Бесплатное порно. 'Джунгли' - 57 видео. Природа, Тайка, Минет, Азиатка, Лес, От первого лица, Молодая и другое. Sexual trauma is far from an isolated issue. Dr. Lori Brotto sees patients with a variety of sexual difficulties and explains how to heal sexual trauma. Sex otkritiy. Annamammedowumyt Salam ; 7 videos; views; Last updated on Dec 15, Play all. Share. Loading Save.
Watch Bengali Belly Dance Sex Videos Bengali Belly Dance Sex videos Download. Бесплатное порно. 'Секс на пляже' - видео. Пляж, Любители, Немка, Публично, Европейский, Ебля, Секс на пляже и другое. (kwansei.info) and Otkritiy medicinskiy club (kwansei.infokwansei.info). We also searched the metaRegister of Controlled Trials.
Бесплатное порно. 'Секс на пляже' - видео. Пляж, Любители, Немка, Публично, Европейский, Ебля, Секс на пляже и другое. Vesyoliy, chestniy,simpotichniy s otkritiy dushoy. If you knew the world chestnost i dobrost; What quality do you value most in the opposite sex? chestniy silniy. Pornhub is home to the widest selection of free Blowjob sex. . sindhu sex net com. Hotbird otkritiy porno kanali kendra wilkinson xxx pic.
However, use of fluoroquinolones could shorten the length of treatment and improve other outcomes in these people. Two authors independently applied inclusion criteria, assessed the risk of bias in the trials, and extracted data. We identified five RCTs participants that met the inclusion criteria. None of the included trials examined regimens of less than six months duration. Relapse and treatment failure were not reported. For death, sputum conversion, and adverse events we are uncertain if there is an effect one trial, participants, very low quality evidence for all three outcomes.
Sex relapse, we are uncertain if there is an effect one trial, participants, very low quality evidence. No sex reported on treatment failure. For death, sputum culture conversion at eight weeks, or serious adverse events we do not know if there was an effect three trials, participants, very low quality evidence for all three outcomes.
A single trial participants substituted moxifloxacin for isoniazid. Treatment failure and relapse were not reported. For otkritiy, sputum culture conversion, or serious adverse events the substitution may have little or no difference one trial, participants, low quality evidence for all three outcomes. Six trials are currently in progress otkritiy shorter regimens with fluoroquinolones.
Much larger trials with fluoroquinolones in short course regimens of four months are currently in progress. Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis bacteria. We examined the research published up to 6 March and we identified five randomised controlled trials people that met the inclusion criteria.
We found no studies that examined the effect of including fluoroquinolones in a standard six month TB treatment regimen on treatment failure. We do not know whether adding fluoroquinolones or substituting fluoroquinolones for ethambutol in a standard six month TB treatment regimen reduces treatment failure, relapse, death, or adverse events. Substituting fluoroquinolones for isoniazid in a standard six month TB treatment regimen may have little or no difference upon death and adverse events. Currently, there are nine randomised controlled trials ongoing.
Also, the primary outcomes of all the included trials were reached before initiation of antiretroviral treatment. The result may not be generalized to other situations. Levofloxacin was added to the standard regimen: mg daily for two weeks induction phase ; then mg levofloxacin thrice weekly for six weeks; then standard regimen only continuation phase.
Only four deaths sex reported: one in the intervention group and three in the controls. Of these only two sex deemed to be due to TB; one in each group. The result is not statistically significant. The adverse effects are described as: nausea, vomiting, peripheral neuropathy, dermatologic reactions with fever, haematological adverse events, renal or metabolic toxicity, and sex toxicity. All three trials were considered at high risk of bias due to high levels of exclusions from the final analysis.
It was conducted in adults in Brazil between and and is not easily generalized to other fluoroquinolones or populations. This study was underpowered to detect an effect. Moxifloxacin, gatifloxacin, and ofloxacin have been compared to ethambutol and moxifloxacin in three trials, and gatifloxacin and ofloxacin in sex trial each.
These were conducted in adults from Brazil between andNorth America, and Africa dates not givenand South Africa between and Much larger trials would be necessary to show an effect. CIs of two of three studies are wide and studies remain underpowered. All three trials were underpowered to detect difference and CIs are wide. Only seven deaths occurred and three were deemed related to TB.
This single study was underpowered to detect an effect. Only 14 serious adverse events occurred and they were equally distributed between comparison groups. Although the incidence of TB has declined since otkritiy, the global burden of the disease remains high with an estimated 8.
Active TB disease may be fatal if left untreated or if treated inappropriately. In1. Effective pharmacological treatment for TB has been available since the s.
Ethambutol is believed to be a weak drug used otkritiy to prevent the emergence of resistance. Levofloxacin is included as an alternative based on availability and programme considerations WHO b.
The mechanism of action is inhibition of the DNA gyrase enzyme which is responsible for supercoiling of nucleic acid, an essential process for all bacteria. This mechanism is distinct from that of other antituberculous drugs, raising the possibility of synergistic activity. The favourable combination of pharmacodynamic and pharmacokinetic characteristics of fluoroquinolones Ginsburg could give the following benefits when added to antituberculous regimens:.
Induce resistance sex M. The problem of resistance to fluoroquinolones is sex complicated by the broad indications of this class of antimicrobials in treatment of various lower respiratory tract and other infections. This may at least be partially responsible for the rising resistance rates among M. Retrospective studies have shown that empiric antituberculous treatment with fluoroquinolones or fluoroquinolone use for misdiagnosed pneumonia delayed diagnosis of TB in an endemic area and impaired outcomes Yoon ; Wang These drugs are likely to be used as substitutes for existing drugs or as an addition to current treatment regimens in regimens based on rifampicin and pyrazinamide of six months duration or less.
Are four month regimens with fluoroquinolone as good as six months of the standard regimen HRZE? Randomized controlled trials RCTs. We also planned to compare regimens containing fluoroquinolone drugs but given for less than six months to this standard regimen.
Treatment failure, defined as sex or recurrent positive sputum cultures after four months of treatment, in participants in whom medication ingestion was assured. Relapse, defined as becoming sputum smear or culture positive up to two years after being culture negative having completed therapy. Time to sputum culture or smear conversion, defined as a continuous outcome providing an estimate of time in weeks or months needed to achieve the first sex sputum culture otkritiy smear.
We attempted to identify all relevant trials regardless of language or publication status published, unpublished, in press, and in progress. Lilia E. We independently applied the inclusion criteria using an eligibility form and resolved any disagreements by discussion. We obtained the full text article if we agreed it was relevant and in cases of uncertainty. Finally, where we were still unsure if the study otkritiy be included because further information was necessary, we allocated the study to the list of those awaiting assessment otkritiy we then attempted to contact the study authors for clarification.
We excluded studies that did not meet the inclusion criteria and gave the reason for exclusion in the ' Characteristics of excluded studies ' section. We independently LEZ and GDAV extracted data on trial characteristics, including methods, participants, interventions, and outcomes as well as data on dose and drug ratios of the combinations using a standardized data extraction form. We resolved any differences in the extracted data by referring to the original otkritiy and through discussion.
Where data were insufficient or missing we attempted to contact the trial authors for additional information. For binary efficacy outcomes, we extracted the number of participants with the event and the number analyzed to allow for complete case analysis in each treatment group. We extracted the number of serious adverse events and have presented these data in a forest plot.
Where the trial data permitted we extracted the total number of participants with adverse events and with fluoroquinolone specific adverse events. We followed the guidance to assess whether adequate steps had been taken to reduce the risk of bias across six domains: sequence generation; allocation concealment; blinding of participants, personnel, and outcome assessors ; incomplete outcome data; selective outcome reporting; and other sources of bias.
We have categorized these judgments as 'low risk of bias', 'high risk of bias', or 'unclear'. Where we judged risk of bias as unclear, we attempted to contact the trial authors for clarification.
We presented dichotomous data and we combined them using risk ratios. If the same trial was included in the analysis more than once, we split the numbers of participants in the control group proportionately.
Where data from the trial reports were insufficient, unclear, or missing, we attempted to contact the trial authors for additional information.
The complete case analysis does not make an assumption about the outcome of missing patients. The potential effects of missing data were explored through a series of sensitivity analyses Appendix 2. For this reason we conducted a sensitivity analysis which aimed to restore the integrity of the randomization process as is usual in trial analysis and test the robustness of the results to this methodology.
For a summary of the methodology and sensitivity analysis see Appendix 2. Complete case analysis: We extracted the total numbers of failures, relapses, deaths, and sputum otkritiy conversions and we used them as numerators. The denominator excludes participants for whom an outcome was not available e. We did not present funnel plots due to the small number of trials.
We used Review Manager 5 to analyze the data and we grouped the trials according to comparisons. We planned to investigate potential sources of heterogeneity through the following subgroup analyses if the number of trials permitted: HIV status, participant age, fluoroquinolone dose, length of treatment, and allocation concealment.
We would have explored the impact of risk of bias on the results if there were more studies that met the inclusion criteria. We identified five RCTs that otkritiy the inclusion criteria out of 71 potentially relevant trials see ' Characteristics of included studies 'and nine trials that sex still in progress see ' Characteristics of ongoing studies '. We illustrated these results in the study flow diagram Figure 1. The five RCTs that met the inclusion criteria included otkritiy, with a range of to over participants per trial.
The participants were aged 18 years or older. Study locations were diverse and three trials included multiple centres. Three trials Burman ; Rustomjee a ; Conde substituted a fluoroquinolone for ethambutol for the first two months of treatment.
The drugs tested were moxifloxacin mg daily Burman ; Rustomjee a ; Condegatifloxacin mg daily Rustomjee a or ofloxacin mg daily Rustomjee a. Rustomjee a was a four arm trial in which three different fluoroquinolones substituted for ethambutol were compared to the control. One trial Dorman compared moxifloxacin mg daily substituting for isoniazid. None of the included trials addressed the third research question of this review on the potential of fluoroquinolones to reduce treatment duration from six months to four months.
The treatment doses of standard antituberculous drugs isoniazid, rifampicin, pyrazinamide, and ethambutol were within the recommended body weight adjusted limits but varied among the trials. All of the included trials ensured the adherence of participants by administering the drugs under direct observation with special nursing facilities in outpatient settings or in hospital settings see Characteristics of included studies. Trials did not report in a uniform way on time to culture conversion.
Many women are greatly distressed that their bodies get aroused—and for some women they even reach orgasm—during an unwanted sexual encounter, and this leaves them confused about whether they did or did not provide consent. The genital sexual response in women is somewhat automatic. In other words, it is possible for physical arousal to take place even if a woman feels completely turned off or disgusted in her mind. Physical arousal is not the same as consent, and just because she may have had vaginal lubrication, this does not mean that she agreed to the sex.
Only her words can convey whether she has consented. Your practice is partly based in cognitive behavioral therapy CBT. How can this form of therapy help women who have been sexually abused? For example, although she may have been victimized by a man at night, this does not mean that all men are perpetrators or that being out at night is dangerous.
Another critical component of CBT involves teaching women skills to help them cope with anxiety. For example, there are effective muscle relaxation skills that can be practiced on a daily basis to cope with the heightened sense of tension and anxiety that many women experience.
Another core aspect of CBT for dealing with sexual trauma is exposure. This might involve having the woman write about or talk about the trauma repeatedly until it does not evoke psychological distress or dissociation. Mindfulness is an incredibly powerful tool that is based on an incredibly simple practice: bring the attention to a focus point in the present moment, and do so while being kind to yourself.
Mindfulness has been found in many studies to be an effective way of managing anxiety. In other words, a person may be afraid of something that may happen, or they may avoid a situation for fear of something. Mindfulness guides the person to focus their attention to the present moment, and in so doing, they learn to view their worrisome thoughts as simply by-products of brain activity, rather than predictions of proof.
Not only do they experience a reduction in anxiety and worry, but they also learn to take great joy in living in the present moment after learning how to incorporate mindfulness into their life. Can you offer any takeaway or tools for those outside of your practice who have suffered some sort of sexual trauma? If you do not feel adequately supported or understood by someone, find another person. Finding a therapist you feel comfortable with is key to healing.
What are some good resources for women who have experienced sexual trauma, or for women who have loved ones who have? Lori Brotto Q How many of your patients have experienced sexual trauma? A In my clinical practice, about half the women I see have experienced a sex-related trauma.
Q How can sexual trauma be defined? Q How do lasting effects manifest in the lives of your patients today? Q Is it possible for women who have experienced sexual trauma to begin to enjoy sex again? A Absolutely. Q Is it ever too late to resolve an issue around sexual trauma? A Not at all. Q How do you begin therapy with a patient who has been sexually abused? A In my experience, one of the most important things I can provide my client is validation.
We refined the conclusions. History Protocol first published: Issue 2, Review first published: Issue 3, Date Event Description 3 May New search has been performed , Issue 7: We updated the search and included two new trials. Titarenko joined the author team. We refined the c onclusions. Differences between protocol and review , Issue 3 first review version : We did not search SIGLE because we searched for conference proceedings using alternative sources.
Characteristics of studies Characteristics of included studies [ordered by study ID] Burman Moxifloxacin mg daily orally plus basic regimen 5 days a week or thrice a week for both dosing regimens for 2 months 2. Ethambutol 0. Bayer Pharmaceuticals donated moxifloxacin and moxifloxacin placebo tablets. Two of 12 authors had a financial relationship with the commercial entity that had an interest in the subject of the manuscript. Risk of bias Bias Authors' judgement Support for judgement Random sequence generation selection bias Unclear risk "randomised in a factorial design"; "Randomisation was stratified by continent of enrolment and presence of pulmonary cavitation".
Allocation concealment selection bias Unclear risk Method of concealment not described. Review authors judged that the efficacy outcomes were not likely to be influenced by lack of blinding. Review authors judged that the safety outcomes were not likely to be influenced by lack of blinding. Blinding of outcome assessment efficacy outcomes ;detection bias All outcomes Low risk Not described in the study report. Blinding of outcome assessment safety outcomes ;detection bias Low risk Not described in the study report.
Quote: "we excluded 1 patients who took non study therapy or required more than 70 days to complete the intensive phase, 2 patients who died during the intensive phase of therapy, and 3 patients whose sputum cultures were overgrown with bacteria or yeast.
Patients who received at least one dose of study drug were included in the safety analysis". Selective reporting reporting bias Unclear risk Insufficient information to permit judgement Other bias Unclear risk Two of 12 authors had a financial conflict of interest. Interventions Fluoroquinolone moxifloxacin substituted into regimen replacing ethambutol for 2 months 8 weeks under direct supervision 1.
Moxifloxacin mg daily with an ethambutol placebo orally plus basic regimen 5 days a week for 2 months 8 weeks 2. Time to culture conversion: no numerical data 6. Chaisson's participation. Bayer Healthcare donated moxifloxacin and matching placebo. Risk of bias Bias Authors' judgement Support for judgement Random sequence generation selection bias Low risk "permuted block randomisation with blocks of four". Allocation concealment selection bias Low risk Adequate: "allocation slips sealed in opaque envelopes opened after enrolment".
Patients, study clinicians, and study staff were unaware of the treatment assignments of patients with the exception of the pharmacist who dispensed medication packets. Blinding of outcome assessment efficacy outcomes ;detection bias All outcomes Low risk Double dummy placebo control was used.
Though not specifically stated in the study report laboratory staff were likely blinded to treatment assignment. Blinding of outcome assessment safety outcomes ;detection bias Low risk Double dummy placebo control was used. Patients, study clinicians and study staff were unaware of the treatment assignments of patients with the exception of the pharmacist who dispensed medication packets. Quote: "Randomised patients were excluded if their baseline culture did not grow M.
Selective reporting reporting bias Unclear risk Insufficient information to permit judgement. Other bias Unclear risk The authors declared no conflict of interest. Bayer Healthcare donated moxifloxacin and matching placebo, but had no input into the study design, execution, or analysis. Authors described the role of the funding source in the trial from design to publication of report. Interventions Fluoroquinolone moxifloxacin substituted into regimen replacing isoniazid for 2 months 8 weeks under direct observation 1.
Moxifloxacin mg daily with an isoniazid placebo orally plus basic regimen 5 days a week or 7 days per week during the first two weeks for 2 months 8 weeks 2. Isoniazid mg plus moxifloxacin placebo daily orally 5 days a week or 7 days per week during the first two weeks for 2 months 8 weeks plus basic regimen Basic regimen: rifampicin, pyrazinamide, ethambutol, and pyridoxine in accordance with published guidelines Blumberg Outcomes 1.
Time to sputum culture conversion no numeric data provided 3. Bayer Pharmaceuticals provided moxifloxacin and moxifloxacin placebo tablets. Three out of 19 authors had a financial relationship with a commercial entity that had an interest in the subject of the manuscript. Risk of bias Bias Authors' judgement Support for judgement Random sequence generation selection bias Unclear risk Study report specified "randomly assigned" but did not mention the method of randomization.
Allocation concealment selection bias Unclear risk Not described. Review authors judged that efficacy outcomes were unlikely to have been influenced by a lack of blinding. Review authors judged that safety outcomes were unlikely to have been influenced by a lack of blinding. Laboratory staff assessing bacteriological outcomes were likely blinded to the treatment assignment.
Quote: "Two efficacy analysis groups were prespecified. A modified ITT group excluded participants whose enrolment specimen failed to grow M. For safety analyses, all participants who received at least one dose of study treatment were included". Other bias Unclear risk Three out of 19 authors had a financial conflict of interest. Interventions Fluoroquinolone levofloxacin added to regimen: 1. Levofloxacin plus standard regimen mg levofloxacin daily for 2 weeks induction phase ; then mg levofloxacin three times weekly for 6 weeks; then standard regimen only continuation phase 2.
Drugs were supplied by manufacturers. Risk of bias Bias Authors' judgement Support for judgement Random sequence generation selection bias Unclear risk Quote: "Stratified permuted block randomisation was used in both phases of this study, with the research unit being the stratification factor".
However, the specific method of randomization was not mentioned. Allocation concealment selection bias Unclear risk Allocation concealment not described. Blinding of outcome assessment efficacy outcomes ;detection bias All outcomes Low risk Study report gave no information on blinding but laboratory staff were likely blinded to treatment allocation and "all TB endpoints were reviewed by an independent clinical events committee blinded to treatment group".
Other bias High risk No conflict of interest statement. The medical findings for haematology, chemistry, liver enzymes, and cardiovascular function were not to exceed grade 2 of the Division of Microbiology and Infectious Disease. Patients weighing between 38 to 50 kg received three tablets and those weighing between 50 to 80 kg received four tablets.
Outcomes 1. Death from any cause 2. Sputum culture conversion at 8 weeks 4. Serious adverse events 5. Rate of late phase elimination of organisms as measured by serial sputum viable colony counting 6. Quote: "Patients were randomly allocated in successive blocks of 20 equally to one of four regimens for the first 8 weeks of treatment". Review authors judged that study procedures could have been affected by a lack of blinding.
Review authors judged that assessment of safety outcomes could have been affected by a lack of blinding. Blinding of outcome assessment efficacy outcomes ;detection bias All outcomes Unclear risk Not described. Review authors judged that bacteriological efficacy outcomes were unlikely to have been at high risk of bias. Blinding of outcome assessment safety outcomes ;detection bias High risk Not described.
Incomplete outcome data attrition bias All outcomes High risk 18 participants 8. Selective reporting reporting bias High risk Authors did not present data on the most frequent adverse events by study group or on cause of death by study group, or time of death.
This obscured the data. Serious adverse events occurred in 18 patients. Deaths were due to progression of AIDS in two patients, and to haemoptysis and to epileptic seizure in two other patients. Of the remaining 14 patients, two had elevated liver enzymes, three had arthralgia and the remaining nine developed one of the following events: renal failure, pancytopaenia, thrombocytopaenia, deep vein thrombosis, gastroenteritis, gastritis, Pneumocystis carinii infection, spontaneous pneumothorax or worsening pulmonary TB with AIDS.
There were no serious glycaemic events in any arm. Minor grades of hypoglycaemia or hyperglycaemia were no more evident during therapy than at baseline, nor were they more common in the Gati arm. There was no evidence of prolongation of the QTc interval in electrocardiograms". Agarwal Reported as an abstract only. No randomization. Andries Experimental animal study, plus a small section in healthy human volunteers tolerability ; not a trial report. Anonymous No randomization or control group.
Barmina Not relevant research question: roncoleukin versus basic regimen. Chambers The outcome, early bactericidal activity, not in review. Chang Not relevant research question: hepatotoxicity of pyrazinamide. Chang Not relevant research question: participants with community acquired pneumonia or exacerbation of bronchiectasis. Chen No randomization and the intervention was a combination of levofloxacin plus capreomycin.
Chukanov Mixed intervention of ciprofloxacin, ofloxacin, or levofloxacin plus kanamycin or amikacin added to the basic regimen in study group versus streptomycin added to the basic regimen in control group. Diacon b The outcome, bactericidal activity, not in review. Estebanez Exclusively urogenital TB.
Fouad Review paper, not RCT. Gosling The outcome, early bactericidal activity, not in review. Grishin No randomization; cohort study. Heemskerk Protocol for TB meningitis. Ho Reported as an abstract only, not a trial report. Johnson The outcome, early bactericidal activity, not in review. Kawahara No randomization. Kennedy Intervention: ciprofloxacin substituted for pyrazinamide and ethambutol, not in review.
Kumar Study in healthy volunteers, not a trial report, in which the outcome was uric acid concentration in urine samples excreted over 0 to 8 hours. Lee A retrospective study, not a RCT. Marra Retrospective safety study; not a trial report. Moadebi Review paper, not a trial report. Mohanty Intervention: ciprofloxacin substituted for rifampicin, not in review.
Moulding Correspondence paper, not a trial report. O'Brien Communication to the Editor of Chest; not a trial report. Pletz The outcome, early bactericidal activity, not in review. Ruslami TB meningitis, not in review. Rustomjee b The outcome, early bactericidal activity, not in review. Sirgel The outcome, early bactericidal activity, not in review. Sokolova No randomization; cohort study. Suo No randomization; not a controlled study.
Thwaites Participants: TB meningitis, not in review. TRC No control arm, that is, a group treated without the studied fluoroquinolone ofloxacin , a different fluoroquinolone, or different dose. Valerio No randomization and outcomes not reported. Venter The outcome, indices of adrenocortical function, not in review; none of the included outcomes reported, too small 20 participants.
Wang Retrospective study; not a trial report. Wolbers TB meningitis, not in review. Yoon Not a RCT report, fluoroquinolone substitution for rifampicin, not in review. Zhang The efficacy of bronchofibrescope and catheter intervention with ofloxacin and amikacin studied in comparison with traditional chemotherapy.
Zhang The efficacy of rifabutin versus rifapentine containing antituberculous regimens studied, both regimens included levofloxacin; study question not in review. Zhao No randomization. Zheng Mixed intervention of levofloxacin plus pasiniazide plus M. Zhu The efficacy of rifabutin versus rifapentine containing antituberculous regimens studied, both regimens included levofloxacin; study question not in review. Zhu A review paper, not a RCT report. Zvada Not a RCT report.
Method of allocation concealment: sequentially numbered, sealed, opaque envelopes. Blinding and masking: open label Participants Inclusion criteria: patients aged 18 years and above, residing in or around Chennai or Madurai will be eligible for enrolment to the study.
Patients will be enrolled to the study when two sputum smears are positive and will be retained for analysis only if two cultures are positive. They should consent to attend the treatment centre for supervised treatment for 6 months and for home visits by the staff of the centre.
They should give written informed consent. Interventions 1. Combined rate of failure at the end of treatment and relapse, measured at 18 months. Occurrence of serious adverse events at any time during chemotherapy, recorded as they present themselves throughout the course of the trial.
Sputum culture results at 2 months after the initiation of chemotherapy, measured at all visits. Rate of completion of chemotherapy according to the protocol, measured at all visits. Number of observed doses of chemotherapy ingested, measured at all visits. Any adverse events, recorded as they present themselves throughout the course of the trial.
Standard antituberculous regimen Outcomes 1. Percentage of relapses by 24 months following treatment cure. Percentage of adverse events. Time to relapse. Percentage of smear and culture conversion at 8 weeks. Percentage of patient cured at the end 6. Time to a composite "unsatisfactory" endpoint. Distribution of type and grading of adverse events. Interventions Participants will be randomized to receive gatifloxacin, levofloxacin, moxifloxacin, or isoniazid control , and after these arms are enrolled, they will be randomized to receive either linezolid mg once daily or linezolid mg twice daily or isoniazid control.
After the initial treatment, all participants will receive 6 months of standard antituberculous treatment outside of the hospital. Early bactericidal activity. Extended early bactericidal activity. Safety evaluations including clinical examination, complete blood counts, and serum total bilirubin, aspartate aminotransferase, and creatinine, and urinalysis will be followed to monitor for drug toxicity. Starting date February Contact information John Johnson jlj po. Week 8: no.
To compare the safety and tolerability of the 2 intensive phase regimens. Weekly or more frequent: yes. Secondary: to compare the time to respiratory culture conversion of the 2 intensive phase regimens, using data from weekly cultures. Weekly: no. To compare, by treatment group, the proportions of subjects who experience treatment failure. Month 6: no. To compare, by HIV serostatus, a the safety of the 2 intensive phase regimens, b the proportions of patients with negative sputum cultures at the end of intensive phase therapy, and c the time to culture conversion using data from weekly cultures.
Weekly or more frequently: yes. To store serum for future assessment of hypersensitivity to study drugs, should it occur; to store plasma for future assessment of drug concentrations. Randomized, parallel group, placebo controlled trial. Method of generating randomization sequence: random number table.
Serum total bilirubin level less than 2. Haemoglobin level of at least 7. Serum potassium greater than 3. Exclusion criteria: unable to take oral medication; previously enrolled in this study; received any investigational drug in the past 3 months; received an antibiotic active against M. Interventions Intervention 1: moxifloxacin in combination with ethambutol, pyrazinamide, and rifampicin: moxifloxacin, ethambutol, rifampicin, pyrazinamide for 2 months and moxifloxacin, rifampicin, and isoniazid placebo for 2 months and then isoniazid and rifampicin placebo for 2 months.
Dose depend upon weight of the patient. Intervention 2: moxifloxacin in combination with isoniazid, pyrazinamide, and rifampicin: moxifloxacin, isoniazid, rifampicin, pyrazinamide for 2 months and moxifloxacin, isoniazid, and rifampicin for 2 months. Isoniazid and rifampicin placebo for 2 months. Rifampicin and isoniazid and placebo for 4 months. Dose depend upon the weight of the patient. Outcomes Primary: 1.
Efficacy: combined failure of bacteriological cure and relapse within one year of completion of therapy as defined by culture using solid media. Safety: both comparisons: proportion of patients with grade 3 or 4 adverse events.
Timepoint: 1. Combined failure of bacteriological cure and relapse within one year of completion of therapy as defined by culture using liquid media.
The following endpoints will be measured separately using both solid and liquid media. Proportion of patients who are culture negative at eight weeks. Time to first culture negative sputum sample. Speed of decline of sputum viable count. Arora apothecaries. For drug sensitive TB treatment arms, subjects should be newly diagnosed and previously untreated. Exception: participants can be included in the trial if they were diagnosed and treated for TB greater than 5 years prior to screening and can provide documentation of cure for that episode.
Resistance to R and H will be determined using the rapid screen test Hain Plus. If the first spot sputum shows an indeterminate result, the test must be repeated on freshly collected spot sputum or overnight sputum and that result may be used.
Therefore to be eligible for this study women of childbearing potential should either: 1 use a double barrier method to prevent pregnancy i. They must also be willing to continue these contraceptive measures until one week after the last dose of study medication or one week after discontinuation from study medication in case of premature discontinuation.
The use of the above mentioned birth control method does not apply if the male participant has been vasectomized or has had a bilateral orchidectomy minimally three months prior to screening, or is not heterosexually active, or practices sexual abstinence, or if the female sexual partner has had a bilateral oophorectomy, tubal ligation or hysterectomy or both, or has been postmenopausal for at least 12 consecutive months.
Exclusion criteria: evidence of clinically significant as judged by the investigator , metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities other than the indication being studied including myasthenia gravis and malaria; end stage liver failure class Child Pugh C ; poor general condition where any delay in treatment cannot be tolerated per discretion of the Investigator; clinically significant evidence of extrathoracic TB e.
Secondary: proportion of participants with adverse events and proportion of participants who discontinue due to an adverse event in each experimental arm time frame: over 8 weeks. Proportion of patients with sputum culture conversion at 8 weeks time frame: 8 weeks. Time to sputum conversion using data from weekly cultures through 8 weeks separately, on solid and liquid media time frame: over 8 weeks. For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to entry.
Willingness to be hospitalized for approximately 16 days. Exclusion criteria: receipt of INH prophylaxis or TB therapy for more than 7 cumulative days in the last 6 months, or of any fluoroquinolone in the 1 month prior to entry; currently or within 30 days on antiretroviral treatment ART or expected to initiate ART within 2 weeks after study entry; breastfeeding; known intolerance to any of the study drugs; resistance to rifampicin determined by GeneXpert within 7 days prior to study entry; known history of resistance to isoniazid or rifampin or known close exposure i.
This test must be done in the study laboratory. The patient is aged at least 18 years at the day of informed consent. The patient has a body weight in light clothing and without shoes of at least 35 kg, but not more than 90 kg. Female patients of childbearing potential must have a negative serum pregnancy test, and consent to practise an effective method of birth control until week Effective birth control for female patients has to include two methods, including methods that the patient's sexual partner s use.
At least one must be a barrier method. Contraception by male participants must be practised until at least week 24 to cover the period of spermatogenesis. Contraceptive methods used by male participants may include hormonal methods used by the partner s. The patient has a firm home address that is readily accessible for visiting and willingness to inform the study team of any change of address during trial participation, or will be compliant to study schedule, in the discretion of the investigator.
Exclusion criteria 1. Circumstances that raise doubt about free, uncoerced consent to study participation e. Poor general condition where delay in treatment cannot be tolerated or death within three months is likely. The patient has an HIV infection and is receiving ART, or is likely to require ART during the twelve weeks of experimental study treatment as per local guidelines, or both. The patient has a known intolerance to any of the study drugs, or concomitant disorders or conditions for which SQ, rifampicin, moxifloxacin, or standard TB treatment are contraindicated.
The patient has an history or evidence of clinically relevant metabolic, gastrointestinal, neurological, psychiatric, or endocrine diseases, malignancy, or any other condition that will influence treatment response, study adherence or survival in the judgement of the investigator, especially: clinically significant evidence of severe TB e.
History of previous TB within the last five years. The patient has had treatment with any other investigational drug within 1 month prior to enrolment, or enrolment into other clinical intervention trials is planned during week 1 to Contributions of authors LEZ was the author of the original review and was responsible for this update. University of Liverpool, UK.
Wellcome Trust, UK. Moxifloxacin versus ethambutol in the first two months of treatment for pulmonary tuberculosis. Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis. A Phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. European Respiratory Journal ; 10 Suppl European Respiratory Journal ; 12 Suppl Treatment of resistant tuberculosis in Indian patients of Eastern Uttar Pradesh having isolates resistant to isoniazid, rifampicin and quinolones.
Respirology ; 12 4 :A A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. A controlled study of rifabutin and an uncontrolled study of ofloxacin in the retreatment of patients with pulmonary tuberculosis resistant to isoniazid, streptomycin and rifampicin. Roncoleukin in enhancing the efficiency of complex therapy for infiltrative pulmonary tuberculosis in adolescents. Newer fluoroquinolones for treating respiratory infection: do they mask tuberculosis?
Efficiency of a new standard chemotherapy regimen in the treatment of patients with recurrent pulmonary tuberculosis. Treatment of urogenital tuberculosis with ofloxacin.
Preliminary study. Moxifloxacin as an alternative or additive therapy for treatment of pulmonary tuberculosis. The bactericidal activity of moxifloxacin in patients with pulmonary tuberculosis. Lomefloxacin in phthisiatric practice. Respirology ; 12 Suppl 4 :A Observation of the clinical efficacy of sparfloxacin in the treatment of multiple drug resistance pneumonial tuberculosis.
Clarithromycin vs ciprofloxacin as adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy.
Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Randomized controlled trial of a drug regimen that includes ciprofloxacin for the treatment of pulmonary tuberculosis. Early bactericidal and sterilizing activities of ciprofloxacin in pulmonary tuberculosis. Prospective comparative study of ofloxacin or ethambutol for the treatment of pulmonary tuberculosis. Antituberculosis effect of levofloxacin.
Levofloxacin treatment of active tuberculosis and the risk of adverse events. Trials; Vol. Fluoroquinolones for the treatment of pulmonary tuberculosis. International Journal of Tuberculosis and Lung Disease ; 12 9 Chest ; 4 Population pharmacokinetics of levofloxacin, gatifloxacin, and moxifloxacin in adults with pulmonary tuberculosis. Early bactericidal activity of moxifloxacin in treatment of pulmonary tuberculosis: a prospective, randomized study.
Early bactericidal activity and pharmacokinetics of the diarylquinoline TMC in treatment of pulmonary tuberculosis. The early bactericidal activity of ciprofloxacin in patients with pulmonary tuberculosis. Lomefloxacin in complex treatment of acute progressive form of pulmonary tuberculosis.
A randomized controlled study of sparfloxacin and ofloxacin in the treatment of multiple drug resistant pulmonary tuberculosis. Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis. Shortening short course chemotherapy: a randomized clinical trial for treatment of smear positive pulmonary tuberculosis with regimens using ofloxacin in the intensive phase.
Empirical treatment with a fluoroquinolone delays the treatment for tuberculosis and is associated with a poor prognosis in endemic areas. Sample size requirements for separating out the effects of combination treatments: randomised controlled trials of combination therapy vs. Impact of fluoroquinolones on the diagnosis of pulmonary tuberculosis initially treated as bacterial pneumonia. Effectiveness and safety of levofloxacin for multidrug resistant pulmonary tuberculosis: A systematic review.
References to ongoing studies ICMR. Controlled comparison of two moxifloxacin containing treatment shortening regimens in pulmonary tuberculosis. Michael Hoelscher. The clinical use of fluoroquinolones for the treatment of mycobacterial diseases. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic.
An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. Fluoroquinolones: a new treatment for tuberculosis? Fluoroquinolones, tuberculosis, and resistance. Contacts of cases of active pulmonary tuberculosis.
GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. Chapter 8: Assessing risk of bias in included studies. Available from www. Jacobs MR. Activity of quinolones against mycobacteria. PLoS One ; 4 9 :e The global tuberculosis situation and the new control strategy of the World Health Organization.
Chapter 6: Search for studies. Martindale: the extra pharmacopoeia. London: Royal Pharmaceutical Society, Review Manager RevMan. Version 5. Treatment of tuberculosis: guidelines for national programmes.
Stop TB Dept. WHO model list of essential medicines: 15th edition. Geneva: World Health Organization, accessed August World Health Organization.
Fact File: 10 Facts about tuberculosis. World Health Organisation. Geneva, Switzerland: World Health Organization, Global tuberculosis control: WHO report WHO Model list of essential medicines: 17th edition.
Sputum culture conversion at 8 weeks. Fluoroquinolone substitution for ethambutol. Fluoroquinolone substitution for isoniazid. Sensitivity analysis 1 — Worst case: Negative outcomes b. Sensitivity analysis 2 — Best case: Negative outcomes. Sensitivity analysis 1 — Worst case: Positive outcomes culture conversion at eight weeks. Sensitivity analysis 2 — Best case: Positive outcomes c culture conversion at eight weeks. Serious adverse events: Burman participants. Conde participants. Assessed at weekly clinic visits.
Rustomjee a participants. Dorman participants. Assessed at baseline and weeks 2, 4, 6, and 8 of treatment: symptoms, blood tests for AST, bilirubin, creatinine, and complete blood count. We carried out a new search, included one new trial, restructured the review and refined the conclusions. We c onverted to a new review format with minor editing. Fluoroquinolone moxifloxacin substituted into regimen replacing ethambutol for 2 months 8 weeks , initial 2 weeks of daily therapy under "supervision" 1.
Not described in study report. Blinding of outcome assessment efficacy outcomes ;detection bias All outcomes. Not described in the study report. Blinding of outcome assessment safety outcomes ;detection bias. Two of 12 authors had a financial conflict of interest. Fluoroquinolone moxifloxacin substituted into regimen replacing ethambutol for 2 months 8 weeks under direct supervision 1. Adequate: "allocation slips sealed in opaque envelopes opened after enrolment".
Double dummy placebo control was used. The authors declared no conflict of interest. Fluoroquinolone moxifloxacin substituted into regimen replacing isoniazid for 2 months 8 weeks under direct observation 1.
Isoniazid mg plus moxifloxacin placebo daily orally 5 days a week or 7 days per week during the first two weeks for 2 months 8 weeks plus basic regimen Basic regimen: rifampicin, pyrazinamide, ethambutol, and pyridoxine in accordance with published guidelines Blumberg Study report specified "randomly assigned" but did not mention the method of randomization.
Three out of 19 authors had a financial conflict of interest. Fluoroquinolone levofloxacin added to regimen: 1. Quote: "Stratified permuted block randomisation was used in both phases of this study, with the research unit being the stratification factor".
Study report gave no information on blinding but laboratory staff were likely blinded to treatment allocation and "all TB endpoints were reviewed by an independent clinical events committee blinded to treatment group". No conflict of interest statement.
Hazard ratio of culture conversion in Cox regression. Not described. Authors did not present data on the most frequent adverse events by study group or on cause of death by study group, or time of death.
Abdullah Agarwal Andries Experimental animal study, plus a small section in healthy human volunteers tolerability ; not a trial report. Anonymous Barmina Not relevant research question: roncoleukin versus basic regimen. Bartacek Carroll Chambers The outcome, early bactericidal activity, not in review.
Chang Not relevant research question: hepatotoxicity of pyrazinamide. Not relevant research question: participants with community acquired pneumonia or exacerbation of bronchiectasis. Chen