By U. Ismael. Harris-Stowe State College.
Newer drugs such as pritelivir buy 7.5 mg meloxicam with mastercard can u get arthritis in your neck, that do not inhibit DNA polymerase but rather heli- case meloxicam 15 mg lowest price arthritis medication sulfasalazine, another herpes virus enzyme trusted meloxicam 15 mg arthritis knee numbness, have been effective in clinical trials (Tyring 2011 7.5mg meloxicam with amex arthritis diagnosis, Wald 2014). However, additional studies are warranted to define the potential of helicase inhibitors. A local anesthetic that can be produced by the pharmacist can be prescribed in addi- tion for painful mucocutaneous lesions. Unfortunately, the approved tetracaine solu- tion (HervirosTM) has been taken off the market. Some pharmacists can, however, confect something similar in-house. However, a meta-analysis of almost 2000 patients in eight randomized studies showed that acyclovir can reduce the risk of both HSV and HZV disease by more than 70%. The introduction of ART has changed the relevance of this data. Nevertheless, it can still make sense, even today, to treat persistent recurrences with long-term low-dose acyclovir or valacyclovir (DeJesus 2003, Warren 2004). However, short bursts of subclinical genital HSV reactivation are frequent, even during high- dose acyclovir therapy (Johnston 2012). Herpes simplex vaccines are still in early stages of development (Belshe 2012). Treatment/prophylaxis of HSV infection (daily doses) Acute therapy Duration: 7–14 days Treatment of choice Acyclovir Acyclovir 1 tab. Large randomized studies demonstrated that during anti-HSV therapy, HIV replication is also inhibited. During treatment with acyclovir, HIV plasma viremia is decreased by 0. High dose valacyclovir resulted in a slightly greater reduction of HIV replication (Mugwanya 2011, Perti 2013). Even the rate of disease progression can be reduced. In a large randomized trial in Uganda, acyclovir showed a significant clinical benefit, with the greatest effect in individuals with a high baseline viral load (Reynolds 2012). Despite the fact that acyclovir does not prevent the transmission of HIV (Celum 2008+2010, Watson-Jones 2008), these results have recently revived the interest in acyclovir therapy (Vanpouille 2009). Possibly new derivatives will be developed that are better tolerated and more effec- tive in terms of HIV antiviral potency. Efficacy results of a trial of a herpes simplex vaccine. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. A comparison of topical application of penciclovir 1% cream with acyclovir 3% cream for treatment of genital herpes: a randomized, double-blind, multicentre trial. Valaciclovir versus aciclovir for herpes simplex virus infection in HIV-infected individuals: two randomized trials. Valacyclovir for the suppression of recurrent genital herpes in HIV-infected subjects. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. Clinical efficacy of high-dose acyclovir in patients with HIV infection: a meta-analysis of randomized individual patient data. Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials. Resistance of herpes simplex virus infections to nucleoside analogues in HIV-infected patients. Meta-analysis of randomized trials on the association of prophy- lactic acyclovir and HIV-1 viral load in individuals coinfected with herpes simplex virus-2. High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a ran- domized, crossover trial. Valaciclovir: a review of its long term utility in the management of genital herpes simplex virus and cytomegalovirus infection Perti T, Saracino M, Baeten JM, Johnston C, Diem K, Ocbamichael N, Huang ML, Selke S, Magaret A, Corey L, Wald A. High-dose valacyclovir decreases plasma HIV-1 RNA more than standard-dose acyclovir in persons coin- fected with HIV-1 and HSV-2: a randomized crossover trial. Effect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-con- trolled trial.
There was no difference in overall adverse events or in withdrawals due to adverse events generic 7.5mg meloxicam with mastercard arthritis diet blog. A one-year open-label extension of this trial was 128 conducted to assess the longer-term safety of zaleplon in older patients cheap 15mg meloxicam overnight delivery arthritis dogs natural. In a subgroup analysis of our adjusted indirect meta-analysis order meloxicam 7.5mg without prescription arthritis in back at 30 years old, there was no difference between any of the newer insomnia drugs in sleep latency in older patients generic meloxicam 7.5mg without prescription arthritis gaps diet. In a subgroup analysis of a study of ramelteon in older adults with severe sleep-onset insomnia (>60 minutes), there were significant reductions in subjective sleep latency with 94 ramelteon 8 mg (-23. Improvement over placebo was also evident at weeks 3 and 5. Insomnia Page 39 of 86 Final Report Update 2 Drug Effectiveness Review Project A case-control study (N=6110) of the relationship between use of zolpidem or other medications and occurrence of hip fracture in older women found an increased risk of fracture in 145 patients using zolpidem (adjusted odds ratio 1. This risk was higher than the risk with benzodiazepines (adjusted odds ratio 1. The study did not include other newer insomnia drugs, and so it provides no information for comparing the risk associated with zolpidem with the risk associated with other newer drugs for insomnia. An observational study used data from a representative survey of Medicare beneficiaries to determine if the increased risk of hip fracture observed with sedative hypnotic use might be 143 due to confounding factors that are not available from claims data. Potential confounders were body mass index, current smoking status, activities-of-daily-living score, cognitive impairment, and Rosow-Breslau physical impairment scale. The authors found that the activities-of-daily- living score was the strongest confounder, causing an overestimation of 10% in comparisons of zolpidem users with benzodiazepine users. They conclude, however, that the magnitude of the effect of unmeasured confounders is unlikely to explain completely the greater incidence of hip fracture observed in older users of sedative hypnotic. A good-quality systematic review and meta-analysis compared the risks and benefits of a 126 variety of pharmacological treatments for insomnia in people at least 60 years old. The review included studies of newer sedative hypnotics, benzodiazepines, and over-the-counter medications such as antihistamines. Results were combined for all sleep agents for most outcomes, so this review cannot be used to make conclusions about the comparative efficacy and safety between newer sedative hypnotics or between newer sedative hypnotics and other sleep agents. Studies comparing zaleplon, zopiclone, and zolpidem (combined) with benzodiazepines found no significant difference in cognitive adverse events (odds ratio 1. For all sedative hypnotics (newer and older) compared with placebo, the number needed to harm for all adverse events was 6 (95% CI 4. On the basis of these results, the authors concluded that in older people the benefit of sleep agents may not outweigh their risks. Pregnancy A prospective cohort study in Canada evaluated pregnancy outcomes after first-trimester 133 exposure to zopiclone in 40 women. The sample consisted of women who had initiated contact with a program that provides counseling for pregnant women, thus it is not representative of the total population of women who were exposed to zopiclone during pregnancy. Newborns in the zopiclone group had a significantly lower mean birth weight than newborns never exposed to the drug (3249 ± 676 grams compared with 3624 ± 536 grams; P=0. Once birth weight was adjusted for gestational age, the differences were no longer significant. There was no difference in outcome of pregnancy, delivery method, assisted deliveries, fetal distress, presence of meconium at birth, preterm deliveries, or neonatal intensive care admissions between zopiclone and control groups. A 1998 report of prescription-event monitoring studies of newly marketed drugs, conducted in general practices in the UK, includes information on pregnancy outcome in 23 146 women exposed to zolpidem and 18 exposed to zopiclone during pregnancy. In women who had taken zolpidem, there were 2 spontaneous and 6 legal abortions. In women who had taken Insomnia Page 40 of 86 Final Report Update 2 Drug Effectiveness Review Project zopiclone, there were 3 spontaneous and 3 legal abortions, and in one the outcome is unknown. There were no congenital anomalies among the 18 live births in women exposed to either drug. Comorbid conditions Active-control trials show that zopiclone is similar to benzodiazepines for sleep outcomes and 23 adverse effects in patients withdrawing from alcohol, patients with generalized anxiety 34 41 disorder, and in patients with stroke living in a residential care facility. Zolpidem 5 mg, but not 10 mg, was more effective than triazolam 0. Zaleplon has been studied in placebo-controlled trials in patients undergoing 109 kidney dialysis. Zopiclone has been compared with placebo in trials of patients with 76 75, 82 97 rheumatoid arthritis or fibromyalgia and in patients who are shiftworkers. Eszopiclone 112 was more effective than placebo for insomnia in patients with rheumatoid arthritis, in patients 78 with depression who were also taking fluoxetine, in patients with generalized anxiety disorder 214 114 who were also taking escitalopram, and in peri- and postmenopausal women. In a single- dose study, ramelteon 16 mg improved polysomnographic sleep duration, total sleep time, and WASO in patients with mild to moderate chronic obstructive pulmonary disease; there was no difference between ramelteon and placebo on subjective sleep measures or on objective sleep 215 latency. While these studies provide evidence that these drugs are effective for some sleep outcomes in patients with particular comorbid conditions, they do not provide evidence about the comparative efficacy of newer insomnia drugs in these subgroups.
Convenience samples may or may not be representative of a population that would normally be receiving an intervention 7.5mg meloxicam for sale arthritis swollen knee exercises. Crossover trial: A type of clinical trial comparing two or more interventions in which the participants order meloxicam 7.5mg on line arthritis foundation gout diet, upon completion of the course of one treatment generic 15mg meloxicam otc arthritis urethritis conjunctivitis, are switched to another 15mg meloxicam arthritis in dogs hind legs treatment. 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 Drug Effectiveness Review Project reports. Dosage form: The physical form of a dose of medication, such as a capsule, injection, or liquid. The route of administration is dependent on the dosage form of a given drug. Various dosage forms may exist for the same compound, since different medical conditions may warrant different routes of administration. 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 Long-acting opioid analgesics 47 of 74 Final Update 6 Report Drug Effectiveness Review Project in trials, its meaning can vary to include blinding of patients, caregivers, investigators, 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, when an oral agent is compared with an injectable agent). Effectiveness: The extent to which a specific intervention used under ordinary circumstances does what it is intended to do. Effectiveness outcomes: Outcomes that are generally important to patients and caregivers, such as quality of life, responder rates, number and length of hospitalizations, and ability to work. Data on effectiveness outcomes usually comes from longer-term studies of a “real-world” population. Effect size/estimate of effect: The amount of change in a condition or symptom because of a treatment (compared to not receiving the treatment). It is commonly expressed as a risk ratio (relative risk), odds ratio, or difference in risk. Efficacy: The extent to which an intervention produces a beneficial result under ideal conditions in a selected and controlled population. Equivalence level: The amount which an outcome from two treatments can differ but still be considered equivalent, as in an equivalence trial, or the amount which an outcome from treatment A can be worse than that of treatment B but still be considered noninferior, as in a noninferiority trial. Equivalence trial: A trial designed to determine whether the response to two or more treatments differs by an amount that is clinically unimportant. This lack of clinical importance 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. Exclusion criteria: The criteria, or standards, set out before a study or review. Exclusion criteria are used to determine whether a person should participate in a research study or whether an individual study should be excluded in a systematic review. Exclusion criteria may include age, previous treatments, and other medical conditions. External validity: The extent to which results provide a correct basis for generalizations to other circumstances. For instance, a meta-analysis of trials of elderly patients may not be generalizable to children. Studies are assumed to be measuring the same overall effect. Fixed-dose combination product: A formulation of two or more active ingredients combined in a single dosage form available in certain fixed doses. Forest plot: A graphical representation of the individual results of each study included in a meta- analysis and the combined result of the meta-analysis. The plot allows viewers 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 represented as a diamond. The center of the diamond is at the pooled point estimate, and its horizontal tips show the confidence interval. Long-acting opioid analgesics 48 of 74 Final Update 6 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. Half- life: The time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.
For example discount 15 mg meloxicam free shipping dr oz arthritis relief gloves, in one study quality 7.5mg meloxicam arthritis in neck causing pins and needles, 10% 52 genes were investigated in plasma cells derived from healthy No end-organ damage* SMM Serum M-protein 3 g/dL and/or light-chain controls buy cheap meloxicam 7.5mg online arthritis in the inner knee, MGUS buy 15mg meloxicam with mastercard arthritis treatment bangalore, SMM, and multiple myeloma patients; the investi- restricted BM plasma cells 10% gators showed that hierarchical clustering identiﬁed 4 groups from No end-organ damage* GEP analysis. The percentage of plasma cells is low (by End-organ damage* deﬁnition 10%), so that there is signiﬁcant contamination with other kinds of cells despite selection of CD138 cells on magnetic Based on expert discussions at the IMWG meeting in Stockholm in June 2013, it is anticipatedthatupdatedconsensuscriteriawillbedeﬁnedinthenearfuture. In addition, in MGUS patients—unlike in multiple myeloma studies suggest that additional features such as BM plasmacytosis 60%,48 an patients—monoclonal plasma cells are likely to be signiﬁcantly abnormal sFLC ratio 100 (involved kappa) or 0. Until we have *One or many of the following features: hypercalcemia with calcium level 11. Among 71 patients who (through loss of heterozygosity, gene ampliﬁcation, mutation, or during a 10-year follow-up time developed multiple myeloma, epigenetic changes) additional genetic hits over time. Based on current nant clonal population and fail to take into account the presence of standard technologies (eg, FISH), the molecular makeup of my- 24,25 intratumoral subclonal heterogeneity. Using single nucleotide eloma precursor disease states and multiple myeloma are strikingly polymorphism–based mapping arrays, a progressive increase in the similar and no deﬁning molecular features unique to multiple incidence of copy number abnormalities from MGUS to SMM and myeloma have been identiﬁed. In addition, the transformative to multiple myeloma (median 5, 7. The hyperdiploid group includes recurrent tri- somies with 48-74 chromosomes. IgH rearrangements were found at similar preva- lence rates among 78/189 (41%) MGUS, 44/125 (35%) SMM, and from MGUS/SMM to multiple myeloma is likely, from a Darwinian- 183/398 (46%) multiple myeloma patients. Based on this understand- myeloma patients compared with MGUS patients (25%), studies ing, it is becoming increasingly plausible that, after disease initia- suggest a higher frequency among patients with t(4,14) and t(4,16) tion, the molecular events that are necessary for myeloma develop- rearrangements. Indeed, the BM microenvironment consists of 3 components: the cellular component (hematopoietic and nonhema- topoietic cells, including the vasculature); the extracellular matrix component (ﬁbrous proteins, proteoglycans, glycosaminoglycans, and small integrin-binding ligand N-linked glycoproteins [SIBLING]); and the soluble component (cytokines, growth factors, adhesion molecules, and other factors). Shared positive and negative interactions among a range of cells in the BM (such as: stromal cells, osteoclasts, osteoblasts, immune cells (T lymphocytes, dendritic cells), other hematopoietic cells and their precursors, and vascular endothelial cells34,35) are mediated by a variety of adhesion molecules, cyto- kines, and receptors. Additional stimuli such as hypoxia result in activation of HIF-1 and secretion of VEGF. Such aspects include homing to the BM, spread to secondary BM sites by the bloodstream, generation of paracrine factors (eg, IL-6, IGF-1, and APRIL), osteoclastogenesis, inhibition of osteogenesis, humoral and cellular immunodeﬁciency, angiogenesis, and ane- Figure 1. However, it is more likely that the pathway to myeloma is qualitatively similar to those of abnormal plasma cells; however, in through branching pathways typical of those that are associated with the MGUS/SMM, the composition of cells in the BM microenviron- evolution of species (B). The key molecular events leading to disease ment is altered. This simple branching model clearly has implications for cells, if the altered composition of cells in the BM microenviron- targeted treatment because the multiple distinct subclones could lead to ment precedes proliferation/activation of abnormal plasma cells, or differential responses to treatment. Reprinted with permission from if there is a combination of these mechanisms. The sFLC ratio has been used as a prognostic indicator both in patients Little is known about the epigenetic changes necessary for progres- with MGUS37 and SMM. Based on recent advances in immunophenotyping plasma cells and The BM microenvironment plays a key role in MGUS/SMM measuring sFLC, 2 independent risk stratiﬁcation schemes for initiation and propagation. At 20 years, patients with risk-factor models, the most recently updated 2010 IMWG guide- no risk factors had a 5% risk of progression compared with 21%, lines6 propose the following clinical management of individuals 37%, and 58% for patients with 1, 2, or 3 risk factors, respectively. Recently, a study screening for sFLC abnormalities without a detectable M-protein found a much lower risk of progression to multiple myeloma compared with conventional MGUS. At 5 years, risk of progression to multiple myeloma Aggressive disease monitoring is based on whether patients ﬁt into was 25%, 51%, and 76% for patients with 1, 2 or 3 risk factors, MGUS or SMM precursor disease and the above outlined risk 8,38 factors in the Mayo Clinic model and Spanish study group model. In contrast, the risk stratiﬁcation scheme of the PETHEMA Study Group has focused on the use of multiparameter For the ﬁrst time, the 2010 IMWG guidelines suggest risk stratify- ﬂow cytometry of the BM to quantify the ratio of abnormal, ing all patients with MGUS and SMM and differentially monitoring neoplastic plasma cells (aPCs) to normal plasma cells. At 5 years of patients on the basis of their risk category. Per study protocol, each MGUS patients with any risk factor (ie, intermediate- or high-risk patient was assigned risk scores based on both the Mayo and the MGUS) should be evaluated with baseline BM examination with Spanish models. The Mayo Clinic model identiﬁed 38, 35, and 4 cytogenetics and FISH studies in addition to bone imaging studies patients as low, medium, and high risk, respectively. There was signiﬁcant discor- 6 ﬁrst year, followed by annual SPEP and routine laboratory tests. In SMM, beyond mandatory baseline before clinicians can determine whether initiation of early treatment BM examination and skeletal survey, the guidelines recommend is beneﬁcial to patients with high-risk SMM. Using baseline serum It is critical to recognize that in a disease such as multiple myeloma, samples (available for 999 persons) obtained within 30 days of an in which deﬁning criteria rely on the presence or absence of MGUS diagnosis at Mayo Clinic (1960-1994), quantitation of end-organ damage, diagnosis is only as good as the tools and individual heavy/light chains (for example, IgG in IgG MGUS technology able to detect end-organ damage. HLC- while playing a central role in disease monitoring. For example, in pair suppression was a signiﬁcant risk factor for progression (hazard SMM or high-risk MGUS patients highly suspicious as harboring ratio [HR] 2.
Altman RD generic meloxicam 15mg overnight delivery define arthritis deformans, Dreiser R-L buy discount meloxicam 7.5 mg is arthritis in back painful, Fisher CL cheap meloxicam 7.5 mg visa arthritis knee wrap, Chase WF discount 7.5mg meloxicam mastercard arthritis diet gout, Dreher DS, Zacher J. Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo- controlled trial. Barthel HR, Haselwood D, Longley S, 3rd, Gold MS, Altman RD. Randomized controlled trial of diclofenac sodium gel in knee osteoarthritis. Topical diclofenac patch in patients with knee osteoarthritis: a randomized, double-blind, controlled clinical trial. Roth S, Willoughby DA, Maddin S, Vanzieleghem M, Fraser R. A controlled clinical investigation of 3% diclofenac/2. Efficacy of topical diclofenac diethylamine gel in osteoarthritis of the knee. DHEP plasters as a topical treatment of knee osteoarthritis--a double-blind placebo-controlled study. A placebo-controlled study of the efficacy and tolerability of a nonsteroidal anti-inflammatory drug, DHEP plaster, in inflammatory peri- and extra- articular rheumatological diseases. Simon LS, Grierson LM, Naseer Z, Bookman AAM, Zev Shainhouse J. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of Nonsteroidal antiinflammatory drugs (NSAIDs) 45 of 72 Final Report Update 4 Drug Effectiveness Review Project topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. Celecoxib for the prevention of sporadic colorectal adenomas. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. Kearney PM, Baigent C, Godwin J, Halls H, Emberson J R, Patrono C. Do selective cyclo- oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis: meta-analysis of randomised trials (Structured abstract). Risk of cardiovascular events associated with selective COX-2 inhibitors. Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Significant upper gastrointestinal events associated with conventional NSAID versus celecoxib. Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? Gastroduodenal ulcers associated with the use of non-steriodal anti-inflammatory drugs: a systematic review of preventative pharmacological interventions. Canadian Coordinating Office for Heatlh Technology Assessment, Technology Overview no. Selective cyclooxygenase 2 inhibitors and cardiovascular events. Advisory Committee Briefing Document: Celecoxib and Valdecoxib Cardiovascular Safety. Renal safety and tolerability of celecoxib, a novel cyclooxygenase-2 inhibitor. Effects of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal antiinflammatory agents and placebo on cardiovascular thrombotic events in patients with arthritis. Nonsteroidal antiinflammatory drugs (NSAIDs) 46 of 72 Final Report Update 4 Drug Effectiveness Review Project 90. Celebrex Capsules (Celecoxib) NDA 20-998/S-009 Medical Officer Review. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygnease 2 selective and non-selective non- steroidal anti-inflammatory drugs: nested case-control study. Risk of myocardial infarction in patients taking cyclo- oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs: a population-based case-control study. Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction.
As an example order meloxicam 15 mg free shipping arthritis exclusion diet, the Addis Ababa unacceptable charges or delays in performing a Fistula Hospital is well endowed and with its five cesarean section meloxicam 7.5mg line arthritis relief gifts. This could be because of satellite hospital cares for over 2500 patients a year volume of cases as at some teaching hospitals and provides a holistic approach including the best and lack of or inadequately trained staff at possible care for the incurable cases purchase 15mg meloxicam overnight delivery rheumatoid arthritis mouth sores. Women need to an expert and to obtain further personal training buy meloxicam 15mg low cost arthritis group. There must be better emergency transport guidelines as to the cases a novice could consider infrastructure to well-equipped and well-staffed repairing. While small steps are being made in the the whole spectrum of fistula surgery has already right direction there remains a large backlog of been published by the author2. The complexity of cases varies enormously: 25% It must be clearly understood that any attempt to are reasonably simple, 50% present a variety of repair obstetric fistula should not be undertaken technical challenges, and the final 25% can be ex- lightly. It is perfectly possible to repair fistula with tremely challenging to cure. Even experts cannot limited resources and one of the world’s most cure every case; in about 1 in 50 cases there is too experienced surgeons has largely taught himself and much damage to even attempt a repair. The most operated for over 30 years in Northern Nigeria with experienced surgeons claim that 95% of fistulae can the absolute minimum of resources1 and the author be closed although they may have to operate on up has operated successfully in several small hospitals to 10% a second or third time to achieve this figure. Some Fistula surgery has a justifiable reputation for being 15–20% will have severe stress incontinence be- demanding, but it may not be sufficiently appreci- cause the urethra and bladder have been so badly ated that up to 25% of cases are not difficult to cure. A few may improve in time, but, for The first operation carries the best chance of success those who do not, the operation has failed. A badly performed and failed re- ably experienced surgeon who takes on almost all pair makes a second attempt much more difficult. It is essential that doctors working in de- he or she should only be operating on the 234 Vesico-vaginal and Recto-vaginal Fistula less-damaged cases. If below this figure there is a problem with selection or surgical skill. Anyone who watches a master fistula surgeon at work will marvel at the ease with which he or she demonstrates the art of fistula surgery. Even experi- enced surgeons who come new to fistula surgery will be surprised at how demanding the operations are and how difficult they seem at the start. The distorted anatomy and rigidity of tissues come as a shock. One not only has to know what must be done but also have the skill to do it. Accurate dis- section and suturing in a confined space is difficult and requires more than average manual dexterity. There is a long learning curve owing to the com- plexity of many cases, and experience can only be gained by hands-on work and regular visits to work Figure 1 The hatched area is the site of maximum with a more experienced surgeon. A competency-based training manual has 3 exhaustion or especially if multiparous, a ruptured recently been published. Nursing care is equally important as the surgery, and can be made simple provided certain basic principles are observed. It is the surgeon’s responsi- THE OBSTRUCTED LABOR INJURY bility to be familiar with and to supervise all aspects COMPLEX of pre- and postoperative care. A fistula patient suffers from much more than a hole in the bladder. It is THE CAUSE AND NATURE OF VESICO- important to understand the full impact of the VAGINAL FISTULAE damage to the physical and mental well-being of the patient. These can the mother cannot reach help and have assistance be divided into primary conditions directly due to the head collapses and she eventually delivers a still- the ischemia from the obstructed labor and condi- born infant (if she survives that long). When the tions that are secondary to this ischemic damage. This is a communication between the genital and The extent of the injury depends on the dura- urinary tract, always involving the bladder and tion of labor and the strength of the mother to sur- often the urethra. In the most severe cases, ischemia will affect the whole of the anterior wall of the Recto-vaginal fistulae vagina, the bladder base, much of the urethra and sometimes the rectum as well, leading to a recto- Recto-vaginal fistulae may coexist with vesico- vaginal fistula. In the most extreme cases, the vaginal fistulae in more severe cases of ischemia. Varying degrees of The incidence of combined fistulae ranges from 5% vaginal stenosis are common. Attitudes to fistula patients vary from region to region: in some areas the Ureteric fistulae can arise in two ways: family can be very supportive; however, the longer a • They can result from involvement of the woman has had a fistula, the more likely it is that her uretero-vesical junction in the ischemic process, husband will divorce her. Many patients will be un- so that the ureter then drains directly into the able to socialize or to go to market, church or com- vagina outside the fistula margin. It is not surprising that many fistula patients are se- verely depressed. A prolonged labor with a still- Renal damage birth followed by incontinence is too much to A few fistula patients develop a stricture of the bear. One hundred per cent of fistula patients in lower ureter leading to hydronephrosis and loss of Ethiopia test positive for psychological disorder renal function.