Although opioids offer potent analgesia for severe acute and chronic noncancer pain, adverse gastrointestinal effects potentially undermine their clinical utility. In particular, between 40% and 95% of patients develop opioid-induced constipation (OIC). Therefore, there is a consensus that patients should commence laxatives at the start of opioid therapy and continue throughout treatment. Nevertheless, laxatives are not routinely coprescribed with opioids. Even when concurrent laxatives are prescribed, approximately half the patients treated for OIC do not achieve the desired improvement. Moreover, laxatives do not target the underlying cause of OIC (opioid binding to the μ-receptors in the enteric system) and as such are not very effective at managing OIC. The failure of lifestyle modification and laxatives to treat adequately many cases of OIC led to the concurrent use of peripherally acting opioid antagonists (such as methylnaltrexone bromide and naloxone) to reduce the incidence of gastrointestinal adverse events without compromising analgesia. Judicious use of the various options to manage OIC should allow more patients to benefit from opioid analgesia. Therefore, this paper reviews the causes, consequences, and management of OIC to help clinicians optimise opioid analgesia.

Background Chemotherapy-induced peripheral neuropathy (CIPN) is the presence of tingling, burning, itching, and unpleasant sensations in hands and feet due to nerve damage by chemotherapy. Exercise rehabilitation has potential to prevent or alleviate CIPN. Objective The aim of this study was to assess the effectiveness of muscle strengthening and balancing exercises on CIPN pain and quality of life (QOL) among cancer patients. Methods The randomized controlled trial included 45 cancer patients from a tertiary care hospital in India receiving chemotherapeutic drugs paclitaxel and carboplatin and found to have CIPN. Subjects were randomly allocated to exercise (n1 = 22) and usual care (n2 = 23) groups. The exercise group received home-based muscle strengthening and balancing exercise for 10 weeks. Data regarding demographic, clinical characteristics, CIPN, neuropathic pain, and QOL were collected by structured questionnaires Chemotherapy-Induced Peripheral Neuropathy Assessment Tool, nerve conduction velocity, Leeds Assessment of Neuropathic Symptoms and Signs pain scale, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire. Results The 2 groups were homogenous regarding demographic variables. In clinical characteristics, the exercise group had larger body surface area and received a higher dose of paclitaxel. Significant reduction in neuropathic pain scores (P < .0001) and improvement in Functional QOL (P = .0002), Symptom QOL (P = .0003), Global Health Status QOL (P = .004) scores were observed after intervention in the exercise group than the usual-care group. Conclusion Muscle strengthening and balancing exercises are effective in reducing CIPN pain and improving QOL among cancer patients. Implications for Practice Muscle strengthening and balancing exercises can be used as a complementary therapy for effective management of CIPN.

To the Editor: Stem cell therapy has shown potential benefit in heart failure caused by ischemic heart disease (1). There is no data on the role of stem cell therapy in nonischemic dilated cardiomyopathy. We undertook a pilot study of intracoronary stem cell implantation in patients with dilated cardiomyopathy.From a cohort of 44 patients, 24 were randomly allocated to the stem cell therapy arm and 20 to the control arm. All patients were having dilated cardiomyopathy with an ejection fraction (EF) of Յ35%, were New York Heart Association (NYHA) functional class II or more symptomatic for more than 6 months, had normal coronary arteries, and had no other comorbidities such as chronic renal or liver failure or any malignancy.Patients in the treatment arm underwent bone marrow aspiration (50 to 60 ml) from the iliac crest. Mononuclear cells were separated from the bone marrow using Ficoll density gradient separation. The mononuclear cells constituted 89 Ϯ 2% of the cells, were 28 Ϯ 16 million /ml, and CD 34ϩ cells were 1.6 million/ml. The viability of these cells was 99 Ϯ 1%. The patients then underwent right heart catheterization and endomyocardial biopsy from the right side of the interventricular septum. The coronary sinus was then engaged using a Swan-Ganz catheter (Arrow International, Reading, Pennsylvania) that was passed up the coronary sinus, and the balloon was inflated. This was done so that the coronary circulation was slowed and the stem cells would get more time to transmigrate into the myocardium. Once the coronary sinus catheter was inflated, the stem cells were slowly injected into the coronary arteries by hooking the arteries with a Judkins catheter. Two-thirds of the mononuclear cell concentrate was injected into the left coronary artery and one-third was injected into the right coronary artery. The coronary sinus balloon was kept inflated for 3 min during the intracoronary injection. The patients were kept under monitoring for 24 h with electrocardiographic monitoring and serial cardiac enzymes. Follow-up was done at 1 week, 1 month, and then every 3 months for 1 year. At 3 months, Holter monitoring, an echocardiogram, and an endomyocardial biopsy were repeated. An echocardiogram was also repeated at 1 year. Left ventricular function assessment was performed offline by the modified Simpson method by 2 observers blinded to the underlying treatment. All patients were on the maximum tolerated doses of angiotensin-converting enzyme inhibitors and beta-blockers. Diuretic doses (including frusemide and torsemide, and spironolactone) were adjusted to ensure the absence of pedal edema. Informed consent was obtained from all patients, including control patients. The end points of the study were: 1) change in NYHA functional class, 2) a change in left ventricular function, 3) mortality, and 4) endomyocardial biopsy and histopathologic evaluation.Continuous variables were compared by a Wilcoxon 2-sample test (for within-group differences) and the Mann-Whitney U test (between-group differences). Differences...

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Cerebral vasospasm following subarachnoid hemorrhage (SAH) is characterized by prolonged severe constriction of the basilar artery, which often leads to ischemic brain damage. Locally elevated concentrations of spasmogenic substances induce persistent depolarization of myocytes in the basilar artery, leading to continuous influx of calcium (Ca2+) through voltage-sensitive Ca2+ channels and myocyte contraction. Potassium (K+) channel openers may have therapeutic utility to oppose membrane depolarization, dilate the arteries, and reduce ischemia. Here, we examined the involvement of vascular Kv7 K+ channels in the pathogenesis of cerebral vasospasm and tested whether Kv7 channel openers are effective therapeutic agents in a rat model of SAH. Patch-clamp experiments revealed that three different spasmogens (serotonin, endothelin and vasopressin) suppressed Kv7 currents and depolarized freshly isolated rat basilar artery myocytes. These effects were significantly reduced in the presence of a Kv7 channel opener, retigabine. Retigabine (10 μmol/L) also significantly blocked L-type Ca2+ channels, reducing peak inward currents by >50%. In the presence of a selective Kv7 channel blocker, XE991, the spasmogens did not produce additive constriction responses measured using pressure myography. Kv7 channel openers (retigabine or celecoxib) significantly attenuated basilar artery spasm in rats with experimentally-induced SAH. In conclusion, we identify Kv7 channels as common targets of vasoconstrictor spasmogens and as candidates for therapeutic intervention for cerebral vasospasm.