Es) and Dominance (Do) scales when compared with controls. Conclusions.— Patients with MOH and episodic headache showed very similar patterns, differentiating only in the Hypochondriasis and Health Concerns scales. Surprisingly, there were no significant differences in the scores of the scales measuring dependence‐related behavior. The clinical role of MMPI‐2 in discriminating MOH patients with dependency from drugs is discussed, in order to implement a complete tests' battery for headache patients' assessment.     

Ophthalmic Presentation in the Emergency Department: A Case Report of a Girl With “Shimmering Eyes”

Background

Ophthalmic complaints are commonplace in the emergency department (ED) and are often initial presentations of a systemic illness. We present a 2-year-old girl presenting to the ED with ataxia and “shimmering” eyes.

Case Report

The patient was diagnosed with opsoclonus-myoclonus syndrome (OMS) involving involuntary, multi-vectorial (mostly horizontal), conjugate fast eye movements without intersaccadic intervals. The ophthalmic presentation led to a paraneoplastic work-up, which revealed an abdominal mass measuring 5.3 × 3.3 × 4.3 cm, suggestive of neuroblastoma. The patient's opsoclonus improved after a 5-day course of dexamethasone and intravenous immunoglobulin.

Why should an emergency physician be aware of this?

This case illustrates the importance of recognizing pathognomonic ophthalmic complaints in the ED. We present an overview of classic ophthalmic presentations associated with systemic illnesses.     

The “Ram's Horns Sign”: A Case Report of an Unusual Side Effect of OnabotulinumtoxinA in a Chronic Migraine Patient

OnabotulinumtoxinA (BoNT‐A) has been reported as an effective prophylactic treatment for chronic migraine to reduce disease severity improving health‐related quality of life. However, BoNT‐A, due to its activity on either the injected or adjacent muscles of the upper face, may induce well‐known side‐effects, such as the eyebrow or eyelid ptosis. However, unusual muscular side effects, related to the neurotoxic mechanism, may also arise. We describe the clinical case of a 55‐year‐old male patient who has been treated for chronic migraine by the injection of BoNT‐A, according to the PREEMPT protocol. Two weeks later, the patient developed two symmetrical bumps on the upper part of the forehead similar to the horns of a ram. We report, for the first time, this peculiar BoNT‐A side effect and suggest that the injection of additional BoNT‐A doses in the upper medial frontal fibers, for each side, can normalize the forehead shape over two weeks.