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By I. Hamid. Metropolitan College of New York.

This review focuses on clinical practice guidelines for transfusion of three blood components: RBCs buy 10 mg reglan, platelets and plasma discount reglan 10mg on line. In addition, we provide the approach used to implement clinical practice guidelines at our own institution. Introduction clinical practice guidelines that can become a part of comprehensive Transfusion of blood and blood components (ie, RBCs, platelets, PBM. However, the Clinical practice guidelines are defined as systematically developed decision to transfuse or not to transfuse is one of the more complex statements to assist with practitioner and patient decisions about appropriate health care for specific clinical circumstances. Clearly no medical intervention is without risks, but in principle, these risks should be is a growing body of literature on the best approaches to develop offset or justified by immediate or long-term benefits. One system that is used more frequently than others is the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. After clini- infectious disease tests), pretranfusion testing, recipient identifi- cal practice guidelines are developed, their adoption by individual cation, and multiple improvements in blood component character- physicians, clinical practices, and healthcare systems is accom- istics and quality (eg, leukoreduction, irradiation, pathogen plished in different ways. Initial broad-based education efforts are inactivation). These developments have resulted in improved strengthened by the development of critical pathways, hospital safety profiles for transfused components and a perception of policies, and systems to support adherence. At the same time, the introduction of patient blood management (PBM), defined as an evidence-based approach to Although the development of clinical practice guidelines is time optimizing the care of patients who might need transfusion, consuming and expensive, several professional societies and health shows that the need for transfusion can be minimized in many authorities have participated in the development of transfusion- patients by implementation of thoughtful processes often begin- specific clinical practice guidelines to support evidence-based ning days or even weeks before the actual decision to transfuse or transfusion practice. These clinical practice guidelines support not is being made. Are the assumed benefits of transfusion universal or are Successful implementation of clinical practice guidelines in transfu- they limited to only a well-defined population of patients? What sion medicine can often be supported by computerized physician triggers should be used to administer blood components and when order entry systems and order auditing. What component dose is sufficient and/or necessary to confer clinical benefit? The answers to these In this short review, we highlight current clinical practice guidelines questions have been sought in multiple randomized clinical trials. Guidelines for RBC transfusion The development of clinical practice guidelines for RBC transfusion has been challenged by a limited availability of high-quality evidence to support practice recommendations. There is general agreement that RBC transfusion is typically not indicated for hemoglobin (Hb) levels of 10 g/dL and that transfusion of RBCs should be considered when Hb is 7 to 8 g/dL depending on patient characteristics. As more studies addressing RBC transfusion become available, it becomes increasingly clear that liberal transfusion strategies are not necessarily associated with superior outcomes and may expose patients to unnecessary risks. The most recently published guidelines from the AABB (formerly the American Association of Blood Banks) are based on a system- atic review of randomized, controlled trials evaluating transfusion thresholds. This strong recommendation is based on high-quality evidence from clinical trials comparing outcomes in liberal versus restrictive transfusion strategies in this patient population. In this population, transfu- sion should be considered when Hb levels are 8 g/dL or for symptoms such as chest pain, orthostatic hypotension, tachycardia unresponsive to fluid resuscitation, or congestive heart failure. Additional clinical practice guidelines exist that specify Hb targets for critical care patients with conditions including sepsis, ischemic stroke, and acute coronary syndrome. Much remains to be learned about the optimal resuscitation of the bleeding patient, and this topic is outside of the scope of this review. However, a recent study examining transfusion in patients with active upper gastrointestinal bleeding showed superior outcomes in patients treated with a restrictive transfusion strategy ( 7 g/dL). Laboratory monitoring of the Hb level is performed to assess the response to transfusion and the need for ongoing blood component support. Transfusion Medicine Service (TMS) physicians are available on call at all times to assist with the appropriate transfusion support of patients requiring massive transfusion. Our guidelines for RBC transfusion in stable nonbleeding patients were developed by the transfusion committee in collaboration with medical and surgical providers based on a synthesis of existing clinical evidence, practice guidelines, and institutional preferences (Table 2). Stable, nonbleeding medical and surgical inpatients patients are considered candidates for RBC transfusion when the Hb level is 7 g/dL. Triggers for transfusion of RBCs at our institution lower dose of platelets is noninferior to a larger dose when Hemoglobin level Patient population measured by incidence of World Health Organization (WHO) Grade 2 or above bleeding.

The frequency of screening depends on the clinical scenario cheap 10mg reglan visa. If the initial Pap smear after HIV diagnosis is normal 10 mg reglan for sale, then a second screening should be done approximately 6 months later. If both results are normal, then an annual Pap smear is sufficient. Consider more frequent screening in women with a higher risk of cervical dysplasia, e. Table 1: Gynecological/Pap smear screening Screening frequency Clinical scenario Every year Routine control 6 months First year of HIV diagnosis, then every year <6 months Abnormal Pap smear HPV infection After therapy for cervical dysplasia Symptomatic HIV infection CD4 T cells <200/μl Basic gynecological evaluation A full gynecological examination consists of inspection of the external genital and perianal region, bimanual examination of the inner genital area, rectal examination, colposcopy, microscopic examination of vaginal secretions and a Pap smear. In HIV+ women palpation of inguinal and axillary lymph nodes is important, since enlarged lymph nodes are often present and may need a rapid mammographic/ultrasound evaluation. Since 2013, German- Austrian guidelines recommend an annual anal cytologic smear for all HIV+ men and women. HIV and Gynecology 523 Menstrual cycle/menopause Data on the influence of HIV on the menstrual cycle are conflicting. Older studies demonstrate a cycle prolongation (Shah 1994), whereas the WIHS study shows at most a slight increase of very short cycles (Harlow 2000). It is also unknown whether or not HIV accelerates the beginning of menopause. There is only limited data in small populations (Clark 2000, Greenblatt 2000). In contrast, it is clear that post- menopause as well as HIV infection and antiretroviral treatment have adverse effects on bone, lipid and glucose metabolism and may contribute to osteoporosis and cardiovascular disease. Contraception When choosing a contraceptive method be aware of the expectations of the woman. Condoms are the most common form of contraception (and they protect from STIs). Nevertheless their contraceptive effectiveness is comparatively limited. Condoms have a Pearl Index (number of pregnancies per 100 patient years) of 1–12 while con- traceptive pills have a Pearl Index of 0. Other methods are contraceptive pills containing varying hormone combinations and dosages, depot and transdermal for- mulations as well as intrauterine devices (IUD). Hormone-containing contraception has no influence on the course of HIV infection, but this method may increase the risk of transmitting or acquiring HIV (Stringer 2009, Heffron 2012). Intrauterine devices made of copper as well as the levonorgestrel-containing device (Mirena), which increases cervical mucus viscosity, have proved to be safe and effective in HIV+ women (Stringer 2007, Heikinheimo 2006). In HIV+ patients on ART, interactions should be taken into account. Oral contra- ceptives interact with PIs and NNRTIs with almost unpredictable consequences. There are limited reliable studies of such interactions, and these interactions are agent-spe- cific (El-Ibiary 2008, Heikinheimo 2008). The same is true of new parenteral oral contraceptives like the hormone-containing vaginal ring (NuvaRing), the etono- gestrel implant (Implanon), transdermal hormone patches and emergency contra- ception and abortion pills. It is essential to inform patients about potential interac- tions when starting ART. Exceptions are unboosted atazanavir and indinavir, etravirine, maraviroc and raltegravir in combinations without ritonavir. In an ACTG study depot formulations containing 150 mg medroxyprogesterone acetate (e. Infections In the pre-ART era genital infections, especially genital herpes, vulvovaginal can- didiasis and bacterial vaginosis, were more common in HIV+ women. The preva- lence and severity of these infections correlate with the CD4 T cell count and HIV viral load. Today only vaginal candidiasis seems to be more common, which may be a consequence of a higher rate of antibiotic treatment (Watts 2006).

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Untreated STIs generic reglan 10mg line, excluding HIV discount 10 mg reglan mastercard, are estimated to account for 17% of the economic loss due to MANAGEMENT AND TREATMENT disease. Most importantly, for both men and OF SYMPTOMATIC SEXUALLY women, STIs are associated with an increased risk TRANSMITTED INFECTIONS AND of both acquisition and transmission of HIV. The REPRODUCTIVE TRACT INFECTIONS risk of HIV transmission is about two to five times higher in people with an STI, highest in people Sexually transmitted infection syndromes with an ulcerative STI9,10 (level 1 evidence). Re- and the syndromic approach to patient cent evidence suggests that genital herpes (herpes management simplex 2) may be responsible for fuelling a large 11 Although many different pathogens cause STIs or part of HIV infection (level 1 evidence). RTIs, many have a similar or overlapping clinical STIs are more frequent in young women than appearance, known as signs (what the individual or men and more frequent in low-income countries the healthcare provider sees on examination) and where diagnostics and treatment are limited. Signs and symptoms can help health pro- in low-income countries are demographic factors viders make a diagnosis. For example, profuse, (more young people), urbanization, migrant labor, purulent, malodorous vaginal discharge is seen in prostitution, concurrent partnerships, lack of access trichomoniasis. But vaginal discharge is also seen in to quality care for STIs, and for prevention efforts, 12 infections other than STIs, such as bacterial vagino- including screening programs. Often more than Another important factor is that a number of one etiological cause/microbe is involved in the in- STIs are asymptomatic which hampers control fection. Thus the signs and symptoms are often not significant proportion of men with gonococcal specific enough to make an etiological diagnosis. But, tests for STIs are mostly not available at first-line health facilities and often not at district Common complications of sexually hospital level in low-resource settings. Some transmitted infections laboratory investigations for diagnosing STIs are Besides the higher risk of HIV infection, STIs cause expensive or demand advanced techniques. Particularly, untreated is why WHO has recommended a syndromic chlamydial infection is estimated to be the cause of approach to diagnosis and management of STIs in at least a third of female infertility. Also, women low- and middle-income countries since the 1990s 184 Sexually Transmitted Infections and Reproductive Tract Infections and it has been the approach of choice since then in charts are promoted to assist health workers to most settings. The approach is based on a group of decide on the best treatment (Figures 1 and 2). There in different languages3 and many countries have is much evidence, that syndromic management is adapted them to the locally observed resistance effective for treating STIs and has an impact on the patterns of STIs. Dramatic declines in STI rates have The advantage of using this signs and symptom- been observed following the introduction of con- based approach is that the management of STIs is trol measures based on the syndromic approach13. Moreover not only specialists but also clinicians • Urethral discharge in men and nurses can treat patients effectively. However, • Genital ulcer syndromic management is not unanimously • Inguinal bulbo supported. Syndromic management of STIs has • Scrotal swelling been reviewed as being generally effective in treat- • Vaginal discharge ing urethral discharge and genital ulcer disease STIs • Lower abdominal pain in women 14 in men (level 1 evidence). The antimicrobial regimens are chosen Another big challenge for the control of STIs is to cover major pathogens responsible for the syn- that infections are often asymptomatic. Thus guide- management is not suitable for treating asympto- lines differ from country to country in accordance matic infections that require a screening approach. Typically, flow- lower-resource countries, except syphilis testing Patient complains of vaginal discharge, vulval itching or burning Take history, examine patient and assess risk1 • Educate and counsel Abnormal discharge No Any other No • Promote and provide condoms present or vulval genital disease? Yes Yes Use flowchart for Treat for Chlamydia trachomatis, Vulval edema/curd- No lower abdominal pain gonococcal infection, bacterial like discharge, erythema, • Educate and counsel vaginosis and Trichomonas vaginalis excoriations present? Source: WHO treatment modules, 2007 185 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS Patient complains of lower abdominal pain Take history, (including gynecological) and examine (abdominal and vaginal) No Any of the following present? Yes Continue treatment until completed • Educate and counsel • Promote and provide condoms • Offer HIV counseling and testing if both facilities are available Figure 2 Syndromic management: lower abdominal pain. Source: WHO treatment modules, 2007 during pregnancy which therefore provides an im- in all countries according to the epidemiological portant opportunity not to be missed (see more pattern of STIs and resistance against antibiotic reg- under Linkages). Furthermore, control efforts need imens, we will not include any specific syndromic to be put on many pillars, where treatment of management treatment advice. We would also like symptomatic diseases is one, but prevention of risky to promote the use of the STI training modules sexual relations, partner notification, screening available from the WHO homepage: http://www. The following sections aim to give an overview The syndromic approach has been particularly about clinical presentation, signs and symptoms and designed for the primary healthcare level.

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Some studies included minority populations but did not present 310 subgroup analyses on these populations 10 mg reglan free shipping. Thus buy 10mg reglan, there are very limited data on the comparative effectiveness of pioglitazone and rosiglitazone among persons with various demographic characteristics and no conclusions can be drawn as to which drug is more efficacious or effective, or associated with fewer side effects in population subgroups. Most of the studies identified in this review examined persons with type 2 diabetes without significant comorbidities such as coronary heart disease, heart failure, or renal insufficiency. Thus there is a paucity of data on the interaction of TZDs and micro- and macrovascular diseases that are highly prevalent among persons with diabetes, and no conclusions can be drawn on the comparative effectiveness of the 2 drugs under review among populations with significant comorbidities. Subgroups based on demographic characteristics 311 Kreider and colleagues pooled the results of 8 randomized controlled trials examining monotherapy with rosiglitazone and examined subgroups of age less than and greater than 70 years. They found no differences between the 2 age groups for HbA1c and found rosiglitazone well tolerated in both age groups. The percentage of persons with at least 1 adverse event was comparable between the rosiglitazone and placebo groups, and between persons older and younger than 70 years. The incidence of anemia was higher in older patients taking rosiglitazone than in younger patients taking the drug and treatment patients had higher rates of anemia than patients in the placebo group. Weight gain was higher in the under-seventy group (2. Several studies examined racial or ethnic minorities. King compared Mexican Americans with non-Hispanic persons in a retrospective cohort study and found that HbA1c and weight 312 changed to a similar degree in both populations. Jun and colleagues examined 100% Hispanics, and pioglitazone produced a decrease in HbA1c of 2. Twelve Chinese persons with nephropathy and type 2 diabetes were exposed to rosiglitazone over 15. In the updated Drug Effectiveness Review Project TZDs report (2008), several additional 143, 147, 170, 176 studies of rosiglitazone provided data on subgroups based on demographic data. In a combination therapy, double-blind study (N=365) both groups received combination tablets of glyburide/metformin. The addition of rosiglitazone achieved greater reduction in HbA1c than the addition of placebo (between-group difference −1. An improvement in HbA1c 170 was demonstrated across age, sex, and racial subgroups. In a double-blind study (N=318) in subjects who had failed to achieve adequate control 143 on metformin, metformin 1000 mg/glibenclamide 5 mg was compared with metformin 1500−2000 mg plus rosiglitazone 4 mg daily. Reduction in HbA1c was greater in the glibenclamide group at 24 weeks follow-up as noted above. This larger decrease in HbA1c occurred in the glibenclamide group across strata defined by sex, race, age, baseline HbA1c, or entry metformin dose. An analysis using data from 1,840 women and 2,511 men randomly assigned in ADOPT to rosiglitazone, metformin, or glyburide examined time to first fracture, rates of occurrence, and 309 sites of fractures. In men, fracture rates did not differ between treatment groups. In women, the study identified an increased risk of fractures with rosiglitazone. The cumulative incidence of fractures at 5 years was 15. Thus, in women, the hazard ratios comparing rosiglitazone with metformin and glyburide were 1. A systematic review and meta-analysis of 10 randomized controlled trials and 2 observational studies found similar results, concluding that long-term TZD use doubles the risk of fractures among women with type 2 diabetes, without significant increase in risk of fractures 204 among men with type 2 diabetes. The risk of fractures overall in the 10 randomized controlled trials was increased with TZDs (odds ratio 1. Five randomized controlled trials showed an increased risk among women (odds ratio 2. Comorbidities and other population characteristics Patients with impaired renal function were examined in several studies. Agrawal and 233 colleagues examined patients with renal impairment (creatinine clearance 30-80 mL/min) and found that rosiglitazone had similar effects on HbA1c in patients with and without renal 316 impairment. In a retrospective chart review of patients on dialysis with end stage renal disease, rosiglitazone was associated with weight gain and a decrease in hematocrit at 3-month follow-up compared with pioglitazone.

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