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Obesity is a multifactorial, chronic disorder that has reached epidemic proportions in most industrialised countries and is threatening to become a global epidemic. Clinical management of obese patients is complex and serious doubts have arisen with regard to safety and efficacy of drug therapy. Following the withdrawal of fenfluramine and dexfenfluramine in 1997, interest has focused on novel anti-obesity drugs. Pharmacological approaches to the management of obesity can, in broad terms, use different distinct strategies: firstly, to reduce energy intake; secondly, to increase energy expenditure; and thirdly, to alter the partitioning of nutrients between fat and lean tissue. Sibutramine is a serotonin-noradrenaline (norepinephrine) reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. The pharmacological mechanisms by which sibutramine exerts its weight loss effect are likely due to a combination of reduced appetite, feelings of satiety and possibly the induction of thermogenesis. The efficacy of sibutramine for inducing initial weight loss and the subsequent maintenance of weight loss is well proven in short- and long-term clinical trials of up to 2 years' duration. Most individual placebo-controlled trials and pooled estimates found that the drug produced statistically significant greater weight loss than placebo at all observed endpoints (weighted mean difference for weight change at 8 weeks: -3.4 kg; mean difference range for weight change at 6 months: -4.0 to -9.1 kg; and at 1 year: -4.1 to -4.8 kg). The most frequent dosage regimen in these trials was 10-20 mg daily. Findings suggested a dose-effect relationship in terms of weight loss. Sibutramine was also associated with better weight maintenance relative to placebo (statistically significant difference). Results from mainly small trials showed that sibutramine produced more favourable outcomes in terms of loss of fat mass, reduction in body mass index and loss of > or = 5-10% of initial bodyweight. The most commonly reported adverse effects of sibutramine are headache, constipation and nausea. Certain adverse events associated with the nervous system, including dizziness, dry mouth and insomnia, are reported by > 5% of patients receiving sibutramine. Increases in blood pressure and heart rate were possible adverse effects that require regular monitoring especially in obese hypertensive patients. Neither left-sided cardiac valve disease nor primary pulmonary hypertension was associated with the use of sibutramine. The assessment of the benefit-risk profile of sibutramine remained positive, although the product must be kept under regular review.
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PMID:A benefit-risk assessment of sibutramine in the management of obesity. 1458 64

The fast ripening of fruits means they may contain various harmful properties. A commonly used agent in the ripening process is calcium carbide, a material most commonly used for welding purposes. Calcium carbide treatment of food is extremely hazardous because it contains traces of arsenic and phosphorous. Once dissolved in water, the carbide produces acetylene gas. Acetylene gas may affect the neurological system by inducing prolonged hypoxia. The findings are headache, dizziness, mood disturbances, sleepiness, mental confusion, memory loss, cerebral edema and seizures. We report the case of a previously healthy 5 year-old girl with no chronic disease history who was transferred to our Emergency Department with an 8-h history of coma and delirium. A careful history from her father revealed that the patient ate unripe dates treated with calcium carbide.
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PMID:Calcium carbide poisoning via food in childhood. 1730 29

Studies of populations with chronic cancer pain have shown a high prevalence of breakthrough pain (BTP), defined as transitory, severe flares of pain that occur on a background of otherwise controlled, persistent pain. High BTP prevalence rates have also been reported in patients with chronic noncancer pain, although data in these patient populations are more limited. The incidence of BTP appears to be associated with progression of chronic disease, with more than 80% of patients reporting BTP with far-advanced, end-stage cancer and noncancer terminal conditions (1). The most widely accepted therapeutic approach for the management of BTP involves use of short-acting opioids taken as needed in addition to the around-the-clock opioid regimen being used for the continuous component of the persistent pain syndrome. For some patients, an optimal treatment outcome for BTP may be unattainable because of a mismatch between the time course of the BTP episode and the onset of analgesia of short-acting opioids. Breakthrough pain typically reaches peak intensity within a few minutes, whereas the onset of analgesia with traditional, orally administered short-acting opioids is between 30 and 60 minutes (2-7). Consequently, treatment outcomes for BTP are likely to be improved with agents that have a more rapid onset of analgesia. Fentanyl buccal tablet (FBT) is a new formulation of fentanyl indicated for the management of BTP in patients with cancer who are already receiving, and who are tolerant to, opioid therapy for their underlying persistent cancer pain. The FBT formulation uses OraVescent (Cephalon, Inc., Frazer, PA, USA) drug delivery technology to provide rapid absorption of fentanyl through the buccal mucosa. In pharmacokinetic studies in healthy volunteers, FBT demonstrated high, early systemic absorption. In addition, FBT delivered a larger proportion of the fentanyl dose transmucosally and produced a greater early systemic exposure than oral transmucosal fentanyl citrate (OTFC), which is also indicated for the management of BTP in opioid-tolerant cancer patients. A number of short-term studies have evaluated the efficacy, safety and tolerability of FBT in the management of BTP in opioid-tolerant patients with chronic pain. All these studies included an open-label dose-titration phase prior to randomized, placebo-controlled, double-blind treatment. Pain Intensity of a BTP episode was measured using an 11-point scale (0 = no pain, 10 = worst pain), and the primary outcome measure was the Summed Pain Intensity Difference (SPID) at a specified time point. Secondary efficacy measures included Pain Relief, Pain Intensity Differences, and the proportion of BTP episodes demonstrating >or=33% and >or=50% improvement in Pain Intensity scores at each time point postdose, and the proportion of BTP episodes requiring supplemental medication. In a pivotal study of opioid-tolerant patients with cancer-related chronic pain and BTP, the primary outcome measure, SPID at 30 minutes (SPID(30)), significantly favored FBT compared with placebo (mean +/- SE: 3.0 +/- 0.12 vs. 1.8 +/- 0.18, p<0.0001). Better efficacy was also observed with FBT compared with placebo for pain relief, Pain Intensity Differences, and the proportion of episodes showing >or=33% and >or=50% improvement in Pain Intensity Scores. Treatment with FBT was generally well tolerated. Most adverse events were mild to moderate in severity and typical of those associated with opioid use (e.g., nausea, dizziness) (8). Similar results have been observed in studies of opioid-tolerant patients with BTP in association with noncancer-related chronic pain. In a study of patients with chronic low back pain, the primary outcome measure, SPID(60), significantly favored FBT over placebo (mean +/- SE: 8.3 +/- 0.66 vs. 3.6 +/- 0.57, p <0.0001). All secondary efficacy measures were similarly improved, with Pain Intensity Differences and Pain Relief scores showing significant differences versus placebo as early as 10 and 15 minutes, respectively. As in the study of cancer patients, treatment with FBT was well tolerated (9). Across all studies, there was no simple linear relationship between the effective dose of FBT and the dose of the around-the-clock opioid regimen or the previous supplemental opioid, indicating that doses of FBT should be individually titrated to effectiveness rather than calculated as a percentage of existing opioid regimens. This monograph summarizes current data on the clinical pharmacology, efficacy, safety and tolerability of FBT relating to the management of opioid-tolerant patients with BTP in association with chronic pain.
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PMID:Fentanyl buccal tablet. 1830 3

Epilepsy is a common chronic disorder that requires long-term antiepileptic drug therapy. Approximately one half of patients fail the initial antiepileptic drug and about 35% are refractory to medical therapy, highlighting the continued need for more effective and better tolerated drugs. Levetiracetam is an antiepileptic drug marketed since 2000. Its novel mechanism of action is modulation of synaptic neurotransmitter release through binding to the synaptic vesicle protein SV2A in the brain. Its pharmacokinetic advantages include rapid and almost complete absorption, minimal insignificant binding to plasma protein, absence of enzyme induction, absence of interactions with other drugs, and partial metabolism outside the liver. The availability of an intravenous preparation is yet another advantage. It has been demonstrated effective as adjunctive therapy for refractory partial-onset seizures, primary generalized tonic-clonic seizures, and myoclonic seizures of juvenile myoclonic epilepsy. In addition, it was found equivalent to controlled release carbamazepine as first-line therapy for partial-onset seizures, both in efficacy and tolerability. Its main adverse effects in randomized adjunctive trials in adults have been somnolence, asthenia, infection, and dizziness. In children, the behavioral adverse effects of hostility and nervousness were also noted. Levetiracetam is an important addition to the treatment of epilepsy.
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PMID:Levetiracetam in the treatment of epilepsy. 1883 Apr 35

Pregabalin and gabapentin are widely used analgesic, anticonvulsant and anxiolytic agents as they are relatively reliable and easily tolerated. However, they may cause some side effects such as dizziness, somnolence, dose-dependent peripheral edema, and weight gain, which may cause patients to abandon their use. Furthermore, there are a few reports in the literature addressing elderly patients with serious chronic disease and cardiac history, who develop heart failure during pregabalin application. In this report, we present a patient with no cardiac history treated with 300 mg/kg pregabalin due to neuropathic pain, who developed peripheral and then central edema, which were determined after advanced investigations. After stopping pregabalin, the situation regressed. Then, peripheral edema developed associated with the recommended dose of gabapentin, which was used in place of pregabalin. Despite the lack of any published evidence, the New York Heart Association issued a warning about using caution when prescribing pregabalin to type III-IV heart failure patients. Though the effect mechanisms of pregabalin and gabapentin are not well known, the calcium channel relationship may lead to these side effects. In summary, we believe that pregabalin and gabapentin, which is mostly used nowadays, should be administered with care not only in patients with advanced cardiac pathology but also in all patients, due to the potential side effects.
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PMID:Possible heart failure associated with pregabalin use: case report. 2164 8

Dizziness and vertigo are among the most common symptoms in neurology and medicine in general. The differential diagnosis may be simplified by systematic and careful assessment of presenting symptoms. The most common conditions associated with vertigo and dizziness can be diagnosed by patient history and physical examination alone. Extensive apparative diagnostic work-up is seldomly required and often not helpful. The majority of these disorders can be well treated and have an excellent prognosis, when diagnosed adequately and within a reasonable time frame to prevent the development of chronic disease.
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PMID:[Chronic dizziness and vertigo from a neurologists' perspective]. 2336 51

Fibromyalgia (FM) is a prevalent and disabling chronic disease. Recent studies have found elevated levels of glutamate in several brain regions, leading to hypotheses about the usefulness of glutamate-blocking drugs such as memantine in the treatment of FM. The aim of this study was to evaluate the efficacy of memantine in the treatment of pain and other clinical variables (global function, clinical impression, depression, anxiety, quality of life) in FM patients. A double-blind, parallel randomised controlled trial was developed. A total of 63 patients diagnosed with FM were recruited from primary health care centres in Zaragoza, Spain. Memantine was administered at doses of 20mg/d after 1 month of titration. Assessments were carried out at baseline, posttreatment, and 3- and 6-month follow-up. Compared with a placebo group, memantine significantly decreased ratings on a pain visual analogue scale (Cohen's d=1.43 at 6 months) and pain measured with a sphygmomanometer (d=1.05). All other secondary outcomes except anxiety also improved, with moderate-to-large effect sizes at 6 months. Compared with placebo, the absolute risk reduction obtained with memantine was 16.13% (95% confidence interval=2.0% to 32.6%), and the number needed to treat was 6.2 (95% confidence interval=3 to 47). Tolerance was good, with dizziness (8 patients) and headache (4 patients) being the most frequent side effects of memantine. Although additional studies with larger sample sizes and longer follow-up times are needed, this study provides preliminary evidence of the utility of memantine for the treatment of FM.
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PMID:Efficacy of memantine in the treatment of fibromyalgia: A double-blind, randomised, controlled trial with 6-month follow-up. 2521

Organic farming has been promoted in Thailand by King Rama the ninth. In addition to being healthier for consumers, organic farming is healthier for agricultural workers. The cross-sectional study was conducted to investigate the frequency of chronic disease conditions, accidents, health symptoms, and ergonomic problems among 243 conventional (pesticide using) farmers and 235 organic farmers. Data were collected using questionnaires in face-to-face interviews. The results indicated symptoms that could be related to pesticide exposure (skin rashes, water blisters, headache, dizziness, and loss of appetite) were significantly higher among conventional farmers than organic farmers. The organic farmers reported significantly more health symptoms such as hives, chest pain, mild fever, flatulence, and frequent urination than the conventional farmers. The organic farmers reported significantly more pain, numbness, or weakness in the wrists/hands, fingers, upper back, hips, and ankles/feet than conventional farmers.
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PMID:Difference in Accidents, Health Symptoms, and Ergonomic Problems between Conventional Farmers Using Pesticides and Organic Farmers. 3102 8

Anxiety disorders are debilitating psychological disorders characterized by a wide range of cognitive and somatic symptoms. Anxiety sufferers have a higher lifetime prevalence of various medical problems. Chronic medical conditions furthermore increase the likelihood of psychiatric disorders and overall dysfunction. Lifetime rates of cardiovascular, respiratory, gastrointestinal, and other medical problems are disproportionately high in anxiety and panic/fear sufferers. The heightened comorbidity is not surprising as many symptoms of anxiety and panic/fear mimic symptoms of medical conditions. Panic disorder specifically is strongly linked to medical conditions due to its salient somatic symptoms, such as dyspnea, dizziness, numbness, chest pain, and heart palpitations, all of which can signal danger and deterioration for chronic disease sufferers. This chapter identifies shared correlates of medical illness and anxiety disorders and evidence for misinterpretation of symptoms as medically relevant and offers an analysis of implications for treatment of both types of conditions. We will concentrate on medical conditions with high associations for anxiety and panic by aspects of symptomatology, specifically neurological disorders (fibromyalgia, epilepsy, cerebral palsy), diabetes, gastrointestinal illness (irritable bowel syndrome, gastroesophageal reflux disease), and cardiovascular and respiratory illnesses (asthma).
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PMID:Anxiety Disorders and Medical Comorbidity: Treatment Implications. 3200 33

Anemia is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). It can be asymptomatic or associated with non-specific symptoms such as irritability, headaches, fatigue, dizziness and anorexia. In IBD patients, the etiology of anemia is often multifactorial. Various causes include iron deficiency, anemia of inflammation and chronic disease, vitamin deficiencies, hemolysis, or myelosuppressive effect of drugs. Anemia and iron deficiency in these patients may be underestimated due to their insidious onset, lack of standardized screening practices, and possibly underappreciation that treatment of anemia is also required when treating IBD. Practitioners may hesitate to use oral preparations due to their intolerance, while intravenous preparations are underutilized due to fear of adverse events, availability, and cost. Several publications in recent years have documented the safety and comparative efficacy of various intravenous preparations. This article reviews management of anemia in children with IBD, including diagnosis, etiopathogenesis, evaluation of a patient, protocol to screen and monitor patients for early detection and response to therapy, treatment including parenteral iron therapy, and newer approaches in management of anemia of chronic disease. This report has been compiled by a group of pediatric gastroenterologists serving on the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) IBD committee, in collaboration with a pediatric hematologist, pharmacist, and a registered dietician who specializes in pediatric IBD (IBD Anemia Working Group), after an extensive review of the current literature. The purpose of this review is to raise awareness of under-diagnosis of anemia in children with IBD and make recommendations for screening, testing, and treatment in this population.
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PMID:Anemia in Children with Inflammatory Bowel Disease: A Position Paper by the IBD Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition. 3274 May 14


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