Health food stores' recommendations for nausea and migraines during pregnancy

BACKGROUND: Many pregnant women use dietary supplements during pregnancy; however, relatively scant information is available on the safety of these products. Consumers of dietary supplements often rely on employees of health food stores to provide recommendations. OBJECTIVE: To evaluate recommendations made by health food store employees in the Phoenix metropolitan area regarding treatment of nausea/vomiting and migraines during pregnancy. METHODS: Phone calls were made by a disguised shopper to 155 health food stores in the greater Phoenix area. The caller posed as a woman 8 weeks' pregnant asking for recommendations for treatment of nausea/vomiting and migraines. Responses and recommendations were recorded and then compared with current scientific evidence obtained during a search of the literature using MEDLINE (1966-September 2004) as to whether or not the supplements and the methods of their use during pregnancy were contraindicated. RESULTS: Eighty-nine percent of stores offered recommendations for nausea/vomiting, and 82% provided recommendations for migraines. The use of ginger was the most recommended therapy for nausea/vomiting. Only 3.6% of respondents recommended correct usage, but failed to supply the correct dosage and duration. A total of 15 of 278 (5%) recommendations, for both nausea/vomiting and migraines, were for products contraindicated in pregnancy. CONCLUSIONS: In light of the increased use of dietary supplements by women during pregnancy, the willingness of personnel in health food stores to make any recommendations should foster concerns by patients and healthcare providers alike. Use of dietary supplements contraindicated in pregnancy could cause significant harm to the mother and/or fetus. Studies are needed to address the need for more stringent guidelines regarding health food stores and their recommendations.     

Ginger for nausea and vomiting of pregnancy

Clinical questionCan ginger treat nausea and vomiting of pregnancy?Bottom lineIn the first trimester ginger might improve nausea and vomiting by about 4 points on a 40-point scale or stop vomiting for 1 in 3 women at 6 days. The largest study suggests no increase in fetal malformations or stillbirths, but smaller studies suggest otherwise.     

5-HT3 receptor antagonists for prevention of late acute-onset emesis

OBJECTIVE: To review the currently available literature on the efficacy of the 5-HT(3) receptor antagonists in the prevention of late acute-onset chemotherapy-induced nausea and vomiting (12-24 h after cytotoxic treatment). DATA SOURCES:Primary articles were identified by PubMed search (performed in March 2004) and through secondary sources. Search terms included granisetron, ondansetron, tropisetron, dolasetron, acute, chemotherapy, nausea, and vomiting (a further search was performed for palonosetron in March 2004). STUDY SELECTION AND DATA EXTRACTION: All studies that performed regular assessments (every 2-6 h) of antiemetic control over the first 24 hours with 5-HT(3) receptor antagonists were evaluated. DATA SYNTHESIS: Current guidelines recommend the use of 5-HT(3) receptor antagonists for the control of chemotherapy-induced nausea and vomiting but do not differentiate between the available agents. However, there is variability in the pharmacokinetic and pharmacodynamic profiles of these agents, and this has implications for dosing regimen, safety, efficacy, and potential drug-drug interactions. Cytotoxic agents vary in the time profile of their emetic effect; this must be considered when choosing an appropriate 5-HT(3) receptor antagonist. The optimal agent should be simple to administer and provide safe and effective antiemetic protection over the whole 24-hour period. CONCLUSIONS: The differences between the 5-HT(3) receptor antagonists have important consequences for their dosing and efficacy in the control of late acute-onset chemotherapy-induced nausea and vomiting.     

Aprepitant: a novel antiemetic for chemotherapy-induced nausea and vomiting

OBJECTIVE: To evaluate the safety and efficacy of aprepitant in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). DATA SOURCES: MEDLINE and PubMed database searches were conducted from 1966 to May 2004 using the following search terms: aprepitant, Emend, substance P, neurokinin-1, chemotherapy, nausea, vomiting, L-754,030, and MK-869. STUDY SELECTION AND DATA EXTRACTION: Large, randomized Phase II and III clinical trials examining the use of aprepitant for CINV, as well as all published drug interaction studies with aprepitant, were included and reviewed. Data lacking in published trials were supplemented with the manufacturer product information. DATA SYNTHESIS: The pharmacokinetics of aprepitant are favorable for once-daily oral dosing. Based on the results of published clinical trials, aprepitant appears to augment the effects of corticosteroids and 5-HT3 antagonists when given prior to highly emetogenic chemotherapy, including cisplatin. Aprepitant appears to have the most benefit in the prevention of delayed CINV and in preventing emesis rather than nausea. Data in pediatric patients, patients undergoing stem-cell transplantation, and those receiving multiple-day or moderately emetogenic chemotherapy are lacking. Common adverse effects are limited to hiccups, asthenia, and diarrhea. More serious but rare adverse effects include neutropenia. Because aprepitant is a CYP3A4 substrate, a 3A4 inhibitor and inducer, and a 2C9 inducer, close monitoring for drug interactions is warranted. CONCLUSIONS: Triple antiemetic therapy with aprepitant, a corticosteroid, and a 5-HT3 antagonist appears to provide improved efficacy in the prevention of emesis in patients receiving highly emetogenic chemotherapy. Due to its novel mechanism of action and demonstrated efficacy in this combination, aprepitant should be considered for formulary addition.     

Nebulized morphine for relief of dyspnea due to chronic lung disease

OBJECTIVE: To evaluate the efficacy and safety of nebulized morphine for the management of dyspnea in chronic pulmonary diseases. DATA SOURCES: MEDLINE (1966-May 2004), EMBASE (1980-May 2004), and International Pharmaceutical Abstracts (1970-May 2004) searches were performed. Key search terms included morphine, dyspnea, and inhalation. DATA SYNTHESIS: Nine studies have evaluated the efficacy of nebulized morphine in relieving dyspnea. Three trials had positive results, but the rest failed to show improvement after treatment with doses ranging from 1 to 40 mg nebulized morphine. The small number of subjects, variety of disease states, and different outcome measures limit interpretation of the studies. CONCLUSIONS: Results from several small studies do not support the use of nebulized morphine for treatment of dyspnea; however, several positive case reports have been published.     

Low-dose granisetron for postoperative nausea and vomiting prophylaxis

OBJECTIVE: To evaluate the use of low-dose granisetron in postoperative nausea and vomiting prophylaxis. DATA SOURCES: Clinical trials available through PubMed and OVID (1966-July 2003), as well as information supplied by the drug manufacturer, were accessed. DATA SYNTHESIS: Safety concerns associated with droperidol and limited availability of other agents have created a need to restructure prophylaxis guidelines for postoperative nausea and vomiting. It has recently been proposed that granisetron may be effective at a dose that is one-tenth of the Food and Drug Administration-approved dose. Conflicting evidence for this regimen is evaluated. CONCLUSIONS: Based on the scarcity of supporting data, this regimen is not recommended for prophylaxis in patients at risk for postoperative nausea and vomiting.     

Teriparatide for severe osteoporosis

OBJECTIVE: To review the pharmacology, toxicology, pharmacokinetics, pharmacodynamics, efficacy, safety, therapeutic controversies, administration, patient counseling, and formulary recommendations for teriparatide (rDNA origin). DATA SOURCES: A MEDLINE search (1966-May 2003) of articles using the key words parathyroid hormone and osteoporosis, parathyroid hormone and fracture, and teriparatide was conducted to identify relevant literature in the English language. Additional references were obtained from bibliographies of those articles. Some clinical trial data not yet published were obtained from the manufacturer. STUDY SELECTION AND DATA EXTRACTION: All articles obtained from the data sources were reviewed; all data deemed relevant were included. DATA SYNTHESIS: Teriparatide, recombinant human parathyroid hormone (1-34) [rhPTH (1-34)], is the first anabolic agent to treat postmenopausal women with osteoporosis and men with idiopathic or hypogonadal osteoporosis who are at high risk for osteoporotic fracture. Daily subcutaneous injections of teriparatide significantly increase both spine and hip bone-mineral density (BMD) while decreasing the incidence of fractures in both women and men. Common adverse effects noted with teriparatide use were nausea, headache, dizziness, and arthralgias. An increased incidence of osteosarcoma in rats during preclinical trials with teriparatide led to a black box warning for the drug. CONCLUSIONS: Teriparatide substantially increases spine and hip BMD and may offer additional benefits to patients with severe osteoporosis. Clinical trials comparing teriparatide with other available agents to treat osteoporosis are needed to more clearly define its place in therapy. Long-term safety and efficacy are not known.     

Ginger: history and use

Ginger is well known in the form of ginger sticks or ginger ale. If these are consumed during travel, the traveler imbibes, albeit subconsciously, a healing plant for motion sickness. The efficacy of ginger rhizome for the prevention of nausea, dizziness, and vomiting as symptoms of motion sickness (kinetosis), as well as for postoperative vomiting and vomiting of pregnancy, has been well documented and proved beyond doubt in numerous high-quality clinical studies. The use of this ancient medicine for gastrointestinal problems (stimulation of digestion) has been given scientific approval. Today, medicinal ginger is used mainly for prevention of the symptoms of travel sickness.     

Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting

Goals of work  Ginger has been used to treat numerous types of nausea and vomiting. Ginger has also been studied for its efficacy for acute chemotherapy-induced nausea and vomiting (CINV). However, its efficacy for delayed CINV in a diverse oncology population is unknown. Materials and methods  We performed a randomized, double-blind, placebo-controlled trial in 162 patients with cancer who were receiving chemotherapy and had experienced CINV during at least one previous round of chemotherapy. All participants were receiving a 5-HT₃ receptor antagonists and/or aprepitant. Participants were randomized to receive either 1.0 g ginger, 2.0 g ginger daily, or matching placebo for 3 days. The primary outcome was change in the prevalence of delayed CINV. Secondary outcomes included acute prevalence of CINV, acute and delayed severity of CINV, and assessment of blinding. Main results  There were no differences between groups in the prevalence of delayed nausea or vomiting, prevalence of acute CINV, or severity of delayed vomiting or acute nausea and vomiting. Participants who took both ginger and aprepitant had more severe acute nausea than participants who took only aprepitant. Participants were able to accurately guess which treatment they had received. Ginger appeared well tolerated, with no difference in all adverse events (AEs) and significantly less fatigue and miscellaneous AEs in the ginger group. Conclusions  Ginger provides no additional benefit for reduction of the prevalence or severity of acute or delayed CINV when given with 5-HT₃ receptor antagonists and/or aprepitant. This trial is registered in ClinicalTrials.gov ID: NCT00065221.     

Meta-analysis of the use of rescue antiemetics following PONV prophylactic failure with 5-HT3 antagonist/dexamethasone versus single-agent therapies

OBJECTIVE: To assess the use of rescue antiemetic medication following 5-HT3 receptor antagonist (5-HT3RA) plus dexamethasone therapy versus monotherapy with a 5-HT3RA for prophylaxis of postoperative nausea and vomiting (PONV). DATA SOURCES: Reports of randomized, controlled trials were identified via a MEDLINE search (1966-September 2005) using the key terms ondansetron, dolasetron, tropisetron, granisetron, 5-HT3, PONV, vomiting, emesis, and nausea. STUDY SELECTION AND DATA EXTRACTION: Randomized, controlled trials of adult populations that had treatment arms comparing 5-HT3RA/dexamethasone combination therapy with 5-HT3RA or dexamethasone monotherapies versus placebo or 5-HT3RA versus dexamethasone or placebo were selected for analysis. Another criterion was that a proportion of patients required rescue medication 48 hours or less following surgery. DATA SYNTHESIS: Odds ratios (ORs) with 95% confidence interval were calculated to determine incidence rates for use of rescue medications within early (0-6 h), late (6-24 h), and overall (0-24 or 48 h) postoperative periods. Overall effect sizes were calculated by pooling ORs within fixed and random effects models. CONCLUSIONS: Prophylaxis with 5-HT3RA/dexamethasone was associated with lower use of rescue antiemetics than 5-HT3RA (OR(pooled) = 0.48; 95% CI 0.29 to 0.77) or dexamethasone (OR(pooled) = 0.26; 95% CI 0.12-0.57) monotherapy during the overall postoperative period. Insufficient data were available to assess rescue use during early or late postoperative periods. It appears that patients at high risk of PONV who are treated prophylactically with combination 5-HT3RA/dexamethasone therapy are overall less likely to require rescue medication than if treated with 5-HT3RAs or dexamethasone alone. Additional large prospective studies are needed to determine the optimal regimen and timing of administration of prophylactic antiemetic therapy for different surgical populations.     

Incretin mimetics as emerging treatments for type 2 diabetes

OBJECTIVE: To review the physiology, pharmacology, and clinical efficacy of glucagon-like peptide (GLP-1) and the incretin mimetics exenatide and liraglutide in clinical studies. DATA SOURCES: Primary literature obtained via MEDLINE (1966-April 2004) and International Pharmaceutical Abstracts (1970-April 2004) searches; abstracts obtained from meeting sources and manufacturers. STUDY SELECTION AND DATA EXTRACTION: All English-language studies and abstracts evaluating GLP-1, exenatide, and liraglutide in the treatment of patients with type 2 diabetes were reviewed. Data from animal studies were also included if human data were not available. Primary and review articles related to the physiology, development, and evaluation of GLP-1s were reviewed. DATA SYNTHESIS: GLP-1, exenatide (exendin-4, AC2993), and liraglutide (NN2211) are incretin mimetics that have been shown in human studies to be an effective treatment to improve glycemic control in patients with type 2 diabetes. Mechanisms by which these compounds improve glycemic control include enhancing glucose-dependent pancreatic secretion of insulin in response to nutrient intake, inhibiting glucagon secretion, delaying gastric emptying, and promoting early satiety. GLP-1 has been shown to promote pancreatic progenitor cell differentiation and improve beta-cell function and lifespan. Reported adverse effects of exenatide and liraglutide include nausea, vomiting, and transient headache, as well as increased risk of hypoglycemia when used with sulfonylureas. CONCLUSIONS: Clinical studies show that GLP-1, exenatide, and liraglutide improve glycemic control for patients with type 2 diabetes through unique mechanisms not available with current pharmaceutical products. Ongoing Phase III studies will help to further position these compounds as treatment options for patients with type 2 diabetes.     

Use of methylphenidate in traumatic brain injury

OBJECTIVE: To review literature regarding the effectiveness of methylphenidate in the management of the cognitive and behavioral changes observed following traumatic brain injury (TBI). DATA SOURCES: A literature search was conducted using the following databases: MEDLINE (1966-June 2004); Cochrane Central Register of Controlled Trials, fourth quarter 2004 (1988-June 2004); and International Pharmaceutical Abstracts (1970-June 2004). Methylphenidate and brain injury were the key search terms used. Limits were set to include clinical trial publications, human subjects, and English language. DATA SYNTHESIS: Ten clinical trials evaluating the efficacy and safety of methylphenidate in pediatric and adult patients with TBI are reviewed. Improvements in different aspects of cognition and behavior were evaluated before, during, and after treatment with methylphenidate. The results demonstrated that methylphenidate is likely to improve memory, attention, concentration, and mental processing, but its effects on behavior have not been determined. CONCLUSIONS: Larger, double-blind, placebo-controlled studies are needed to determine optimal doses, during which phase of recovery to begin treatment, length of treatment, and long-term effects for patients with mild, moderate, and severe TBI.     

Isolation from "being alive": coping with severe nausea and vomiting of pregnancy

BACKGROUND: Despite ongoing investigations into specific causes of and treatments for pregnancy-related nausea and vomiting, it remains a common phenomenon of varying intensity that affects the quality of life for both affected women and their families. OBJECTIVE: To understand how women cope with severe nausea, vomiting, and/or retching during pregnancy. METHOD: Women hospitalized with severe symptoms (N = 24) were purposely selected to participate in 24 semistructured interviews and one focus group (N = 4). RESULTS: A process was identified wherein women experienced severe and unrelenting nausea and related symptoms which became progressively more debilitating, leaving them feeling uncertain about when and if they would recover. This caused the women to isolate themselves from their world in an effort to cope with symptoms. CONCLUSIONS: Severe nausea and vomiting of pregnancy is a complex and overwhelming syndrome. Rather than emphasizing a specific treatment for a particular symptom (e.g., vomiting), nurses can intervene to reduce the impact of factors that affect the magnitude of nausea, vomiting, and retching.     

Intensive lipid-lowering therapy in patients with coronary heart disease

OBJECTIVE: To describe current data evaluating the use of intensive lipid-lowering therapy in patients with coronary heart disease. DATA SOURCES: A literature search using MEDLINE (1966-September 2004) was conducted using the search terms lipoproteins, low-density lipoprotein cholesterol (LDL-C), hydroxymethylglutaryl-coenzyme A reductase inhibitors, coronary arteriosclerosis, and coronary disease to identify published trials comparing the effects of intensive and conventional lipid-lowering therapy. DATA SYNTHESIS: Intensive lipid-lowering therapy reduces LDL-C levels significantly more than conventional treatment and appears to reduce cardiovascular morbidity and mortality in patients who have recently experienced acute coronary syndrome (ACS). However, evidence suggesting clinical benefits in patients with stable coronary heart disease is currently lacking. CONCLUSIONS: Although data are limited, patients with ACS may benefit from intensive lipid-lowering therapy. Several studies are underway to determine the appropriate role of intensive lipid-lowering therapy.     

Mifepristone

OBJECTIVE: To review the efficacy and safety of mifepristone (with misoprostol) for the termination of early pregnancy. DATA SOURCES: A MEDLINE search (1966-October 2000) was conducted, and additional references listed in articles were included; unpublished data obtained from the manufacturer were used to identify data from the scientific literature. Studies evaluating mifepristone were considered for inclusion. STUDY SELECTION: Human clinical studies in the English language were reviewed and evaluated. Clinical trials selected for detailed review were limited to those including the regimens of mifepristone and misoprostol, recently approved by the Food and Drug Administration for early pregnancy termination. DATA SYNTHESIS: Mifepristone is an antiprogestin available for pregnancy termination in combination with a prostaglandin such as misoprostol. Mifepristone offers efficacy similar to, if not better than, other drugs used for pregnancy termination, but appears less efficacious overall than surgical termination of pregnancy. Mifepristone in combination with misoprostol commonly causes adverse effects such as abdominal pain and, less commonly, can cause serious adverse effects such as incomplete abortion; endometritis; and bleeding warranting transfusion, hospitalization, or surgery. Mifepristone is metabolized by the cytochrome P450 system. Thus, the potential for drug interactions with this agent exists, although this has not been well studied. Data are included from clinical trials evaluating the safety, tolerability, efficacy, and pharmacoeconomics of mifepristone combined with misoprostol for early pregnancy termination. Data comparing the use of these agents with surgical abortion and other drugs used for pregnancy termination are included where available. CONCLUSIONS: Mifepristone in combination with misoprostol for the termination of early pregnancy (amenorrhea of < or = 49 d) is effective in 92-95% of women. Incomplete abortion requiring surgical abortion after the fact occurs in 3-5% of women, and pregnancy continues 1-2% of the time. Mifepristone with misoprostol treatment is not without significant risks, including hemorrhage, infection, and potential for long-term emotional consequences.     

The potential role of HMG-CoA reductase inhibitors in pediatric nephrotic syndrome

OBJECTIVE: To evaluate the safety and efficacy of the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as a potential treatment option for the dyslipidemia associated with childhood nephrotic syndrome. DATA SOURCES: Searches of MEDLINE (1966-April 2004), Cochrane Library, International Pharmaceutical Abstracts (1977-April 2004), and an extensive manual review of journals were performed using the key search terms nephrotic syndrome, familial hypercholesterolemia, dyslipidemia, and HMG-CoA reductase inhibitor. STUDY SELECTION AND DATA EXTRACTION: Two prospective uncontrolled studies evaluating the safety and efficacy of statin therapy in pediatric nephrotic syndrome were included. DATA SYNTHESIS: While an extensive amount of data is available in adult nephrotic syndrome in which statin therapy decreases total plasma cholesterol 22-39%, low-density lipoprotein cholesterol (LDL-C) 27-47%, and total plasma triglycerides 13-38%, only 2 small uncontrolled studies have been conducted evaluating the utility of these agents in pediatric nephrotic syndrome. These studies indicate that statins are capable of safely reducing total cholesterol up to 42%, LDL-C up to 46%, and triglyceride levels up to 44%. CONCLUSIONS: Lowering cholesterol levels during childhood may reduce the risk for atherosclerotic changes and may thus be of benefit in certain patients with nephrotic syndrome. Statins have demonstrated short-term safety and efficacy in the pediatric nephrotic syndrome population. Implementing pharmacologic therapy with statins in children with nephrotic syndrome must be done with care until controlled studies are conducted in this population.     

Pemetrexed therapy for malignant pleural mesothelioma

OBJECTIVE: To review pemetrexed, a novel multi-targeted antifolate agent. DATA SOURCES: A literature search was conducted (1985-September 2004) using MEDLINE and CANCERLIT. Recent abstracts from the American Society of Clinical Oncology were also included, along with the manufacturer's information. Key words were pemetrexed, LY-231514, Alimta, multi-targeted antifolate, malignant pleural mesothelioma. STUDY SELECTION AND DATA EXTRACTION: Relevant information on pharmacology, pharmacokinetics, and safety and efficacy of pemetrexed from clinical trials was selected. DATA SYNTHESIS: Pemetrexed inhibits folate metabolism and purine/pyrimidine synthesis. Based on Phase I and II trials, pemetrexed has antitumor activity in solid tumors such as lung, colorectal, and cervical. A pivotal Phase III study in patients with malignant pleural mesothelioma (MPM) demonstrated survival superiority of pemetrexed-cisplatin regimen versus cisplatin. CONCLUSIONS: Pemetrexed is a promising new drug for the treatment of solid malignancies, most notably MPM.     

Prevalence and severity of nausea and vomiting of pregnancy and effect of vitamin supplementation.

OBJECTIVE: Although nausea and vomiting of pregnancy is the most common medical condition during pregnancy, there are many unanswered questions regarding its cause, epidemiologic features and optimal management. The objectives of this study were to ascertain the prevalence of nausea and vomiting in a sample of Canadian women, to characterize the distribution of their severity and to investigate the role of vitamin B6 deficiency in their etiology. DESIGN: Prospective study. SETTING: Antenatal counselling service for pregnant women. PATIENTS: Three cohorts of women: a prospective, population-based cohort of 193 women, to estimate the rate and severity of nausea and vomiting (cohort A); a cohort of 555 women who sought advice for nausea with or without vomiting, to study the correlation between the maximal daily number of episodes of vomiting and maximal weight loss (cohort B); and a prospective cohort of 301 women who reported vomiting, to correlate vitamin supplementation with vomiting (cohort C). INTERVENTIONS: All 3 cohorts were interviewed during the counselling session, and cohort B was followed up prospectively. OUTCOME MEASURES: Frequency of nausea and vomiting, weight loss, maximal number of daily episodes of vomiting, rate of multivitamin supplementation. RESULTS: Overall, 67% of the women in cohort A reported experiencing nausea or vomiting, or both; 22% reported vomiting, and 9% experienced weight loss. In cohort B there was a significant correlation between the maximal number of daily episodes of vomiting and maximal weight loss, although there was wide variation (r2 = 0.25, p < 0.001). There was a highly significant correlation between the number of daily vomiting episodes and mean weight loss (r2 = 0.99). In cohort C, vomiting was significantly associated with lack of supplementation with multivitamins before 6 weeks' gestation (p = 0.002). CONCLUSIONS: The relation between number of daily vomiting episodes and mean weight loss may serve as a clinical tool to assess the severity of nausea and vomiting in pregnancy and the success of anti-emetics and rehydration regimens. Further study is needed to elucidate the biologic basis of the observed association between vomiting and lack of multivitamin supplementation in early pregnancy.