Annalise E. Zemlin

HbA1c of 6.5% to Diagnose Diabetes Mellitus — Does It Work for Us? — The Bellville South Africa Study

Background HbA1c has been the gold standard for glycaemic control follow-up for decades. In 2009, a level of 6.5% (48 mmol/mol) was proposed as diagnostic for diabetes. We test this cut-off in our community. Methods Participants (946) from a community-based study were screened for diabetes using either a fasting blood glucose or oral glucose tolerance test (OFTT). The HbA1c cut-off of 6.5% was tested for each group. A receiver operator characteristic (ROC) curve for both groups was generated to establish an optimal cut-off. Results Our study included 224 (23.7%) males and 722 (76.3%) females. Using fasting blood glucose alone, 117 (14%) were diagnosed with diabetes −50% had an HbA1c value of ≥6.5% (48 mmol/mol). Using an OGTT, 147 (18%) were diagnosed with diabetes −46% had an HbA1c value of ≥6.5% (48 mmol/mol). ROC curves found a level of 6.1% (43 mmol/mol) to be optimal in both groups (AUC 0.85 and 0.82 respectively). The sensitivities were 80% and 75% and the specificities 77% and 78% respectively. Conclusions A cut off of 6.5% (48 mmol/mol) is a good diagnostic tool with its high specificity; however the low sensitivity limits its use. We found a level of 6.1% (43 mmol/mol) to be optimal. This emphasizes the need for evidenced based values to be established in various population groups.

Role of inflammation in HIV-1 disease progression and prognosis.

Abstract Inflammation and immune activation have been thrust to center stage in the understanding of HIV-1 disease pathogenesis and progression. Early work demonstrated that heightened levels of immune activation correlated with the extent of CD4 + T cell death in lymphoid tissue; however, this concept was not incorporated into the general view of disease pathogenesis. Since these early studies, the extension of life for patients on combination antiretroviral therapies (cART) has heralded a new era of non-AIDS-related diseases and incomplete restoration of immune function. The common link appears to be ongoing inflammation and immune activation. Thus, despite good control of viral loads, persons living with HIV (PLWH) remain at increased risk of inflammatory-associated complications such as cardiovascular disease and certain cancers. HIV-specific mechanisms as well as non-specific generalized responses to infection contribute to ongoing activation of the immune system. An early loss of gastrointestinal (GI) tract mucosal integrity, the pro-inflammatory cytokine milieu, co-infections and marked destruction of lymph node architecture are all factors contributing to the ongoing activation of the immune system as well as impaired immune recovery. It is becoming increasingly evident that the CD4 count and viral load do not provide a complete picture of the underlying state of the immune system. Heightened levels of inflammatory markers have been shown to predict increased mortality and other adverse events. Therefore, it will be important to incorporate these markers into management algorithms as soon as possible. This is particularly relevant in resource-poor countries where difficulties in cART roll-out and access are still encountered and, therefore, a mechanism for prioritizing individuals for therapy would be of value. This review will focus on the closely inter-related concepts of immune activation and inflammation. Both are broad concepts involving the interaction of various key players in the immune system. Importantly, immune activation promotes inflammation and thrombosis and similarly, inflammation and thrombosis induce immune activation. These concepts are thus intricately linked. Studies highlighting the potentially harmful effects of ongoing inflammation/immune activation are reviewed and the contributions of the GI tract “damage” and other co-infections such as CMV are explored. The complications resulting from persistent immune activation include enhanced CD4 + T cell death, lymphoid tissue destruction, and various pathologies related to chronic inflammation. Ultimately, we envision that the long-term management of the disease will incorporate both the identification and the amelioration of the potentially harmful effects of ongoing immune activation and inflammation.

Incomplete laboratory request forms: the extent and impact on critical results at a tertiary hospital in South Africa:

Background Research has demonstrated that most laboratory errors occur in the preanalytical phase of testing. In view of the paucity of studies examining preanalytical errors, we evaluated our laboratory request forms for the frequency and impact of incomplete data. Methods This study examined all request forms received at our laboratory during a five-day period. The forms were scrutinized for the presence of specific parameters. The impact of abbreviated diagnoses was analysed, as well as how lack of ward or telephone details affects the communication of critical results to clinicians. Results A total of 2550 request forms were analysed. Medication(s) used by the patient (89.6%) and doctor’s contact number (61.2%) were the most incomplete parameters. No diagnosis was provided on 19.1% of forms, and when a diagnosis was present it was an abbreviated form in 37.3%. This resulted in 35.5% of diagnoses not being recorded by reception staff. Incomplete ward information was found on 4.9% of forms. In a separate search, the impact of 151 request forms (collected over a period of eight months), with incomplete ward location information and corresponding to critical results was assessed. Critical results were not communicated by telephone to clinicians in 19.9% of cases. Conclusion As laboratory data influences 70% of medical diagnoses, incorrect or incomplete data provided to the laboratory could significantly impact the success and cost of overall treatment.

Chemistry and haematology sample rejection and clinical impact in a tertiary laboratory in Cape Town

Abstract Background: Recent publications report that up to 70% of total laboratory errors occur in the pre-analytical phase. Identification of specific problems highlights pre-analytic processes susceptible to errors. The rejection of unsuitable samples can lead to delayed turnaround time and affect patient care. Methods: A retrospective audit was conducted investigating the rejection rate of routine blood specimens received at chemistry and haematology laboratories over a 2-week period. The reasons for rejection and potential clinical impact of these rejections were investigated. Thirty patient files were randomly selected and examined to assess the impact of these rejections on clinical care. Results: A total of 32,910 specimens were received during the study period, of which 481 were rejected, giving a rejection rate of 1.46%. The main reasons for rejection were inappropriate clotting (30%) and inadequate sample volume (22%). Only 51.7% of rejected samples were repeated and the average time for a repeat sample to reach the laboratory was about 5 days (121 h). Of the repeated samples, 5.1% had results within critical values. Examination of patient folders showed that in 40% of cases the rejection of samples had an impact on patient care. Conclusions: The evaluation of pre-analytical processes in the laboratory, with regard to sample rejection, allowed one to identify problem areas where improvement is necessary. Rejected samples due to factors out of the laboratory’s control had a definite impact on patient care and can thus affect customer satisfaction. Clinicians should be aware of these factors to prevent such rejections.

Serum adenosine deaminase and total immunoglobulin G correlate with markers of immune activation and inversely with CD4 counts in asymptomatic, treatment-naive HIV infection

PurposeHIV-infection is characterized by aberrant immune activation and ongoing inflammation. Markers of inflammation are now recognized to have prognostic value for adverse events, independent of viral loads and CD4 counts. This study aimed to delineate a panel of affordable markers of immune activation in untreated HIV-infection that may have an impact on the management of HIV in resource-limited settings.MethodsThis was a cross-sectional study of 86 untreated newly diagnosed HIV-infected patients and 54 matched controls attending a voluntary testing clinic in Cape Town, South Africa. Serum levels of adenosine deaminase (ADA), total immunoglobulin G (IgG), soluble CD14 and lipopolysaccharide-binding protein (LBP) were measured and correlated with CD4 counts, viral loads and expression of CD38 on CD8+ T cells.ResultsADA, IgG and LBP were all significantly increased in the HIV infected group (p < 0.0001) compared with uninfected controls. Soluble CD14 was also significantly increased (p = 0.0187). Furthermore, all these parameters correlated inversely with CD4 counts (r = −0.481 p < 0.0001; r = −0.561; p < 0.0001; r = −0.387 p = 0.0007 and r = −0.254 p = 0.0240, respectively). Only ADA correlated with viral load (r = 0.260 p = 0.0172). Importantly, ADA, IgG and LBP correlated directly with %CD38 on CD8+ T cells (r = 0.369 p < 0.0001; r = 0.284 p = 0.001; r = 0.408 p = 0.0006, respectively).ConclusionAffordable parameters such as serum ADA and IgG correlated significantly with immune activation levels and markers of disease progression in untreated HIV-infection and therefore may add value to the management of these patients in resource-limited settings.

A Six Sigma approach to the rate and clinical effect of registration errors in a laboratory

Background Laboratory errors made during the pre-analytical phase can have an impact on clinical care. Quality management tools such as Six Sigma may help improve error rates. Aim To use elements of a Six Sigma model to establish the error rate of test registration onto the laboratory information system (LIS), and to deduce the potential clinical impact of these errors. Methods In this retrospective study, test request forms were compared with the tests registered onto the LIS, and all errors were noted before being rectified. The error rate was calculated. The corresponding patient records were then examined to determine the actual outcome, and to deduce the potential clinical impact of the registration errors. Results Of the 47 543 tests requested, 72 errors were noted, resulting in an error rate of 0.151%, equating to a sigma score of 4.46. The patient records reviewed indicated that these errors could, in various ways, have impacted on clinical care. Conclusion This study highlights the clinical effect of errors made during the pre-analytical phase of the laboratory testing process. Reduction of errors may be achieved through implementation of a Six Sigma programme.

An audit on the reporting of critical results in a tertiary institute

Background Critical result reporting is a requirement for accreditation by accreditation bodies worldwide. Accurate, prompt communication of results to the clinician by the laboratory is of extreme importance. Repeating of the critical result by the recipient has been used as a means to improve the accuracy of notification. Our objective was to assess the accuracy of notification of critical chemical pathology laboratory results telephoned out to clinicians/clinical areas. We hypothesize that read-back of telephoned critical laboratory results by the recipient may improve the accuracy of the notification. Methods This was a prospective study, where all critical results telephoned by chemical pathologists and registrars at Tygerberg Hospital were monitored for one month. The recipient was required to repeat the result (patient name, folder number and test results). Any error, as well as the designation of the recipient was logged. Results Of 472 outgoing telephone calls, 51 errors were detected (error rate 10.8%). Most errors were made when recording the folder number (64.7%), with incorrect patient name being the lowest (5.9%). Calls to the clinicians had the highest error rate (20%), most of them being the omission of recording folder numbers. Conclusion Our audit highlights the potential errors during the post-analytical phase of laboratory testing. The importance of critical result reporting is still poorly recognized in South Africa. Implementation of a uniform accredited practice for communication of critical results can reduce error and improve patient safety.

The impact of repeat-testing of common chemistry analytes at critical concentrations.

Abstract Background: Early notification of critical values by the clinical laboratory to the treating physician is a requirement for accreditation and is essential for effective patient management. Many laboratories automatically repeat a critical value before reporting it to prevent possible misdiagnosis. Given today’s advanced instrumentation and quality assurance practices, we questioned the validity of this approach. We performed an audit of repeat-testing in our laboratory to assess for significant differences between initial and repeated test results, estimate the delay caused by repeat-testing and to quantify the cost of repeating these assays. Methods: A retrospective audit of repeat-tests for sodium, potassium, calcium and magnesium in the first quarter of 2013 at Tygerberg Academic Laboratory was conducted. Data on the initial and repeat-test values and the time that they were performed was extracted from our laboratory information system. The Clinical Laboratory Improvement Amendment criteria for allowable error were employed to assess for significant difference between results. Results: A total of 2308 repeated tests were studied. There was no significant difference in 2291 (99.3%) of the samples. The average delay ranged from 35 min for magnesium to 42 min for sodium and calcium. At least 2.9% of laboratory running costs for the analytes was spent on repeating them. Conclusions: The practice of repeating a critical test result appears unnecessary as it yields similar results, delays notification to the treating clinician and increases laboratory running costs.

The iron status of a healthy South African adult population

INTRODUCTION Iron deficiency is associated with significant morbidity and mortality, can present with or without haematological changes and is a major cause of microcytic anaemia. In South Africa and Africa in general, there is a paucity of studies on the iron status of healthy adult non pregnant females and males >18years of age. The aim of the study was to determine the prevalence of iron deficiency in a healthy South African population. METHODS A total of 651 healthy adults >18years were included in the study. Blood samples were taken for the determination of iron status, haematological and inflammatory parameters. A ferritin level of <30μg/L was used to define iron deficiency and these subjects were further divided into those with and without anaemia. Diet and menstrual history in females was further investigated. RESULTS Overall, the prevalence of anaemia was 12.6% and iron deficiency was found in 78% of anaemic subjects. The prevalence of iron deficiency was 39.8% in all participants and females and Black Africans had a very high prevalence of 56.6% and 50.7% respectively. Significant (p<0.05) differences were found in concentrations of ferritin, haemoglobin, iron, transferrin, transferrin saturation, MCV and MCH between the groups. CONCLUSION Anaemia is a minor health problem but a large proportion of subjects with iron deficiency do not present with anaemia. The prevalence of iron deficiency was high especially in females and Black African participants.

Demand management: an audit of chemical pathology test rejections by an electronic gate-keeping system at an academic hospital in Cape Town

Background Demand management is an area of laboratory activity, which is becoming increasingly important. Within the health-care system, demand management can be defined as the use of health resources to maximise its utility. Tygerberg Hospital has introduced an electronic gate-keeping system. Chemistry tests which generate the highest cost are subjected to this system and may be automatically rejected according to a set of rules. This study aimed: (1) to identify the number of chemistry tests rejected by the eGK; (2) to identify which of these rejected tests were subsequently restored and (3) to assess the impact of rejections on clinical outcome and cost-saving. Methods A retrospective audit was conducted to determine the number of chemistry tests rejected and subsequently restored over a 6-month period. The case-notes of patients for whom requested tests previously rejected had been restored were randomly selected and investigated to assess clinical impact. Any cost-saving was calculated. Results A total of 68,480 tests were subjected to gate-keeping, and 4605 tests (6.7%) were rejected while 679 (14.7%) of these were restored by the requestor phoning the laboratory after obtaining authorisation. After examining a subset of clinical notes it was found that in most cases (80%), patient care was unaffected. The total cost saved was £25,387. Conclusions The majority of the rejected tests were unnecessary and following rejection, real savings were made. Electronic gate-keeping is a simple, effective and sustainable method of demand management.