Association between glycaemic control and quality of life in diabetes mellitus

Background: Relationship between quality of life (QOL) and haemoglobin A1c (HbA1c) amongst diabetics in the community setting is unclear. Aims: Assess the association between QOL and change in HbA1c in diabetic patients over one year. Settings and Design: Cohort study of patients from four community clinics in California, USA. Methods: Diabetic patients identified from databases using International Classification of Disease (ICD-9) codes were asked to complete Short Form 36 (SF-36), which measures health-related QOL, and invited to attend monthly diabetes workshops. From December 2000 to December 2001, data were collected on multiple parameters, including HbA1c. SF-36 surveys were re-collected at project termination. Statistical Analysis: Regression analysis was used to correlate change in HbA1c with change in QOL physical component summary (PCS) and mental component summary (MCS) scores, while considering potential confounders. Results: Of 1679 eligible patients, 380 completed SF-36 at project initiation. 243 of those completed SF-36 at project termination. Pre and post HbA1c data were available for 170 of the 243 who completed SF-36 at both times. Average MCS increased by 8.46% and PCS decreased by 2.24%. After adjustment, a 5% decrease in HbA1c values was associated with a 1% increase in MCS. No association between changes in HbA1c and PCS was observed. Conclusions: Association between better HbA1c and improved mental, but not physical, QOL may reflect physical inconvenience of increased regimen complexity and mental empowerment from proactive disease management. Larger cohort studies with longer follow-up are needed to further elucidate the relationship between glycemic control and QOL

Evaluation of time-varying availability in multi-echelon spare parts systems with passivation

10.1016/j.ejor.2004.06.022European Journal of Operational Research170191-105EJOR

Performance of Xpert MTB/RIF and sputum microscopy compared to sputum culture for diagnosis of tuberculosis in seven hospitals in Indonesia

IntroductionTuberculosis (TB) is a major public health concern in Indonesia, where the incidence was 301 cases per 100,000 inhabitants in 2020 and the prevalence of multi-drug resistant (MDR) TB is increasing. Diagnostic testing approaches vary across Indonesia due to resource limitations. Acid-fast bacilli (AFB) smear is widely used, though Xpert MTB/RIF has been the preferred assay for detecting TB and rifampicin resistance since 2012 due to higher sensitivity and ability to rapidly identify rifampicin resistance. However, <1,000 Xpert instruments were available in Indonesia as of 2020 and the Xpert supply chain has suffered interruptions.MethodsWe compared the performance of Xpert MTB/RIF and AFB smear to facilitate optimization of TB case identification. We analyzed baseline data from a cohort study of adults with pulmonary TB conducted at seven hospitals across Indonesia. We evaluated sensitivity and specificity of AFB smear and Xpert MTB/RIF using Mycobacterium tuberculosis (Mtb) culture as the gold standard, factors associated with assay results, and consistency of Xpert MTB/RIF with drug susceptibility test (DST) in detecting rifampicin resistance.ResultsSensitivity of AFB smear was significantly lower than Xpert MTB/RIF (86.2 vs. 97.4%, p-value <0.001), but specificity was significantly better (86.7 vs. 73.3%, p-value <0.001). Performance varied by hospital. Positivity rate for AFB smear and Mtb culture was higher in subjects with pulmonary cavities and in morning sputum samples. Consistency of Xpert MTB/RIF with DST was lower in those with rifampicin- sensitive TB by DST.DiscussionAdditional evaluation using sputa from primary and secondary Indonesian health centers will increase the generalizability of the assessment of AFB smear and Xpert MTB/RIF performance, and better inform health policy.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT027 58236]

Safety and Immunogenicity of an HIV Adenoviral Vector Boost after DNA Plasmid Vaccine Prime by Route of Administration: A Randomized Clinical Trial

In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor.This multicenter, open-label, randomized trial, HVTN 069, compared routes of administration on safety and immunogenicity of a DNA vaccine prime given intramuscularly at 0, 1 and 2 months and a recombinant replication-defective adenovirus type 5 (rAd5) vaccine boost given at 6 months by intramuscular (IM), intradermal (ID), or subcutaneous (SC) route. Randomization was computer-generated by a central data management center; participants and staff were not blinded to group assignment. The outcomes were vaccine reactogenicity and humoral and cellular immunogenicity. Ninety healthy, HIV-1 uninfected adults in the US and Peru, aged 18-50 were enrolled and randomized. Due to the results of the Step Study, injections with rAd5 vaccine were halted; thus 61 received the booster dose of rAd5 vaccine (IM: 20; ID:21; SC:20). After the rAd5 boost, significant differences by study arm were found in severity of headache, pain and erythema/induration. Immune responses (binding and neutralizing antibodies, IFN-γ ELISpot HIV-specific responses and CD4+ and CD8+ T-cell responses by ICS) at four weeks after the rAd5 booster were not significantly different by administration route of the rAd5 vaccine boost (Binding antibody responses: IM: 66.7%; ID: 70.0%; SC: 77.8%; neutralizing antibody responses: IM: 11.1%; ID: 0.0%; SC 16.7%; ELISpot responses: IM: 46.7%; ID: 35.3%; SC: 44.4%; CD4+ T-cell responses: IM: 29.4%; ID: 20.0%; SC: 35.3%; CD8+ T-cell responses: IM: 29.4%; ID: 16.7%; SC: 50.0%.)This study was limited by the reduced sample size. The higher frequency of local reactions after ID and SC administration and the lack of sufficient evidence to show that there were any differences in immunogenicity by route of administration do not support changing route of administration for the rAd5 boost.ClinicalTrials.gov NCT00384787

The Impact of Matching Vaccine Strains and Post-SARS Public Health Efforts on Reducing Influenza-Associated Mortality among the Elderly

Public health administrators do not have effective models to predict excess influenza-associated mortality and monitor viral changes associated with it. This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan's influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. A negative binomial model was developed to estimate Taiwan's monthly influenza-associated mortality among the elderly. We calculated three winter and annual excess influenza-associated mortalities [pneumonia and influenza (P&I), respiratory and circulatory, and all-cause] from the 1999–2000 through the 2006–2007 influenza seasons. Obtaining influenza virus sequences from the months/years in which death from P&I was excessive, we investigated molecular variation in vaccine-mismatched influenza viruses by comparing hemagglutinin 1 (HA1) of the circulating and vaccine strains. We found that the higher the isolation rate of A (H3N2) and vaccine-mismatched influenza viruses, the greater the monthly P&I mortality. However, this significant positive association became negative for higher matching of A (H3N2) and public health efforts with post-SARS effect. Mean excess P&I mortality for winters was significantly higher before 2003 than after that year [mean ± S.D.: 1.44±1.35 vs. 0.35±1.13, p = 0.04]. Further analysis revealed that vaccine-matched circulating influenza A viruses were significantly associated with lower excess P&I mortality during post-SARS winters (i.e., 2005–2007) than during pre-SARS winters [0.03±0.06 vs. 1.57±1.27, p = 0.01]. Stratification of these vaccine-matching and post-SARS effect showed substantial trends toward lower elderly excess P&I mortalities in winters with either mismatching vaccines during the post-SARS period or matching vaccines during the pre-SARS period. Importantly, all three excess mortalities were at their highest in May, 2003, when inter-hospital nosocomial infections were peaking. Furthermore, vaccine-mismatched H3N2 viruses circulating in the years with high excess P&I mortality exhibited both a lower amino acid identity percentage of HA1 between vaccine and circulating strains and a higher numbers of variations at epitope B. Our model can help future decision makers to estimate excess P&I mortality effectively, select and test virus strains for antigenic variation, and evaluate public health strategy effectiveness

Ring vaccination versus mass vaccination in event of a smallpox attack.

Since vaccination is critical in responding to smallpox exposure, vaccination strategies must be evaluated during bioterrorism preparedness. Information on historical factors, smallpox characteristics, public health capabilities and hypothetical attack scenarios was used to evaluate major vaccination strategies. In event of a smallpox attack, the optimal strategy is situational, mass vaccination may be best for dense island populations such as Oahu

Social impact of preventive HIV vaccine clinical trial participation: A model of prevention, assessment and intervention

Preventive HIV vaccine trial participants may experience problems related to trial participation, including difficulties with personal relationships, employment, education, health care, housing, health insurance, disability insurance, life insurance, travel or immigration. During the 19 years that the U.S.-based National Institute of Allergy and Infectious Diseases (NIAID) has conducted preventive HIV vaccine trials, we have developed a model to prevent and resolve social impact related to study participation and assist study participants who report such events. Key elements of the model include: informing potential volunteers of risks prior to enrollment; standardizing data collection methods on social impact events; reviewing and following-up on reported social impact events; assisting participants, including provision of free HIV testing to differentiate HIV infection from vaccine-induced HIV antibody; implementing broad-based and targeted community education programs for achieving community support; communicating with scientific and health care communities; and working with government agencies, non-government agencies and industry on mechanisms to address SI. This approach, established in collaboration with NIAID-funded clinical trial groups, serves as a model for prevention, assessment, monitoring, and intervention for social impact related to preventive HIV vaccine clinical trial participation. Although further research is necessary, this model could be adapted for use in different clinical trials.Social impact Social harm HIV vaccine Clinical trial USA NIAID

Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection

Antiretroviral therapy (ART) effectively reduces cycles of viral replication but does not target proviral populations in cells that persist for prolonged periods and that can undergo clonal expansion. Consequently, chronic human immunodeficiency virus (HIV) infection is sustained during ART by a reservoir of long-lived latently infected cells and their progeny. This proviral landscape undergoes change over time on ART. One of the forces driving change in the landscape is the clonal expansion of infected CD4 T cells, which presents a key obstacle to HIV eradication. Potential mechanisms of clonal expansion include general immune activation, antigenic stimulation, homeostatic proliferation, and provirus-driven clonal expansion, each of which likely contributes in varying, and largely unmeasured, amounts to maintaining the reservoir. The role of clinical events, such as infections or neoplasms, in driving these mechanisms remains uncertain, but characterizing these forces may shed light on approaches to effectively eradicate HIV. A limited number of individuals have been cured of HIV infection in the setting of bone marrow transplant; information from these and other studies may identify the means to eradicate or control the virus without ART. In this review, we describe the mechanisms of HIV-1 persistence and clonal expansion, along with the attempts to modify these factors as part of reservoir reduction and cure strategies

Association between glycaemic control and quality of life in diabetes mellitus

Background: Relationship between quality of life (QOL) and haemoglobin A1c (HbA1c) amongst diabetics in the community setting is unclear. Aims: Assess the association between QOL and change in HbA1c in diabetic patients over one year. Settings and Design: Cohort study of patients from four community clinics in California, USA. Methods: Diabetic patients identified from databases using International Classification of Disease (ICD-9) codes were asked to complete Short Form 36 (SF-36), which measures health-related QOL, and invited to attend monthly diabetes workshops. From December 2000 to December 2001, data were collected on multiple parameters, including HbA1c. SF-36 surveys were re-collected at project termination. Statistical Analysis: Regression analysis was used to correlate change in HbA1c with change in QOL physical component summary (PCS) and mental component summary (MCS) scores, while considering potential confounders. Results: Of 1679 eligible patients, 380 completed SF-36 at project initiation. 243 of those completed SF-36 at project termination. Pre and post HbA1c data were available for 170 of the 243 who completed SF-36 at both times. Average MCS increased by 8.46% and PCS decreased by 2.24%. After adjustment, a 5% decrease in HbA1c values was associated with a 1% increase in MCS. No association between changes in HbA1c and PCS was observed. Conclusions: Association between better HbA1c and improved mental, but not physical, QOL may reflect physical inconvenience of increased regimen complexity and mental empowerment from proactive disease management. Larger cohort studies with longer follow-up are needed to further elucidate the relationship between glycemic control and QOL