By X. Shawn. State University of New York at Buffalo.
Adverse event: An adverse outcome that occurs during or after the use of a drug or other intervention but is not necessarily caused by it order cheap celebrex. Active-control trial: A trial comparing a drug in a particular class or group to another drug outside of that class or group buy on line celebrex. Allocation concealment: The process by which the person determining randomization is blinded to a study participant’s group allocation purchase generic celebrex on-line. Before-after study: A type non-randomized study where data are collected before and after patients receive an intervention. Before-after studies can have a single arm or can include a control group. Bias: A systematic error or deviation in results or inferences from the truth. Several types of bias can appear in published trials, including selection bias, performance bias, detection bias and reporting bias. Blinding: The process of preventing those involved in a trial from knowing to which comparison group a particular participant belongs. Trials are frequently referred to as “double-blind” without further describing if this refers to patients, caregivers, investigators or other study staff. Case series: A study reporting observations on a series of patients, all receiving the same intervention with no control group. Case study: A study reporting observations on a single patient. Case-control study: A study that compares people with a specific disease or outcome of interest (cases) to people from the same population without that disease or outcome (controls). Clinically significant: A result that is large enough to affect a patient’s disease state in a manner that is noticeable to a patient and/or caregiver. Cohort study: An observational study in which a defined group of people (the cohort) is followed over time and compared to a group of people who were exposed or not exposed to a particular intervention or other factor of interest. A prospective cohort study assembles participants and follows them into the future. A retrospective cohort study identifies subjects from past records and follows them from the time of those records to the present. Confidence interval: The range of values calculated from the data such that there is a level of confidence, or certainty, that it contains the true value. The 95% confidence interval is generally used in DERP reports. Confounder: A factor that is associated with both an intervention and an outcome of interest. Controlled clinical trial: A clinical trial that includes a control group but no or inadequate methods of randomization. Controller medications for asthma 210 of 369 Final Update 1 Report Drug Effectiveness Review Project Convenience sample: A group of individuals being studied because they are conveniently accessible in some way. Convenience samples may or may not be representative of a population that would normally be receiving an intervention. Cross-over trial: A type of clinical trial comparing two or more interventions in which the participants, upon completion of the course of one treatment, are switched to another. Direct analysis: The practice of using data from head-to-head trials to draw conclusions about the comparative effectiveness of drugs within a class or group. Results of direct analysis are the preferred source of data in DERP reports. Dose-response relationship: The relationship between the quantity of treatment given and its effect on outcome. In meta-analysis, dose-response relationships can be investigated using meta- regression. Double-blind: The process of preventing those involved in a trial from knowing to which comparison group a particular participant belongs. While double-blind is a frequently used term in trials, its meaning can vary to include blinding of patients, caregivers, investigators and/or other study staff. Double-dummy: The use of two placebos in a trial that match the active interventions when they vary in appearance or method of administrations (for example, an oral agent compared to an injectable agent). Effectiveness: The extent to which a specific intervention, when used under ordinary circumstances, does what it is intended to do. Effectiveness outcomes: Those outcomes that are generally important to patients and caregivers, such as quality of life, hospitalizations and ability to work. Data on effectiveness outcomes usually comes from longer-term studies of a “real-world” population. Efficacy: The extent to which an intervention produces a beneficial result under ideal conditions in a selected and controlled population. Estimate of effect: The observed relationship between an intervention and an outcome. Estimate of effect can be expressed in a number of ways, including number needed to treat, odds ratio, risk difference and risk ratio. Equivalence trial: A trial designed to determine whether the response to two or more treatments differs by an amount that is clinically unimportant. This is usually demonstrated by showing that the true treatment difference is likely to lie between a lower and an upper equivalence level of clinically acceptable differences. External validity: The extent to which reported results are generalizable to a relevant population. Fixed-effect model: A model that calculates a pooled effect estimate using the assumption that all observed variation between studies is caused by the play of chance. Studies are assumed to be measuring the same overall effect. Forest plot: A graphical representation of the individual results of each study included in a meta- analysis together with the combined meta-analysis result. The plot also allows readers to see the heterogeneity among the results of the studies. The results of individual studies are shown as squares centered on each study’s point estimate. A horizontal line runs through each square to show each study’s confidence interval - usually, but not always, a 95% confidence interval. The overall estimate from the meta-analysis and its confidence interval are shown at the bottom, represented as a diamond. The centre of the diamond represents the pooled point estimate, and its horizontal tips represent the confidence interval. Controller medications for asthma 211 of 369 Final Update 1 Report Drug Effectiveness Review Project Funnel plot: A graphical display of some measure of study precision plotted against effect size that can be used to investigate whether there is a link between study size and treatment effect. Generalizability: see External Validity Hazard ratio: The increased risk with which one group is likely to experience an outcome of interest. For example, if the hazard ratio for death for a treatment is 0.
We received dossiers from 2 pharmaceutical manufacturers: Eli Lilly and Company and Forest Laboratories Inc discount celebrex 100 mg otc. By applying the eligibility and exclusion criteria to titles and abstracts of all identified citations purchase celebrex 200 mg without a prescription, we obtained full-text copies of 119 citations purchase celebrex cheap. After re-applying the criteria for inclusion, we ultimately included 51publications. Five included studies were identified after expanding the population inclusion 38-42 criteria to include a broadened definition of fibromyalgia or fibrositis. See Appendix E for a list of excluded studies and reasons for exclusion at this stage. Drugs for fibromyalgia 17 of 86 Final Original Report Drug Effectiveness Review Project a Figure 1. Results of literature search 1121 records identified from 27 additional records identified database searches after through other sources removal of duplicates 1148 records screened 1029 records excluded at abstract level 68 full-text articles excluded 119 full-text articles assessed • 5 non-English language for eligibility • 7 ineligible outcome • 22 ineligible intervention • 9 ineligible population 51 publications included in • 9 ineligible publication type qualitative synthesis • 10 ineligible study design • 38 trials (+2 companion • 7 ineligible systematic review publications) • 3 systematic reviews • 8 others (include pooled analysis, post hoc analysis of trials etc). Trials included in quantitative synthesis (meta-analysis): • Pain = 16 • Fatigue = 9 • FIQ, PGIC = 10 • 30% and 50% response = 11 • SF-36 = 6 • Overall withdrawal = 16 • Overall adverse events = 13 • Withdrawals due to adverse events = 14 a 1 The Drug Effectiveness Review Project uses a modified PRISMA flow diagram. Drugs for fibromyalgia 18 of 86 Final Original Report Drug Effectiveness Review Project Key Question 1. For adults with fibromyalgia, what is the comparative effectiveness/efficacy of included interventions? Summary of Findings General We found no eligible studies of treatment for fibromyalgia with desipramine, imipramine, desvenlafaxine, venlafaxine, escitalopram, fluvoxamine, sertraline, mirtazapine, bupropion, nefazodone, carbamazepine, divalproex, ethotoin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenytoin, tiagabine, topiramate, valproic acid, or zonisamide We found no eligible studies of included interventions when used as adjunctive therapy. Direct evidence There was low-strength evidence that immediate-release paroxetine is superior to amitriptyline in reducing pain (−28% compared with −1%; z= −5. Indirect evidence Pooled analysis All trials included used the drugs as monotherapy and no trial evaluated the effectiveness of the drugs as adjunctive therapy Pain, 50% response rate, Patient Global Impression of Change: Pooled analysis of placebo-controlled trials of amitriptyline, pregabalin, milnacipran, and duloxetine found that all drugs were superior to placebo Fatigue: Pooled analysis of placebo-controlled trials of amitriptyline, pregabalin, and milnacipran found that these drugs were superior to placebo for short-term results, but not in longer-term trials of 24 to 28 weeks in duration. Indirect meta-analysis Pain: Indirect meta-analysis of short-term trials (8-15 weeks) of amitriptyline, pregabalin, milnacipran, and duloxetine on measures of pain found that duloxetine was superior to milnacipran (mean difference, −0. Comparisons to placebo • Gabapentin significantly improved pain severity and response, overall impact of fibromyalgia, global status, and sleep, but not tender point pain threshold, depression or overall quality of life • Compared with placebo, a significant reduction in pain severity was only found with cyclobenzaprine in 1 of 3 trials • Among selective serotonin reuptake inhibitors, only fluoxetine, at a higher dose (45 mg), resulted in significantly greater improvements than placebo in pain, fatigue, and Fibromyalgia Impact Questionnaire Total Score • Controlled-release paroxetine did not significantly decrease pain, disability, or depressiveness or increase the number of patients with a 50% or greater response, but did significantly decrease the Fibromyalgia Impact Questionnaire Total Score, fatigue, and improved global status • Citalopram did not significantly improve pain or fatigue and only reduced depression and improved sleep in 1 of 2 trials. Detailed Assessment Direct evidence Direct evidence regarding the comparative effectiveness among included interventions was limited and only available from 4 small randomized controlled trials that compared amitriptyline 43 44 45 to cyclobenzaprine (N=208), fluoxetine (N=31), nortriptyline (N=118), and immediate- 46 release paroxetine (N=68). All patients met the American College of Rheumatology 1990 criteria for classification of fibromyalgia. Three trials reported duration of fibromyalgia, which 46 43 ranged from 36 months to 101 months. Participants were 95% female with mean ages ranging 46 45 from 36 years to 53. Race was 100% Caucasian in the fluoxetine trial conducted in 44 45 Massachusetts, 62% Caucasian and 38% non-Caucasian in the Brazilian trial of nortriptyline, 43 and was not reported in the Canadian study of cyclobenzaprine or the Turkish study of 46 43, 45 immediate-release paroxetine. Trial settings included outpatient rheumatology clinics and a 44 46 tertiary referral center, but was not well described in the Turkish study. Trial durations ranged 44, 46 43 44, 45 46 from 6 weeks to 6 months. Mean dosages for the comparator drugs were 20 mg for cyclobenzaprine, 20 mg for fluoxetine, 20 mg for immediate-release paroxetine, and 25 mg for nortriptyline. The main limitation of the poor-quality trial was that its analyses excluded a large proportion of the data – Drugs for fibromyalgia 20 of 86 Final Original Report Drug Effectiveness Review Project over one-third; consequently, its results will not be discussed here, but can be found in Evidence 44 Tables 1 and 2. However, differences between immediate-release paroxetine and amitriptyline were not significant for change in fatigue (−9% compared with −5%; z=0. Otherwise, the remaining 2 trials provided low-strength evidence of no significant 43 45 differences between amitriptyline and cyclobenzaprine or nortriptyline in any efficacy outcomes. The 2 head-to-head trials were inconsistent in their methods for assessing all efficacy outcomes. Compared with amitriptyline, similar reductions were found for cyclobenzaprine in visual analog scores for pain (−33% compared with −28%) and fatigue (−33% compared with −32%), McGill Pain Questionnaire Pain Rating Index scores (−32% compared with −31%), Depression Scale scores from the Arthritis Impact Measurement Scale (−25% compared with −20%), and in the Health Assessment Questionnaire Disability Index (−15% for both drugs). Similar proportions of patients were classified as responders based on meeting at least 4 of the following 6 criteria: 50% improvement in pain, sleep, fatigue, patient global assessment, or physician global assessment, and increase of 1 kg in mean total myalgic score (33% compared 43 with 36%). Also compared with amitriptyline, similar reductions were found for nortriptyline in mean number of tender points (−3 compared with −2. We found 5 systematic reviews that assessed multiple drugs for the treatment of 47-51 47-50 fibromyalgia. Four reviews were graded as good quality and 1 was graded as fair 47 quality. Only 1 of these reviews performed an indirect meta-analysis to compare the effectiveness between duloxetine, milnacipran, and pregabalin in fibromyalgia from placebo- 49 controlled trials of individual drugs. Although it was a recent review, we chose to update the indirect meta-analysis to include evidence from 2 new trials for milnacipran that are now 52, 53 available. The remaining reviews had limited usefulness for this report as none provided any additional direct or indirect comparative data. One systematic review reported evidence on 51 antidepressant drugs used for the treatment of fibromyalgia. No meta-analysis was performed and the only individual drug data reported was the means across studies for amitriptyline. We conducted a meta-analysis comparing amitriptyline to other drugs to treat fibromyalgia so did not 51 use the data reported in this review. One systematic review reported a calculated effect size for 47 amitriptyline and tramadol but only a class effect for antidepressants. Given the new criteria for diagnosis of fibromyalgia released in 2010, we extended our inclusion criteria and included earlier studies of fibromyalgia not included in their review so did not report on their outcomes. One systematic review of amitriptyline reported on 10 randomized controlled trials but did not 50 perform a meta-analysis due to large clinical variability and statistical heterogeneity. The Drugs for fibromyalgia 21 of 86 Final Original Report Drug Effectiveness Review Project results are considered as appropriate below. One systematic review pooled data of pregabalin and gabapentin and reported on a class effect size rather than comparative data which limited its 48 usefulness for this report. Indirect evidence Indirect meta-analysis Of the 8 drugs included in this review, we found that only 4 drugs had multiple trials with sample sizes adequate to perform a comparative analysis. All trials used the drugs as monotherapy and no trial evaluated the effectiveness of the drugs as adjunctive therapy. We 39, 43, 45, 54-56 performed a meta-analysis of 6 placebo-controlled trials of amitriptyline, 4 placebo- 57-60 52, 53, 61-64 controlled trials of pregabalin, 5 placebo-controlled trials of milnacipran, and 4 65-69 placebo-controlled trials of duloxetine. Two trials of amitriptyline were identified by expanding our definition of fibromyalgia to include criteria for fibrositis that would fall under the 39, 70 umbrella of the updated definition of fibromyalia in 2010. One additional trial of pregabalin was included but did not contribute data to our analysis due to significant methodological variance from the other trials and given that its outcome was loss of 71 effectiveness in responders.
Efficacy and safety of valacyclovir for the suppression and episodic treatment of herpes simplex virus in patients with HIV order celebrex with american express. Helicase-primase inhibitor pritelivir for HSV-2 infection order 100 mg celebrex otc. Effect of herpes simplex suppression on incidence of HIV among women in tanzania celebrex 200mg online. Opportunistic Infections (OIs) 375 Herpes zoster Herpes zoster is the reactivation of an earlier infection with varicella virus, which subsequently maintains a lifelong residence in the spinal ganglia. Herpes zoster episodes can occur even in HIV+ patients with relatively good immune status, and are also seen during immune reconstitution (Martinez 1998). Given the still high incidence of zoster episodes in HIV+ patients, herpes zoster can be regarded as an indicator disease for HIV infection (Søgaard 2012, Moanna 2013). With more advanced immunodeficiency, herpes zoster tends to become generalized. In addition to involvement of one or more dermatomes, dangerous involvement of the eye (affecting the ophthalmic branch of the trigeminal nerve, “herpes zoster ophthalmicus”, with corneal involvement) and ear (herpes zoster oticus) may occur. Most feared is involvement of the retina with necrotizing retinitis. The neurological complications include meningoencephalitis, myelitis and also involvement of other cranial nerves (Brown 2001). Signs and symptoms There are often prodromal signs with headache, malaise, and photophobia, accom- panied only rarely by fever. The affected areas are initially hypersensitive, and then become pruritic and/or painful within hours or days. Lesions often show segmental, yet always unilateral, erythema with herpetiform blisters within one or more dermatomes. Lesions ulcerate, are often hemorrhagic, and gradually dry up. They should be kept dry and clean to avoid bacterial superinfection. Involvement of several dermatomes often leaves treatment- resistant pain syndromes with zoster neuralgia. Post-herpetic neuralgia can be assumed if pain persists for more than a month (Gnann 2002). Diagnosis Cutaneous involvement usually allows clinical diagnosis of herpes zoster. However, diagnosis may be difficult especially on the extremities and in complicated zoster cases. Typical cases do not require further diagnostic tests. If there is uncertainty, a swab may be taken from a blister and sent to the laboratory in viral culture media. An immunofluorescence assay is presumably more reliable. HZV encephalitis is only detectable through analysis of CSF by PCR. Herpes zoster oticus should be consid- ered in cases of unilateral, peracute hearing loss, which is not always visible from the outside. Either examine the ear yourself or consult an ENT specialist! For visual impairment the same rules apply as for CMV retinitis – refer the patient to the oph- thalmologist as quickly as possible. Treatment Monosegmental zoster can be treated on an outpatient basis with oral acyclovir. Systemic therapy is always necessary, and doses are higher than for HSV. Lesions dry up more rapidly if calamine lotion is used, which also relieves pain. Gloves should be worn, given that the lesions are highly infectious initially. Likewise, unvaccinated individuals without a history of chick- enpox should not come into close contact with a case of herpes zoster. Analgesics (novaminsulfone, or better still tramadole) should be given generously. Any complicated, multi-segmental or facial herpes zoster should always be treated with intravenous therapy. As with HSV, several alternatives for treatment include valacyclovir, famcyclovir and brivudine (see HSV). There is still controversy if the unpleasant post-herpetic neu- ralgia allegedly occurs less frequently under these drugs than under acyclovir (Li 376 AIDS 2009, McDonald 2011). Valacyclovir, famcyclovir and brivudine have not been tested widely in HIV+ patients, and are not licensed for treatment of immunocompromised patients. They are also substantially more expensive than the numerous acyclovir formulations. Acyclovir resistance may occur in the thymidine kinase gene, but is rare (Gershon 2001, Saint-Leger 2001). Novel anti-HZV drugs have recently been evaluated in clinical trials but are still in early phases of development (Review: Andrei 2011). Pain management of post-herpetic neuralgia is problematic. Since November 2007 lidocaine medicated plasters (Versatis) are licensed in Europe which can be pasted to painful areas. Herpetic lesions should be healed before use (Garnock-Jones 2009). In 2009, the FDA approved Qutenza 8% patch for the management of neuropathic pain due to postherpetic neuralgia. Qutenza delivers a synthetic form of capsaicin, the substance in chili peppers that gives them their heat sensation, through a dermal delivery system. The patch is applied by a physician or a healthcare professional. Prophylaxis Varicella vaccination, previously contraindicated in HIV patients, seems to be fairly safe and effective for patients with more than 400 CD4 T cells/µl (Gershon 2001, Weinberg 2010). It should be considered if HZV serology is negative. In individuals with negative serology and exposure to highly infectious HZV, administration of hyperimmunoglobulin (2 mg/kg IV) may be attempted in individual cases.
Factor XI knockout mice are protected against several forms 21-24 Another inhibiting factor XII antibody buy genuine celebrex online, 3F7 purchase celebrex 200 mg, has been developed of artiﬁcially induced thrombosis purchase 100mg celebrex with visa, both arterial and venous. Furthermore, this antibody proved to be as factor XI, factor XI antisense oligonucleotides, and “naturally effective as heparin in preventing ﬁbrin deposition and thrombosis occurring” factor XI inhibitors derived from bats. Without excep- using an extracorporeal membrane oxygenation system in mice and tion, these approaches showed thromboprotective effects in rodent 22-26 rabbits. Treatment with 3F7 did not impair hemostasis, suggesting thrombosis models using ferric chloride or vena cava ligation. By inhibiting factor primates, which paved the way for human studies using factor XII, it is therefore possible to affect clot structure directly, which XI antisense oligonucleotides. Human data from patients undergo- may be an interesting strategy for the treatment of thrombosis. Factor XII synthesis can also be blocked by antisense oligonucleo- All of the prothrombotic models were performed on mice with a tides. Similar to what was seen for factor XI, antisense oligonucleo- normal, healthy vasculature. However, many thrombotic disorders tides to factor XII reduced thrombus formation in several mouse are caused by atherosclerosis and occur at later age. Recently, we 40 thrombosis models in both venous and arterial beds. To our investigated whether factor XI inhibition with antisense oligonucle- knowledge, no human trials have been performed with factor otides would be successful in reducing thrombus formation in an 31 XII-inhibiting agents. ApoE knockout mice were given a Western-type diet containing 0. Factor XI was not involved in platelet Because PK is essential for factor XII activation, its inhibition plug and initial thrombus formation. However, inhibition of factor should theoretically produce similar results to factor XII inhibition. Hematology 2014 63 Indeed, PK antisense oligonucleotides revealed thromboprotective constitutes a natural procoagulant cofactor in blood coagulation. Proc effects in mouse models of chemically and mechanically induced Natl Acad Sci U S A. Polyphosphate: an ancient molecule knockout mice, which indicates that PK inhibition could be a that links platelets, coagulation, and inﬂammation. Monocytes, neutrophils, and contradictory results: inhibition of plasma kallikrein with different 42 platelets cooperate to initiate and propagate venous thrombosis in mice inhibitors produced a prothrombotic state, which is a relevant in vivo. Misfolded proteins activate factor XII in humans, leading to kallikrein formation without HK initiating coagulation. Knock-down of the murine kininogen gene 1 resulted in a mouse 10. Activation of the human contact without HK and low-molecular-weight kininogen. Furthermore, targeting HK reduced thrombus ization of prolylcarboxypeptidase as an endothelial cell prekallikrein formation in ischemic vessels and improved cerebral blood in mice, 44 activator. Physiologic activities of the contact activation system. Formation of bradykinin: a major contributor to The contact system provides a direct link between coagulation and the innate inﬂammatory response. Cleavage of HK by kallikrein produces the vasoac- 14. Plasma kallikrein: the bradykinin- tive protein BK, which has several inﬂammatory effects, but is also producing enzyme. Mice deﬁcient for the BK B2 receptor are branch of innate immunity generating antibacterial peptides. These data provide evidence for an anticoagulation strategy target- 2009;7(Suppl 1):84-87. Increased activity of coagulation The contact pathway has seen a resurgence in interest because of the factor XII (Hageman factor) causes hereditary angioedema type III. Bork K, Wulff K, Meinke P, Wagner N, Hardt J, Witzke G. A novel of the contact proteins are protected against thrombosis. These mutation in the coagulation factor 12 gene in subjects with hereditary observations led to the development of several compounds targeting angioedema and normal C1-inhibitor. Missense mutations in the coagulation factor XII approach to target (one of the) contact proteins would constitute an (Hageman factor) gene in hereditary angioedema with normal C1 effective and safe strategy for antithrombotic treatment. In addition, it will be essential to identify the deﬁciency. Effects of factor IX or factor XI deﬁciency on ferric chloride-induced carotid artery occlusion in mice. Effects of factor XI deﬁciency on Conﬂict-of-interest disclosures: J. FXI is essential for thrombus formation following FeCl3-induced injury of the carotid artery in the Correspondence mouse. Meijers, PhD, Department of Plasma Proteins, Sanquin factor XI prolongs APTT without increased bleeding risk in cynomolgus Research, Plesmanlaan 126, 1066 CX Amsterdam, the Netherlands; monkeys. Phone: 31-20-5123151; Fax: 31-20-5123310; e-mail: j. Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel References antithrombotic strategy with lowered bleeding risk. A role for factor XIIa-mediated 2010:104(5):867-874. The procoagulant and proinﬂammatory plasma contact 3981-3989. The coagulation system and its function in anti-human factor XI antibodies prevent cessation of blood ﬂow in a early immune defense. Thrombosis as an intravascular effector of antisense factor XI oligonucleotide treatment in primates. Prevention of vascular graft 64 American Society of Hematology occlusion and thrombus-associated thrombin generation by inhibition of 39. Factor XI Regulates generation through direct interaction with ﬁbrin. Girolami A, Candeo N, De Marinis GB, Bonamigo E, Girolami B. Defective thrombus formation deﬁciency on haemostasis and thrombosis in mice: murine ortholog of in mice lacking coagulation factor XII. Factor XIIa inhibitor dase depletion induces vascular dysfunction with hypertension and recombinant human albumin Infestin-4 abolishes occlusive arterial faster arterial thrombosis. Factor XII regulates brain barrier damage, and inﬂammation. Factor XII inhibition knockout mice are protected from thrombosis by increased nitric oxide reduces thrombus formation in a primate thrombosis model. A factor XIIa inhibitory decrease thrombosis in Bdkrb2 / mice by increasing NO and antibody provides thromboprotection in extracorporeal circulation with- prostacyclin to reduce platelet spreading and glycoprotein VI activation.
To mobilize fully the contralateral side of the birth buy celebrex pills in toronto. A his- bladder and support the anastomosis with a tory of a live birth increases suspicion of this type of psoas hitch stitch 200mg celebrex visa. To make a tube out of the dome of the bladder while stitching the corners of the lower segment buy celebrex uk. Anastomose the cut ureter end to side to the the ureter may slough and urine can escape into the uninjured ureter. Others occur after an emergency hysterectomy The steps of the operation are shown in Figure 20. Considering the difficult con- There is no need to splint or drain the anastomosis ditions and the inexperience of many doctors called as a routine when the ureter comes into the bladder upon to treat a ruptured uterus in rural areas, these without tension. If in doubt a ureteric catheter can injuries are understandable. Any urine leaking into be passed through the anastomosis. It will decom- the pelvis will soon find its way out between the press the ureter should there be any hold up at the sutured vaginal vault or cervical remnant. The distal end can be brought out cause is unrecognized injury to a ureter at the time alongside a urethral catheter or through a separate of a vesico-vaginal fistula repair. In this situation it stab incision in the anterior bladder wall. The ure- may be possible at a later date to catheterize the teric catheter if used can be removed on day 7 and ureter and implant it into the bladder transvaginally. If the patient has enough living children, and an abdominal operation is planned, do not forget to Labial fat grafts and fistula repair discuss the option of tubal ligation. It is so easy to For many years it was believed that a labial fat graft do it at the same time. An ultrasound scan showing sutured between the bladder and vaginal repair im- a distended ureter on one side is helpful confirma- proved the success rate, especially for the complex tion. But it is essential to confirm again on the table cases although there is no proof of this. Almost all that the dye test is really negative and that urine experienced fistula surgeons have given up using fat appears in the vagina after giving furosemide. In grafts without apparently compromising their results. The abdominal approach is usually quite easy and the results uniformly successful. The affected ureter REPAIR OF ANAL SPHINCTER INJURIES must be identified in the pelvic side wall and traced Immediate repair down to the point of injury. Four times out of five the affected Tears seen within 24 h of delivery should be repaired ureter is found to be dilated and thickening can at once. The patient’s usually be felt at the site of injury. If the ureter is future continence depends on the skill with which 260 Vesico-vaginal and Recto-vaginal Fistula (a) (d) (b) (e) (c) Figure 20 (a) A very dilated ureter has been clamped at the level of the cervix. If not very dilated it should be spatulated a little. The sutures just pick up the underlying bladder muscle. Then close the vagina and perineal skin taking good Repair under local anesthesia is possible but it is mattress sutures to build up the perineal body. It is important to realize that the torn Secondary repair anal sphincters retract to the 3 and 9 o’clock posi- tion. First, close the ano-rectal mucosa, then iden- If the repair cannot be done within 24 h it is best to tify the torn ends of the external sphincter (the wait several weeks. Sometimes patients with an old internal sphincter cannot be identified as a separate complete tear say they have no symptoms, so be layer). Suture these accurately taking quite big ‘bites’ sure that your patient really does have troublesome using Vicryl if possible. Experts would repair the fecal leakage before you recommend repair. In the sphincter by an overlapping technique but a novice best hands, only 80% of repairs restore complete would be best to stick to an accurate simple end-to- continence. Again it is important to realize that the 261 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS (a) (d) (b) (e) (c) (f) Figure 21 A typical fourth-degree tear. The external sphincter should margins of the tear and suturing this will not to give not be dissected out to its muscle fibers alone. These will not hold sutures well, but rather a block 262 Vesico-vaginal and Recto-vaginal Fistula (g) of tissue which contains the sphincter ends is mobi- lized and overlapped. RECTO-VAGINAL FISTULA A recto-vaginal fistula is only produced in the most prolonged episodes of obstruction and so is usually associated with a bad vesico-vaginal fistula and neurological damage. Isolated recto-vaginal fistulae due to obstructed labor are extremely rare but may be caused by sexual violence in war situations or in underage marriage. Anal sphincter tears usually occur in isolation unrelated to obstructed labor and should not be classified as a recto-vaginal fistula unless there is sig- (h) nificant extension into the rectum. Incompletely repaired sphincter tears are another source of low recto-vaginal fistulae. Classification is largely des- criptive, based on the distance from the anal verge and the amount of scar. When scar is prominent the rectal lumen can be considerably narrowed. In extreme cases the rectum is completely stenosed and all the feces enter the top of the vagina. Surgery is demanding and except for the lowest and most mobile should be referred to fistula experts. It has been tradition in some quarters to con- sider doing a colostomy for the bad cases before referring the patients. This does not make life any easier for the patient and experienced surgeons can repair the majority of rectal fistulae transvaginally without any preliminary colostomy. A more likely (i) scenario is that a well-meaning surgeon does a colostomy but the patient never finds a surgeon who can repair her fistula (Figure 22a). When colostomies are inexpertly done a colostomy pro- lapse may develop to add to her misery. The only person who should consider performing a colos- tomy is the surgeon who is going to repair her fistula. The principles in repairing a recto-vaginal fistula are the same as for a vesico-vaginal fistula – good exposure, flap splitting of vagina from rectum, followed by closure of the rectum in two layers (Figure 22). Most surgeons will repair the bladder and rectal fistula at the same time although for really bad cases Figure 21 (cont) (g) The rectum is closed with a the recto-vaginal fistula may be repaired alone as continuous suture down to the anal verge previously the first stage. It is unlikely that a beginner in fis- marked by a suture.