By U. Benito. Trevecca Nazarene University.

The myelosuppressive potential of AZT is known (de Jesus 2004) cheap flomax 0.4 mg with amex. Most commonly affected are patients with advanced HIV infection and preexisting myelosuppression on chemotherapy or comedication with other myelotoxic drugs such as cotrimoxazole flomax 0.2mg for sale, pyrimethamine order flomax 0.4 mg otc, amphotericin B, ribavirin, and interferon or with other antiretrovirals. MCV is always elevated, even in patients on AZT without anemia, and can be therefore an indicator of adherence. For thrombocytopenia see chapter on HIV-associated Thrombocytopenia. Increased bleeding episodes HIV+ patients with hemophilia A or B, after some weeks of treatment with PIs, may have increased episodes of spontaneous bleeding into joints and soft tissues. Rarely, intracranial and gastrointestinal bleeding has occurred. During clinical trials with tipranavir/r, the manufacturer received 14 reports of intracranial hemorrhage, among them 8 fatal cases, in 13 out of 6840 HIV+ indi- viduals. Most of them occurred more than one year after initiating therapy. Tipranavir was observed in vitro to inhibit human platelet aggregation (Graff 2008). Tipranavir/r should be avoided in patients with CNS lesions, head trauma, recent neurosurgery, coagulaopathy, hypertension or alcohol abuse, or those who were receiving antico- agulant or antiplatelet agents. Lactic acidosis Lactic acidosis is a rare but life-threatening complication due to mitochondrial toxicity. It occurs most frequently on treatment with d4T and ddI, and less so in patients on AZT, abacavir and 3TC (Garrabou 2009). Risk factors are obesity, female sex, pregnancy and therapy with ribavirin or hydroxyurea, a diminished creatinine clearance and a low CD4 T cell nadir (Bonnet 2003, Butt 2003, Wohl 2006). Cases of severe lactic acidosis can occur without prior symptomatic hyperlactatemia. Lactate levels do not need to be monitored routinely, as increases are not predictive and may lead to unnecessary changes in treatment (Brinkman 2001, Vrouenraets 2002). In contrast, lactate levels should be tested immediately in symptomatic patients complaining of fatigue, sudden weight loss, abdominal disturbances, nausea, vomiting or sudden dyspnea, in pregnant women on NRTI treatment and in patients on NRTIs post-lactic acidosis (Carr 2003). Management of Side Effects 291 Lipodystrophy syndrome The HIV lipodystrophy syndrome include metabolic complications and altered fat distribution. Fortunately, modern regimens are much less likely to lead to fat tissue abnormalities. The metabolic abnormalities may harbor a significant risk of developing cardiovascular disease. In addition, several studies report a reduced quality of life in patients with body habitus changes leading to a reduced treatment adherence. Despite the impact of lipodystrophy syndrome on HIV management, little is known about the pathogenesis, its prevention, diag- nosis and treatment. Current data indicate a rather multifactorial pathogenesis where HIV infection, ART, and patient-related factors are all major contributors. The lack of a clear and easy definition reflects the clinical heterogeneity, limits a clear diagnosis and impairs the comparison of results among clinical studies. Therapeutic and pre- vention strategies have so far been of only limited clinical success, where avoiding the use of thymidine analogues appears to be most effective in avoiding peripheral fat loss. General recommendations include dietary changes and lifestyle modifica- tions, ART modification (replacing PIs with NNRTIs or replacing d4T and AZT with abacavir or tenofovir or switching to an NRTI-free regimen, e. Clinical manifestation Lipodystrophy was originally described as a condition characterized by regional or generalized loss of subcutaneous fat. Non-HIV-associated forms, such as congenital or familial partial lipodystrophy, have a very low prevalence. Generally, these forms are associated with complex metabolic abnormalities and are difficult to treat. The term “lipodystrophy syndrome” was introduced to describe a complex medical con- dition including an apparent abnormal fat redistribution and metabolic disturbances in HIV+ patients receiving protease inhibitor therapy (Carr 1998). Now, years after its first description, there is still no consensus on a case definition for lipodystrophy syndrome in HIV. Thus, the diagnosis of lipodystrophy in clinical practice often relies on a more individual interpretation than on an evaluated classification. Finally, changes in fat distribution have to be considered as being part of a rather dynamic process. In most cases, peripheral lipoatrophy is clinically diagnosed when signifi- cant fat loss of about 30% has already occurred.

York order flomax 0.4 mg amex, UK: NHS Centre for Reviews and Dissemination; 2001 buy flomax 0.2mg. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials cheap flomax 0.4 mg with mastercard. Initial highly-active antiretroviral therapy with a protease inhibitor versus a non-nucleoside reverse transcriptase inhibitor: discrepancies between direct and indirect analyses. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. Methods for Meta-Analysis in Medical Research: John Wiley & Sons, Inc. R: A Language and Environment for Statistical Computing [computer program]. Vienna, Austria: R Foundation for Statistical Computing; 2006. Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b. Peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C in Saudi patients commonly infected with genotype 4. Arizcorreta A, Brun F, Fernandez-Gutierrez C, et al. Modifications of haematological series in patients co-infected with human immunodeficiency virus and hepatitis C virus during treatment with interferon and ribavirin: differences between pegylated and standard interferon. Pegylated interferons for hepatitis C Page 43 of 65 Final Report Drug Effectiveness Review Project 36. Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Bosques-Padilla F, Trejo-Estrada R, Campollo-Rivas O, et al. Peginterferon alfa-2a plus ribavirin for treating chronic hepatitis C virus infection: analysis of Mexican patients included in a multicenter international clinical trial. The results of a randomized trial looking at 24 weeks vs 48 weeks of treatment with peginterferon alpha-2a (40 kDa) and ribavirin combination therapy in patients with chronic hepatitis C genotype 1. Peginterferon alfa-2b plus ribavirin for naive patients with genotype 1 chronic hepatitis C: a randomized controlled trial. Viral kinetics in genotype 1 chronic hepatitis C patients during therapy with 2 different doses of peginterferon alfa-2b plus ribavirin. Open, randomized, multicentre italian trial on PEG-IFN plus ribavirin versus PEG-IFN monotherapy for chronic hepatitis C in HIV- coinfected patients on HAART. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. Peginterferon alpha-2b plus ribavirin vs interferon alpha-2b plus ribavirin for chronic hepatitis C in HIV-coinfected patients. Derbala M, Amer A, Bener A, Lopez AC, Omar M, El Ghannam M. Pegylated interferon-alpha 2b-ribavirin combination in Egyptian patients with genotype 4 chronic hepatitis. Response of hepatitis C genotype-4 naive patients to 24 weeks of Peg-interferon-alpha2b/ribavirin or induction-dose interferon- alpha2b/ribavirin/amantadine: a non-randomized controlled study. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Pegylated interferons for hepatitis C Page 44 of 65 Final Report Drug Effectiveness Review Project 51. The impact of peginterferon alfa-2a plus ribavirin combination therapy on health-related quality of life in chronic hepatitis C. HCV-related advanced fibrosis/cirrhosis: randomized controlled trial of pegylated interferon alpha-2a and ribavirin. Efficacy and tolerability of peginterferon alpha-2a with or without ribavirin in thalassaemia major patients with chronic hepatitis C virus infection.

Excise the lesion (from a semi-circular incision above the In any cases of fever or obvious infection monitor the full blood count order 0.2mg flomax. Prolactin may be helpful to rule out a prolactinoma in galactorrhea of female or male patients discount 0.2mg flomax with amex. This is a costly investigation for high-resource settings purchase 0.2mg flomax visa. In low-resource settings the patient must be referred to a specialized center. You might as well give bromocriptine as a thera- peutic trial (see below). DIFFERENTIAL DIAGNOSIS AND TREATMENT See flow chart in Figure 5. Mastitis puerperalis Figure 4 Semicircular incisions directly above the Refer to a textbook of obstetrics for mastitis occur- lesions should be used in the breast if breast cancer is ring during breastfeeding and keep in mind that suspected even breastfeeding women can develop breast Patient with breast problems Palpable tumor Pain Nipple discharge Bloody, Fluid on Echo-dense mass Associated with Serous, Redness/warning unilateral ultrasound on ultrasound menstruation bilateral (bilateral) Hormonal Simple cyst Fibroadenoma Mastodynia Mastitis Papilloma imbalance Always consider breast cancer as a differential diagnosis! Figure 5 Flow chart of leading signs/symptoms – differential diagnosis 306 Benign Disease of the Breast cancer! Any mastitis or abscess that doesn’t resolve Persisting nipple discharge/galactorrhea (in under antibiotic or surgical treatment should raise female and male) your suspicion of malignancy. Certain medication/drugs may induce hyperpro- lactinemia leading to galactorrhea! Ask about Mastitis non-puerperalis phenothiazine, tricyclic antidepressants, haloperi- This is a condition often associated with hyper- dol (Haldol), methyldopa, metoclopramide, cime- prolactinemia. Therefore treatment with antibiotics tidine, domperidone and heroine. In case there is should be accompanied by bromocriptine 5 mg o. Side-effects (hypotension and head- imbalance, you may suspect hyperprolactinemia. A Ask about oligomenorrhea, fertility problems and course of antibiotics and anti-inflammatory medica- visual problems (reduced field of vision). In cases of a newly forming asking the patient to follow your finger sideways and abscess, red light may help. In cases of abscess forma- say when she doesn’t see it anymore. If the patient tion, an incision with removal of necrotic tissue and has visual problems she may have a macroprolactin- drainage may be necessary (Figure 6). At that point oma (located in the pituitary gland occupying space you can take tissue for histology/cytology as well. A compression of the optical nerves) and needs referral drain (glove-drain = 3 × 10 cm piece of sterile for special investigations. Often a microprolactinoma glove) may be put in (consider two communicating causes symptoms of hyperprolactinemia. A micro- incisions – one for the drain below, one for irriga- prolactinoma does not occupy space in the sella tion from above). Regular irrigation with normal region of the brain; no impairment of the vision is saline (e. If she has only oligomenorrhea and prob- Keep in mind that breast cancer can present itself lems in conceiving, give bromocriptine 2. So if your treatment doesn’t work after some time, consider breast cancer as the diagnosis. Other infections In case a chronic fistula has developed, surgical treatment must include the complete excision of These are rather rare. This should be done by an experienced the breast, but can be found more frequently in the surgeon. Usually it has secondarily developed from primary pulmonary tuberculosis. Appearance is typically with a painless swelling, increasing in size and even- tually pus will be expelled, but atypical signs are seen as well such as mastitis or multiple fistulae (Fig- ure 7). Treatment is according to local guidelines on tuberculosis. A patient with syphilis may also develop lesions in the breast – especially hard ulcers. Treatment is according to local guidelines (see Chapter 17 on sexually transmitted diseases). Mastodynia ‘Pain in the breast’ is present in the last week before menstruation in many women (up to 50%). This may be accompanied with nausea, headache and mood fluctuations – called premenstrual syndrome. Figure 6 Irrigation of breast abscess (grey) – top incision to infuse irrigation by syringe, the fluid will rinse out from Exclude other underlying causes (any tumor, infec- the lower incision.

Dolasetron compared with ondansetron 101 generic 0.2 mg flomax with amex, 110-115 Seven trials in adults compared intravenous dolasetron with intravenous ondansetron discount 0.4 mg flomax with mastercard. One study focused on adult outpatients at high risk for postoperative nausea and vomiting buy flomax 0.2mg overnight delivery, as determined by a score of 3 or more on the Surgical Prophylactic Antiemetic Intervention 115 Assessment Scale. Complete response rates were reported in all but 1 trial, which instead 101 found no significant difference in incidence of total treatment failure (39% in both groups). Overall, complete response rates were not significantly different between drugs but varied widely across the trials, from a low of 17% with dolasetron in a study of women undergoing gynecologic surgery to a high of 98% in a study of “superficial surgical procedures” with 37% men. In addition to differences in surgical procedures and proportions of women, these studies also varied in dose of antiemetic. While ondansetron 4 mg was used in every trial, the dolasetron dose varied more. The 50 mg dose was superior to the 25 mg dose on total response rate at 24 Antiemetics Page 32 of 136 Final Report Update 1 Drug Effectiveness Review Project hours (no emesis plus no rescue medication plus no nausea), and both dolasetron 50 mg and ondansetron 4 mg were superior to dolasetron 25 mg on complete response (no emesis plus no 111 rescue medication use) at 24 hours. Aprepitant compared with ondansetron Two fair-quality trials (N=1727) compared oral aprepitant 40 mg and 125 mg with intravenous 116, 117 ondansetron 4 mg in primarily females undergoing open abdominal surgeries. Both trials were originally designed to test the superiority of aprepitant over ondansetron on the primary efficacy endpoint of complete response, defined as no emesis and no use of rescue medication for the first 24 hours after surgery. In the first trial, no significant difference was seen between aprepitant 40 mg or 125 mg and ondansetron (45% compared with 43% compared with 42%), but both doses of aprepitant were significantly better than ondansetron on the secondary endpoint 117 of no vomiting. The odds ratio of no vomiting for aprepitant compared with ondansetron was 3. Before the second trial was completed, its plan for statistical analysis was adjusted to accommodate dual primary endpoints: (1) noninferiority of aprepitant for complete response and (2) superiority of aprepitant for no vomiting during the first 24 hours after surgery. For the complete response endpoint, noninferiority was defined as a lower bound of a 1-sided 95% CI of 0. In this trial, complete response rates were 64%, 63%, and 55%, respectively, for aprepitant 40 mg, aprepitant 125 mg, and ondansetron 4 mg. Noninferiority was confirmed based on the following odds ratios and lower bounds of the associated 1-sided 95% CI (in parentheses): aprepitant 40 mg to ondansetron 1. Additionally, as in the first trial, significantly more patients had no vomiting during the first 24 hours in the aprepitant 40 mg group (84%; odds ratio 2. Ondansetron: orally disintegrating tablet compared with intravenous We included 2 trials that compared the oral disintegrating tablet and intravenous forms of ondansetron. Both trials were conducted in Turkey and both found no significant differences in 118, 119 postoperative nausea and vomiting outcomes. In the first trial, oral disintegrating tablet ondansetron 8 mg, intravenous ondansetron 4 mg, and placebo were compared in 150 young men 119 undergoing minor elective surgeries. In this trial, neither oral disintegrating tablet nor intravenous ondansetron was found to be significantly better than placebo in reducing incidence of postoperative nausea and vomiting, vomiting, or use of rescue medication during the first 24 hours after surgery. In the second trial, oral disintegrating tablet ondansetron 8 mg, intravenous ondansetron 8 mg, and placebo were compared in 90 women undergoing major gynecologic 118 surgery (mean age = 47 years). In this trial, both oral disintegrating tablet and intravenous forms of ondansetron were found to be better than placebo in reducing incidence of nausea and vomiting during the first 6 hours after surgery. There were no significant differences between the 2 forms of ondansetron. Dolasetron compared with granisetron Two trials compared dolasetron 12. In the trial of mostly women (84%) undergoing a variety of surgical procedures, a complete response was significantly more frequent with Antiemetics Page 33 of 136 Final Report Update 1 Drug Effectiveness Review Project 120 granisetron 1 mg intravenous (54. However, in a trial of women undergoing gynecological and breast surgeries, rate of total treatment failure did not differ significantly between low-dose granisetron intravenous (0. In both trials, patient satisfaction was not significantly different between the granisetron and dolasetron groups. One trial reported time to first intake of fluids or solids and quality of first postoperative 120 night sleep. There was no significant difference between granisetron and dolasetron in these outcomes. Placebo-controlled trials Head-to-head trials rarely reported patient satisfaction, quality of life, functional capacity, or hospital stays. Therefore, we included placebo-controlled trials to address these gaps (Evidence 121-159 Tables 11 and 12). Dolasetron was the only 5-HT3 antagonist that consistently showed significantly 121, 128, 148, 152 improved patient satisfaction compared with placebo across 4 trials. Ondansetron 131, 140 was superior to placebo in improving patient satisfaction in only 2 of 12 placebo-controlled 130, trials and was not significantly different than other antiemetics in trials with active controls.