Prognostic Factors for Success After Irrigation and Debridement With Modular Component Exchange for Infected Total Knee Arthroplasty.

BACKGROUND: Irrigation and debridement with modular component exchange (IDMCE) can treat prosthetic joint infection (PJI) after total knee arthroplasty (TKA). Compared to 2-stage revision, IDMCE is associated with lower morbidity but may carry higher infection recurrence rates. We aimed to identify prognostic factors associated with successful IDMCE in patients with PJI. METHODS: We identified 99 consecutive patients who underwent IDMCE following TKA PJI at a tertiary academic medical center from November 2009 through January 2016. Examined variables included age, gender, symptom duration, body mass index, Charlson comorbidity index, total protein, albumin, hemoglobin A1c, erythrocyte sedimentation rate (ESR), C-reactive protein, white blood cell count, gram stain results, final cultures, and use of long-term antibiotic suppression. Success was defined as no further operation on the ipsilateral knee. We used t tests and chi-square analyses to determine whether each preoperative factor was associated with IDMCE reoperation. RESULTS: At mean follow-up of 2.6 years, 64 patients who underwent IDMCE were defined as successful. Thirty-five patients required one or more additional procedures for recurrent infection; of these, 20 patients underwent 2-stage revision. Patients with symptom duration of less than 2 days avoided additional surgery in 88% of cases. Elevated ESR >47 mm/h was the only variable associated with reoperation (P = .005). There were no associations among the other examined variables. CONCLUSION: Using IDMCE for PJI after TKA required reoperation in 35% of cases. Elevated preoperative ESR laboratory values and duration of symptoms >2 days were associated with reoperation.

Tuberculosis control in South African gold mines: mathematical modeling of a trial of community-wide isoniazid preventive therapy.

A recent major cluster randomized trial of screening, active disease treatment, and mass isoniazid preventive therapy for 9 months during 2006-2011 among South African gold miners showed reduced individual-level tuberculosis incidence but no detectable population-level impact. We fitted a dynamic mathematical model to trial data and explored 1) factors contributing to the lack of population-level impact, 2) the best-achievable impact if all implementation characteristics were increased to the highest level achieved during the trial ("optimized intervention"), and 3) how tuberculosis might be better controlled with additional interventions (improving diagnostics, reducing treatment delay, providing isoniazid preventive therapy continuously to human immunodeficiency virus-positive people, or scaling up antiretroviral treatment coverage) individually and in combination. We found the following: 1) The model suggests that a small proportion of latent infections among human immunodeficiency virus-positive people were cured, which could have been a key factor explaining the lack of detectable population-level impact. 2) The optimized implementation increased impact by only 10%. 3) Implementing additional interventions individually and in combination led to up to 30% and 75% reductions, respectively, in tuberculosis incidence after 10 years. Tuberculosis control requires a combination prevention approach, including health systems strengthening to minimize treatment delay, improving diagnostics, increased antiretroviral treatment coverage, and effective preventive treatment regimens.

Cost-effectiveness of tenofovir gel in urban South Africa: model projections of HIV impact and threshold product prices.

BACKGROUND: There is urgent need for effective HIV prevention methods that women can initiate. The CAPRISA 004 trial showed that a tenofovir-based vaginal microbicide had significant impact on HIV incidence among women. This study uses the trial findings to estimate the population-level impact of the gel on HIV and HSV-2 transmission, and price thresholds at which widespread product introduction would be as cost-effective as male circumcision in urban South Africa. METHODS: The estimated 'per sex-act' HIV and HSV-2 efficacies were imputed from CAPRISA 004. A dynamic HIV/STI transmission model, parameterised and fitted to Gauteng (HIV prevalence of 16.9% in 2008), South Africa, was used to estimate the impact of gel use over 15 years. Uptake was assumed to increase linearly to 30% over 10 years, with gel use in 72% of sex-acts. Full economic programme and averted HIV treatment costs were modelled. Cost per DALY averted is estimated and a microbicide price that equalises its cost-effectiveness to that of male circumcision is estimated. RESULTS: Using plausible assumptions about product introduction, we predict that tenofovir gel use could lead to a 12.5% and 4.9% reduction in HIV and HSV-2 incidence respectively, by year 15. Microbicide introduction is predicted to be highly cost-effective (under $300 per DALY averted), though the dose price would need to be just $0.12 to be equally cost-effective as male circumcision. A single dose or highly effective (83% HIV efficacy per sex-act) regimen would allow for more realistic threshold prices ($0.25 and $0.33 per dose, respectively). CONCLUSIONS: These findings show that an effective coitally-dependent microbicide could reduce HIV incidence by 12.5% in this setting, if current condom use is maintained. For microbicides to be in the range of the most cost-effective HIV prevention interventions, product costs will need to decrease substantially.

Attaining realistic and substantial reductions in HIV incidence: model projections of combining microbicide and male circumcision interventions in rural Uganda.

OBJECTIVES: This study simulates the potential impact of male circumcision and female microbicide interventions, singularly and in combination, in rural Uganda. METHODS: A dynamic model was parameterised and fitted to setting-specific data, and used to estimate the impact on HIV transmission of a microbicide and/or male circumcision intervention over 15 years. The proportion of circumcised men or women using microbicides was assumed to increase linearly from 0.18 (male circumcision) or 0.00 (microbicide use) to the final proportion 10 years later, then remain constant for 5 years. Women using microbicides were assumed to use the product in 80% of penile-vaginal sex acts. Male circumcision or microbicide use was assumed to reduce the per-act probability of HIV acquisition in men or women, respectively, by 60%. RESULTS: Independently, to obtain a 30% relative reduction in HIV incidence at 15 years, the model suggests that the final proportion of women using microbicides would need to be 0.91 (95% CI 0.75 to 1.00) or the proportion of circumcised men would need to be 0.96 (0.83 to impact not possible). The same impact could be achieved by combining the interventions, eg, if the proportion of women using microbicides was 0.49 (0.39 to 0.56) and the proportion of circumcised men was 0.67 (0.57 to 0.74). CONCLUSIONS: Under these assumptions, as separate interventions it is unlikely that increases in either the proportion of men circumcised or of women using microbicides could reduce HIV incidence by 30% or more at 15 years. A combination-prevention strategy using complementary interventions may be a more feasible approach to achieve substantial reductions in incidence.

Unintended consequences of machine learning in medicine?

Machine learning (ML) has the potential to significantly aid medical practice. However, a recent article highlighted some negative consequences that may arise from using ML decision support in medicine. We argue here that whilst the concerns raised by the authors may be appropriate, they are not specific to ML, and thus the article may lead to an adverse perception about this technique in particular. Whilst ML is not without its limitations like any methodology, a balanced view is needed in order to not hamper its use in potentially enabling better patient care.

Using Twitter to investigate opinions about multiple sclerosis treatments: a descriptive, exploratory study.

BACKGROUND: Multiple sclerosis (MS) is a common complex disorder, with new treatment options emerging each year. Social media is being increasingly used to investigate opinions about drugs, diseases and procedures. In this descriptive exploratory study, we sought to investigate opinions about currently available MS treatments. METHODS: The Twitter resource Topsy was searched for tweets mentioning the following MS treatments: Aubagio, Avonex, Betaferon or Betaseron, Copaxone, Extavia, Gilenya, Lemtrada, Novantrone, Rebif, Tysabri and Tecfidera between 1 Jan 2006 to 31 Jul 2014. Tweets were normalised and sentiment analysis performed. RESULTS: In total, there were 60037 unique tweets mentioning an MS treatment. About half of the tweets contained non-neutral sentiment. Mean sentiment scores were different for treatments ranging from -0.191to 0.282 when investigating all tweets. These differences in sentiment scores between treatments were statistically significant (P<0.001). Sentiment scores tended to be higher for oral MS treatments than injectable treatments. CONCLUSIONS: Many tweets about MS treatments have a non-neutral sentiment. The analysis of social media appears to be a potential avenue for exploring patient opinion about MS treatments.

The impact of syphilis screening among female sex workers in China: a modelling study.

BACKGROUND: In China, female sex workers (FSWs) are at high risk of syphilis infection, but are hard to reach for interventions. Point-of-care testing introduces opportunities for expanding syphilis control measures. Modelling is used to estimate the impact of using rapid tests to screen FSWs for syphilis. In other settings, modelling has predicted large rebounds in infectious syphilis following screening, which may undermine any impact achieved. METHODS: A deterministic syphilis transmission model among FSWs and clients was fitted to data from Yunnan Province (FSW syphilis prevalence = 7.5%), and used to estimate the impact of rapid syphilis testing and treatment for FSWs. Impact projections were compared for different model structures that included risk heterogeneity amongst FSWs, incoming syphilis infections amongst new FSWs and clients and re-infection from FSWs' regular non-commercial partners. The rebound in syphilis prevalence after screening ceased was explored. RESULTS: All model structures suggest yearly syphilis screening could substantially reduce (by 72-88%) syphilis prevalence amongst FSWs in this setting over five years. However, incoming syphilis infections amongst new FSWs and clients or re-infections from regular non-commercial partners of FSWs can considerably reduce (>30%) the proportion of infections averted. Including heterogeneity in risk amongst FSWs had little effect upon the proportion of infections averted. In this setting, the rebound in syphilis prevalence after screening ceased is predicted to be slight, but it could be large in high prevalence settings. CONCLUSIONS: Rapid test screening could dramatically reduce syphilis prevalence amongst hard-to-reach groups, but strategies to reduce re-infection from regular non-commercial partners are needed to maximise impact.

Prevalence and under-detection of gambiense human African trypanosomiasis during mass screening sessions in Uganda and Sudan.

BACKGROUND: Active case detection through mass community screening is a major control strategy against human African trypanosomiasis (HAT, sleeping sickness) caused by T. brucei gambiense. However, its impact can be limited by incomplete attendance at screening sessions (screening coverage) and diagnostic inaccuracy. METHODS: We developed a model-based approach to estimate the true prevalence and the fraction of cases detected during mass screening, based on observed prevalence, and adjusting for incomplete screening coverage and inaccuracy of diagnostic algorithms for screening, confirmation and HAT stage classification. We applied the model to data from three Médecins Sans Frontières projects in Uganda (Adjumani, Arua-Yumbe) and Southern Sudan (Kiri). RESULTS: We analysed 604 screening sessions, targeting about 710,000 people. Cases were about twice as likely to attend screening as non-cases, with no apparent difference by stage. Past incidence, population size and repeat screening rounds were strongly associated with observed prevalence. The estimated true prevalence was 0.46% to 0.90% in Kiri depending on the analysis approach, compared to an observed prevalence of 0.45%; 0.59% to 0.87% in Adjumani, compared to 0.92%; and 0.18% to 0.24% in Arua-Yumbe, compared to 0.21%. The true ratio of stage 1 to stage 2 cases was around two-three times higher than that observed, due to stage misclassification. The estimated detected fraction was between 42.2% and 84.0% in Kiri, 52.5% to 79.9% in Adjumani and 59.3% to 88.0% in Arua-Yumbe. CONCLUSIONS: In these well-resourced projects, a moderate to high fraction of cases appeared to be detected through mass screening. True prevalence differed little from observed prevalence for monitoring purposes. We discuss some limitations to our model that illustrate several difficulties of estimating the unseen burden of neglected tropical diseases.

Constraints to estimating the prevalence of trypanosome infections in East African zebu cattle.

BACKGROUND: In East Africa, animal trypanosomiasis is caused by many tsetse transmitted protozoan parasites including Trypanosoma vivax, T. congolense and subspecies of T. brucei s.l. (T. b. brucei and zoonotic human infective T. b. rhodesiense) that may co-circulate in domestic and wild animals. Accurate species-specific prevalence measurements of these parasites in animal populations are complicated by mixed infections of trypanosomes within individual hosts, low parasite densities and difficulties in conducting field studies. Many Polymerase Chain Reaction (PCR) based diagnostic tools are available to characterise and quantify infection in animals. These are important for assessing the contribution of infections in animal reservoirs and the risk posed to humans from zoonotic trypanosome species. New matrices for DNA capture have simplified large scale field PCR analyses but few studies have examined the impact of these techniques on prevalence estimations. RESULTS: The Whatman FTA matrix has been evaluated using a random sample of 35 village zebu cattle from a population naturally exposed to trypanosome infection. Using a generic trypanosome-specific PCR, prevalence was systematically evaluated. Multiple PCR samples taken from single FTA cards demonstrated that a single punch from an FTA card is not sufficient to confirm the infectivity status of an individual animal as parasite DNA is unevenly distributed across the card. At low parasite densities in the host, this stochastic sampling effect results in underestimation of prevalence based on single punch PCR testing. Repeated testing increased the estimated prevalence of all Trypanosoma spp. from 9.7% to 86%. Using repeat testing, a very high prevalence of pathogenic trypanosomes was detected in these local village cattle: T. brucei (34.3%), T. congolense (42.9%) and T. vivax (22.9%). CONCLUSIONS: These results show that, despite the convenience of Whatman FTA cards and specific PCR based detection tools, the chronically low parasitaemias in indigenous African zebu cattle make it difficult to establish true prevalence. Although this study specifically applies to FTA cards, a similar effect would be experienced with other approaches using blood samples containing low parasite densities. For example, using blood film microscopy or PCR detection from liquid samples where the probability of detecting a parasite or DNA molecule, in the required number of fields of view or PCR reaction, is less than one.