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ObjectiveDirect-acting antivirals have opened an opportunity for controlling hepatitis C virus (HCV) infection in Pakistan, where 10% of the global infection burden is found. We aimed to evaluate the implications of five treatment programme scenarios for HCV treatment as prevention (HCV-TasP) in Pakistan.DesignAn age-structured mathematical model was used to evaluate programme impact using epidemiological and programme indicators.SettingTotal Pakistan population.ParticipantsTotal Pakistan HCV-infected population.InterventionsHCV treatment programme scenarios from 2018 up to 2030.ResultsBy 2030 across the five HCV-TasP scenarios, 0.6–7.3 million treatments were administered, treatment coverage reached between 3.7% and 98.7%, prevalence of chronic infection reached 2.4%–0.03%, incidence reduction ranged between 41% and 99%, program-attributed reduction in incidence rate ranged between 7.2% and 98.5% and number of averted infections ranged between 126 221 and 750 547. Annual incidence rate reduction in the first decade of the programme was around 6%–18%. Number of treatments needed to prevent one new infection ranged between 4.7–9.8, at a drug cost of about US$900. Cost of the programme by 2030, in the most ambitious elimination scenario, reached US$708 million. Stipulated WHO target for 2030 cannot be accomplished without scaling up treatment to 490 000 per year, and maintaining it for a decade.ConclusionHCV-TasP is a highly impactful and potent approach to control Pakistan’s HCV epidemic and achieve elimination by 2030.

Introduction and objectives Epidemiologic studies have implicated aeroallergens and respiratory infections as triggers underlying seasonal increases in asthma exacerbations in spring and autumn months. These seasonal factors may trigger or amplify airway inflammation in atopic, Type 2 high asthma patients that precipitates acute worsening of symptoms. Biologic therapies targeting Type 2 cytokine pathways have demonstrated efficacy in reducing the rate of severe asthma exacerbations, particularly in patients selected on the basis of Type 2 biomarkers. In children with asthma, increased inhaled corticosteroid or anti-IgE therapy has been found to reduce the rate of seasonal exacerbations. We hypothesised that lebrikizumab (anti-IL-13) therapy would likewise be effective in reducing seasonal exacerbations in adults with asthma. Methods We conducted post-hoc analyses of the Phase III LAVOLTA studies (NCT01867125 and NCT01868061) to assess the seasonal dependence of exacerbations and efficacy of lebrikizumab in 2,148 adults with moderate to severe asthma. We employed Poisson regression utilising linear mixed models to estimate the per-month (normalised by hemisphere) annualised exacerbation rate and treatment effect of lebrikizumab in reducing exacerbations (percent rate reduction). Results Per-month exacerbation rates in placebo treated eosinophil-low ( Conclusions We conclude that seasonal spikes in exacerbations may be primarily dependent on Type 2 inflammatory processes. The molecular pathways underlying asthma exacerbations are heterogeneous and therapeutic strategies targeting Type 2 biology alone may have the greatest efficacy in limiting seasonal spikes in exacerbation rates. Overall, these data highlight that a significant proportion of asthma exacerbations may be independent of seasonal influences and/or Type 2 biology and that increased therapeutic efficacy may require targeting multiple distinct pathways in asthma.

Chance variability makes it impossible to assess reliably whether individual trusts are meeting annual targets for reduction in the risk of MRSA infection One of the core standards set by the Department of Health is to achieve year on year reductions in rates of infection with methicillin resistant Staphylococcus aureus (MRSA).1 This was clarified in November 2004 by the (then) health secretary John Reid, who said that he expected “MRSA bloodstream infection rates to be halved in our hospitals by 2008,” that “NHS Acute Trusts will be tasked with achieving a year on year reduction,”2 and that such a target was “achievable, measurable, and not too burdensome.” Several problems can arise, however, when measuring change in rates, particularly when the observed number of events is fairly low. These include the effects of chance variability, regression to the mean, and low power to detect genuine underlying changes. These problems are accentuated with an infectious disease, since cases tend to cluster and hence rates are “over-dispersed” relative to chance variation.3 So how should we interpret government targets on MRSA infections? The government target of a 50% reduction in cases over three years essentially corresponds to a 20% annual reduction. But the term target is ambiguous: does it refer to an observed change in rates or a true underlying reduction in risk? At a national level this distinction may be unnecessary because of the large numbers involved, but for individual trusts the play of chance can mean that an observed rate reduction that meets the target may not accurately reflect a corresponding change in underlying risk and, conversely, that a true risk reduction may not be reflected in the observed rates, which might even increase. This lack of clarity can give rise to a range of possible criteria to determine …

Sheikh Khalifa Medical City's (SKMC) Surgery Institute was identified as a high outlier in Surgical Site Infections (SSI) based on the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) - Semi-Annual Report (SAR) in January 2012. The aim of this project was to improve SSI rates through accurate wound classification. We identified SSI rate reduction as a performance improvement and safety priority at SKMC, a tertiary referral center. We used the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) best practice guidelines as a guide. ACS NSQIP is a clinical registry that provides risk-adjusted clinical outcome reports every six months. The rates of SSI are reported in an observed/expected ratio. The expected ratio is calculated based on the risk factors of the patients which include wound classification. We established a multidisciplinary SSI taskforce. The members of the SSI taskforce included the ACS NSQIP team members, quality, surgeons, nurses, infection control, IT, pharmacy, microbiology, and it was chaired by a colorectal surgeon. The taskforce focused on five areas: pre-op showering and hair removal, skin antisepsis, prophylactic antibiotics, peri-operative maintenance of glycaemia, and normothermia. We planned audits to evaluate our wound classification and our SSI rates based on the SAR. Our expected SSI rates in general surgery and the whole department were 2.52% and 1.70% respectively, while our observed SSI rates were 4.68% and 3.57% respectively, giving us a high outlier status with an odd's ratio of 1.72 and 2.03. Wound classifications were identified as an area of concern. For example, wound classifications were preoperatively selected based on the default wound classification of the booked procedure in the Electronic Medical Record (EMR) which led to under classifying wounds in many occasions. A total of 998 cases were reviewed, our rate of incorrect wound classification assignment was 36%, and the worst rates were in appendectomies (97%). Over time our incorrect wound classification decreased down to 22%, while at the same time our actual SSI wound occurrences per month and our odds ratio of SSI in the department have decreased an average of six to three per month. We followed the best practice guidelines of the ACS NSQIP. Accurate assessment of wound classification is necessary to make sure the expected SSI rates are not falsely high if wounds are under-classified. The present study shows that accurate wound classification in contaminated and dirty wounds can lead to lower odds ratio of SSI.

The efficacy of combining rate and pressure reduction during weaning by synchronous intermittent mandatory ventilation (SIMV) were compared with weaning by patient triggered ventilation (PTV) (pressure reduction alone) in two randomised trials. Regardless of ventilation mode, pressure was reduced to the same level according to the size of the infant. In the first trial, the SIMV rate was also reduced progressively to a minimum of 20 breaths/minute, and in the second to five breaths/minute. Forty premature infants aged 15 days of age or less were randomly allocated into each trial. No significant differences were found in the first trial between ventilation modes in either the duration of weaning or the number of infants in whom weaning failed. In the second trial, the duration of weaning was shorter by PTV than by SIMV (median 24 hours, range 7-432 v 50 hours, range 12-500; p < 0.05); weaning failed in two infants in the PTV group and in five in the SIMV group. It is concluded that weaning by a combination of pressure and rate reduction, such as can be achieved during SIMV, offers no significant advantage over pressure reduction alone.