Effectiveness of the community-based DOTS strategy on tuberculosis treatment success rates in Namibia

Setting: Directly Observed Treatment Short-course is a key pillar of the global strategy to end tuberculosis. Objective: The effectiveness of community-based compared to facility-based DOTS on tuberculosis treatment success rates in Namibia was assessed. Methods: Annual tuberculosis treatment success, cure, completion and case notification rates were compared between 1996 and 2015 by interrupted time series analysis. The intervention was the upgrading by the Namibian government of the tuberculosis treatment strategy from facility-based to community-based DOTS in 2005. Results: The mean annual treatment success rate during the pre-intervention period was 58.9% (range: 46-66%) and significantly increased to 81.3% (range: 69-87%) during the post-intervention period. Before the intervention there was a non-significant increase (0.3%/year) in the annual treatment success rate. After the intervention, the annual treatment success rate increased abruptly by 12.9% (p <0.001) and continued to increase by 1.1%/year thereafter. The treatment success rate seemed to have stagnated at approximately 85% at the end of the observation period. Conclusion: Expanding facility-based DOTS to community-based DOTS significantly increased the annual treatment success rates. However, the treatment success rate at the end of the observation period had stagnated below the targeted 95% success rate

Clinical pharmacy activities in chronic kidney disease and end-stage renal disease patients: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent worldwide health problems with an epidemic extent. Therefore, attention must be given to the optimisation of patient care, as gaps in the care of CKD and ESRD patients are well documented. As part of a multidisciplinary patient care strategy, clinical pharmacy services have led to improvements in patient care. The purpose of this study was to summarise the available evidence regarding the role and impact of clinical pharmacy services for these patient populations.</p> <p>Methods</p> <p>A literature search was conducted using the <it>Medline</it>, <it>Embase </it>and <it>International Pharmaceutical Abstracts </it>databases to identify relevant studies on the impact of clinical pharmacists on CKD and ESRD patients, regarding disease-oriented and patient-oriented outcomes, and clinical pharmacist interventions on drug-related problems.</p> <p>Results</p> <p>Among a total of 21 studies, only four (19%) were controlled trials. The majority of studies were descriptive (67%) and before-after studies (14%). Interventions comprised general clinical pharmacy services with a focus on detecting, resolving and preventing drug-related problems, clinical pharmacy services with a focus on disease management, or clinical pharmacy services with a focus on patient education in order to increase medication knowledge. Anaemia was the most common comorbidity managed by clinical pharmacists, and their involvement led to significant improvement in investigated disease-oriented outcomes, for example, haemoglobin levels. Only four of the studies (including three controlled trials) presented data on patient-oriented outcomes, for example, quality of life and length of hospitalisation. Studies investigating the number and type of clinical pharmacist interventions and physician acceptance rates reported a mean acceptance rate of 79%. The most common reported drug-related problems were incorrect dosing, the need for additional pharmacotherapy, and medical record discrepancies.</p> <p>Conclusions</p> <p>Few high-quality trials addressing the benefit and impact of clinical pharmacy services in CKD and ESRD patients have been published. However, all available studies reported some positive impact resulting from clinical pharmacist involvement, including various investigated outcome measures that could be improved. Additional randomised controlled trials investigating patient-oriented outcomes are needed to further determine the role of clinical pharmacists and the benefits of clinical pharmacy services to CKD and ESRD patients.</p

Cellular Islet Autoimmunity Associates with Clinical Outcome of Islet Cell Transplantation

Islet cell transplantation can cure type 1 diabetes (T1D), but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function.Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG) induction and tacrolimus plus mycophenolate mofetil (MMF) maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively) and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively). Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome.In this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG-tacrolimus-MMF immunosuppression. Tailored immunotherapy targeting cellular islet autoreactivity may be required. Monitoring cellular immune reactivity can be useful to identify factors influencing graft survival and to assess efficacy of immunosuppression.Clinicaltrials.gov NCT00623610

Nonsteroidal Antiinflammatory Drugs - Restrictive Or Non-restrictive Hepatic-clearance

Based on their hepatic extraction ratio and unbound fraction in plasma or blood drugs can be categorized as being restrictively ol non-restrictively eliminated The general perception is that drugs with very small plasma clearances and extensive plasma protein binding, such as warfarin, are eliminated restrictively. However, based on literature data for 18 non-steroidal anti-inflammatory drugs (NSAIDs) with low plasma clearances (< 60 mll min), we have shown that most of these low-extraction compounds are non-restrictively eliminated ie. their hepatic extraction ratio exceeds their unbound action in plasma. For 4 NSAIDs considered in this survey, ie. phenylbutazone and the oxicams piroxicam, isoxicam and tenoxicam, the hepatic extraction ratio is smaller than their unbound fraction in plasma, and their hepatic elimination, therefore, is restrictive. Our conclusion that most low-clearance NSAIDs are non-restrictively extracted is based an a number of realistic assumptions concerning their pharmacokinetic characteristics. 1. their elimination is exclusively hepatic, 2. bioavailability of their oral dosage form is complete, and 3. they do not undergo extensive reversible biotransformation enterohepatic circulation

Effect of hepatic insufficiency on pharmacokinetics and drug dosing

The liver plays a central role in the pharmacokinetics of many drugs. Liver dysfunction may not only reduce the plasma clearance of a number of drugs eliminated by biotransformation and/or biliary excretion, but it can also affect plasma protein binding which in turn could influence the processes of distribution and elimination. In addition, reduced liver blood flow in patients with chronic liver disease will decrease the systemic clearance of flow limited (high extraction) drugs and portal-systemic shunting may substantially reduce their presystemic elimination (first-pass effect) following oral administration. When selecting a drug and its dosage regimen for a patient with liver disease additional considerations such as altered pharmacodynamics and impaired renal excretion (hepatorenal syndrome) of drugs and metabolites should also be taken into account. Consequently, dosage reduction is necessary for many drugs administered to patients with chronic liver disease such as liver cirrhosis