The Effects of Oral Challenges on Antibiotic Prescribing Practices for Acute Bacterial Sinusitis - Juniper Publishers

Journal of Otolaryngology - Juniper Publishers

Keywords: Sinusitis; Antibiotics; Antibiotic allergies; Oral challenges; Bacterial rhinosinusitis

Abbreviations: CPT: Procedure Code Terminal; PPO: Preferred Provider Organization; HMO: Health Maintenance Organization; CDHP: Consumer Directed Health Plan; HDHP: High Deductible Health Plan; OR: Odds Ratios; CI: Confidence Intervals; EMR: Electronic Medical Record

Introduction

Beta-lactams, antibiotics that irreversibly inhibit the transpeptidation needed for bacterial cell wall synthesis, have been used for decades to treat a number of infections. Bacterial rhinosinusitis is most commonly caused by Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenza [1]. A rhinosinusitis diagnosis requires purulent nasal discharge accompanied by facial pressure/pain/fullness and/or congestion of the nasal pathways [2]. Bacterial etiology is usually considered more likely over viral etiology if symptoms fail to improve within ten days or if there is an acute worsening of symptoms after prior improvement within the first ten days [1,2]. In the case of acute bacterial rhinosinusitis, the first-line treatment in adults is a five-to-seven-day course of high-dose amoxicillin-clavulanate [3].

Despite their broad utility for the treatment of rhinosinusitis among many other medical conditions, the use of beta-lactam antibiotics is often limited by the presence of penicillin allergy labels in patient medical records. In the United States, about 8% of the population report a penicillin allergy history; in practice, however, less than five percent of that group will acutely react to a full-dose oral challenge [4]. Several reasons may account for this over-estimated burden of penicillin allergy history. First, data shows that three-quarters of penicillin allergy labels are acquired before three years of age [5]. Many of these unnecessary labels are attributed to rashes, which are common features of many of the viral infections that affect the pediatric population [5]. Additionally, penicillin allergies tend to wane with time. Over ten years, for example, 80% of people with reaction histories to penicillin will no longer be allergic [6].

Given the prevalence of beta-lactam allergy labels and the well-defined detriments of carrying a penicillin allergy in one’s medical record, we sought to evaluate the impact of oral challenges on antibiotic prescribing practices for the treatment of acute bacterial sinusitis since first-line therapy is amoxicillin with clavulanic acid [3]. An oral challenge is a procedure commonly performed by an allergist in order to determine whether or not a patient is truly allergic to food, or medication in the case of this study. It specifically entails administering the substance in question in increasing amounts to patients while closely monitoring them for signs of an allergic reaction and is considered successful if the patient can tolerate it without difficulty. We hypothesized that drug oral challenges with subsequent antibiotic allergy delabeling increased the use of beta-lactam antibiotics for the treatment of acute bacterial sinusitis.

Methods

We performed a retrospective analysis using data from 2013 to 2018 from the Truven Health MarketScan Commercial Claims and Encounters database (hereby referred to as MarketScan). The database consists of reimbursed healthcare claims that include individual-level data of patients covered by diverse private insurance plans across all 50 US states and covers approximately 50 million privately insured individuals every year [7]. MarketScan (Cambridge, MA, USA) has information covering all insurance claims such as inpatient/outpatient claims, prescription drug claims, and other health care resource utilization claims. We included patients with no food allergy aged 18-64 who had at least one inpatient or outpatient medical claim for diagnosed acute sinusitis (using International Classification of Diseases, Ninth and Tenth Revision [ICD-9/ICD-10] code 461 and J01, respectively) from 2013 to 2018. Patients with food allergies were excluded because MarketScan is unable to differentiate food oral challenges from drug oral challenges.

Furthermore, the presence of a penicillin allergy was not an inclusion criterion. The comparison groups were acute sinusitis patients who received oral challenge (Procedure code Terminal (CPT) 95076) compared with those who did not receive oral challenge. Each participant with oral challenge was matched to three participants without oral challenge, according to sex and year of birth (Figure 1). The main outcome of interest was the receipt of a first-line antibiotic (amoxicillin and amoxicillin/ clavulanic acid) within 30 days after the index date of an acute sinusitis diagnosis. Given the lack of statistical power caused by a small sample size, we were not able to examine other secondary outcomes such as infection with Clostridium difficile, multi-drug resistant organisms, and death. Demographic variables included age, sex, place of residence, and US regions. Another covariate of interest was insurance health plan types such as preferred provider organization (PPO), health maintenance organization (HMO), consumer directed health plan (CDHP), and high deductible health plan (HDHP).

SAS statistical software version 9.4 (SAS Institute, Cary, NC, USA) was used to conduct all statistical analysis using a two-tailed P value of < 0.05 as the significance level. We first examined the distribution of covariates between participants receiving oral challenges and those without. A multivariable analysis was conducted using conditional logistic regression models that accounted for matching variables, such as age and sex, and adjusting for place of residence (urban/rural) in US regions to estimate the adjusted odds ratios (aOR) and their 95% confidence intervals (CI). Crude OR was estimated using unadjusted conditional logistic regression that accounted for matching variables (age and sex). This study was approved by The Pennsylvania State University Institution Review Board.

Results

A total of 7,768 patients with bacterial sinusitis were included in the study (Table 1). Of these patients, 1,942 patients received an oral challenge, while 5,826 did not receive an oral challenge (Table 1). When considering patients who received the first-line beta-lactam-containing antibiotics, 6.3% (n=123) of the patients had received an oral challenge (Figure 2). This was significantly higher compared to the 5.1% (n=298) of patients who did not receive an oral challenge (Figure 2). When considering the converse, 93.7% (n=1,819) of patients who had received an oral challenge did not receive first-line antibiotics (Figure 3a). Additionally, 94.9% (n=5,528) of patients in the group without the oral challenge did not receive first-line antibiotics (Figure 3b).

Regardless of oral challenge status, however, an overwhelming majority of patients did not receive first-line antibiotics, which we assume is secondary to failure to remove the penicillin allergy designation versus inappropriate antibiotic prescribing practices.

Discussion

Data obtained from our research utilizing MarketScan demonstrate that patients who received an oral challenge were statistically more likely to receive the first-line beta-lactamcontaining antibiotics for the treatment of acute bacterial sinusitis compared to those who did not receive an oral challenge. Another key finding of this study was that, regardless of oral challenge status, first-line beta-lactam-containing antibiotics are not being frequently prescribed. While the data cannot provide any explanation for this finding, there may be a few reasons. First, the way a drug reaction is documented into the electronic medical record (EMR) can influence prescribing practices. A study conducted in Australia found that over 20% of reports of adverse drug reactions did not even include a description of the reaction [8]. Additionally, about 10% of the reports described as a penicillin allergy were actually more consistent with a drug intolerance, such as gastrointestinal symptoms [8].

Finally, a study conducted in a pediatric population in Saudi Arabia found that over 35% of antibiotic allergy descriptions in the EMR were “poor” [9]. From the perspective of antimicrobial stewardship, the presence of drug allergy labels, especially those that may be inaccurate, can be detrimental to both patients and to the healthcare system. Disadvantages of using alternate antibiotics include higher treatment costs, greater severity of side effects, and decreased treatment efficacy [5]. Additionally, a cohort study found that patients with a penicillin allergy label had significantly longer hospital stays and increased rates of infections with methicillin-resistant Staphylococcus aureus, Clostridium difficile, and vancomycin-resistant Enterococcus compared to those without a penicillin allergy label [10]. One study found that the presence of drug allergy labels was associated with increased use of quinolones and carbapenems and an overall increased rate of inappropriate use of antibiotics [11].

In the case of bacterial rhinosinusitis, second-line antibiotic treatments include doxycycline or respiratory fluoroquinolones (e.g., levofloxacin) [1,3]. The use of broad antibiotics such as levofloxacin can theoretically increase rates of antimicrobial resistance. Prior research found that S. pneumoniae-containing sputum samples had higher rates of antibiotic resistance (though not shown to be statistically significant) in patients with penicillin allergies compared to patients without penicillin allergies [12]. The presence of the penicillin drug allergy label in combination with a lack of meaningful reaction descriptions would likely deter clinicians from prescribing those antibiotics. The previously mentioned Australian study additionally found that the vast majority of the reaction descriptions could have warranted further evaluation and that about half of the documented histories appeared consistent with low-risk penicillin reactions [8]. Despite the demonstrated opportunities for further evaluation by allergists, the specialty is underutilized. For example, the study conducted in Saudi Arabia found that under 40% of the patients with concern for antibiotic allergies were referred for further evaluation [9].

Additional research showed that over 80% of research participants did not even know that penicillin drug allergy testing was available [13]. While these data show the potential impact of successful oral challenges, there are a number of limitations to the study. The most significant limitation was the small sample size of patients in the oral challenge group who received firstline antibiotics. A significant contributing factor to this limitation lies within the study design itself. As mentioned, the data was obtained through the use of MarketScan, which is limited to private insurance claims. As a result, the results are not directly generalizable to other kinds of insurance such as Medicare and Medicaid. Additionally, a diagnosis of food allergy was excluded from the patient population since MarketScan is unable to differentiate food oral challenges from drug oral challenges, subsequently reducing the generalizability of the provided data.

Finally, the CPT codes precluded us from being able to determine the identity of the drugs for which the oral challenges were intended or the outcomes of the oral challenges (e.g., whether or not the allergy label was removed from the medical record). Given how common beta-lactam allergies are, however, it is likely that the majority of the oral challenges were conducted for this particular class of medications. It should also be noted that MarketScan is unable to identify patients with a penicillin allergy label. Since the population studied is not definitively classified as having a penicillin allergy label, the reported difference in betalactam use for the treatment of acute bacterial rhinosinusitis between the group that has received an oral challenge versus the group that has not received an oral challenge could be an overestimation. While additional research is needed to better delineate the study population, the data interestingly highlights the lack with which these first-line antibiotics are used for acute bacterial rhinosinusitis.

Future work can focus on expanding the study population to include a broader array of insurance plans like Medicare and Medicaid. Given that most of the penicillin allergy labels are acquired during childhood, future studies might also be expanded to include the pediatric population. Such measures would likely increase sample size while broadening generalizability. Additionally, the types of antibiotics that are prescribed in place of these beta-lactams can also be examined. Finally, additional valuebased research can be conducted in order to further quantify the overall cost savings of drug oral challenges relative to the healthcare expenses associated with the use of alternative, less appropriate antibiotics.

While our study helps demonstrate the potential benefits of oral challenges, it appears that first-line antibiotics remain under-utilized even when allergy is excluded. In order to rectify this situation, further awareness (e.g., through the education of medical providers at all stages of training and practice) of the importance of penicillin allergy testing, penicillin challenges, education of the patient, and complete removal of a penicillin allergy label are crucial for promoting antimicrobial stewardship and improving health outcomes.

To Know more about  Global Journal of Otolaryngology 

Click here: https://juniperpublishers.com/gjo/index.php

To Know more about our Juniper Publishers

Click here: https://juniperpublishers.com/index.php

Female Sexual Dysfunction and a Plant-Based Diet - Juniper Publishers

 

Gynecology and Womens Health - Juniper Publishers

Abstract

Female Sexual Dysfunction (FSD) is a multi-causal and a multi–dimensional medical problem, comprising anatomical, physiological, psychological as well as social-interpersonal components, that adversely affects physical health and emotional well-being. A meta study showed that 41% of women had some level or form of Female Sexual Dysfunction. FSD is especially prevalent among women with chronic diseases such as metabolic syndrome, type 2 diabetes, hypertension, dyslipidemia and coronary artery disease, Hashimoto’s thyroiditis, Graves’ disease and Parkinson’s disease. A plant-based diet can lower the risk of Female Sexual Dysfunction (FSD) by substantially by lowering the risk of several pathologies that are risk factors for it.

Female sexual function, especially arousal, is significantly affected by genital vascular impairment which can lead to vaginal dryness and impaired genital engorgement mediated arousal. The plant-based diet is a safe and effective prophylaxis and treatment for hypercholesterolemia and atherosclerosis. The Mediterranean diet is a plant-strong diet that results in better female sexual function in a dose-dependent manner, regardless of menopausal and metabolic syndrome status. The plant-based diet has the potential to be at least as good a treatment of FSD. A plant-based diet has the significant advantage of having no contraindications or adverse reactions, and is an affordable prophylaxis for all patients over the long-term.

Keywords: Atherosclerosis; Clitoris; Dyslipidemia; Dyspareunia; Orgasmic disorder; Vaginal atrophy; Vaginismus; Vegan; Vegetarian

Abbreviations: FSD: Female Sexual Dysfunction; MD: Mediterranean Diet; NO: Nitric Oxide

Introduction

A healthy and satisfying experience of sexuality is often an important component of overall well-being for women (defined for the purposes of this article as individuals who have female genitalia), associated with increased life satisfaction, higher perceived and objective health status, and even increased longevity [1-4].

In addition, several significant health benefits have been identified for women related to regular sexual activity. These include postponement of natural menopause (and the subsequent hypoestrogenism) [5], reduced frequency of hot flushes during menopause [6], better vaginal health and less vaginal atrophy in post-menopausal women [7], better cognitive function in older adult women, [8] and a reduced risk of subsequent new severe disabilities in disabled women living with their spouse [9]. Some studies also showed that the thresholds for pain tolerance and pain detection were significantly increased when paired with genital self-stimulation, and considerably more so when achieving orgasm [10]. Female sexual function is a complex process coordinated by the neurological, vascular and endocrine systems [11]. Female Sexual Dysfunction (FSD) is a multi-causal and a multi–dimensional medical problem, comprising anatomical, psychological, physiological, as well as social-interpersonal components, that adversely affects physical health and emotional well being [12-16]. FSD is a general term comprising several sexual health concerns that can be distressing for patients, including female sexual interest/arousal disorder, female orgasmic disorder, and genito-pelvic pain/penetration disorders, including dyspareunia and vaginismus. [17,18].

Our understanding of female sexuality was only first formally addressed roughly 50 years ago. During this period and even today, the treatment of FSD has primarily focused on psychosocial/cultural therapy, and highlights that our limited knowledge is reflective of the inadequate treatment options available. Due to the complexity of FSD, a multifaceted approach, addressing neurobiological, vasoactive, hormonal as well as psychosocial/cultural aspects is necessary [19]. This article addresses only the physical etiological factors and symptoms.

Epidemiology

A 2016 systematic review and meta-analysis assessed the prevalence rate of female sexual dysfunction in 215,740 reproductive-age women worldwide and found the 41% of these women report some form of female sexual dysfunction [20]. Dysfunction is especially prevalent in women with chronic health problems, including metabolic syndrome, hypertension, dyslipidemia, coronary heart disease, diabetes, overweight and obese body mass indices (BMIs), anxiety, and depression [3,21-28]. In patients with overt cardiovascular disease, FSD is even more prevalent [29]. Studies have shown a positive association between cardiovascular diseases and sexual dysfunction in females [30]. Diabetes, heart disease, urinary tract disorders, and chronic illness are also significant risk factors for female sexual dysfunction [31].

Pathophysiology

The first phase of the female sexual response, associated with neurotransmitter-mediated vascular smooth muscle relaxation, results in increased vaginal lubrication, wall engorgement and luminal diameter as well as increased clitoral length and diameter. Physiologically, healthy pelvic blood flow is necessary for vaginal lubrication. Normal blood pressure pushes a transudative fluid through capillaries, which ultimately coalesces at the vaginal surface epithelium [32,33]. This process relies on vessels being both patent and able to dilate effectively. Therefore, low atherosclerotic burden and sufficient nitric oxide (NO) activity are protective against sexual dysfunction [33].

Evidence shows that female sexual function, especially arousal, is significantly affected by genital vascular impairment, which can lead to FSD. Specific physiologic impairments of vasculogenic female sexual dysfunction include vaginal engorgement and clitoral erectile insufficiency. Orgasmic female sexual dysfunction may be related in part to vasculogenic impairment of the hypogastric-vaginal/clitoral arterial bed [34]. These syndromes exist when during sexual stimulation, abnormal arterial circulation into the vagina or clitoris, usually from atherosclerotic vascular disease, interferes with normal vascular physiologic processes [35].

Clinical symptoms may include delayed vaginal engorgement, diminished vaginal lubrication, dyspareunia, diminished vaginal sensation, diminished vaginal orgasm, diminished clitoral sensation or diminished clitoral orgasm [35]. Some chronic illnesses, such as vascular disease, diabetes mellitus, neurologic disease, and malignancy, can directly or indirectly impact sexual function [36,37]. Type 2 diabetes, hypertension, dyslipidemia, chronic kidney disease, atherosclerosis, and traumatic injury are associated with diminished vaginal and clitoral blood flow and impaired sexual functioning [38,39]. For many cardiometabolic risk factors and diseases, such as hypertension, diabetes, dyslipidemia and metabolic syndrome, an adverse impact on women’s endothelial function, as well as an association with FSD, has been recognized [40].

A doppler ultrasound study found that the Clitoral Pulsatility Index - an index of vascular resistance in the clitoris - was positively correlated with body mass index, waist circumference, insulin, triglycerides, total cholesterol, and low density lipoprotein cholesterol [41]. Women who have neurologic diseases such as Parkinson's disease or multiple sclerosis may also have FSD [42]. Chronic diseases affecting multiple systems, such as thyroid disease, may also have an impact upon the female sexual function [42].

Nutrition

Nutrition plays a significant role in cardiometabolic disease, suggesting one pathway through which diet influences sexual health in females in the form of vaginal dryness and impaired genital engorgement-mediated arousal [43,44]. Atherosclerotic risk is minimized with a nutrient-dense diet whose foundation is plant-based foods [45]. Meanwhile, nitric oxide (NO) can function best when inflammation is minimal [33]. [46]. A high-quality diet can be a source of antioxidants, and nitrate-rich foods can directly increase NO stores [47,48]. Diet can also indirectly support NO availability through preventing and ameliorating conditions associated with inflammatory and pro-oxidant activity, such as metabolic syndrome, obesity, and atherosclerosis [33,48,49].

A plant-based diet can help prevent and treat diseases such as type II diabetes and cardiovascular disease, and can be very efficacious [50,51]. For instance in one study, a plant-based diet was found to be twice as efficacious in treating type 2 diabetes as Metformin [52]. A plant-based diet can also lower cholesterol as much as lovastatin [53]. In addition, a plant-based diet can reduce the risk of other chronic diseases that have been shown to promote FSD, such as Graves’ disease and Hashimoto’s disease, rheumatoid arthritis, chronic kidney disease, and Parkinson’s disease [54-57]. With regards to specific foods, consumption of soy is associated with increased vaginal blood flow, lubrication, and vaginal collagen content and decreased dyspareunia [58-60].

Fruits such as apples, watermelon, and cacao have been linked to enhanced vascular and sexual health. Daily apple consumption is associated with improved vaginal lubrication and general sexual function [61]. Apples are high in polyphenols, other antioxidants, and phytoestrogens, which together support an anti-inflammatory and anti-atherosclerogenic environment. It can be expected that other fruits would perform similarly, though further research is needed to confirm this. Watermelon in particular supports vascular health via an additional distinct mechanism. It is a rich source of citrulline, which the body readily converts to the NO precursor, arginine [62-64]. Chocolate, derived from the cacao bean, is rich in flavonoids and has been found to increase NO-mediated vasodilation, with promise for supporting sexual function [65,66]. Although more research is needed, these findings on individual foods offer support and further insight into how a plant-based dietary pattern can benefit female sexual health.

Intervention Studies

The Mediterranean diet (MD) is the most widely studied dietary pattern in this context. The Mediterranean diet is characterized by a high intake of plant foods, a high intake of olive oil, a moderate intake of dairy products, zero to four eggs a week, with fish and poultry consumed in low to moderate amounts and red meat consumed in low amounts [15]. Multiple randomized controlled trials and cross-sectional studies have analyzed the long-term effect of the MD on reported sexual function. They find that adherence to this diet results in better sexual function in a dose-dependent manner, regardless of menopausal and metabolic syndrome status [67-69]. ther lifestyle changes may help improve sexual function. These modifications include physical activity, nutrition counseling, and adequate sleep, in addition to a healthy plant-based diet. [70].

Clinical Considerations

Based on cultural norms and biases, conversations about sex are sometimes thought of as taboo in American society and in many other cultures worldwide. This is especially true for women, and particularly when sex is for pleasure rather than reproductive purposes. Failure to have informative discussions about sex often leads to misperceptions about sex and sexuality, including a sense that pain or lack of interest in sexual activity is inevitable and nonmodifiable, which can also lead to women not seeking the care they need. In addition, women sometimes assume that older people do not, or should not, engage in sexual activity [71].

Several U.S. and international surveys of women recently found that the majority of women surveyed did not discuss their sexual health-related symptoms with their health care provider, and discomfort and/or embarrassment with having this discussion was often cited as a reason for avoiding the conversation [72-75]. This finding was consistent for women across different demographics, including age, sexual orientation, race/ethnicity, educational level, and relationship status [76]. Given this situation, physicians need to develop clinical strategies when approaching their patient. For instance, a physician treating a female patient with type 2 diabetes should inquire as to her sexual function since their patient might not raise the issue. One study showed that 54% of women with type 2 diabetes had FSD [77]. Identification of concurrent comorbidities and implementation of lifestyle changes will help improve overall health and may improve sexual function [78,79].

A plant-based diet has the significant advantage of having no contraindications or adverse reactions, and is an affordable prophylaxis for all patients over the long-term. When treating a patient with a plant-based diet it is important to titrate relevant medications, for pathologies such as hypertension and type II diabetes in particular, as the effects of the diet become evident. Patient compliance on plant-based diets has been good in almost all studies. The degree of compliance has often been very high. For instance, one study obtained a 99% compliance [39]. In a 22-week study 94% of subjects on a vegan diet were compliant [40]. In a somewhat longer study, 84% of the participants in each group completed all 24 weeks [41]. In studies of patients placed on plant-based diets for coronary artery disease, high compliance has been noted even over several years. For instance, one study of patients placed on a plant-based diet showed 89% compliance for 3.7 years [42].

Evidence suggests that vitamin D and iron deficiencies are risk factors for sexual dysfunction, and resolution of these deficiencies may well be therapeutic [80-83]. Vitamin D receptors exist on the uterus and ovaries, where they can influence steroidogenesis and testosterone aromatization, with consequent effects on sex hormone levels [84-86]. In iron-deficiency anemia, fatigue is thought to mediate the relationship between deficiency and sexual dysfunction [82]. Testing for vitamin D and iron deficiency may be considered as a relatively simple and low-cost addition to the workup for female sexual dysfunction.

Discussion

Quality of life has become a large concern of patients with a wide variety of diseases. Patients with diseases ranging from several forms of cancer to rheumatoid arthritis want a satisfying sex life. Patient and nonprofit organizations are offering patients general advice on how they can have sex while they are being treated. While many patients may be reluctant to ask their physician about FSD, they may well be appreciative of the physician asking them about it.

While a plant-based diet can’t treat aspects of FSD such as psychological and social factors, it does deserve a place in its treatment. It can be used as a monotherapy in some cases, or as an adjunct to other treatments. It may be especially helpful in treating vascular causes of FSD. It can also help prevent and can efficaciously treat several risk factors for FSD including atherosclerosis, metabolic syndrome, type 2 diabetes, dyslipidemia and chronic kidney disease. It has no adverse reactions or contraindications and is affordable. This becomes even more important considering that many patients with FSD have comorbidities.

A plant-based diet, and specifically manufactured plant-based foods, are now considered mainstream and several studies have shown good patient compliance. Increasing numbers of physicians are prescribing a plant-based diet for their patients in order to prevent and treat disease. Asking a patient about their diet, and prescribing a plant-based diet, should be considered a new standard of care for FSD.

To Know more about Journal of Gynecology and Womens Health 

Click here:  https://juniperpublishers.com/jgwh/index.php

To Know more about our Juniper Publishers

Click here: https://juniperpublishers.com/index.php

Recent Development of Laser Photo-Chemotherapy (LPC) for Bone Tumors-JuniperPublishers

Journal of Orthopedics and Rheumatology-Juniper Publishers

Introduction

Photodynamic therapies (PDT) have become increasingly popular in the adjuvant treatment of different tumor entities [1]. Chemotherapeutic agents, such as cisplatin may be used in combination with laser-induced thermal therapy (LITT) in an improvement to PDT, known as laser photo chemotherapy (LPC) [1,2]. Based on recent reports on the application of laser photo chemotherapy (LPC) on malignant bone cells under chemotherapeutic conditions with cisplatin or zolendronic acid, the authors feel compelled to describe in this mini-review some relevant aspects of such combined therapy as a potential therapeutic strategy for osteosarcoma [3].

Chemotherapy is regularly used for treating Ewing sarcoma and osteosarcoma, but it isn't often used for other bone cancers, like chordomas and chondrosarcomas, because they aren't very sensitive to chemo [4]. However, it can be useful for some special types of chondrosarcoma, like the dedifferentiated and mesenchymal lineag [3,4]. Anti-cancer agents are sometimes used for bone cancer that has spread through the bloodstream to the lungs and/or other organs [5]. The drugs mainly used for this condition include: Doxorubicin (Adriamycin®), Cisplatin, Carboplatin, Etoposide (VP-16), Ifosfamide (Ifex®), Cyclophosphamide (Cytoxan®), Methotrexate and Vincristine (Oncovin®) [3,5]. In this regard, a number of investigators have shown that some of the above anti-cancer agents are likely candidates for light and or heat activation in cancer cells, as laser photo chemotherapy (LPC) has been consistently used for treatment of retinoblastoma since 1996 [3,6-8].

The propensity for survivors of heritable retinoblastoma to develop second primary osteosarcomas at substantially greater frequency than either the general population or survivors of nonheritable retinoblastoma is well known [9,10]. There is some molecular genetic evidence that the development of these two disparate tumor types involves specific somatic loss of constitutional heterozygosity for the region of human chromosome 13 that includes the RB1 locus [11]. In regards to chemotherapy a number of investigators have shown that anthracyclines and cis-platinum are likely candidates for light or heat activation in cancer cells [1,2,12]. In this sense, Heyman et al. [3] have recently reported a significant decrease of cell bioviability and histomorphological alterations suggestive of higher apoptical activity in osteosarcoma cell lines (Saos-2) treated by cisplatin and zolendronic acid followed by diode laser irradiation, when compared with non-irradiated cells. Therefore, LPC outcomes for retinoblastoma may suggest that a conceptual approach towards osteosarcoma treatment may be possible based on recent clinical studies on combined therapy [12,13-18].

Photo chemotherapy with lasers is an alternative therapy which consists of using a monochromatic light delivered via external irradiation or via interstitial fiber optics to enhance the "killing" threshold in tumors containing light and/or heat-sensitive anticancer agents [12]. The development of photoactivatable pro-drugs of platinum-based antitumor agents is aimed at increasing the selectivity and thereby lowering toxicity of this important class of antitumor drugs [19-21]. Hence, laser photo chemotherapy explores three distinct mechanisms of antitumor action: direct anti-cancer effect

i. Additionally: thermal
ii. Light sensitizer
iii. Effects [1,2,22].

These drugs may be injected intravenously at concentrations lower than normal chemotherapeutic levels, or at higher intratumor doses reducing systemic toxicity while enhancing local tumoricidal effects by laser photoactivation in situ [2,23,24]. Anthracyclines have also been identified that have greater photosensitization potential than daunomyucin [25]. With all the supporting evidence of translational and clinical protocols laser photo chemotherapy has established itself as an alternative treatment for retinoblastoma [18,26,27]. Most of these studies were conducted in children where there has been a few standardized clinical protocols, in particular for unilateral retinoblastoma [27,28]. One ofthese studies by Ventura et al. [29] was sophisticated enough to direct intra-arterial chemotherapy for combined laser photo activation in an advanced unilateral case in an 8-year old girl with no other options for treatment [29].

In sum, bone tumors are rare neoplasm that causes significant morbidity and mortality that despite important medical advances in the past 20 years produced few significant changes in function or survival for patients affected with these diseases. Based on the successful establishment as an alternative treatment for retinoblastoma LPC may become an alternative option for this devastating disease.

To know more about Journal of Orthopedics and Rheumatology

Click here: https://juniperpublishers.com/oroaj/index.php

To know more about JuniperPublishers

Click here: https://juniperpublishers.com/index.php

The Effectiveness of Ferric Carboxymaltose in Childbearing Age with Iron Deficiency Anemia-Juniper Publishers

Journal of Gynecology and Women’s Health

Iron deficiency is the most common minerals deficiency worldwide. Iron has a major role in producing hemoglobin in red blood cells, which is responsible for carrying oxygen to the body’s tissues. Treatment for an iron inadequacy depends on the cause and severity of the condition. Intravenous iron preparations are highly recommended when anemic pregnant women unable to tolerate, respond accordingly with better adherence to the regimen.

Aim of the research: This study is conducted to evaluate the possibility of using ferric carboxymaltose (FCM) as a first line treatment in pregnant women with IDA; and the effect of other contributor factors such as age, education, occupation, number of pregnancies and most importantly is the time of receiving FCM in term of first, second and third trimesters.

Methodology: Participants were gone through out personal interview answering some questions about their gestational situation and habits to achieve the study outcomes. All participants were pregnant women with abnormal hemoglobin whose either already received their first dose of FCM or those who are scheduled to take their first dose.

Result: Eighty-eight (88) pregnant women were participated in this study and their ages were divided into groups. The average of post FCM hemoglobin (10.99) after injection was significantly higher compared to the baseline hemoglobin (9.06). A shift to healthy and better response was shown after the FCM were shown in all participants.

Conclusion: A single intravenous injection of FCM improves the hemoglobin level in a significant consideration in anemic pregnant women. It showed also that the respond of sever anemic cases were more positive in improving the level of hemoglobin than mild and/or moderate cases. Blood transfusion could be avoided by using FCM injection to optimize the iron stores rapidly and effectively. Intravenous injection of FCM could be used as trend in the first and second trimester during pregnancy with or without IDA if the hemoglobin level is low.

Keywords: Ferric carboxymaltose; Iron deficiency; Iron deficiency; Hemoglobin

Introduction

Anemia is a blood disorder in which hemoglobin (Hgb) concentration is less than the normal Hgb level. It is affected by age, sex, physiological condition(s) and altitude above the sea level of that person [1]. It is a global public health problem with major consequences affecting both developing and developed countries [2]. The most common type of anemia is Iron deficiency anemia (IDA), which is defined as anemia because of insufficient iron [3]. Iron deficiency is the most common minerals deficiency worldwide. Women are at higher risk compared with men [4,5]. Iron has a major role in producing hemoglobin in red blood cells which is responsible for carrying oxygen to the body’s tissues [6]. Iron is a mineral naturally found in food and supplements, and it is available in two dietary forms: heme like in (meat, poultry, and seafood) and non-heme in (iron-fortified foods, plants- beans, nuts and vegetables). Essentially, meat and seafood are the richest sources of iron. However, some vegetables such as spinach, broccoli, and beetroot are considered as a good source for iron too. Although this disagrees with previous review concludes that “Vegetarians have a higher risk for developing low iron stores, iron depletion, and associated iron deficiency anemia, compared to non-vegetarians” [7].

According to world health organization (WHO) data, the prevalence of IDA in Saudi Arabia is 32.0% of pregnant women and 32.3% of women of reproductive age with anemia, which presents a moderate public health risk. Hemoglobin estimation is the most common and classical hematological screening test used for iron deficiency. According to (WHO), anemia is defined as low hemoglobin status; the cut off value for the pregnant women is Hgb<12g/dl, mild anemia (10.0-11.9g/dl), moderate (8.0-9.9g/dl) and severe (≤ 7.9g/dl). However, bone marrow aspiration is the definitive test to assess iron stores and diagnose its deficiency. Serum ferritin is an alternative to the bone marrow aspiration, and it is the best test to distinguishing those with IDA from those who are not iron deficient [2,8,9].

The level of serum ferritin, hemoglobin and hematocrit, and transferrin or total iron-binding capacity could evaluate iron inadequacy. The symptoms of iron deficiency vary, depending on its severity. Iron deficiency anemia can cause chronic fatigue, hair loss, cold hands and feet, shortness of breath and many other symptoms in addition to several physical signs. One of the characteristics symptoms is pagophagia, which is known by a craving to eat substance without nutritional value such as ice, dust or paint due to iron deficiency [10,11].

The reasons behind iron deficiency anemia during pregnancy can be classified into three causes. First, it can be as a result of the decrease in the hemoglobin level due to an increase in the maternal plasma volume. Second, begin the pregnancy with inadequate iron storage, which can lead to an inability to meet the requirements throughout the pregnancy. Last, an increase in the maternal demand for iron [12]. The body requirements for iron in pregnant woman nearly increases to 1000mg, which can be divided by, 350mg for placental and fetal growth, 250mg for blood loss at the delivery and the biggest part will be for the dilation in the red blood cell mass that will consume approximately 500mg iron [13]. Iron deficiency anemia lead to health problems such as rapid or irregular heartbeat, premature births and low birth weight babies and delayed growth and development [14].

Treatment for an iron inadequacy depends on the cause and severity of the condition. Iron deficiency anemia could be treated either orally or by intravenous (IV) injection. In spite of the fact that oral iron supplementations are considered as the first line option for the majority of pregnant women with IDA due to their effectiveness, safety, and lower cost; yet an intolerable side effects (gastrointestinal side effects), non-compliance and/or predisposing pathology such as malabsorption (celiac disease) may limit the use of oral ferrous supplements [15].

On the other hand, intravenous iron preparations are highly recommended when anemic pregnant women unable to tolerate, respond accordingly with better adherence to the regimen. Ferric carboxymaltose (FCM) is a new type of iron III complex, dextran free, which makes it possible to be administered without a test dose for hypersensitivity, has a neutral PH (5.0-7.0) and physiological osmolality. Therefore, up to 1000 mg as single dose can be infused over 15-30 minutes, with lower side effects than oral iron supplement thus the patients are more compliant with injectable dosage form. If the patient did not respond adequately after a single dose of FCM, another dose can be administered one week later [10,16-18].

Ferrous as an element is a trend use for all pregnant women in most if not all gynecological clinics, usually the practitioners start with ferrous sulfate (FS) 325mg orally or ferrous gluconate (FG) 300mg orally. However, the starting point to prescribe ferrous is crucial to decide whether if the first, second or third trimester; moreover, what is the most appropriate and effective way to initiate FCM injection during pregnancy; and what is the most cost-effective treatment specifically if the pregnant women with IDA [19].

Methodology

Study Design

This is a cross-sectional, prospective study conducted to monitor symptoms improvement and normalization of hemoglobin level of the recruited participants.

Subjects

This study was conducted with a sample of eighty-eight (88) pregnant women aged between (20) and (44) years old; whom participated through out personal interview answering some questions about their gestational situation and habits to achieve the study outcomes. All participants were pregnant women with abnormal hemoglobin whose either already received their first dose of ferric carboxymaltose or those who are scheduled to take their first dose. Women who are post-delivery or pregnant women with normal hemoglobin are excluded from the study

Data Analysis

Data were analyzed using SPSS 21.0 version statistical software. Descriptive statistics (mean, standard deviation, frequencies and percentages) were used to describe the quantitative and categorical variables. Student’s paired t test was used to compare the mean values of quantitative variables (Hgb) between the baseline and post ferric carboxymaltose (FCM). One-way analysis of variance was used to compare the mean difference of Hgb values in relation to the categorical variables, which has more than two categories. A p-value of ≤0.05 was used to report the statistical significance of findings to report the precision of results.

Setting

Research data were obtained from the King Abdullah University Hospital at the Princess Noura bint Abdulrahman University.

Ethical Consideration

All the participants involved in this study provided written informed consent acknowledging the investigation’s purpose and were assured of the confidentiality of the results. Institutional review board approval for the research was obtained from Health Sciences Research Center at Princess Noura bint Abdulrahman University, with IRB Log Number: 18-1098.

Result

Eighty-eight (88) pregnant women were participated in this study and their ages were divided into groups, from 20-25 years were 13 participants (14.8%), from 26-30 years 28(31.8%), from 31 to 35 years 27 (30.7%), and for 36 years and older were 20(22.7%). Their educational level was distributed as following: under high school 2(2.3%), high school 32(36.4%), bachelor’s degree 41 (46.6%), and master’s degree or above 13(14.8%). Their occupational status was assigned as employed 48 (54.5%) and un-employed 40(45.5%). More detail for the timing of FCM injection during the gestational trimester whether if it is first, second or third trimester, were shown in (Table 1), together with information related to the number of deliveries. The average of post ferric carboxymaltose hemoglobin (10.99) after injection was significantly higher compared to the baseline hemoglobin (9.06) (P<0.0001; 95% CI: 1.65-2.21).

In regard to age groups and its efficient in absorbing Hgb before FCM injection as a baseline and after FCM injection, compared to the whole group as shown in (Figure1). The range of hemoglobin level between baseline and after FCM injection was (9.06-10.99), showing the response of the participants after FCM injection with a difference of 1.93 for the whole group, where the maximum difference was 2.16 found with the group of 25 years and lower with no significant difference (p>0.05) compared with any of other age group including the minimal difference for the age group of 30-35 years with 1.7.

Another comparison for level of hemoglobin was found when FCM was injected within the gestational trimester, first, second and third trimester. It was found that although the third trimester with the highest hemoglobin level compare to the others, yet the first trimester showed the best response with a difference between the baseline and post FCM injection with 2.15. None of these differences were calculated as significantly different. Figure 2 showed relative differences between gestational trimesters first, second and third trimester compared with the total group before and after receiving one full dose of FCM.

Participants (at the baseline) were classified in accordance with WHO classification to mild, moderate and sever anemia. A shift to healthy and better response was shown after the FCM with 14 participants were shown within healthy hemoglobin level, compared with none at the baseline. Then a big shift 8, 70 and 10 out of the total participants as baseline before FCM injection for severe, moderate and mild anemia correspondingly. The improvement had shown after the FCM injection with only one participant with severe anemia or low hemoglobin level, 15 participants for moderate, and 58 participants become with mild anemia. It is also shown that 14 participants were getting full improvement and considered as health or non-anemic women. Table 2 showed full detail for all the data of this study mainly the shift of hemoglobin level during sever, moderate and mild to moderate, mild and healthy hemoglobin level before and after receiving FCM.

Discussion

This is the first prospective study for ferric carboxymaltose in Saudi Arabia among pregnant women presenting with IDA. An intravenous ferric carboxymaltose was remarkably increased hemoglobin levels without serious side effects were recorded. Only one case in this study had experienced dizziness, which were reported at the emergency department after FCM injection. FCM shown to be effective in childbearing age women with IDA, this phenomenon had been shown noticeable with those who aged with 25 or younger, where they have remarkably better response compared with other groups of age due to the ability to quickly absorb of iron as shown in (Figure 1). This difference is numerically deferent but not statistically deferent. Age as a factor in pregnant women with IDA had not been studied elsewhere; whereas in this study, age was divided into 4 age groups to study the associated differences of Hgb levels post FCM injection.

Results from this FCM analysis of pregnant women with IDA during first, second and third trimester of pregnancy showed that Hgb levels increased after FCM treatment with full safety parameters; therefore, intravenous FCM could be considered as a first line treatment for IDA pregnant women in case of severe cases. This is in contrast to CDC [20], WHO [21] and Society of Obstetricians and Gynecologists of Canada [22], where all these authorities recommended oral iron supplementation in pregnant women as first line therapy. Intravenous iron is recommended when oral iron is poorly tolerated, absorption is likely to be impaired, the response to oral iron is inadequate, or when rapid restoration of Hgb and iron stores is required [23].

Oral iron supplementation could increase hemoglobin and ferritin levels in pregnancy, with or without IDA. This study demonstrated safe and effective use of FCM infusion in pregnant women during the first, second, and third trimesters of pregnancy. Safety profile for intravenous FCM had been shown, having the practical advantage of allowing a higher iron dose in one time of administration (minimizing repeated administration times and increasing patient comfort) [24]. Another study showed Hgb levels significantly increased above baseline levels with 66% of women reported an improvement of their wellbeing with mostly minor and self-limiting side effects [25]. The cases described in this study was also in line with the retrospective case-control study from the Netherlands reporting similar significant increases in maternal Hgb levels above baseline and low rates of adverse outcomes [24]. Third trimester cases in this study had improvement with 21.3% with a single dose of intravenous injection of FCM (Figure 2).

It was noticed from this study that Ferric Carboxymaltose (FCM) was significantly increased hemoglobin levels, this increment in Hgb had been noticed started at 3 to 4 weeks interval post FCM dose; this achievement also had been previously studied [26]. The responses of severe anemic cases are more positive in improving the level of hemoglobin than mild and/or moderate cases after a single dose (1000mg) FCM. All cases related to severity of IDA had been shifted from sever, moderate, mild to moderate, mild, healthy respectively. Only one case with severe IDA remained severe after using FCM, therefore another dose maybe warranted.

Treatment of IDA will never lead to iron toxicity, however, incase of injection of higher dose above the requirements, it needs further monitoring although teratogenicity is with limited possibility, specifically if the treatment within the first trimester. If iron accumulation has been noticed, intravenous deferoxamine should be administered as chelation therapy [27]. Excessive Hgb levels were not observed in this study, all participants on FCM injection had elevated levels that fell within normal ranges.

Traditionally, blood transfusion is considered as an option in severe anemic cases; especially when oral replacement is not effectively and rapidly replenished the iron stores. The newly developed iron formulation such as FCM is offering the benefit of administrating a single higher dose with rapid, effective and safe repletion of iron, which can employ to avoid the risk of blood transfusion in severe anemia. This study could not find any correlation between Hgb levels and education, job, number of pregnancies, the consumed iron from food (vegetarian or not), and pagophagia.

A side issue related to the cost of treatment in comparison between FCM and oral ferrous treatment considering that the cost of FCM is 200$ per injection of 1000mg single dose with almost absolute treatment for more than 6 months and only one visit comparing with multiple visits, cost more than 200$ USD per each visit, and irregular treatment subjecting premature births and low birth weight babies and delayed growth and development.

Conclusion

This study approved that one intravenous injection of FCM improves the hemoglobin level in a significant consideration in anemic pregnant women. Also, it showed that the respond of sever anemic cases were more positive in improving the level of hemoglobin than mild and/or moderate cases. Only one case remained severe despite receiving one dose of FCM. Dizziness was experienced and reported by only one pregnant woman at the emergency department post FCM injection, which indicated its effectiveness and safety. Blood transfusion could be avoided by using FCM injection to optimize the iron stores rapidly and effectively. The proposed recommendation is that intravenous injection of FCM could be used as trend in the first and second trimester during pregnancy with or without IDA if the hemoglobin level is low. Moreover, Intravenous iron can be given late in pregnancy in the third trimester when rapid restoration of the iron stores and hemoglobin is required to avoid blood transfusion at delivery, it is also often needed after delivery when there is excessive bleeding in labor.

To Know More About Journal of Gynecology and Womens's Health Please click on: https://juniperpublishers.com/jgwh/index.php

To Know More About Open Access Journals Please click on: ttps://juniperpublishers.com/index.php