Effects of Ginger for Nausea and Vomiting in Early Pregnancy

A Meta-analysis


Maggie Thomson, MD, Renee Corbin, MSc, Lawrence Leung, MBBChir, MFM(Clin(

J Am Board Fam Med. 2014;27(1):115-122

 

Abstract and Introduction

 

Abstract

 

Background: Nausea and vomiting in early pregnancy (NVEP) is commonly encountered in family medicine. Ginger (Zingiber officinale) is a popular nonpharmacological treatment but consensus of its use is lacking.

 

Methods: We conducted a meta-analysis of clinical trials using ginger for NVEP as published in PubMed and EMBASE, CINAHL, Cochrane Library, and all EBM reviews.

 

Studies satisfying 3 criteria were selected: (1) randomized placebo-controlled design; (2) use of ginger or Z. officinale; and (3) extractable data on improvement in NVEP.

 

Data were synthesized into pooled odd ratios based on the random effects model, and results were tabulated with the aid of Forest plots.

 

Results: We identified 135 potentially relevant records; only 6 studies met the final criteria.

 

Of the total 508 subjects, 256 and 252 subjects were randomly assigned to receive ginger and placebo, respectively.

 

The use of ginger (~1 g daily) for at least 4 days is associated with a 5-fold likelihood of improvement in NVEP.

 

Heterogeneity among the clinical studies were acknowledged in the final interpretation of results.

 

Conclusions: Despite the widespread use of ginger in the diet, its clinic value and safety profile in treating NVEP is still unknown. Our meta-analysis suggests that ginger is an effective nonpharmacological treatment for NVEP.

 

Introduction

 

Pregnancy-induced nausea and vomiting is commonly seen in family medicine, and 50% to 90% of pregnancies are affected by nausea with or without vomiting.

 

According to a recent study, up to 63% of women experience nausea and vomiting up to 24 weeks' gestation.

 

[1] While only 0.3% to 2% of these cases are considered severe (called hyperemesis gravidarum, leading to a loss of >5% of prepregnancy body weight), all forms of pregnancy-related nausea can affect quality of life.

 

[2]Compared with the volume of literature regarding the pathogenesis and treatment of pregnancy-induced nausea and vomiting in general, few studies look at nausea and vomiting in early pregnancy (NVEP.(

 

Epidemiology, Risk Factors, and Pathogenesis of NVEP

Nausea and vomiting during pregnancy is known to be more common in younger primigravid women, as well as in Western countries and urban areas.

 

[2] Risk factors for its development include history of estrogen-based medication causing nausea and motion or migraine causing nausea.

 

Multiple gestation pregnancies,[3] women who did not take multivitamins before conception,[4] those with acid reflux,[5] and those with a hydatidiform mole[6] also are known be at increased risk.

 

There seems to be a genetic component to developing hyperemesis gravidarum; several studies demonstrate that daughters of women who experienced the condition are at increased risks.

 

[7,8] It is interesting that alcohol consumption and cigarette smoking have both been demonstrated to be protective.

 

[9] The exact pathogenesis of NVEP remains unclear; however, hormonal changes including elevated serum human chorionic gonadotropin have been implicated,[2] as have psychological factors and stress response.

 

[10] Delayed or dysrhythmic gastric motility also has been postulated as a likely cause of NVEP.[2]

 

 

Diagnosis and Treatment of NVEP

 

Diagnosis of NVEP is purely clinical.

 

There exists no defined diagnostic criteria for the condition. Mean onset is known to be between 5 to 6 weeks of gestation, with the majority of symptoms resolving by 20 weeks.

 

[2] Approximately 20% of women continue to have symptoms into their second and third trimesters.

 


[2] Contrary to popular belief, symptoms occur throughout the day and are often not limited to the morning as the term morning sickness would imply.[2[

Goals of treatment include reducing maternal symptoms and complications and mitigating any effects on the fetus. Antiemetics for NVEP that have been studied include Diclectin (Duchesnay Inc., Blainville, QC, Canada), ondansetron, ginger, various antihistamines, vitamin B6, metoclopramide, and phenothiazines.

 

[2] A recent randomized, double-blind, placebo-controlled trial[11] demonstrated that Diclectin was effective for nausea and vomiting during pregnancy, and this drug is currently recommended as first-line pharmacological treatment for NVEP in Canada.

 

Ondansetron is commonly used as an antiemetic during chemotherapy, with good evidence.

 

[12] However, it has been used for some time in the United States as a first-line (albeit off-label) treatment for pregnancy-related nausea and vomiting.

 

[13] While evidence exists for other pharmacological and nonpharmacological treatments (eg, dietary adjustments, acupressure, and acupuncture), they are beyond the scope of this article.

 

Our study aimed to critically examine the efficacy of ginger in the treatment of NVEP through meta-analysis of published clinical trials.

 

Ginger and Its Medicinal Effects

 

The antinausea effect of ginger was first described in one of the canons of traditional Chinese medicine—the Synopsis of the Prescriptions of Golden Chamber[14]—in 200 AD.

 

Ginger is the underground stem (or rhizome) of the perennial plant Zingiber officinale, which is indigenous to China and India but is cultivated all over the world.

 

From the body of ginger sprouts the peudostems, which branch off to leaves that can reach 2 feet in height.

 

[15] Analysis of ginger reveals 2 major classes of phytochemicals: volatile oils, which give ginger its pleasant smell,

 

[16] and the nonvolatile compounds (eg, gingerols and zingerones), which account for its piquant taste and its pharmacological effects.

 

[17] Many studies of the antiemetic nature of ginger for various conditions have been published but with mixed results. While evidence supports benefits of ginger for seasickness,

 

[18] motion sickness,

 

[19] and postoperative nausea and vomiting,

 

[20] its use in preventing chemotherapy-induced nausea and vomiting is still conflicting.

 

[21,22] Ginger also has been demonstrated to be effective in treating nausea and vomiting in pregnancy to the extent that it is as effective as vitamin B6 alone.

 

[23–27] The exact antiemetic mechanisms of ginger are still unknown, but in vitro studies revealed antagonistic effects of gingerols on serotonergic 5-HT3 [28,29] and cholinergic M receptors.

 

[29] So far, no direct adverse effects on human fetuses or the course of pregnancy have been demonstrated.

 

[24–27] However, there had been concerns about interfering with fetal development, which led to the issuance within Finland and Denmark of warning labels for all supplements containing ginger.

 

[30] It is also recognized that ginger has potent anticoagulant effects, which may enhance bleeding and miscarriages and interact with other medications.

 

[30] At present, there are no large-scale studies ascertaining the safety of ginger. That said, in Europe and North America the current consensus for the maximum safe dose of ginger is 2 g/day in divided doses of 250 mg, even during pregnancy.[30]

 

Methods

 

 

Study Aim

 

NVEP is a commonly encountered condition in family medicine, and ginger has been used as a nonpharmacological remedy.

 

Our meta-analysis aimed to critically examine and synthesize available data from good-quality randomized clinical trials to evaluate the efficacy of ginger in treating NVEP.

 

Eligibility Criteria

 

Our primary interest was the treatment of NVEP using ginger as the

therapeutic intervention.

 

To minimize heterogeneity, we limited our scope to randomized, placebo-controlled trials with a satisfactory score on the Cochrane Risk of Bias assessment tool.

 

Search Strategy

 

A literature search of published medical reports was performed in all languages using PubMed, EMBASE, CINAHL, the Cochrane Library, and all evidence-based medicine reviews using the OVID Portal of Queen's University, Kingston, Ontario.

 

Abstracts were initially obtained using MeSH keywords ofearly pregnancy, nausea, vomiting, and ginger.

 

Manual searches of references and review articles supplemented the computerized search.

 

Study Selection, Data Extraction, and Quality Assessment

Two reviewers (MT and RC) went through the initial abstracts.

 

A simple form was adopted to select trials that satisfied the eligibility criteria stated above.

 

Selected studies were evaluated according to the Cochrane Risk of Bias tool with regard to quality of the study, randomization protocol, adequacy of concealment and blinding, and rigor of follow-up for drop-outs.

 

Information regarding the demography of the study population, duration of the study, the number of affected subjects who improved with treatment and placebo, and finally a numeric score for the Cochrane risk of bias was extracted and tabulated in spreadsheets.

 

Of note, we found only 6 randomized, placebo-controlled trials of ginger that displayed data required for our meta-analysis (see ).

 

The primary outcome was improvement of pregnancy-related nausea and vomiting

 

 

Table 1.  Brief Description of the 6 Studies Included in the Meta-Analysis

 

Study

Intervention

Placebo

Duration of Study

Gestation Stage

Outcome Measure (Nausea and Vomiting)

Basirat et al.31

500-mg ginger powder in biscuit, 5 biscuits/day

Placebo biscuit

4 days

<17 weeks

Nausea scale (VAS) + frequency of vomiting

Ozgoli et al.35

250-mg ginger capsules QID

Lactose capsules

4 days

<20 weeks

Nausea scale (VAS) + frequency of vomiting

Smith et al.26

350-mg ginger capsules TID

Vitamin B6(25-mg capsules)

3 weeks

<16 weeks

Nausea and vomiting scales (Rhodes Index)

Keating et al.32

250-mg ginger syrup QID

Plain syrup

2 weeks

<12 weeks

4-point nausea scale + frequency of vomiting

Vutyavanich et al.34

250-mg ginger capsules QID

Placebo capsules

4 days

<17 weeks

VAS + Likert scale

Fischer-Rasmussen et al.33

250-mg ginger capsules QID

Lactose capsules

4 days

<20 weeks

Unique scoring system

 

 

QID, four times per day; TID, three times per day; VAS, visual analogue scale.

 

Statistical Analysis

 

All data from the 6 appropriate studies of ginger were synthesized in a meta-analysis, and odds ratios (ORs) were calculated with appropriate confidence intervals (CIs) based on the number of subjects reporting improvement in both the intervention and control groups.

 

Where necessary, the value of 1 was added to any arm with zero outcome events according to the Sheele + 1 rule.

 

To assess heterogeneity, we used the Cochrane Q-statistic with 95% confidence CIs.

 

We assumed a P value of <.05 for the Cochran Q-statistic. Forest plots were generated with ORs for each ginger study.

 

Statistical advice was provided by our data analyst at our Centre of Studies in Primary Care.

 

Results

 

We initially identified 135 records using the MeSH keywords of early pregnancy, ginger, nausea, and vomiting.

 

After removing duplicates and further screening, 8 full articles were retrieved. Two of them were excluded because of irrelevance.

 

Consensus was reached among the reviewers to include the final 6 studies.

 

The 2009 PRISMA checklist was used; the PRISMA flow diagram is given in the Appendix.

 

 

42122932014.jpg

 

Appendix.

 

 

PRISMA Flow Diagram

 

In our meta-analysis, a total of 256 patients were randomly assigned to receive ginger, and 252 patients were randomly assigned to receive placebo.

 

Total sample size per study ranged from 23 to 235. The period of intervention lasted from 4 days to 3 weeks.

 

Dose and method of administration of ginger also varied among studies: Basirat et al[31] used 5 biscuits per day, each containing 500 mg of ginger, whereas the others used either capsules or syrup containing approximately 1 g of ginger daily[26,32-35 ( ).[

 

Table 1.  Brief Description of the 6 Studies Included in the Meta-Analysis

 

Study

Intervention

Placebo

Duration of Study

Gestation Stage

Outcome Measure (Nausea and Vomiting)

Basirat et al.31

500-mg ginger powder in biscuit, 5 biscuits/day

Placebo biscuit

4 days

<17 weeks

Nausea scale (VAS) + frequency of vomiting

Ozgoli et al.35

250-mg ginger capsules QID

Lactose capsules

4 days

<20 weeks

Nausea scale (VAS) + frequency of vomiting

Smith et al.26

350-mg ginger capsules TID

Vitamin B6(25-mg capsules)

3 weeks

<16 weeks

Nausea and vomiting scales (Rhodes Index)

Keating et al.32

250-mg ginger syrup QID

Plain syrup

2 weeks

<12 weeks

4-point nausea scale + frequency of vomiting

Vutyavanich et al.34

250-mg ginger capsules QID

Placebo capsules

4 days

<17 weeks

VAS + Likert scale

Fischer-Rasmussen et al.33

250-mg ginger capsules QID

Lactose capsules

4 days

<20 weeks

Unique scoring system


 

QID, four times per day; TID, three times per day; VAS, visual analogue scale.

 

 

We applied the Cochrane Risk of Bias assessment to the 6 studies; they achieved a score of at least 3 of 6 and were deemed to be of satisfactory quality.

 

Our primary outcome was the improvement of pregnancy-related nausea and vomiting, which was reported in all 6 studies: 180 of the 256 subjects in the ginger group and 126 of the 252 subjects in the placebo group reported improvement in symptoms of nausea and vomiting. In view of the interstudy variation in the duration and form of intervention, a random effects model was adopted.

 

The pooled OR was 4.89, with a 95% CI of 1.88 to 12.73 (see ).

 

The Cochrane Q-statistic was significant at 33.72, with a degree of freedom of 5 (P < .0001) ( ). A synthesis Forest plot was generated (Figure 1), and the corresponding funnel plot is included for reference (Figure 2).

 

Relative risk was calculated at 1.76 (95% CI, 1.18–2.65), and the number needed to treat for a positive effect was calculated to be 5.

 

Table 2.  Results from Meta-Analysis Comparing Ginger to Placebo in Improvement of Nausea and Vomiting in Early Pregnancy

 

Study

Intervention Group

Control Group

Odds Ratio

95% CI

Basirat et al.31

28/32

21/30

3.00

0.81-11.1

Fischer-Rasmussen et al.33

19/27

4/27

13.66

3.56-52.43

Keating et al.32

10/13

2/10

13.33

1.78-100.14

Vutyavanich et al.34

28/32

10/35

17.50

4.87-62.87

Ozgoli et al.35

27/32

20/35

4.05

1.26-12.99

Smith et al.26

68/120

69/115

0.87

0.52-1.47

Total (random effects)

180/256

126/252

4.89

1.88-12.73

 

 

CI, confidence interval.

 

Table 3.  Test for Heterogeneity of Studies

 

 

Q-statistic

33.72

Degree of freedom

5

Significance level

P < .0001

 

 

 

 

 

 57122932014.jpg

Figure 1.

 

Forest plot for 6 studies using a random effects model. CI, confidence interval.

 

 

 

59122932014.jpg

Figure 2.

 

Funnel plot displaying the heterogeneity of studies. OR, odds ratio.

 

Discussion

 

Our meta-analysis demonstrated that ginger (Z. officinale) is better than placebo in improving NVEP when administered at a dosage of approximately 1 g/day for a duration of at least 4 days.

 

Despite the common intake of ginger in our diet, no large-scale studies have directly assessed the safety profile of ginger during human pregnancy.

 

In the early 1990s, Backon[36] commented on a theoretical possibility of ginger affecting testosterone receptor binding and sex steroid differentiation in the fetal brain.

 

An antiplatelet effect of ginger through inhibition of thromboxane synthetase has been reported in vitro.

 

[37] However, there have been no reports of increased risk of antenatal or postpartum hemorrhage with ginger use during pregnancy.

 

Increased levels of early embryonic loss due to ginger intake[38] were reported in rats; however, the dosage was far greater than those routinely used in humans.

 

Subsequent study of rats using human-compatible doses of ginger showed no similar adverse effects.[39]

 

A commonly observed side effect of ginger is reflux.

 

In a study by Willets et al,[24] 4 of the 120 subjects withdrew because of symptoms consistent with reflux.

 

Reflux has been commonly reported with ginger use outside pregnancy. In a study of the prevention of postoperative nausea and vomiting, 8% of subjects had heartburn after taking 1 g ginger.

 

[40] Another study of photopheresis-induced nausea demonstrated that 27% of subjects has reflux as a result of ginger use.

 

[41] Apart from gastric discomfort, the side effect of reflux poses no long-term harm or damage, and patients should be warned of this side effect before beginning ginger therapy.

 

There are a few limitations to our meta-analysis. First, there is variability in the dosage and formulation of ginger.

 

While 4 studies administered ginger in capsules,[26,33–35] one study administered ginger in syrup[32] and the other in the form of biscuits.[31] Moreover, the durations of intervention also differed.

 

Four studies administered intervention for 4 days,[31,33–35] while Keating and Chez[32] gave ginger for 2 weeks and Smith et al[26] for 3 weeks.

 

There was also variation in the combined sample size in the studies, which ranged from 23 to 235 (see ).

 

All these translated to a level of heterogeneity that was reflected in the Cochrane Q-statistic, with a significance of P < .0001. A final limitation of our study is the variability of scores used to qualify and quantify outcome measures in NVEP.

 

Vutyavanich et al,[34] Ozgoli et al,[35] and Basirat et al[31] used a visual analog scale, whereas Fischer-Rasmussen et al[33] developed a unique scoring system.

 

Keating and Chez used a symptoms diary and a 4-point scale and Smith et al used the Rhode's index.

 

While this does add heterogeneity to our meta-analysis, the primary endpoint chosen remained the same (ie, improvement of NVEP.(

 

Table 2.  Results from Meta-Analysis Comparing Ginger to Placebo in Improvement of Nausea and Vomiting in Early Pregnancy

 

Study

Intervention Group

Control Group

Odds Ratio

95% CI

Basirat et al.31

28/32

21/30

3.00

0.81-11.1

Fischer-Rasmussen et al.33

19/27

4/27

13.66

3.56-52.43

Keating et al.32

10/13

2/10

13.33

1.78-100.14

Vutyavanich et al.34

28/32

10/35

17.50

4.87-62.87

Ozgoli et al.35

27/32

20/35

4.05

1.26-12.99

Smith et al.26

68/120

69/115

0.87

0.52-1.47

Total (random effects)

180/256

126/252

4.89

1.88-12.73

 

CI, confidence interval.

 

Given its limitations, our meta-analysis demonstrated that ginger is better than placebo in improving NVEP, with an approximate number needed to treat of 5.

 

Further large-scale, multicenter trials should be undertaken to further examine the efficacies of ginger and detail its safety profiles when treating NVEP.

 

Conclusions

 

Ginger is commonly consumed in our diet as an additive in cooking.

 

In traditional Chinese medicine, ginger is indicated specifically as a remedy for NVEP.

 

Based on our meta-analysis, we conclude that ginger is an effective nonpharmacological option for treating NVEP with respect to the inherent heterogeneity of the available studies.

 

Family physicians and other medical professionals should be cognizant of the value of ginger as they contemplate pharmacological options for

suitable patients with NVEP.

 

References

 

Kramer J, Bowen A, Stewart N, Muhajarine N. Nausea and vomiting of pregnancy: prevalence, severity and relation to psychosocial health. MCN Am J Matern Child Nurs 2013;38:21–7.

 

Lee NM, Saha S. Nausea and vomiting of pregnancy. Gastroenterol Clin North Am 2011;40:309– 34, vii.

 

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Gill SK, Maltepe C, Koren G. The effect of heartburn and acid reflux on the severity of nausea and vomiting of pregnancy. Can J Gastroenterol 2009; 23:270 –2.

 

Hou JL, Wan XR, Xiang Y, Qi QW, Yang XY. Changes of clinical features in hydatidiform mole: analysis of 113 cases. J Reprod Med 2008;53: 629 –33.

 

Zhang Y, Cantor RM, MacGibbon K, et al. Familial aggregation of hyperemesis gravidarum. Am J Obstet Gynecol 2011;204:230.e1–7.

 

Fejzo MS, Ingles SA, Wilson M, et al. High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals. Eur J Obstet Gynecol Reprod Biol 2008;141:13–7.

 

Weigel MM, Weigel RM. The association of reproductive history, demographic factors, and alcohol and tobacco consumption with the risk of developing nausea and vomiting in early pregnancy. Am J Epidemiol 1988; 127:562–70.

 

Buckwalter JG, Simpson SW. Psychological factors in the etiology and treatment of severe nausea and vomiting in pregnancy. Am J Obstet Gynecol 2002; 186(5 Suppl Understanding):S210–4.

 

Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol 2010; 203:571.e1–7.

 

Tucker ML, Jackson MR, Scales MD, Spurling NW, Tweats DJ, Capel-Edwards K. Ondansetron: preclinical safety evaluation. Eur J Cancer Clin Oncol 1989;25(Suppl 1):S79 –93.

 

Einarson A, Maltepe C, Navioz Y, Kennedy D, Tan MP, Koren G. The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study. BJOG 2004;111:940 –3.

 

Zhongjing Z. Synopsis of prescriptions of the golden chamber (Jingui Yaolue). Library of Chinese Classics. Middle Island, NY: New World Press; 2008.

 

National Tropical Botanical Garden. Zingiber officinale. Available from: http://ntbg.org/plants/plant_details.php?plantid_11651. Accessed July 1, 2013.

 

Govindarajan VS. Ginger–chemistry, technology, and quality evaluation: part 1. Crit Rev Food Sci Nutr 1982;17:1–96.

 

Govindarajan VS. Ginger–chemistry, technology, and quality evaluation: part 2. Crit Rev Food Sci Nutr 1982;17:189 –258.

 

Grontved A, Brask T, Kambskard J, Hentzer E. Ginger root against seasickness. A controlled trial on the open sea. Acta Otolaryngol 1988;105:45–9.

 

Mowrey DB, Clayson DE. Motion sickness, ginger, and psychophysics. Lancet 1982;1:655–7.

 

Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S, Leeprakobboon K, Leelasettagool C. The efficacy of ginger for the prevention of postoperative nausea and vomiting: a meta-analysis. Am J Obstet Gynecol 2006;194:95–9.

 

Haniadka R, Rajeev AG, Palatty PL, Arora R, Baliga MS. Zingiber officinale (ginger) as an anti-emetic in cancer chemotherapy: a review. J Altern Complement Med 2012;18:440–4.

 

Marx WM, Teleni L, McCarthy AL, et al. Ginger (Zingiber officinale) and chemotherapy-induced nausea and vomiting: a systematic literature review. Nutr Rev 2013;71:245–54.

 

Niebyl JR, Goodwin TM. Overview of nausea and vomiting of pregnancy with an emphasis on vitamins and ginger. Am J Obstet Gynecol 2002;186(5 Suppl Understanding):S253–5.

 

Willetts KE, Ekangaki A, Eden JA. Effect of a ginger extract on pregnancy-induced nausea: a randomised controlled trial. Aust N Z J Obstet Gynaecol 2003; 43:139–44.

 

Portnoi G, Chng LA, Karimi-Tabesh L, Koren G, Tan MP, Einarson A. Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy. Am J Obstet Gynecol 2003;189:1374 –7.

 

Smith C, Crowther C, Willson K, Hotham N, Mc- Millian V. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol 2004;103:639–45.

 

Borrelli F, Capasso R, Aviello G, Pittler MH, Izzo AA. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol 2005;105:849 –56.

 

Abdel-Aziz H, Windeck T, Ploch M, Verspohl EJ. Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guineapig ileum. Eur J Pharmacol 2006;530:136–43.

 

Pertz HH, Lehmann J, Roth-Ehrang R, Elz S. Effects of ginger constituents on the gastrointestinal tract: role of cholinergic M3 and serotonergic 5-HT3 and 5-HT4 receptors.

 

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Tiran D. Ginger to reduce nausea and vomiting during pregnancy: evidence of effectiveness is not the same as proof of safety. Complement Ther Clin Pract 2012;18:22–5.

 

Basirat Z, Moghadamnia A, Kashifard M, Sarifi- Razavi A. The effect of ginger biscuit on nausea and vomiting in early pregnancy. Acta Medica Iranica 2009;47:51– 6.

Keating A, Chez RA. Ginger syrup as an antiemetic in early pregnancy.

Altern Ther Health Med 2002; 8:89 –91.

 

Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1991;38:19 –24.

Vutyavanich T, Kraisarin T, Ruangsri R. Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet Gynecol 2001;97:577– 82.

 

Ozgoli G, Goli M, Simbar M. Effects of ginger capsules on pregnancy, nausea, and vomiting. J Altern Complement Med 2009;15:243– 6.

 

Backon J. Ginger in preventing nausea and vomiting of pregnancy; a caveat due to its thromboxane synthetase activity and effect on testosterone binding. Eur J Obstet Gynecol Reprod Biol 1991;42:163– 4.

 

Srivastava KC. Effect of onion and ginger consumption on platelet thromboxane production in humans. Prostaglandins Leukot Essent Fatty Acids 1989;35: 183–5.

 

Wilkinson JM. Effect of ginger tea on the fetal development of Sprague-Dawley rats. Reprod Toxicol 2000;14:507–12.

 

Weidner MS, Sigwart K. Investigation of the teratogenic potential of a zingiber officinale extract in the rat. Reprod Toxicol 2001;15:75– 80.

 

Arfeen Z, Owen H, Plummer JL, Ilsley AH, Sorby- Adams RA, Doecke CJ.

 

A double-blind randomized controlled trial of ginger for the prevention of postoperative nausea and vomiting. Anaesth Intensive Care 1995;23:449 –52.

 

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This article was externally peer reviewed.

 

J Am Board Fam Med. 2014;27(1):115-122. © 2014  American Board of Family Medicine 

 

 

 

 

 

 

 

 

 

 

 

 

 

patient's compliance

Why Are So Many Patients Noncompliant?

 

 

 

 

An Epidemic of Noncompliance

 

The number of patients who are noncompliant has reached epidemic proportions, and doctors' inability to provide optimal care as a result has mushroomed into one of the most pressing problems in healthcare today.


           In the United States, some 3.8 billion prescriptions are written every year,  yet over 50% of them are taken incorrectly or not at all.

 

           In a survey of 1000 patients, nearly 75% admitted to not always taking their medications as directed.

 

           A study of over 75,000 commercially insured patients found that 30% failed to fill a new prescription, and new prescriptions for chronic conditions such as high blood pressure, diabetes, and high cholesterol were not filled 20% - 22% of the time.

 

           Even among chronically ill patients who regularly fill their prescriptions, only about half the doses taken are taken as their physicians intend.

 

           Poor compliance accounts for 33% - 69% of drug-related adverse events that result in hospital admissions.

.

           In a study of over 8400 senior health plan enrollees, only 1 in 3 of those who began treatment with concurrent antihypertensive and lipid-lowering drugs were taking both medications as directed or at all at 6 months.

 

           In a study of over 240,000 patients who were given a new prescription for an antidepressant, less than 30% were still taking the medication 6 months later.

 

28042932014.jpg

 

           Compared with patients who follow instructions, patients who don't take their medications as intended have a risk for hospitalization, re-hospitalization, and premature death that is 5.4 times higher if they have hypertension, 2.8 times higher if they have dyslipidemia, and 1.5 times higher if they have heart disease.

 

           Even after a life-threatening event, compliance with medication regimens remains surprisingly poor.

 

Yet compliance has been exhaustively studied. More than 40,000 peer-reviewed papers on the subject have been published. 

 

"Yet the rates of poor adherence have not changed significantly over the past several decades and continue to remain at an unacceptable level".

 

 

 

Why Research Hasn't Been More Helpful

 

The ocean of data on the compliance has stubbornly resisted attempts at synthesis into a statistically compelling, evidence-based, systematized plan or plans of action for overcoming barriers to compliance across a range of patients, drugs, and diseases.

 

A 2007 Cochrane review of interventions for enhancing medication compliance didn't mince words: "With the astonishing advances in medical therapeutics during the past two decades, one would think that studies of the nature of non-adherence and the effectiveness of strategies to help patients overcome it would flourish. 

 

"On the contrary, the literature concerning interventions to improve adherence with medications remains surprisingly weak."

 

Even the definition of compliance is subject to debate.

 

Is compliance mainly taking one's medications as instructed, a narrow definition adopted by most researchers because it simplifies research to study only one variable at a time, even if it sacrifices environmental complexity? Or should the definition be broader: "the extent to which a person's behavior -- taking medication, following a diet, and/or executing lifestyle changes -- corresponds with the agreed recommendations from a health care provider," as WHO maintains?

 

 

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Steiner tells of his 93-year-old father, who embodies this definitional dilemma.

 

"He discovered to his great delight that as long as he took his statin, he could eat anything he wanted," Steiner says.

 

"By being adherent with his medication, he didn't need to be adherent with his diet. Those are different adherence behaviors, but in his case, one trumps the other".

 


"The problem is with the way the scientific literature evolves," Steiner reflects.

 

"That can make the literature seem fragmented," he says. "We don't tackle the adherence problem at the patient level.

 

We tackle it at the drug or disease level. It's easier to study at that level. Measurements are easier. Costs are lower."

 

 

To be continued in the next edition

 

 

 


Pulmonary Hypertension

A novel drug for treating Pulmonary Hypertension Riociguat

 

Definition

 

Pulmonary hypertension (PH) is increased pressure in the pulmonary arteries. PH causes symptoms such as shortness of breath during routine activity, tiredness, chest pain, and a racing heartbeat.

 

 

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Types of PH

 

The World Health Organization divides pulmonary hypertension (PH) into five groups based on the cause of the condition and treatment options.

 

In all groups, the average pressure in the pulmonary arteries is 25 mmHg or higher. The pressure in normal pulmonary arteries is 8–20 mmHg at rest.

 

Group 1 Pulmonary Arterial Hypertension

           PAH that has no known cause.

           PAH that's inherited

           PAH that's caused by drugs or toxins, such as street drugs and certain diet medicines.

 

           PAH that's caused by conditions such as: Connective tissue diseases, HIV infection, liver disease, Sickle cell disease and Schistosomiasis (An infection caused by a parasite.(

 

 

           PAH that's caused by conditions that affect the veins and small blood vessels of the lungs.

 

Group 2 Pulmonary Hypertension

 

Group 2 includes PH with left heart disease such as mitral heart valve or long term high blood pressure, can cause left heart disease and PH. Left heart disease is likely the most common cause of PH.

 

Group 3 Pulmonary Hypertension

 

Group 3 includes PH associated with lung diseases, such as COPD and interstitial lung diseases. It is also includes PH associated with sleep-related breathing disorders, such as sleep apnea.

 

Group 4 Pulmonary Hypertension

 

Group 4 includes PH caused by blood clots in the lungs or blood clotting disorders.

 

Group 5 Pulmonary Hypertension

 

Group 5 includes PH caused by various other diseases or conditions:

           Blood disorders, such as polycythemia vera and essential thrombocythemia.

           Systemic disorders, such as sarcoidosis and vasculitis.

           Metabolic disorders, such as thyroid disease and glycogen storage disease.

           Other conditions, such as tumors that press on the pulmonary arteries and kidney disease.

 

 

Treatment

 

Pulmonary hypertension (PH) has no cure. However, treatment may help relieve symptoms and slow the progress of the disease.

 

Several treatments may be used for all types of PH. These treatments include:

           Phosphodiesterase-5 inhibitors, such as sildenafil

           Prostanoids, such as epoprostenol

           Endothelin receptor antagonists, such as bosentan and ambrisentan

           Calcium channel blockers, such as diltiazem

           Diuretics

           Blood-thinning medicines.

           Digoxin.

           Oxygen therapy.

           Physical activity.

 

 

Mode of action

 

Riociguat is an investigational drug designed to restore the NO-sGC-cGMP pathway and decrease endothelial dysfunction sensitizing the sGC enzyme to the body’s own NO and also stimulating sGC independently of NO enabling it to work in two ways (giving it a dual mode of action).

 

Riociguat stimulates sGC independently of NO

 

• The ability of riociguat to directly stimulate sGC independently of NO while also increasing the sensitivity of sGC to NO is potentially important in PH as endothelial dysfunction associated with the condition can be related to low levels of NO.

 

• Low levels of NO potentially reduce the ability of other PH therapies, such as phosphodiesterase 5 (PDE-5) inhibitors, to work effectively as these treatments rely on the body’s natural production of NO

 

 

Riociguat

 

Riociguat is the first member of a novel class of compounds, the stimulators of soluble guanylate cyclase (sGC).

 

It is the first in its drug class approved to treat pulmonary hypertension and the first drug of any class to be shown to be effective for patients with CTEPH, according to FDA where no pharmacological treatment is is approved.

 

 

Indications

(1)        Chronic thromboembolic pulmonary hypertension (CTEPH) for use after surgery or for patients who cannot undergo surgery, to improve the ability to exercise;

(2)        Pulmonary arterial hypertension (PAH) of unknown causes (inherited or associated with connective tissue diseases), to improve the ability to exercise and to delay clinical worsening of the condition.

 

 

 

Contraindications

 

Contraindications include pregnancy and use during breastfeeding, use with nitrates or nitric oxide donors in any form, and use with phosphodiesterase inhibitors.

 

Mode of action


Riociguat is an investigational drug designed to restore the NO-sGC-cGMP pathway and decrease endothelial dysfunction sensitizing the sGC enzyme to the body’s own NO and also stimulating sGC independently of NO enabling it to work in two ways (giving it a dual mode of action).

 


Riociguat stimulates sGC independently of NO


• The ability of riociguat to directly stimulate sGC independently of NO while also increasing the sensitivity of sGC to NO is potentially important in PH as endothelial dysfunction associated with the condition can be related to low levels of NO.


• Low levels of NO potentially reduce the ability of other PH therapies, such as phosphodiesterase 5 (PDE-5) inhibitors, to work effectively as these treatments rely on the body’s natural production of NO.

 

 

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Side effects

 

 Common adverse reactions include:

-  Headache

-  Tissue swelling

-  Dizziness

-  Dyspepsia/gastritis

-  Nausea

-  Diarrhea,

-  Hypotension,

-  Vomiting,

-  Anemia,

-  Gastroesophageal reflux

-  Constipation.

 

 

Administration

 

Starting dose is 1 mg orally three times daily, with dosage increases of 0.5 mg at intervals of no sooner than 2 weeks, as tolerated, to a maximum of 2.5 mg three times daily.

 

 

 

 

 

 

 

 

 

 

 

 

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