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Barrier methods used by women are the dia- the cervical cap or sponge is a mushroom phragm discount 80mg innopran xl with amex blood pressure jadakiss lyrics, the female condom and spermicides purchase genuine innopran xl on line hypertension with hypokalemia. Its protection barrier methods that provide protection maximal insertion time is 24 hours buy innopran xl 80 mg with amex blood pressure quizlet. It is effective against sexually transmitted diseases (STDs) has under perfect use (Table 20 cheap 40 mg innopran xl otc blood pressure 9060. Natural Methods Barrier methods prevent conception by avoid- ing contact between sperm and the ovum. It is coitus- est of the woman is birth-spacing, since it has related and thus pregnancy can be the result of been observed that breastfeeding women within either method failure or inconsistency of use. The Sterilisation in women is an effective surgical feature of dual protection and the mechanism of procedure involving the blockage of the fallopian action are the same as those described for the tubes, which transport mature ova from the female condom. The most widely practised Research on the male condom has dealt with techniques are minilaparotomy and laparoscopy. Old condoms Sterilisation is the only permanent contraceptive were made of hard material, acceptability was method and the most prevalent, 180 million low and they were not very resistant to adverse couples have been reported to be sterilised storage conditions. Male condom is the most widely used of bar- rier methods but its use is not more widespread ImmunoContraceptives because it is often not accepted, mainly by the male partner. Condoms have practically no risk Research is in progress for the development of of side-effects. The only concern has been allergy a female vaccine based on the human chorionic to latex in latex condoms. Research is Withdrawal, or coitus interruptus,isalow in progress for the development of a longer- effectiveness method (Table 20. Preparations based on DMPA and from the vagina before ejaculation starts, and thus testosterone and on NET-EN and testosterone are preventing fertilisation. A depot androgen/progestin combination Sterilisation has recently demonstrated high contraceptive efficacy with satisfactory short-term safety and Vasectomy in the male is a simple surgical recovery of spermatogenesis. A possible association between vasectomy and prostate cancer was a safety concern, but obser- NON-HORMONAL CONTRACEPTIVES FOR vational studies have shown that if there is MEN such an association, the increased risk in vasec- Barrier Methods tomised men compared to non-vasectomised men is small. ImmunoContraceptives To assess the effect of hormones on the bleeding Research on vaccines for men is in progress based pattern, IUD users or sterilised women will on antibodies that neutralise the biological effect constitute a control group. An exception to this was one large RCT which allocated women at random to OCs or to vagi- PHASE I/II TRIALS nal methods (consisting of diaphragms, jellies, creams or foams). For When a contraceptive has been assessed to example, in a WHO trial (data not published) be safe in Phase I trials, its research progresses on the effect of two injectable contraceptives to Phase II trials, using the optimal dose and (DMPA and NET-EN) on lipid and lipoprotein administration schedule. Contraceptive Phase II metabolism, women requesting an injectable trials are small-scale investigations into the effec- contraceptive were allocated at random to the tiveness and safety of a contraceptive method, two preparations, and a group of non-hormone- carried out on closely monitored patients. In another have the goal to establish its mechanisms of 324 TEXTBOOK OF CLINICAL TRIALS action, metabolic effects and provide prelimi- and conducting ultrasound of ovaries. Thus, nary estimates of the frequency of common side- information is obtained on the extent to which effects, its effectiveness and its acceptability. Time to onset is recommended to previously conduct repeated- of action and to return to normal ovarian func- dose toxicity and reproduction studies in animals. Other pharmacological effects on the repro- into Phase IIA, studies on the pharmacology of ductive system: effects on the endometrium the drug in patients and Phase IIB, definitive and on the cervical mucus. Effects on other endocrine systems: pituitary, Since steroidal contraceptives are used by adrenal, thyroid. Metabolic effects: effects on hemostatic vari- mum effective dose at the initial stages of clinical ables, plasma lipids and carbohydrate metabolism. The direct assess- and suppressing oestrogen secretion, effect on ment of efficacy in small trials is not possible bone mineral density and bone metabolism. There exist surro- Design gate variables for efficacy of a steroid drug for pregnancy prevention. Phase I trials on contra- For contraception in women, recruitment into ceptives, therefore, are often also used to look Phase I trials is conducted among volunteers of at these surrogates of efficacy in addition to reproductive age, not pregnant or lactating, regu- safety issues, so that Phase I and Phase II tri- larly menstruating, identified in family planning als are combined to evaluate both safety and clinics or selected community groups, who are endocrinological endpoints. Examples of surro- IUD users or sterilised, and therefore, not at risk gates of efficacy are hormone levels as indica- of becoming pregnant. Users of other hormonal tors of inhibition of ovulation in contraceptives contraceptives than the one being studied are not for women, sperm concentration in long-acting acceptable because the method might interfere androgen–progestogen formulations for men as with the assessment of clinical and laboratory an indicator of inhibition of spermatogenesis, and parameters. Other selection criteria depend on amount of serum hCG antibodies in immunocon- the contraceptive being studied. Serological and clin- contraceptive vaccines, acute hypersensitivity to ical diagnoses of pregnancies are also conducted. These studies involve doses that activity of a steroid contained in the contra- are two or three times the initial dose. For each ceptive and its principal metabolites should dose level, a study is conducted in 10–20 healthy be described. Pharmacological action on ovarian function: Selection criteria for Phase II trials on women, the mechanism by which the contraceptive different to those mentioned for Phase I trials, are effect is attained should be described. This being currently exposed to the risk of pregnancy involves, in the first place, a description of and have proven fertility. At this stage, if the ovarian function in women with normal volunteers participating in Phase I studies are ovulatory function, measuring plasma concen- IUD users and they are willing to continue, then tration of ovarian steroids and gonadotrophins the IUD should be removed to assess efficacy. CONTRACEPTION 325 Phase IIB trials require about 50–100 subjects once-a-month preparations. The crossover design to assess efficacy and side-effects of the dosage has been used in a metabolic study to compare determined in early trials (Phase I–IIA). A Phase I trial tested When conducting Phase I/II trials, the fact that the use of progesterone as an alternative. This justifies the assessment 11 women involved one pre-treatment cycle, a of the minimum effective dose at early stages of 3-month treatment phase with an injection of development. Cyclofem every 28 days and then a 3-month When volunteers are advised on the risks and recovery phase. It confirmed that ovulation was benefits of the study in order to seek their inhibited and that inhibition of luteal activity per- informed consent, the specific risks of receiving sists after the last injection for several cycles. A comparative non-randomised study of Cyclo- fem and Mesigyna with 15 women, 8 receiv- PHASE III TRIALS ing Cyclofem and 7 Mesigyna, involved one Objectives pre-treatment cycle, three treatment cycles of 28 days and a 90-day follow-up period. The After a contraceptive is shown to be reasonably results showed that the suppressive effect of effective in Phase II trials, it is essential to com- Cyclofem was greater than Mesigyna. Specific Phase II studies on biochemical variables Design and Trial Size are conducted when required. These variables include lipid and lipoprotein metabolism, coagu- the most common design to compare meth- lation, fibrinolysis and platelet function as well as ods within each broad class of contracep- other physiological events such as vaginal blood tives has been the parallel group design, loss. This was the case for the develop- describe examples of these studies for injectable ment of OCs,5–7 injectables,18,19,22,32,33,38,55,67 326 TEXTBOOK OF CLINICAL TRIALS implants,27 IUDs,40–46 condoms68 and EC hand, the Committee for Proprietary Medicinal regimens. This Examples of comparisons of new versus standard, calculation is based on the criterion that the respectively, are the following: NET-EN ver- difference between the upper 95% confidence sus DMPA (injectables), Norplant II versus Nor- limit for the Pearl index (number of pregnancies plant (implants), steroid-releasing versus copper per 100 women-years) and the point estimate does not exceed 1.

Furthermore 40mg innopran xl free shipping prehypertension values, inevitably arbitrary decisions regarding wedge purchase 40mg innopran xl heart attack 30s, endplate buy generic innopran xl canada blood pressure 14090, or crush deformities purchase generic innopran xl on-line fetal arrhythmia 30 weeks, as assessed in some grading schemes, are not necessary since most fractures Fig. The repro- ducibility of the method for the diagnosis of prevalent and incident vertebral fractures was found to be high, with in- traobserver agreement of 93–99% and interobserver agree- ment of 90–99%. This indicates that close agreement among readers can be reached using this standardized visual semi- quantitative grading method, and that subjectivity in the readings can be reduced. This accounts for experienced and relatively inexperienced readers with reasonable re- sults. There are limitations of this semiquantitative grading scheme that may also apply to other standardized ap- proaches. For example, from the morphometric data on normal subjects we know that vertebrae in the middle tho- racic spine (especially in women) and thoracolumbar junc- tion (especially in men) are slightly more wedged than in other regions. As a result these nor- mal variations may be misinterpreted as mild vertebral de- formities, thereby falsely increasing prevalence values for vertebral fractures. Accurate di- agnosis of prevalent fractures which requires distinguish- ition [3, 42]. Typically six points are used to derive the an- ing between normal variations and the degenerative changes terior height (h ), the central (middle or middle-vertebral, a from true fractures still depends on the experience of the h ) height, and the posterior height (h ; Fig. It has been argued that the diagnosis of mild ver- clusively quantitative approach has, however, a number of tebral fractures (grade 0. The reader may sometimes feel that even duction in vertebral heights such as 15–20% or 3 SD de- though a further height reduction is seen in a previous ver- crease. Furthermore, a significant number of false positives tebral fracture, it may not be justified to assign a higher are found with quantitative techniques. The choice of point fracture grade on a serial radiograph, since some degree of placement in the quantitative technique, but especially the settling or remodeling generally occurs. Therefore in gen- choice of the threshold for defining vertebral deformity, eral, serial radiographs including the baseline radiograph gives results that vary in specificity and sensitivity. Most of a patient should be viewed together so that incident of the moderate to severe deformities are detected by both fractures can be readily identified as only those progres- techniques. However, only expert visual evaluation can sive changes that lead to a full increase in deformity grade detect mild and subtle deformities, as well as appreciate or from a questionable deformity (grade 0. The strength of a semiquantitative approach is that it makes use of the entire spectrum of visible features that Quantitative morphometry and its comparison are helpful in identifying deformities [15, 49]. The visual with the semiquantitative methods interpretation, when performed by the expert eye, also separates true deformities from normal or anomalous ver- Quantitative morphometric assessment of vertebral defor- tebrae. In addition to changes in dimension, vertebral de- mity was introduced in order to obtain an objective and formities are generally detected visually by the presence reproducible measurement, using rigorously defined point of endplate deformities, the lack of parallelism of the end- placement and well-defined algorithms for fracture defin- plates, and the general altered appearance compared with 27 neighboring vertebrae. Some of these visual characteris- on Vertebral Fractures suggested the following procedural tics are not captured by the six-digitization points used in requirements for a qualitative (semiquantitative) assess- quantitative techniques; this can cause some deformities ment of vertebral fractures in osteoporosis research [25]: to remain undetected. For example, only an experienced – Assessments should be performed by a radiologist or observer can make the subtle distinctions between a frac- trained clinician who has specific expertise in the radi- tured endplate and wedge shaped appearance caused by ology of osteoporosis. This is often interpreted as a wedge frac- performed according to a written protocol of fracture ture in quantitative studies. Reference to however, a reader using a visual approach could rather ar- an atlas of standard films or illustrations may be help- bitrarily consider a mild wedge deformity normal, anom- ful. It is recommended that a standardized protocol be alous, or fractured; in such a case, a well-defined quanti- developed by a consensus of expert radiologists. Even here, however, with – the definition of fracture should include deformities of borderline wedge deformity, small subjective difference the endplates and anterior borders of vertebral bodies, in joint placement could result in considerable variation in as well as generalized collapse of a vertebral body. An atlas of stan- Most incident fractures, as with prevalent fractures, are dard films and illustrations may again help to assure easily identifiable visually on sequential radiographs. This can result in the morphometric detection of ing the grading in discrete, exclusive categories may be an incident fracture that would be interpreted visually as problematic at times, particularly for prevalent fractures. These sources of false- However, for the assessment of vertebral fractures in the positive or false-negative interpretation are especially com- form of a fracture/nonfracture dichotomy, trained readers mon when parallax problems due to radiographic technique have achieved excellent results. Serial radiographs of a patient A number of comparative studies have evaluated the should always be viewed together in chronological order relative performance of the quantitative morphometric and to accomplish a thorough and reliable analysis of all new the semiquantitative methods and moderate correlations fractures. Because a vertebral fracture is a permanent event were found in most of them [1, 17, 29, 52]. The concor- that is unlikely to vanish on follow-up radiograph, tempo- dance was high for fractures defined as moderate or se- ral blinding does not appear to be any use: most readers vere by semiquantitative reading. There was, however, a easily identify a temporal sequence of films by new de- significant discordance for fractures defined as mild in the formities as well as by progressive disc degeneration and semiquantitative reading. Additionally, the interobserver osteophyte formation, which are universal among the el- agreement was demonstrated to be better for the visual derly. The authors of these studies concluded that quantitative morphometry should not be performed in isolation, particularly when applying highly Alternatives to radiographic assessment sensitive morphometric criteria at low threshold levels of vertebral fractures without visual assessment to confirm the detected preva- lent or incident vertebral deformities as probable fractures. Because of the difficulty in identifying vertebral fractures clinically, and the practical difficulties preventing routine radiographic assessment at the point of care, vertebral Standardization of visual approaches fracture status is frequently unknown at the time of patient to vertebral fracture assessment evaluation for BMD [18]. Hence the interest in morpho- metric assessment from dual X-ray absorptiometry (DXA) In an effort to develop a standardized consensus protocol images was a natural consequence of the need for quanti- for the visual assessment of vertebral fractures, the United tative fracture evaluation in pharmaceutical trials. High-dose, dual-energy acquisi- tions, while slower, generally provide higher bone con- trast images and sometimes reduce artifacts. The use of fan-beam DXA images for quantitative (morphometric) assessment of spinal fractures has been reported in both research applications and pharmaceutical trials [4, 11, 19, 21, 28, 37, 38, 46]. Clinical studies demonstrated the feasibility of visual evaluation of fan- beam lateral DXA spine images compared to conventional lateral spine radiographs in postmenopausal women, with a strong overall agreement of 96. This agree- ment was approximately as strong as that found among different morphometric techniques [15, 21]. The main shortcoming of the MXA scans in comparison with conventional radiographs is the inferior image qual- ity that limits the evaluation of vertebrae in the upper tho- Fig. This is less of a concern if MXA is used as a lows both visual (a) and quantitative (b) assessment of vertebral fractures screening tool for conventional radiography and this ap- proach may help reduce the radiation dose in the diagno- sis and monitoring of osteoporosis. The use of high-resolution lateral spine images, Conclusion obtained with fan-beam X-ray bone densitometry systems. Most new vertebral fractures, even lar to that used by computed tomography (CT) systems, painful ones, remain unrecognized by patients and their can image the lateral spine in as little as 10 s. It is established that the presence of a verte- scout scans, with about the same image resolution as fan- bral fracture is a strong risk factor for subsequent osteo- beam DXA scans, have been used for vertebral fracture porotic fractures, and that those with low bone density and identification [24, 43, 48]. Large-scale clinical As with radiographs, however, CT images are expen- trials have demonstrated that osteoporosis therapies can sive and are not available clinically without referral. Con- reverse bone loss and reduce fracture rates, and that these sequently CThis not generally an option unless performed benefits are most pronounced in patients with low BMD in conjunction with quantitative CT for BMD assessment. Clinical guidelines promulgated In contrast, DXA images can be performed at the point of by the National Osteoporosis Foundation, International care, in conjunction with standard BMD determination, Osteoporosis Foundation, and others recognize the impor- with a radiation dose as much as 100 times lower than that tance of vertebral fractures, along with BMD, as the key of conventional radiographs.

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Persons being fampin with pyrazinamide have been used to treat LTBI with considered for treatment with this regimen should be in- effectiveness discount innopran xl 80mg with mastercard hypertension zone tool. Although the optimal length of rifampin therapy formed about potential hepatotoxicity and asked whether in children with LTBI is unknown generic innopran xl 40mg mastercard hypertension lowering foods, the American Academy of they have had liver disease or adverse effects from INH order innopran xl toronto hypertension of chronic kidney disease is medicated with. The RIF-PZA regimen is recommended mainly for clients There have been no reported studies of any regimen for treat- who are unlikely to complete longer courses of treatment ment for LTBI in HIV-infected children order innopran xl 40mg free shipping hypertension vasoconstriction. The RIF-PZA regimen does increase risks of hepatotoxicity skin-test reactions (>5 mm) should be treated with one of the in clients with HIV infection. Still, INH daily for 9 months recommended regimens described above, regardless of age. Contacts of patients with INH-resistant, rifampin-susceptible LTBI when completion of treatment can be assured. For patients with intolerance to pyrazinamide, <20 mg/kg/d and a maximum of 2 g/d; giving no more than rifampin alone for 4 months is recommended. If rifampin can- a 2-week supply of rifampin and pyrazinamide at a time; not be used, rifabutin can be substituted. Contacts of patients with multidrug-resistant (MDR)-TB who adherence, tolerance, and adverse effects, and at 8 weeks to are at high risk for developing active TB are generally given document treatment completion. Immunocompetent contacts may be observed with- and seek medical care if abdominal pain, emesis, jaundice, out treatment or treated for 6 months; immunocompromised con- or other symptoms of hepatitis develop. Provider continu- tacts (eg, HIV-infected persons) should be treated for 12 months. Perform liver function tests (eg, serum aspartate and alanine butol are recommended for 9 to 12 months if the isolate is sus- aminotransferases [AST and ALT] and bilirubin) at base- ceptible to both drugs. RIF-PZA treatment should be (continued) 564 SECTION 6 DRUGS USED TO TREAT INFECTIONS BOX 38–2 TREATMENT OF LATENT TUBERCULOSIS INFECTION (LTBI) (Continued) drugs to which the infecting organism is likely susceptible should (eg, the length and complexity, possible adverse effects, and be given. With rifampin, the drug is contraindicated or with intermittent regimens (eg, twice weekly) and when possi- should be used with caution in persons who are taking protease ble with 2-month regimens and in certain settings (eg, institu- inhibitors or nonnucleoside reverse transcriptase inhibitors tional settings, community outreach programs, and for persons (NNRTIs). Rifabutin can be substituted for rifampin in some living in households with patients who are receiving home- circumstances, but it should not be used with hard-gel based DOT for active TB). This is determined by the soft-gel saquinavir and nevirapine because data are limited. For daily INH, the 9-month regimen should include at daily dose (ie, from 300 mg/d to 150 mg/d) with indinavir, least 270 doses in 12 months and the 6-month regimen should in- nelfinavir, or amprenavir and to one fourth the usual dose clude at least 180 doses in 9 months. For twice-weekly INH, the (ie, 150 mg every other day or 3 times a week) with ritonavir. For the 2-month regimen of daily rifampin (or ri- fabutin) and pyrazinamide, at least 60 doses should be given in not recommended as a substitute for rifampin because its 3 months. For the 4-month regimen of daily rifampin alone, at safety, effectiveness, and interactions with anti-HIV medication least 120 doses should be given in 6 months. A history of Bacille Calmette-Guérin though, ideally, patients should receive medication on a regular (BCG) vaccination should not influence the decision to treat schedule until the course of therapy is completed. When Additional Recommendations restarting therapy after interruptions, the original regimen may 1. Before beginning treatment for LTBI, active TB should be be continued as long as needed to complete the recommended ruled out by history, physical examination, chest radiography, duration of the particular regimen or a new regimen may be and bacteriologic studies, if indicated. Allow patients to participate in choosing a treatment regimen, is interrupted for longer than 2 months, the client should be re- when feasible, by discussing options and characteristics of each assessed for active TB before restarting drug therapy. Drugs at a Glance: Primary Antitubercular Drugs Dosage Ranges (Maximum dose) Adults Children Name/Route DAILY TWICE/WEEK DAILY TWICE/WEEK Comments Isoniazid (INH) 5 mg/kg 15 mg/kg 10–20 mg/kg 20–40 mg/kg LTBI: Given at least 6 mo; 9 mo preferred PO or IM (300 mg) (900) (300) (900) Active TB: Given at least 6 mo, with other drugs Rifampin (Rifadin) 10 mg/kg 10 mg/kg 10–20 mg/kg 10–20 mg/kg LTBI: Given 4 mo alone or 2 mo with pyrazinamide PO or IV infusion (600 mg) (600 mg) (600 mg) (600 mg) Active TB: Given for 6 mo, with other drugs Pyrazinamide PO 15–30 mg/kg 50–70 mg/kg 15–30 mg/kg 50–70 mg/kg LTBI: Given 2 mo with rifampin (2 g) (4 g) (2 g) (4 g) Active TB: Given for 2 mo with INH and rifampin Streptomycin IM 15 mg/kg 25–30 mg/kg 20–40 mg/kg 25–30 mg/kg Used for active TB, with other drugs (1 g) (1. It some people are slow acetylators and others are rapid induces hepatic microsomal enzymes and accelerates the acetylators. Slow acetylators have less their serum concentrations, half-lives, and therapeutic effects. In Affected drugs include acetaminophen, anti-AIDS drugs these clients, INH is more likely to accumulate to toxic con- (protease inhibitors and nonnucleoside reverse transcriptase centrations and the development of peripheral neuropathy is inhibitors; see Chap. However, there is no significant difference in the cyclosporine, estrogens, fluconazole, ketoconazole, mexiletine, clinical effectiveness of INH. Rapid acetylators may require methadone, metoprolol, phenytoin, propranolol, quinidine, unusually high doses of INH. They also may be more sus- oral contraceptives, oral sulfonylureas, theophylline, verapamil, ceptible to serious liver injury because of rapid formation of and warfarin. Hepatotoxicity may be mani- concurrent administration with rifampin may precipitate signs fested by symptoms of hepatitis (eg, anorexia, nausea, fa- and symptoms of opiate withdrawal unless methadone dosage tigue, malaise, and jaundice) or elevated liver enzymes. Its mechanism of action is the same as are more than five times the normal values. Hepatitis is more that of rifampin, so that most rifampin-resistant strains are likely to occur during the first 8 weeks of INH therapy and in also resistant to rifabutin. Clients receiving INH should be with HIV infection, to treat Mycobacterium avium complex monitored monthly for signs and symptoms of hepatitis. Be- (MAC) disease, and to substitute for rifampin in patients who cause of the risk of hepatotoxicity, INH should be used cau- need both antitubercular and certain antiviral drugs. Peripheral major advantages of rifabutin over rifampin are a longer neuropathy may be manifested by numbness and tingling in serum half-life (45 hours, on average) and reduced hepatic in- the hands and feet. It is most likely to occur in clients who are duction of microsomal metabolism. Rifabutin has no advan- malnourished or elderly, or who have alcoholism, diabetes tage over rifampin in treatment of tuberculosis but may be mellitus, or uremia. Pyridoxine 25 to 50 mg daily is usually given concurrently with INH to clients who need prophylaxis given with INH to minimize peripheral neuropathy. Rifampin is a rifamycin drug that is bactericidal for both Rifabutin is well absorbed from the GI tract; a dose of intracellular and extracellular tuberculosis organisms. It is mycobacteria by inhibiting synthesis of ribonucleic acid extensively metabolized in the liver (and to a lesser extent in (RNA) and thereby causing defective, nonfunctional proteins the intestinal wall); it is excreted in urine and bile. Its ability to penetrate intact cells contributes Like rifampin, rifabutin and its metabolites may cause a to its effectiveness in tuberculosis because mycobacteria are harmless red-orange discoloration of urine, feces, saliva, harbored in host cells. Soft contact lenses may be combination and eliminate tuberculosis bacilli from sputum permanently stained. Adverse effects include GI upset (nau- and produce clinical improvement faster than any other drug sea, vomiting, diarrhea), hepatitis, muscular aches, neutrope- regimen, unless organisms resistant to one or both drugs are nia, skin rash, and uveitis (an eye disorder characterized by causing the disease. Hepatotoxicity is Rifampin is well absorbed with oral administration and rare. Adverse effects increase when rifabutin is administered diffuses well into body tissues and fluids, with highest con- centrations in the liver, lungs, gallbladder, and kidneys. Peak serum concentration occurs in 1 to 3 hours with oral admin- istration and immediately with IV administration. It is me- Nursing Notes: Apply Your Knowledge tabolized in the liver and excreted primarily in bile; a small amount is excreted in urine. Its elimination half-life is ap- proximately 3 hours with a 300-mg dose and approximately Christine Sommers, during chemotherapy for breast cancer, ex- 5 hours with a 600-mg dose. Because it is a strong inducer of perienced symptoms of tuberculosis (TB) and had an abnormal drug-metabolizing enzymes, its half-life becomes shorter chest x-ray. The drug causes a harmless red-orange with isoniazid and rifampin is started.

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J Bone Miner Res 10:890–902 phase II study with 1-year of follow-up A randomized controlled study order 80 mg innopran xl free shipping prehypertension myth. Black DM buy innopran xl 40 mg cheap blood pressure when sick, Cummings SR order innopran xl with a mastercard blood pressure pulse, Karpf DB buy innopran xl no prescription pulse jet pressure, of risedronate (NE-58095) in post- Intern Med 113:649–655 Cauley JA, et al (1996) Randomised menopausal osteoporosis. Gallagher JC, Riggs BL, Recker RR, trial of effect of alendronate on risk of Int 7:488–495 Goldgar D (1989) the effect of cal- fracture in women with existing verte- 23. Cohen S, Levy RM, Keller M, Boling citriol on patients with postmenopausal bral fractures. Lancet 348:1535–1541 E, et al (1999) Risedronate therapy osteoporosis with special reference to 11. Black DM, Thompson D, Bauer DC, prevents corticosteroid-induced bone fracture frequency. 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