September morn

https://youtu.be/V7eTCbvPMR8

i know i'm not the only one who regrets the things they've done

coming late to this musical story https://www.novonoticias.com/cult/plagio-ou-coincidencia-adele-encontra-martinho-da-vila 'Mulheres' de Martinho da Vila - Bahia Noticias Adele's new album track has arrangements similar to 'Mulheres' by Martinho da Vila The track "Million Years Ago", featured on Adele's album "25", was similar to the arrangements of the classic samba "Mulheres" from Martinho da Vila's "Tá delícia, Tá Gostoso" (1995). The lyrics are very different. While Carioca's music talks about the various types of women with whom it was involved, Adele's song speaks of someone who has seen his life go by and repents of past acts. Compare tracks: https://youtu.be/9LMDg6awPq8 Adele - Million Years Ago (Cover by EMIR) https://youtu.be/tf4zQS4VzGQ Ahmet Kaya Acılara Tutunmak & Adele Million Years Ago by Dila Kalafatoğlu Mulheres - Martinho da Vila (Oficial) https://youtu.be/Dy66LbNvDiM Adele accused of plagiarism over song Million Years Ago http://www.mirror.co.uk/3am/celebrity-news/adele-accused-plagiarism-over-song-6973670#ICID=sharebar_twitter Adele accused of copying ANOTHER song by angry Turkish fans: Is this evidence of THEFT? http://shr.gs/scjnrvE

Countering Alternative Facts: Wikipedia in the Classroom

https://hookandeyeca.wordpress.com/2017/08/11/countering-alternative-facts-wikipedia-in-the-classroom/ via @wordpressdotcom

Which potential harms and benefits of using ginger in the management of nausea and vomiting of pregnancy should be addressed? a consensual study among pregnant women and gynecologists

BMC Complement Altern Med. 2017; 17: 204. Published online 2017 Apr 8. doi: 10.1186/s12906-017-1717-0 PMCID: PMC5385053 Ramzi Shawahnacorresponding author1,2 and Assim Taha3 1Department of Physiology, Pharmacology and Toxicology, Faculty of Medicine and Health Sciences, An-Najah National University, New Campus, Building: 19, Office: 1340, P.O. Box 7, Nablus, Palestine 2An-Najah BioSciences Unit, Centre for Poisons Control, Chemical and Biological Analyses, An-Najah National University, Nablus, Palestine 3Department of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine Ramzi Shawahna, Phone: + (970) 923 45113, Phone: + (970) 92349739, Email: moc.liamtoh@anhawahs_izmar. Abstract Background Nausea and vomiting of pregnancy (NVP) affect approximately 80–90% of the pregnant women. Ginger (Zingiber officinale Roscoe) is the most widely used herbal therapy in the management of NVP. Like conventional therapies, herbal therapies have potential harms and benefits that patients need to be informed about in order to develop their therapy preferences. The aim of this study was to achieve consensus among women who suffered NVP and physicians often consulted by pregnant women on a core list of potential harms and benefits of using ginger to manage NVP to be addressed during clinical consultations. Methods In this study, the Delphi technique was used to achieve consensus on a core list of important harms and benefits of using ginger in the management of NVP to be addressed during the clinical consultation. A Delphi process was followed in two panels in parallel sessions. One panel was composed of 50 gynecologists and other physicians who are often consulted by pregnant women suffering NVP and the other panel was composed of 50 women who suffered NVP. Results Consensus was achieved on 21 (75%) of the 28 potential harms presented to the panelists. Panelists agreed that potential harms of the anticoagulant effects of ginger, risk with other co-morbidities, and risk of potential allergic reactions are important to address during the clinical consultation. Of the 14 potential benefits presented to the panelists in both panels, consensus was achieved on 13 (92.9%). Partial consensus on 7 potential harms and 1 potential benefit was achieved in both panels. Conclusions Addressing important potential harms and benefits of using ginger for the management of NVP during the clinical consultations is important in promoting congruence and reducing patient dissatisfaction in clinical practice. Consensus was achieved on a core list of important harms and benefits of using ginger for the management of NVP to be addressed during the clinical consultations by a panel of women and a panel of physicians. Further studies are still needed to investigate what is being addressed during clinical consultations. Electronic supplementary material The online version of this article (doi:10.1186/s12906-017-1717-0) contains supplementary material, which is available to authorized users. Keywords: Ginger, Nausea and vomiting of pregnancy, Gynecologists, Pregnant women Go to: Background Nausea and vomiting of pregnancy (NVP) rank high among the most common complaints during the early weeks of pregnancy [1]. In clinical practice, both patients and physicians are reluctant to use medications in pregnancy, especially in the first trimesters due to the possibility of harming the unborn fetus [2]. However, in many cases, NVP requires treatment, thus, leaving the pregnant and physician in a dilemma whether to use conventional medications or leave the condition untreated [1, 2]. Unfortunately, many pregnant women opt not to use conventional medications and thus are left helpless against the heavy burden of NVP. NVP affect approximately 80–90% of the pregnant women [3]. Typically, symptoms appear at 4–9 weeks of gestation, reaching a peak at 7–12 weeks, and often subside by week 16 [3]. However, in about 1 in 3 pregnant women, symptoms persist beyond 20 weeks or even throughout of the pregnancy [1, 2]. Many pregnant women might present a severer and more persistent form of vomiting known as hyperemesis gravidarum which can lead to dehydration, electrolyte disturbances, damage the liver, damage of the developing fetus, and in extreme cases, the death of the mother and her fetus. This condition occurs in nearly 2% of pregnancies [1, 2]. Treatment of NVP using conventional medications can be complicated because of the significant physiological changes occurring during the pregnancy such as those in the gastro-intestinal motility, plasma volume, and glomerular filtration [4]. Such changes would certainly affect the different pharmacokinetics of medications including absorption, distribution, metabolism, and excretion. Many medications are able to cross the placenta and reach the fetus. Therefore, not all medications are effective and safe in pregnancy. Herbal therapies have been traditionally regarded as alternatives to conventional medications. In recent years, there has been a growing interest in using herbal therapies to treat many conditions including NVP [2, 5]. Among these herbal therapies, ginger (Zingiber officinale Roscoe) is the most widely used herbal therapy in the management of NVP [2, 5–9]. The safety of herbal therapies has long been taken as granted. This believe might have emerged as herbal therapies are often advertised as gentle, safe, and possessing unique properties not found in other conventional medication therapies [10]. Unfortunately, some healthcare professionals have perpetuated this myth when recommending these herbal therapies as “natural”, thus, mistakenly understood as safe or at least safer than conventional medications [5, 11]. Today, many patients believe that herbal therapies can never be harmful. However, these claims are not true and lack scientific basis. Herbal therapies contain a wide range of chemicals that can be similar to the active ingredients in many conventional medication therapies. In this case, these chemicals act by the same pharmacological mechanism of action in the body and possess similar potential to cause adverse effects. Like conventional medication therapies, herbal therapies have their intended indications, contraindications, precautions and adverse effects. Ginger is no exception, and therefore, should be recommended for the right person, at the right time, in the right dose, at the right frequency, and by the right route of administration [11]. Ginger has been extensively used in the management of NVP. Scientific evidence on the effectives of ginger in managing NVP is still inconclusive in view of the conflicting reports regarding the evidence of its effectiveness [1, 6]. Moreover, prior studies showed that ginger was associated with many health related issues like decreasing platelet aggregation, increasing stomach acid production, herb-herb and herb-medication interactions [1, 12, 13]. Therefore, gynecologists and other physicians who are frequently consulted by pregnant women with NVP should discuss the potential harms and benefits of using ginger in case they opted for using ginger to manage NVP. Currently, the literature does not narrate intensively which potential harms and benefits of using ginger in the treatment of NVP should be addressed from the viewpoint of the women affected, gynecologists and other physicians who are frequently consulted by pregnant women suffering from NVP. The current study is proposed to fill this gap in the literature. When opting for a treatment, in general, the potential benefits in terms of local control should be balanced against the potential harms, taking into account the available alternatives and patient preferences. In today’s clinical practice, patients need to be informed of the most relevant potential harms and benefits of the treatment options in order to develop their preferences [14]. Informing patients would probably prevent overestimation of the impact of treatment on cure [15]. It has also been suggested that well-informed patients experience better health-related quality of life and might cope better with the adverse effects of the treatment [16, 17]. In order to assess congruence with daily clinical practice, consensus was sought among pregnant women, gynecologists and other physicians who are frequently consulted by pregnant women for their NVP on which potential harms and benefits of using ginger for the management of NVP should be addressed during the consultations. In general, there are no recommendations on which potential harms and benefits of using ginger in the management of NVP to communicate to patients. Therefore, the aim of this study was to achieve consensus among women who suffered NVP, gynecologists and other physicians who are frequently consulted by pregnant women for their NVP on a core list of potential harms and benefits of using ginger to manage NVP that should be addressed during clinical consultations on which a decision to use ginger is taken. Go to: Methods Potential harms and benefits of using ginger in NVP Prior to the iterative Delphi rounds, we interviewed 8 key contact gynecologists who frequently recommend pregnant women with NVP to use ginger and 8 women with more than 5 prior pregnancies who were recommended to use ginger to reduce the symptoms of their NVP. The gynecologists were asked to list the potential harms and benefits of using ginger in the treatment of NVP that should be addressed during the clinical consultation in which they advise their patients to use ginger. The women were asked to list the potential harms and benefits of using ginger in the management of NVP that they would like their physicians to address during the clinical consultation. The aim of these interviews were to generate an extensive list of potential harms and benefits of using ginger in the management of NVP. The potential harms and benefits provided by the interviewed gynecologists and women were noted. We then conducted an extensive literature review to identify potential harms and benefits of using ginger in pregnant women [1–3, 6–8, 11, 12, 18–35]. All potential harms and benefits provided by the gynecologists and women as well as those found in the literature were summarized, formulated into statements, and included into a questionnaire. Potential harms and benefits were ordered by the effect of ginger on the health of the pregnant woman or her fetus. Harms and benefits related to costs, convenience or inconvenience were excluded from the list. The questionnaire was piloted with five students of medicine and five lay persons for readability and comprehensibility. Some statements were edited to promote understanding. The Delphi technique In this observational study, the Delphi technique was used to achieve consensus on the potential harms and benefits of using ginger in the management of NVP that should or should not be addressed in the clinical consultation. Since its inception, the Delphi technique has emerged as one of the most commonly used formal consensus techniques in healthcare on subjects with no or limited consensus [36, 37]. The Delphi technique is a combination of qualitative and quantitative approaches in which a multiple-round questionnaire system is administered in iterative rounds over an extended period of time within a panel until consensus is achieved [38]. In other words, items on which consensus was not achieved are often included in a revised questionnaire and presented to the panelists for further subsequent rounds [37]. Statistical summaries and comments made by one panelist are shared with other panelists in an attempt to reduce the number of rounds required to achieve consensus. Panelists are often requested to reconsider their voting in view of the votes and comments of other panelists [36]. In this study, we anticipated differences in views and opinions of physicians and women, therefore, we aimed to achieve consensus in two panels [14, 39]. One panel was composed of gynecologists and other physicians who are frequently consulted by pregnant women with NVP and another panel composed of women who suffered NVP. The Delphi technique was performed in the two panels separately and in paralleled sessions. The study was conducted between November 2016 and February 2017. As in previous Delphi consensus studies [14, 40, 41], we decided to achieve consensus in two consecutive iterative Delphi rounds. Panel of physicians We used a purposive sampling method to recruit and compose a panel of gynecologists and other physicians who are frequently consulted by pregnant women with NVP. Personal contacts in the field were used to identify potential participants. As pregnant women suffering NVP often consult gynecologists, the panel included a large percentage of gynecologists. Selection of the panelists is one of the most critical steps in the Delphi technique as panelists should be rich with information and experience [42]. In this study, the inclusion of panelists was based on their qualifications and experience in the field of treating pregnant women with NVP. Potential participants were approached in person and invited to take part in the study. The design and objectives of the study were explained to potential participants and their consent was obtained before they took part. The inclusion criteria was as follows: 1) possession of a basic or advance degree in medicine, 2) licensed to practice medicine in Palestine, 3) at least 5 years of practicing experience in a healthcare setting attended by pregnant women with NVP, and as prior knowledge of the subject being investigated is a prerequisite for panelists in a Delphi technique, 4) knowledge of the use of ginger in managing NVP. In this study a total of 50 physicians were recruited to the panel. Panelists agreed to participate without any incentives. Panel of women We used a snowball sampling technique to recruit women who were advised to use ginger for the management of their NVP. Personal contacts in the field helped identifying and recruiting potential participants who were approached in person and invited to take part in the study. The design and objectives of the study were explained to potential participants. Verbal consents were taken from all women before participation. The inclusion criteria was as follows: 1) multiparous, 2) suffered NVP, 3) was recommended to use ginger for her NVP, and 4) willingness to participate in the study. In this study, a total of 50 women were recruited to the panel. Again, the panelists agreed to participate without any financial incentives. The first Delphi iterative round In this round, the questionnaire was hand-delivered to 50 physicians and 50 women. The questionnaire contained three parts. In the first part, panelists were asked to provide their sociodemographic and practice characteristics. Physicians were asked to provide their gender, age, qualification, specialty, number of years in practice, place of work, if they recommend herbal therapies for pregnant women suffering NVP, and if they address potential harms and benefits of herbal therapies that pregnant women could be using during the clinical consultations. On the other hand, women were asked to provide their age, the number of pregnancies they had, any history of miscarriage, their educational level, their employment status, if they have been recommended by their physicians to use herbal therapies for their NVP, and if they like to have enough discussion with their physicians on the potential harms and benefits of using herbal therapies during the clinical consultations. The second part of the questionnaire contained 28 statements on potential harms from using ginger to manage NVP. The third part contained 14 potential benefits of using ginger in pregnant women. Both physicians and women were asked to indicate the level of their agreement and disagreement of the importance of addressing or not addressing the potential harm or benefit on a Likert scale of 9-points. Voting 1–3 indicated disagreement of the panelist on the importance of addressing the potential harm or benefit, i.e. it is not important to address the potential harm or benefit during the clinical consultation. Voting 7–9 indicated agreement of the panelist with on the importance of addressing the potential harm or benefit, i.e. it is important to address the potential harm or benefit during the clinical consultation. Voting 4–6 indicated that the panelist partially agrees on the importance of addressing the potential harm or benefit, i.e. the opinion of the panelist is inconclusive if it is important to address the potential harm or benefit during the clinical consultation. Panelists were encouraged to include written comments to justify or qualify their votes. Analysis of the votes Data obtained in the first Delphi iterative round were analyzed using descriptive statistics. Data were entered into an Excel Sheet (Microsoft Excel 2007). The first quartile (Q1), median (Q2), third quartile (Q3), and the interquartile range (IQR) of the votes were computed for each statement. Physicians and women were considered two different panels. Consensus was defined as in previous studies on issues in healthcare [40, 43]. When the median votes was between 7 and 9 and the IQR was between 0 and 2, consensus was said to have been achieved and the potential harm or benefit was included in the list of potential harms and benefits to be addressed during the clinical consultation. When the median vote was between 1 and 3 and the IQR was between 0 and 2, consensus was said to have been achieved and the potential harm or benefit was excluded from the list of potential harms and benefits to be addressed during the clinical consultation. When the median vote was between 4 and 6 or the IQR was larger than 2, the potential harm or benefit was considered equivocal. Consensus was based on the votes of at least 75% of the panelists in each panel. The second Delphi iterative round Potential harms and benefits that were considered equivocal in the first Delphi iterative round were included in a revised questionnaire. The questionnaire was hand-delivered to the panelists in a second Delphi iterative round. The panelists were provided with the followings: 1) the median vote on each equivocal statement along with the IQR, 2) reminder of their own vote, and 3) summary of the comments made by other panelists on the statement to justify or qualify their votes. The panelists were requested to re-consider their votes in view of the votes and comments of other panel members. It is believed that inclusion of such statistics and summaries reduce the number of rounds required to achieve consensus on issues in healthcare [36]. Votes obtained in the second Delphi iterative round were analyzed as in the first Delphi iterative round. Based on the voting and comments made by the panelists in both panels, it was decided that consensus would not be achieved in a further iterative round. Therefore, we decided not to conduct further rounds. Ethics The protocol of this study received approval from the Institutional Review Board (IRB) committee of An-Najah National University (Protocol # 02-NOV-2016). All participants gave verbal consents before participation in this study. Views and opinions of all participants weighed equally in the analysis. Data were made anonymous before analysis. During the Delphi iterative rounds, each panelist remained anonymous to the rest of the panelists. Go to: Results In the first Delphi iterative round, questionnaires were returned by the 50 physicians and 50 women, giving a response rate of 100%. However, in the second Delphi iterative round, questionnaires were returned by 43 (86%) physicians and 45 (90%) women. Characteristics of the panelists The panel of physicians included practitioners of both genders, from different specialties, different geographical locations, belonged to different age groups, and with variable number of years in practice. The vast majority of the panelists were gynecologists. The sociodemographic and practice details of the physicians are presented in Table ​Table11. Table 1 Table 1 Sociodemographic and practice characteristics of the physicians who participated in this study (n = 50) The panel of women included women of different age groups, had a variable number of pregnancies, had history of miscarriage, different educational levels and employment status. The detailed characteristics of the women who took part in this study are shown in Table ​Table22. Table 2 Table 2 Sociodemographic characteristics of the women who participated in this study (n = 50) Use of ginger for NVP When the physicians were asked if they recommend herbal therapy for pregnant women with NVP, 62% of them responded by quite often and the rest of 38% responded by sometimes. When the women were asked if they have been recommended by their physicians to use herbal therapies for their NVP, 70% responded by quite often and 30% responded by sometimes. When the physicians were asked if they address potential harms and benefits of herbal therapies that pregnant women could be using during the clinical consultation, 66% responded by quite often and 34% replied by sometimes. When the women were asked if they like to have enough discussion with their physicians on the potential harms and benefits of using herbal therapies, 76% responded by always and 24% responded by sometimes. Important potential harms and benefits to be addressed during the clinical consultation Table ​Table33 shows the important potential harms to be addressed during the clinical consultation on which consensus was achieved by the panelists. Table 3 Table 3 Important potential harms of using ginger for the management of NVP to be addressed during the clinical consultation By the end of the second iterative round, consensus was achieved on 21 (75%) of the 28 potential harms presented to the panels. The details of the Delphi iteration are shown in Fig. ​Fig.11. Fig. 1 Fig. 1 Details of the Delphi iteration process Panelists agreed that potential harms of the anticoagulant effects of ginger, risk with other co-morbidities, and risk of potential allergic reactions are important to address during the clinical consultation. Of the 14 potential benefits presented to the panelists in both panels, consensus was achieved on 13 (92.9%). These potential benefits are shown in Table ​Table44. Table 4 Table 4 Important potential benefits of using ginger for the management of NVP to be addressed during the clinical consultation Partial consensus on 7 potential harms and 1 potential benefit was achieved by both panels. These potential harms and benefits are presented in Table ​Table5.5. The choice to address these issues or not was left to the clinician depending on the individual clinical situation’s need. Table 5 Table 5 Potential harms and benefits to be addressed or not during a clinical consultation depending on the individual clinical situation’s need Go to: Discussion In this study we sought consensus on a list of important potential harms and benefits of using ginger for the management of NVP that should be addressed during the clinical consultation in the Palestinian clinical practice by a panel of physicians and a panel of women. To the best of our knowledge, this is the first attempt to achieve consensus on such list of potential harms and benefits of ginger in NVP using formal consensus techniques. In this study, we used a purpose sampling technique to recruit the panel of physicians and a snowball sampling technique to recruit the panel of women. In conservative views, these sampling techniques has long been considered biased [44, 45]. However, using other randomized sampling techniques was not possible in this study as these techniques are not suitable for the type of this study. Using these sampling techniques allowed the inclusion of panel members who had prior knowledge of the subject being investigated. In this study, we recruited physicians the majority of which were gynecologists and the rest were physicians who are frequently consulted by pregnant women suffering from NVP. Currently, there is no consensus on the ideal number of panelists in a Delphi panel. Previous studies used panels ranging in size from 10 to 1000 [44]. The number of panelists in this study was larger or similar to those previously used in Delphi consensus studies on issues in healthcare [40, 41, 46]. The advantages of the Delphi technique includes maintaining anonymity of the panelists, possibility of including panelists from different geographic locations, reduces costs and efforts to bring the panelists together compared to focus groups, and ensures immunity against individual domination of the decision compared to nominal or focused groups [44, 47]. The aim of this study was to achieve consensus on a list of the important potential harms and benefits of using ginger for the management of NVP that should be addressed during the clinical consultation. This list would be used by clinicians as a guidance on what potential harms and benefits to address during the clinical consultation. Guidelines on what clinicians should address during the clinical consultation when ginger is advised for NVP do not exist. We, therefore, believe that such lists developed through consensual methods might be beneficial in changing the behavior of physicians during the clinical consultation [14, 40, 43, 46, 48–50]. Prior studies reported high usage of herbal therapies in the Palestinian population including women who were pregnant [51–53]. In this study, 70% of the women reported being quite often recommended to use herbal therapies for their NVP. Similarly, 62% of the physicians admitted recommending quite often herbal therapies for pregnant women suffering NVP. It was reported that about 50% of the users of herbal therapies would not inform their physicians of such use [54]. Similarly, another study reported that physicians seldom ask if the patient was using herbal therapies [55]. Therefore, many patients end up using herbal and conventional therapies concurrently [12]. This has been attributed to poor communication and the insufficient time allocated to the clinical consultation [56]. The panel of women included women who had previous pregnancies, suffered NVP, and used ginger to manage their NVP. Women included in the panel were expected to provide the concerns that pregnant women suffering NVP would like their physicians to address during the clinical consultation. Interestingly, 76% of the women wanted their physicians to address the potential harms and benefits of the herbal therapies during the clinical consultation. High response rates in both Delphi iterative rounds from physicians and women is a major strength that adds to the validity of this study. Previous studies used panels that greatly varied in size ranging from 10 to more than 1000 participants [44, 57]. Studies using the Delphi technique to achieve consensus on issues in healthcare used panels of 50 participants or less [36, 46, 50]. In this study, both panels were composed of 50 members. The panel size used in this study was either comparable to or more than those used in previous studies [36, 40, 43, 46, 50]. The panel of physicians included participants of both genders, from different geographical locations, clinical practice settings, age groups, and experience periods. The panel of women also included participants from different geographical locations, age groups, number of pregnancies, history of miscarriage, employment, and educational levels. This diversity adds to the validity and suitability of addressing the potential harms and benefits that the participants agreed upon in this study. It has been argued that in absence of gold standards, consensual methods provide means of reducing bias, promoting transparency, and validity of judgmental methods when developing certain criteria [58]. Therefore, we believe that addressing these potential harms and benefits of using ginger for NVP during a clinical consultation approached using formal consensus method might be more appealing to clinical practitioners advising pregnant women to use ginger for their NVP. Interestingly in this study, consensus was achieved on six potential harms associated with the potential anticoagulant effects of ginger that should be addressed during the clinical consultation by both women and physicians (Table ​(Table3).3). These findings are not surprising, as previous studies showed that patients wanted to hear more from their healthcare providers on the medications they are taking [59]. The American Society of Anesthesiologists has advised that patients should discontinue all herbal therapies 2 to 3 weeks before an elective surgical procedure to avoid any potential intraoperative adverse events [60]. Recently, Marx et al. systematically reviewed eight clinical trials and two observational studies on the anticoagulant effects of ginger [26]. Considering the risks of bias, methodological variation, timeframe studied, dose of ginger used, and characteristics of the participants, Marx et al. concluded that the evidence that ginger affects platelet aggregation and coagulation is still equivocal and further studies are needed to illustrate a definite conclusion. However, a previous study showed that gingerols, which are compounds found in ginger, and the related compounds were able to inhibit arachidonic acid-induced human platelet serotonin release and aggregation in vitro [25]. The potency of these compounds were comparable to aspirin. Another study showed that 8-paradol, which is a component of ginger, was a relatively potent COX-1 inhibitor and antiplatelet aggregation agent compared to four other components of ginger with antiplatelet activities [27]. In spite of the fact that the anticoagulant effects of ginger are still inconclusive. Bleeding in the first trimester of pregnancy can have detrimental effects on the mother and her fetus. Hasan et al. reported association between heavy bleeding in the first trimester, especially when accompanied with pain, and higher risk of miscarriage in a study with 4539 women [61]. In this study, panelists were of the opinion that physician should address the potential anticoagulant effects of ginger with pregnant women who are at higher risk of bleeding to make a better informed decision whether to use ginger or not. Both physicians and women agreed that the risks associated with abortion should also be addressed during the clinical consultation when pregnant women are advised to take ginger for their NVP (Table ​(Table3,3, items 7–9). Today, there is no conclusive evidence of the adverse effects of ginger on the developing fetus. Therefore, ginger and ginger containing products are labeled differently across the globe. In the United States, ginger is “generally regarded as safe”. However, in Germany, the German E Commission on herbal medicines (does not exist anymore) recommended that ginger to be avoided in pregnancy [11]. Moreover, the Finnish Food Safety Authority Evira recommended that ginger products, ginger tea, and food supplements containing ginger should bear a warning label as not recommended during pregnancy [18]. Previous studies showed that ginger might be associated with spontaneous abortion and impairment of fetal development [21–23, 30]. Portnoi et al. conducted a study in Canada in which the birth outcomes of 187 women who were exposed to ginger in their first trimester of pregnancy were prospectively compared to the birth outcomes of 187 women who were exposed to other nonteratogenic medications that were not antiemetics [29]. The comparison showed that there was no statistically significant difference in terms of live births, spontaneous abortions, therapeutic abortions, birth weight, and/or gestational age between both groups. More recently, Heitmann et al. reported on the safety of using ginger during pregnancy in terms of congenital malformations and selected pregnancy outcomes in a large cohort of 68,522 women in Norway [24]. The study showed that 1020 women which represented 1.5% of the study population used ginger during their pregnancies. The study concluded that there was no increased risk of stillbirth/perinatal death, preterm birth, low birth weight, or low Appearance, Pulse, Grimace, Activity, Respiration (Apgar) score for the women who were exposed and those who were not exposed to ginger. Taking a conservative approach, women should be warned of the still inconclusive association between exposure to ginger and risk on the fetus and continuity of the pregnancy. Ginger could be associated with or could worsen symptoms of other co-morbidities [19, 20, 28, 31]. Ginger might be associated with reducing blood pressure and blood sugar. Ginger can cause dehydration and allergic reactions. In this study, both physicians and women agreed that such possibilities should be addressed during the clinical consultation. Pregnant women should be warned that ginger might precipitate cardiac arrhythmias, stimulate irritable bowel syndrome, duodenal ulcer, secretion of bile, and heartburn. Physicians should address these potential harms during the clinical consultation. For example, pregnant women at risk of cardiac arrhythmias or those taking antiarrhythmic medications might be advised not to take ginger and a suitable alternative might be recommended. Similar measures should be applied to avoid the potential harm of ginger in worsen other conditions. The views of both physicians and women were divisive whether to address the potentials of ginger inducing diarrhea, mild headache, fever, sweating, thirst, mild skin itching, and belching. It is noteworthy to mention that in many studies the seriousness of the reported adverse effects depends on the subjective judgements of the research team taking into account the possibility of these events in normal pregnancies without any interventions [1]. Classifying the potential harms of ginger into major and minor goes beyond the scope of this study, however in general, researchers often classify harms as major when the consequence was serious or detrimental to the mother and/or fetus. When the harm was a merely discomfort and manageable it was considered minor. Both physicians and women agreed that pregnant women suffering NVP might be informed of the potential benefits of ginger for NVP, nausea and vomiting in motion sickness, cough, flu, chronic pulmonary disease, milk production, joint pain, skin health, appetite in eating disorders, weight loss, hypercholesterolemia, diuresis, and dyspepsia. Physicians and women were divisive whether to address that ginger might induce somnolence. When pregnant women need treatment, more care should be exerted when prescribing medications to this vulnerable group of patients. The risks should be weighed against the benefits of using a specific treatment considering the available alternatives and consequences of using or not using these treatments. The same measures should be applied when advising them to take herbal therapies. Go to: Conclusion Addressing important potential harms and benefits of using ginger for the management of NVP during the clinical consultations is important in promoting congruence and reducing patient dissatisfaction in clinical practice. In this study, consensus was achieved on a list of important potential harms and benefits of using ginger for the management of NVP to be addressed during the clinical consultations by a panel of women and a panel of gynecologists and other physicians who are frequently consulted by pregnant women with NVP. This list might serve as a guidance for clinicians on what to address with their patients when recommending ginger for NVP. Some potential harms and benefits were divisive among women and physicians, either they should be addressed or not. The decision to whether to address them or not was left to the clinicians and on the needs of each clinical situation, i.e. to be evaluated on case-by-case basis. The use of such consensual core lists might promote congruence and reduce patient dissatisfaction in clinical practice. More randomized double blind controlled studies are needed to establish the efficacy and safety of ginger. Further studies are still needed to investigate what is being addressed during clinical consultations. Go to: Additional files Additional file 1: Table S1.(27K, docx) The questionnaire used for physicians. (DOCX 27 kb) Additional file 2: Table S2.(28K, docx) The questionnaire used for women. (DOCX 27 kb) Go to: Acknowledgement Authors would like to thank the study participants. Funding This study did not receive any specific funds. Availability of data and materials All data and materials supporting the conclusions of this study are included within the manuscript and the Additional files 1 and 2 or available upon request from the corresponding author (Ramzi Shawahna) at email: ramzi_shawahna@hotmail.com. Authors’ contributions RS designed the study. AT performed data acquisition. RS and AT performed the analysis and drafted the manuscript. All authors read and approved the final manuscript for submission. Competing interests The authors declare that they have no competing interests. Consent for publication Not applicable. Ethics approval and consent to participate This study was ethically approved by the Institutional Review Board (IRB) of An-Najah National University (Protocol # 02-NOV-2016). All study participants gave consent before taking part in the study. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Go to: Abbreviations IRB Institutional Review Board NVP Nausea and vomiting of pregnancy Go to: Contributor Information Ramzi Shawahna, Phone: + (970) 923 45113, Phone: + (970) 92349739, Email: moc.liamtoh@anhawahs_izmar. Assim Taha, Email: moc.liamtoh@6602-3xmisa. Go to: References 1. Viljoen E, Visser J, Koen N, Musekiwa A. 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Safety classification of herbal medicines used in pregnancy in a multinational study

BMC Complement Altern Med. 2016; 16: 102. Published online 2016 Mar 15. doi: 10.1186/s12906-016-1079-z PMCID: PMC4793610 D. A. Kennedy,corresponding author A. Lupattelli, G. Koren, and H. Nordeng PharmacoEpidemiology and Drug Safety Research Group, School of Pharmacy, PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Postbox 1068 Blindern, 0316 Oslo, Norway Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway D. A. Kennedy, Phone: +1-4168137283, Email: ac.oohay@dnydennekd. Contributor Information. corresponding authorCorresponding author. Abstract Background The use of herbal medicines for health prevention and ailments is an increasing trend worldwide. Women in pregnancy are no exception; the reported prevalence of herbal medicine use in pregnancy ranges from 1 to 60 %. Despite a common perception of safety, herbal medicines may have potent pharmacological actions, and historically, have been used for this reason. Methods A multinational, cross-sectional study on how women treat disease and pregnancy-related health ailments was conducted between October 2011 and February 2012 in Europe, North America, and Australia. This study’s primary aim was to evaluate and classify the herbal medicines used according to their safety in pregnancy and, secondly, to investigate risk factors associated with the use of contraindicated herbal medicines during pregnancy. Results In total, 29.3 % of the women (n = 2673) reported the use of herbal medicines in pregnancy; of which we were able to identify 126 specific herbal medicines used by 2379 women (89.0 %). Twenty seven out of 126 herbal medicines were classified as contraindicated in pregnancy, and were used by 476 women (20.0 %). Twenty-eight were classified as safe for use in pregnancy and used by the largest number of women (n = 1128, 47.4 %). The greatest number was classified as requiring caution in pregnancy; these sixty herbal medicines were used by 751 women (31.6 %). Maternal factors associated with the use of contraindicated herbal medicines in pregnancy were found to be working in the home, having a university education, not using folic acid, and consuming alcohol. Interestingly, the recommendation to take a contraindicated herbal medicine was three times more likely to be from a healthcare practitioner (HCP) than an informal source. Conclusion Based on the current literature the majority of women in this study used an herbal medicine that was classified as safe for use in pregnancy. Women who reported taking a contraindicated herb were more likely to have been recommended it use by an HCP rather than informal source(s), indicating an urgent need for more education among HCPs. The paucity of human studies on herbal medicines safety in pregnancy stands in stark contrast to the widespread use of these products among pregnant women. Electronic supplementary material The online version of this article (doi:10.1186/s12906-016-1079-z) contains supplementary material, which is available to authorized users. Keywords: Herbal medicine, Complementary and alternative medicine, Pregnancy, Safety, CAM Go to: Background The use of herbal medicines for health prevention and ailments is an increasing trend worldwide. A recent report on international herbal sales suggests that by 2015 sales are expected to reach $93 billion dollars, up from $33 billion in 2010 [1]. Women in pregnancy are no exception; a review of studies from the Western world, reported that the prevalence of herbal medicine use in pregnancy ranged from 1 to 60 % [2]. The prevalence rates were 34 % in Australia [3], 58 % in the United Kingdom [4], 40 % in Norway [5], 48 % in Italy [6] and 6–9 % in the US and Canada [7, 8]. In pregnancy, women often use herbal medicines due to the perception that these substances are more natural and therefore safer to use as compared to pharmaceutical medicines [2, 9–11]. Research suggests that in many instances, the use of herbal medicines speaks to a woman’s wish to have greater choice in their health and aligns with their desire for a holistic approach to their well-being [2, 12]. In most countries, herbal medicines are available as non-prescription medicines. Given such ease of access, most women report that the decision to use an herbal medicine came from either their own initiative or on the recommendation from family and/or friends. A small percentage of women do report that the recommendation to use an herbal medicine came from a healthcare practitioner (HCP) [2, 13, 14]. One study evaluated 400 different women’s knowledge regarding the indications for use of 10 specific herbal medicines (bearberry, dandelion, echinacea, ginkgo, hops, horsetail, lemon balm, St. John’s wort, sage, and valerian). These researchers found that over 78.3 % of the women surveyed had little knowledge regarding the indications for use of these herbal medicines, even though 31.3 % had used the herbal medicine in their pregnancy [10]. Despite this common perception of safety, herbal medicines may have potent pharmacological actions, and have, in fact, been used for centuries, for example as emmenagogues to promote abortion. Moreover, very little is known about the extent to which potentially harmful herbal medicines are used in pregnancy. Concerns range, with some herbal medicines, from teratogenicity to an increased risk of maternal bleeding or impact on neonatal hormones due to the hormonal nature of the herbal medicine [15]. In a previous study, 39 % of the women reporting having used herbal medicines during pregnancy had used herbal medicines that were considered possibly harmful or herbs where information about safety in pregnancy was missing [16]. This article is a continuation of the investigations of our previously published study on the use of herbal medicines in pregnancy among more than 9000 women across 18 countries and five regions of the world. More than one out of four women (28.9 %) reported using 127 different herbal medicines during pregnancy [13]. The objective of the present study is to evaluate and classify these herbal medicines according to their safety in pregnancy based on current literature and determine the proportion of women using herbals in each of the safety categories. A second objective was to investigate risk factors associated with the use of potentially hazardous herbal medicines during pregnancy. Go to: Methods Study data and population This was a multinational, cross-sectional study conducted in 18 countries (Australia, Austria, Canada, Croatia, Finland, France, Iceland, Italy, Norway, Poland, Russia, Serbia, Slovenia, Sweden, Switzerland, The Netherlands, United Kingdom, and USA) between October 1st 2011 and February 29th 2012. Women were eligible to participate if they were pregnant or had at least one child less than 1 year of age. Women were recruited to complete an online-self-reported questionnaire via the placement of banners (invitation to participate in the study) on national websites and/or social networks frequently visited by pregnant women and new mothers. The banners contained information about the rationale behind the study and the criteria for partcipation such as: “Moms-to-be and new moms, share your thoughts in an international survey about your views on medication use in pregnancy. Click here to read more about the study and take part.” In each participating country, the online questionnaire was available for 2 months. The survey questionnaire was administered by Questback (http://www.questback.com). A detailed description of the study design and methods has been published previously [13]. Consent was obtained from each participant. When a woman clicked on the survey link, a description of the study was presented and she was asked whether she was willing to participate. Informed consent was given by ticking a Yes response. The Regional Ethic Committee, Region South-East in Norway, evaluated the study protocol in its multinational aspect and approved the study. Further approvals were provided from the Faculty of Medicine and Health Science Research Ethics Committee of the University of East Anglia in the UK, The National Bioethics Committee in Iceland and The Scientific Ethic Board, and Provincial Health Service of Trento in Italy. Permission to analyze the herbal medicine study data was also obtained from the Research Ethic Board of the Hospital for Sick Children, Toronto, Canada. All data were handled and stored anonymously. The online questionnaire captured data on maternal health, socio-demographic, and lifestyle characteristics as well as use of herbal and conventional medicines in pregnancy. Maternal characteristics included age, marital status, educational level, mother tongue, employment status, parity, pregnancy intention, and information on use of assisted reproductive technology. Life-style characteristics included folic acid use and smoking status before and during pregnancy and alcohol consumption after awareness of pregnancy. The following question about use of herbal medicine was posed to all study participants “Did you take any herbal preparations during pregnancy (e.g. ginger, echinacea, valerian, cranberries)? If yes, please provide the name of all herbal preparations you have taken during pregnancy”. Herbal medicine use could also be reported under the specific questions about diseases and pregnancy-related health ailments throughout the questionnaire, as described in detail elsewhere [13]. The names of all herbal medicines used during pregnancy were captured as free text. Herbal medicine were defined according to the World Health Organization’s definition: “any medicinal product based on herbs, herbal materials, herbal preparations and finished herbal products, that contain as active ingredients parts of plants, other plant materials, or combinations thereof ” [17]. Medicinal products based on animal components, vitamins, minerals or homeopathic products were not considered herbal medicines. A pre-determined herbal medicine classification list (common name and Latin name) was compiled by the study team and followed the format of the World Health Organization’s Anatomical Therapeutic Chemical (ATC) code convention as a means to standardize the coding in the questionnaire database. The free text responses were coded according to this pre-determined classification list by the national coordinator in each country. When a product name representing a multi-herbal combination or combination product was entered, an internet search on the product name was performed and the botanical ingredient(s) coded according to the pre-determined classification list. Any mineral supplement(s) and vitamins were recorded separately whenever present in the combination product and excluded from the estimation of herbal use. The form of the herbal medicine (tea, tablet, or tincture) was not specifically requested nor was the dose. In the survey, women were asked to identify the source(s) of the recommendation to use the herbal medicine. The reported sources were then categorized into the following groups: informal (including the sources: own initiative, family/friends, internet, magazines/media and herbal shop personnel), healthcare provider (including the sources: physician, midwife/nurse and pharmacy personnel), and other (neither informal nor HCP). Women who had responses from both informal and HCP recommendation sources were classified into the “Both informal and HCP group”. Determination of the safety classification of herbal medicines Herbal medicines were categorized into one of four safety categories; safe, caution, contraindicated or unknown (Table 1) based on a summary of the literature, reference textbooks and monographs. The safety classifications were defined as shown in Table 1. Table 1 Table 1 Overview of herbal medicines used in pregnancy according to safety classification and number of users The safety classification was determined by recording the current classification of each herbal medicine from the available reference sources. Several reference sources were reviewed in order to capture different perspectives when classifying the individual herbal medicines: The Australian text book “The Essential Guide to Herbal Safety” [18] The European Medicines Agency’s [19] and North America (Herbal Medicines in Pregnancy & Lactation [15], Botanical Safety Handbook [20], and Botanical Medicine for Women’s Health [21], and Natural Medicines database [22]). If a particular herbal medicine was not listed in the above mentioned reference sources, additional sources were used; Handbook of Medicinal Herbs [23] and PDR for Herbal Medicines [24]. The Handbook of Medicinal Herbs identifies contraindications from multiple sources, often an earlier edition of the Botanical Safety Handbook. For those herbal medicines which were not listed in any of the referenced books mentioned above, searches in Pubmed, and EBSCO (Alt HealthWatch, AMED, Biomedical Reference Collection, Psychology and Behavioral Sciences Collection, CINHAL Plus, MEDLINE) were performed using first the combination of the terms: “herbal common name and pregnancy” then the “Latin name and pregnancy”. In addition, we performed a search of NCBI’s PubMed database for each of the 125 individual herbal medications reported in the study to identify whether there was evidence of safety in pregnancy. Evidence from controlled studies in human pregnancy was considered first. If no evidence in human studies was available, then in vivo research was considered in the classification. The searches were performed from inception to July 2015. Once the safety classification of each herbal medicine was compiled from the different sources, one author (DAK) reviewed the information and assigned the preliminary classification. The safety classification for each herbal medicine was reviewed by the co-authors (DAK, HN, and Gro Cecilie Havnen) and all discrepancies discussed until agreement was obtained. We made two assumptions to the safety classifications; 1) that the classification is for the herbal medicine itself rather than a concentrated whole herbal extract form or concentrated isolated constituent of the plant, 2) the dose is assumed to be at therapeutic levels, suitable for oral administration, versus excessive consumption of the herbal medicine or an alternate route of administration. If an herbal medicinal product included several herbs, each herbal was assessed individually and classified. Statistical analysis Factors associated with the use of contraindicated herbal medicines in pregnancy (dichotomous variable: contraindicated herbal medicine user versus non-contraindicated herbal medicine user) were explored via the Generalized Estimating Equations (GEE) [25]. The GEE method is often used to analyze correlated response data such as multiple observations over time for the same individual or clustered data where observations are grouped based on sharing some common characteristic. The use of the GEE in the current study permitted the results to account for any clustering on region of residency. Data are presented as adjusted odds ratios (aOR) with 95 % confidence intervals (CI). A two-tailed p-value of <0.05 was considered statistically significant. The multivariate GEE model was developed by first selecting candidate variables whose results, in a univariate model, had a p-value < 0.15. Variables with a p-value >0.05, no effect, or those having less than a 20 % impact on the beta coefficients of the retained variables were not included in the multivariate model. The final multivariate model included statistically significant independent variables (i.e. employment status, education level, folic acid use during pregnancy, alcohol use during pregnancy, and recommendation source) and potential confounders (i.e. age as a continuous variable). All statistical analyses were performed by using the Statistical Package for the Social Sciences (SPSS) version 20.0 (IBM® SPSS® Statistics). Go to: Results Of the 9615 women who indicated their willingness to participate in the study, 9483 (98.6 %) accepted and completed the questionnaire. After exclusion of isolated responses from ineligible countries (n = 4), as well as from the Central (n = 20) and South (n = 346) American regions, we reached a final study population of 9113 women from five different regions and 18 countries. The sample mostly included women from Western (n = 3201), Northern (n = 2820) or Eastern Europe (n = 2342), followed by North America (n = 533) and Australia (n = 217). A detailed participant flow chart was previously published [13]. The sample was representative of the birthing populations in each participating country with respect to age, parity and smoking habits [13]. However, our sample comprised a greater number of women with high educational levels versus the general birthing population in each country. In total, 29.3 % of the women (n = 2673) reported the use of herbal medicines in pregnancy. We were able to identify the specific herbal medicines used by 2379 women (89.0 %). Specific herbals could not be identified for the remaining 294 women (11.0 %), as these women either provided a general response, such as “herbal teas,” the manufacturer’s name rather than that of the herbal medicine or replied that she could not remember. These cases were therefore not included in the safety evaluation. There were 126 different herbal medicines used in pregnancy, and which could be evaluated according to their safety in pregnancy. Twenty-seven out of 126 herbal medicines were classified as contraindicated in pregnancy and these are detailed in Additional file 1: Table S1a. Of the analzed population of 2379 women, contraindicated herbal medicines were used by 476 women (20.0 %) (Table 1). The most frequently used contraindicated herbal medicines were Vaccínium vítis-idaéa (cowberry) (29.8 %), Levisticum officinale (lovage) (19.7 %), and Leonurus cardiaca (motherwort) (16.6 %). Twenty-eight herbal medicines were classified as safe for use in pregnancy (Additional file 1: Table S1b). These herbal medicines were used by the largest number of women (n = 1128, 47.4 %) (Table 1). The most frequently used herbal medicines classified as safe were Zingiber officinale (ginger) (56.7 %), Vaccinium oxycoccus/macrocarpon (cranberry) (55.0 %), and Mentha x piperita (peppermint) (15.9 %) The greatest number of herbal medicines were classified as requiring caution in pregnancy (Additional file 1: Table S1d). Sixty herbal medicines were used by 751 women (31.6 %) (Table 1). Thirty-six (36/60, 60 %) of the herbal medicines in this group had limited evidence of the safety for use in pregnancy whereas the remaining 24 (40 %) had some evidence of potentially harmful effects in pregnancy. The most frequently used herbal medicines classified as requiring caution in pregnancy were Valeriana officinalis (valerian) (n = 388), Rubus idaeus (raspberry) (n = 301) and Rosa canina (dog-rose) (n = 148). There were 11 herbal medicines for which no information on the safety in pregnancy could be found. These herbal medicines were used by only 24 women, representing a small portion of herbal medicine use (1.1 %) (Table 1). These herbs were Algae (algae), Aronia melanocarpa (black chokeberry), Bidens tripartita (water agrimony), Calluna vulgaris (heather), Citricidal sp. (grapefruit extract), Cucurbita pepo (cucurbit/squash), Fagopyrum esculentum (buckwheat), Hippophae rhamnoides (sea buckthorn), Olea europaea (olive), Potentilla reptans (potentilla), and Rhodiola rosea (rhodiola). There was an important difference between regions in terms of safety of herbal medicines used (Fig. 1). North America had the highest number of herbal medicines that were classified as contraindicated in pregnancy (19.5 %); however, a small number of women (10.9 %) used these herbal medicines. Among the contraindicated herbs used by women in North America were Cannabis spp. (marijuana) and Carica papaya (papaya). Fig. 1 Fig. 1 Percentage of herbal medicines used and the number of women who used these herbal medicines by safety classification, overall and by region Eastern Europe had the highest number of users of both contraindicated herbal medicines (33.1 %) and “use with caution in pregnancy” category (36 %). Among the contraindicated herbs used by women in Eastern Europe were Vaccínium vítis-idaéa (cowberry), Levisticum officinale (lovage) and Leonurus cardiaca (motherwort). Women in this region exclusively used these herbal medicines. Risk factors Several important maternal factors were found to be associated with the use of contraindicated herbal medicines in pregnancy; namely, working in the home, having a university education, not using folic acid and consuming alcohol. Despite our initial hypothesis that women would inadvertently use contraindicated herbal medicines based on either their own initiative or upon the recommendation from family or friends, we found that the recommendation to take a contraindicated herbal medicine was three times more likely to be from a HCP than an informal source. Factors associated with the use of contraindicated herbal medicines in pregnancy are summarized in Table 2. Table 2 Table 2 Factors associated with the use of contraindicated herbal medicines in pregnancy Go to: Discussion To our knowledge, this is the first study to explore the safety of herbal medicines use in pregnancy across several regions of the world. Several of the findings are of clinical importance. Firstly, it is reassuring that the majority of women reported using herbal medicines that were considered safe for use during pregnancy. On the other hand, it is of concern that there still are a substantial number of women using potentially harmful herbal medicines during pregnancy. This is especially worrisome since health care professionals more frequently recommended use of these herbal medicines than other sources. Most of the contraindications were because of evidence of being emmenagogues and/or uterine stimulants (Caulophyllum thalictroides (blue cohosh), Cimicifuga racemosa (black cohosh), Capsella bursa-pastoris (shepherd’s purse)) which could result in negative pregnancy outcomes (Table 1). Secondly, it is clear that there are regional differences in herbal traditions. For example, a substantial proportion of women from Eastern Europe exclusively used three herbal medicines. While, the largest group of contraindicated herbal medicine users were those from North America. Clinicians and health care personnel in care of pregnant women in countries with high use of contraindicated herbal medicines in pregnancy should evaluate these findings. Clearly, this represents an opportunity for further detailed investigations with respect to both maternal and neonatal outcomes. Thirdly, this study highlights the urgent need for more data on safety and efficacy of herbal medicine during pregnancy. A recent systematic review on the use of herbal medicine in pregnancy could only identify 14 RCTs evaluating five different herbal medicines [26]. The most studied herbal medicine is Zingiber officinale (ginger) with 10 individual studies. The remaining other herbal medicines were Vaccinium oxycoccus/macrocarpon (cranberry), Hypericum perforatum (St. John’s wort), Rubus idaeus (raspberry) and Allium sativum (garlic) with one study each. This lack of depth in evidence represents a challenge to health care personnel caring for pregnant women. In several instances, where there was no information on the impact of the herbal medicine in human pregnancy, animal studies were used to determine the classification (see references in Additional file 1: Table S1a-d). However, results from animal studies may not be directly extrapolated to humans [20, 27, 28]. Challenges classifying herbal safety in pregnancy This study also presents a practical illustration of how challenging it is to classify safety of herbal medicine. The sources we used gave, at times, different classification recommendations representing different regional traditions or points of view. For example, of the herbal medicines that were included in this study and evaluated by the European Medicines Agency, only two herbal medicines have the status of “may be considered for use” in pregnancy Psyllii semen/Plantago ovata (psyllium) [29] and Salix alba (white willow) [30]. This legislative approach is not reflected in the classifications presented here. Further, traditionally, herbal medicines are often used in combination. However, existing literature sources do not classify combinations of herbal medicines. Although we classified women using several herbals according to the most harmful herbal used, we did not considered potential synergistic effects or interaction between the herbals. With the increasing prevalence of the use of herbal medicines and their availability as non-prescription products designed for self-selection there is a need for high quality information on the safety in pregnancy of both single and combination herbal medicines. Discussion on specific herbals The herbal medicine, Rubus idaeus (raspberry) is classified as “use with caution” in pregnancy despite its long history of traditional and widespread use by women in pregnancy [31]. This classification was done, in part, to highlight the high need for additional research on this herbal medicine and its use in pregnancy. The evidence for its use is currently limited to one RCT and an observational study [26, 31]. Finding from these studies suggest that the intake of raspberry did not have negative fetal or pregnancy outcomes; however, its use did not demonstrate any benefits [31]. With respect to the use of Vaccinium oxycoccus/macrocarpon (cranberry), its’ use was classified as “safe for use” in pregnancy. Cranberry is another frequently used herbal medicine for both urinary tract infection (UTI) prophylaxis and treatment [13, 26]. There is evidence from studies with non-pregnant patients that suggests that Cranberry can be helpful for reducing UTI recurrence [26, 32, 33]; however, the evidence to support its effectiveness in UTI treatment in pregnancy is weak [34]. No negative fetal or pregnancy outcomes were identified in a large retrospective cohort study involving 68522 women, of whom 919 used cranberry in pregnancy [35]. However, as UTIs may have negative effects on pregnancy outcomes [36], it is essential that antibiotics are used to treat UTIs and that herbal medicines are not used as alternative to conventional prescribed medication for UTIs in pregnancy. The herbal medicines Leonarus cardiaca (motherwort) and Levisticum officinale (lovage) are two herbal medicines that were classified as contraindicated for use in pregnancy. The rationale for this classification is based on the emmenagogue action of these herbal medicines [21, 37]. An emmenagogue is an herbal medicine that stimulates menstrual flow and activity [38]. Sources refer also to motherwort as a nervine (having a potentially beneficial effect on the nervous system [38]) and as a cardiotonic (having observable beneficial action on the heart and blood vessels [38]), while lovage also acts as a bitter (having an impact on the digestive system [38]) which can help to address indigestion and anti-spasmodic actions [38]. Both of these herbal medicines were used by women in Russia only and used by 11 % of herbal users in Russia. The scope of the study did not include the collection of fetal and pregnancy outcomes, dosage, nor frequency of use data, so whether the classification of both of these herbal medicines as contraindicated in pregnancy is appropriate requires further study. Strengths and Limitations This was the first study that uniformly collected information regarding the use of herbal medicines in pregnancy and attempted to classify the herbal medicines used, bringing together perspectives from several sources and countries into the classification. The use of a web-based recruitment strategy enabled us to reach a wide segment of the birthing population. Further, we sought to determine the maternal risk factors for the use of contraindicated herbal medicines, highlighting the need for additional education and research for healthcare practitioners with respect to herbal safety in pregnancy. There are some limitations to bear in mind regarding this study. Firstly, women were invited to participate via banners posted on pregnancy-related websites. The study design implied no probability sampling of the target population; respondents were those women who happened to have internet access, visited the website(s) where the invitation was posted, and decided to participate in the survey. Hence, the possibility of a self-selection bias cannot be ruled out. On the other hand, the anonymous web-based approach may be especially appropriate for childbearing-age women residing in countries with high internet penetration rates, as it was in this study (range 60 to 97 %) [39]. Since women have been shown to use the internet in a very high extent during pregnancy to search for pregnancy-related information [40, 41] this population is probably a suitable target group in e-epidemiology. Recent epidemiological studies indicate the validity of web-based recruitment methods [42, 43]. We previously assessed the representativeness of the study participants to the general birthing populations in each study and found that the women in the study had higher education and were slightly more often primiparous than the general birthing populations in the various countries [44]). Moreover, since an online questionnaire was used, it is not possible to calculate a conventional response rate. However, of the women who indicated their willingness to participate, 98.6 % completed the questionnaire. As in all studies based on self-reported data, the accuracy of our data depends on the accuracy of maternal reporting. Our estimates are likely to be an underestimation of the true prevalence of herbal medicine use in pregnancy as we were dependent upon women to recall which herbal medicines were taken and herbal names were not specifically queried in the questionnaire. We did not capture the plant part, type of extract, dose, dose form or, duration of the use of the herbal medicine in pregnancy. Capturing this data would have permitted more extensive evaluations of contraindication or caution for use. Our results should be interpreted with these strengths and limitations in mind. Go to: Conclusion Based on the current literature the majority of women in this study used an herbal medicine that was classified as safe for use in pregnancy. Women who reported taking a contraindicated herb were more likely to have been recommended this use by an HCP rather than informal source(s), indicating an urgent need for more education among HCPs. The paucity of human studies on herbal medicines safety in pregnancy stands in stark contrast to the widespread use of these products among pregnant women. Go to: Acknowledgements The study was supported by the Norwegian Research Council (grant no. 216771/F11). We thank OTIS, all website providers who contributed to the recruitment phase and our national collaborations (Twigg MJ, Zagorodnikova, K, Mårdby AC, Moretti ME, Drozd M, Panchaud A, Hameen-Anttila K, Rieutord A, Gjergja Juraski R, Odalovic M, Kennedy D, Rudolf G, Juch H, Passier JLM, Björnsdóttir I). We would also like to thank Gro Cecilie Havnen, MSc for her contribution in the discussion of the safety classification of the herbal medicines. We are grateful to all the participating women who took part in this study. Go to: Abbreviations aOR adjusted odds ratio ATC anatomical therapeutic chemical CI confidence interval GEE generalized estimating equation HCP healthcare practitioner RCT randomized controlled trial UTI urinary tract infection Additional file Additional file 1:(1.3M, pdf) Detailed listing of herbal medicines used according to their safety classification. (PDF 1342 kb) Go to: Footnotes Competing interests The authors have no conflicts of interest to declare. Gideon Koren held the Research Leadership for Better Pharmacotherapy During Pregnancy and Breastfeeding (Sickkids Hospital) and the Ivey Chair in Molecular Toxicology (University of Western Ontario). Authors’ contributions HN and AL conceived the idea for the study and participated in its design and coordination. DAK analyzed the data, and drafted the manuscript. AL participated in the data analysis. GK, AL, and HN critically reviewed the manuscript and contributed intellectual content. All authors read and approved the final manuscript. Go to: Contributor Information D. A. Kennedy, Phone: +1-4168137283, Email: ac.oohay@dnydennekd. A. Lupattelli, Email: on.oiu.isamraf@illettapul.alegna. G. Koren, Email: moc.oohay@0002_puidig. H. Nordeng, Email: on.oiu.isamraf@gnedron.e.m.h. Go to: References 1. Dennis J. 2012 international herb & botanical trends. Nutraceutical World. 2012. http://www.nutraceuticalsworld.com/issues/2012-07/view_features/2012-international-herb-botanical-trends. 2. Hall HG, Griffiths DL, McKenna LG. The use of complementary and alternative medicine by pregnant women: a literature review. Midwifery. 2011;27(6):817–824. doi: 10.1016/j.midw.2010.08.007. [PubMed] [Cross Ref] 3. Frawley J, Adams J, Sibbritt D, Steel A, Broom A, Gallois C. Prevalence and determinants of complementary and alternative medicine use during pregnancy: results from a nationally representative sample of australian pregnant women. Aust N Z J Obstet Gynaecol. 2013;53(4):347–352. doi: 10.1111/ajo.12056. [PubMed] [Cross Ref] 4. Holst L, Wright D, Haavik S, Nordeng H. Safety and efficacy of herbal remedies in obstetrics-review and clinical implications. Midwifery. 2011;27(1):80–86. doi: 10.1016/j.midw.2009.05.010. [PubMed] [Cross Ref] 5. Nordeng H, Bayne K, Havnen GC, Paulsen BS. Use of herbal drugs during pregnancy among 600 Norwegian women in relation to concurrent use of conventional drugs and pregnancy outcome. Complement Ther Clin Pract. 2011;17(3):147–151. doi: 10.1016/j.ctcp.2010.09.002. [PubMed] [Cross Ref] 6. Lapi F, Vannacci A, Moschini M, Cipollini F, Morsuillo M, Gallo E, Banchelli G, Cecchi E, Di Pirro M, Giovannini MG, Cariglia MT, Gori L, Firenzuoli F, Mugelli A. Use, attitudes and knowledge of complementary and alternative drugs (cads) among pregnant women: a preliminary survey in Tuscany. Evid Based Complement Alternat Med. 2010;7(4):477–86. [PMC free article] [PubMed] 7. Moussally K, Oraichi D, Berard A. Herbal products use during pregnancy: prevalence and predictors. Pharmacoepidemiol Drug Saf. 2009;18(6):454–461. doi: 10.1002/pds.1731. [PubMed] [Cross Ref] 8. Louik C, Gardiner P, Kelley K, Mitchell AA. Use of herbal treatments in pregnancy. Am J Obstet Gynecol. 2010;202(5):439.e431-439.e410. [PMC free article] [PubMed] 9. Holst L, Wright D, Nordeng H, Haavik S. Use of herbal preparations during pregnancy: focus group discussion among expectant mothers attending a hospital antenatal clinic in Norwich, UK. Complement Ther Clin Pract. 2009;15(4):225–229. doi: 10.1016/j.ctcp.2009.04.001. [PubMed] [Cross Ref] 10. Nordeng H, Havnen GC. Impact of socio-demographic factors, knowledge and attitude on the use of herbal drugs in pregnancy. Acta Obstet Gynecol Scand. 2005;84(1):26–33. doi: 10.1111/j.0001-6349.2005.00648.x. [PubMed] [Cross Ref] 11. Pallivalappila AR, Stewart D, Shetty A, Pande B, McLay JS. Complementary and alternative medicines use during pregnancy: a systematic review of pregnant women and healthcare professional views and experiences. Evid Based Complement Alternat Med. 2013;2013:10. doi: 10.1155/2013/205639. [PMC free article] [PubMed] [Cross Ref] 12. Warriner S, Bryan K, Brown AM. Women’s attitude towards the use of complementary and alternative medicines (cam) in pregnancy. 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Mills SY, Bone K. The essential guide to herbal safety. St. Louis, Mo: Elsevier Churchill Livingstone; 2005. 19. European medicines agency [http://www.ema.europa.eu/ema/]. Last accessed: 05 Sep 2014. 20. Gardner ZE, McGuffin M, American Herbal Products Association . American herbal products association’s botanical safety handbook. 2. Boca Raton: American Herbal Products Association, CRC Press; 2013. 21. Romm AJ. Botanical medicine for women’s health. St. Louis, Mo: Churchill Livingstone/Elsevier; 2010. p. 694. 22. Natural medicine In: Natural Medicine. Somerville, MA: Natural Medicine. [Published 2015; Accessed 17 Jul 2015]. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/. 23. Duke JA, Duke JA. Handbook of medicinal herbs. 2. Boca Raton, FL: CRC Press; 2002. 24. Gruenwald J, Brendler T, Jaenicke C. Pdr for herbal medicines. 4. Montvale, NJ: Medical Economic Company; 2000. 25. Hardin JW, Hilbe J. Generalized estimating equations. 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Diabetes Destiny in our Hands: Achieving Metabolic Karma

Indian J Endocrinol Metab. 2017 May-Jun; 21(3): 482–483. doi: 10.4103/ijem.IJEM_571_16 PMCID: PMC5434738 Sanjay Kalra, Jignesh Ved,1 and Manash P. Baruah2 Department of Endocrinology, Bharti Hospital, Karnal, Haryana, India 1Department of Medical Affairs, Boehringer Ingelheim, Mumbai, Maharashtra, India 2Department of Endocrinology, Excel Hospitals, Guwahati, Assam, India Address for correspondence: Dr. Sanjay Kalra, Department of Endocrinology, Bharti Hospital, Karnal, Haryana, India. E-mail: moc.liamg@lnkedirb Abstract Karma is the ancient Indian philosophy of cause and effect, which implies that an individual's intentions, and actions, both have consequences. None can escape the consequences of one's actions. Applying the principle of karma to medicine and healthcare, the significance of optimal and timely interventions at various stages of disease, may be realized. A holistic approach to metabolic control in diabetes translates into improved clinical outcomes, as evident from the result of STENO-2, EMPA-REG OUTCOME, or LEADER trials. The principle of karma in the management of diabetes may have implications at the transgenerational level during pregnancy and nursing, at the individual patient-level based on phenotype, and at the community level in preventive medicine. The concept of metabolic karma can be used as an effective motivational tool to encourage better health care seeking behavior and adherence to prescribed interventions. Keywords: Gestational diabetes mellitus, glycemic legacy, metabolic memory, type 2 diabetes Go to: Introduction “It is not in the stars to hold our destiny but in ourselves.” -William Shakespeare Go to: The Legacy Effect The concept of glycemic legacy or metabolic memory is well understood by physicians, who aim to achieve optimal long-term therapeutic outcomes by achieving tight glucose control. This concept has been extended to other spheres of management, with vascular legacy being noted for diverse interventions such as lifestyle modification, lipid-lowering therapy, and debatably for antihypertensive therapy.[1] Go to: The Philosophy of Karma Indian philosophy suggests the existence of “karma” in life. Loosely translated as destiny or fate, karma (Sanskrit) or kamma (Pali) is defined as the sum of a person's actions in this and previous states of existence, and viewed as deciding their fate in future existences. In Hindu, Buddhist and Tao philosophy, karma serves the purpose of serving as an etiology or cause of various experience of life. It also serves as a strong motivator, ensuring “ethical” conduct as prophylaxis against future suffering. Karma is used not only as a goal or target but also as the sum of actions executed to achieve this aim. It contrasts with a similar Sanskrit word, “kriya” which describes just the activity, along with steps and effort in action, but does not encompass the ethical nature, or outcome, of such activity. Go to: Karma in Medicine Karma suggests that one's own actions lead to various states of existence. Some of these may be modifiable, while others may not. This is similar to what we encounter in modern medical research. Some determinants of health may be genetic in nature, i.e., carried over from a “previous existence.” Yet others may be environmental or related to the current life lifestyle. Thus, the concept of karma can straddle the entire spectrum of modern noncommunicable disease, including diabetes. Go to: Karma in Diabetes Thomas has used the term “metabolic karma” to explain the phenomenon of glycemic legacy in diabetes.[2] We appreciate his use of Sanskrit, India's ancient language, to convey this meaning in a wholesome manner. Karma is not only the sum of all action, but also includes the intent behind these actions as well. From a diabetes care perspective, we would take this to mean consideration of targets, and the techniques for achieving such targets. Timely and optimal interventions, aimed at achieving recommended metabolic targets, do contribute to a sustainable improvement in overall outcomes of diabetes. The holistic approach of metabolic karma encompasses diagnostic as well as therapeutic considerations, at various stages of disease. The different dimensions of preventive medicine,[3] as enlisted in Table 1, nicely exemplify a holistic approach to metabolic karma. Table 1 Table 1 Holistic approach to metabolic karma: Learnings from preventive medicine Multiple trials have proved that appropriate glucose-lowering, blood pressure, and comprehensive management can improve long-term outcomes. The benefits accrued by such management strategies are maintained even when the initial difference in control is lost. Most recently, the STENO2 study reported an increased survival of 7.9 years, if comprehensive control was instituted, over a follow-up of 22 years. The words “metabolic karma,” therefore, are more appropriate than the phrase “glycemic karma.”[4] As a corollary, use of drugs associated with poor efficacy or appropriateness, poor tolerability, high risk of hypoglycemia, or high glycemic variability, can be termed as “bad pharmacological karma” or suboptimal therapeutic karma. The use of an inappropriate glucose-lowering drug, or an unsuitable insulin regime, to achieve an unwarranted target, is bad “glycemic karma,” which will, in turn, lead to suboptimal outcomes or bad clinical karma. Go to: Positive Outlook However, good metabolic karma can be achieved in real world experience. This can be done by timely institution of a healthy lifestyle, glucose lowering, blood pressure lowering, lipid-lowering, and weight lowering drugs if required. The results of EMPA REG OUTCOME and LEADER trials suggest that appropriate choice of drugs (empagliflozin and liraglutide, respectively) does influence long-term outcomes.[5,6] This supports the thought that Diabetes Destiny can be modified by appropriate “metabolic kriya.” Go to: Transgenerational Karma Metabolic or glycemic karma may affect the unborn generation as well. Women who can prevent or manage their gestational diabetes mellitus effectively give birth to healthier newborns. On the contrary, children of women with uncontrolled diabetes during pregnancy have poorer long-term outcomes. Thus, metabolic karma has a transgenerational impact, similar to the transexistential persistence of karma. Go to: Transindividual Karma As diabetes care professionals, it is our responsibility to achieve good metabolic control in every person with diabetes. The phenotypic characteristics of each individual patient, including the demographic, glycemic, cardiometabolic, or renal phenotypic characteristics, have considerable clinical implications. The actions we undertake, after considering all these factors, are our karma. Good karma (intention and action), performed by us, will benefit not only the person with diabetes, and the community at large, but will also impact and transform our karma (fate or destiny) in a positive manner. Thus, every correct clinical decision that we make has a multifold cascading effect on karma, both ours and the patient's. Go to: Summary The concept of karma is an appealing one. It helps understand the advantages of achieving tight glycemic and metabolic control in persons with diabetes, using appropriately individualized patient-centric therapy. Good karma can be gained within the same life, may transfer to the unborn offspring of antenatal women with diabetes, and also accrues to the diabetes care professional who works sincerely to control the diabetes endemic. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Go to: References 1. Jermendy G. Vascular memory: Can we broaden the concept of the metabolic memory? Cardiovasc Diabetol. 2012;11:44. [PMC free article] [PubMed] 2. Thomas MC. Glycemic exposure, glycemic control, and metabolic karma in diabetic complications. Adv Chronic Kidney Dis. 2014;21:311–7. [PubMed] 3. Kalra S, Sreedevi A, Unnikrishnan AG. Quaternary prevention and diabetes. J Pak Med Assoc. 2014;64:1324–6. [PubMed] 4. Gæde P, Oellgaard J, Carstensen B, Rossing P, Lund-Andersen H, Parving HH, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia. 2016;59:2298–307. [PMC free article] [PubMed] 5. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28. [PubMed] 6. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22. [PMC free article] [PubMed] Articles from Indian Journal of Endocrinology and Metabolism are provided here courtesy of Wolters Kluwer -- Medknow Publications