Impact of azole antifungal treatment on outcome in acute invasive fungal rhinosinusitis with orbitocranial involvement: a surgical perspective.

PURPOSE: To provide real-life data on azole treatment outcomes and the role of surgery in the current management of invasive fungal rhinosinusitis complicated by orbitocranial fungal infection (OCFI). METHODS: Data was collected retrospectively from a chart review from four participating centers and a systematic literature review. The study group included patients with OCFI treated with azole antifungals. The control cases were treated with other antifungal agents. The cranial and orbital involvement degree was staged based on the imaging. The extent of the surgical resection was also classified to allow for inter-group comparison. RESULTS: There were 125 patients in the azole-treated group and 153 in the control group. Among the patients with OCFI cranial extension, 23% were operated on in the azole-treated group and 18% in the control group. However, meninges and brain resection were performed only in the controls (11% of patients) and never in the azole antifungals group. Orbital involvement required surgery in 26% of azole-treated cases and 39% of controls. Despite a more aggressive cranial involvement, azole-treated patients' mortality was significantly lower than in controls, with an OCFI-specific mortality rate of 21% vs. 52%. A similar, though not statistically significant, trend was found for the extent of the orbital disease and surgery. CONCLUSION: Despite less aggressive surgical intervention for cranial involvement, OCFI patients treated with azoles had a higher survival rate. This finding suggests we may improve morbidity with a more conservative surgical approach in conjunction with azole treatment. The same trend is emerging for orbital involvement.

Influence of intragenic CCL3 haplotypes and CCL3L copy number in HIV-1 infection in a sub-Saharan African population.

Two CCL3 haplotypes (HapA1 and Hap-A3) and two polymorphic positions shared by the haplotypes (Hap-2SNP (single nucleotide polymorphism)) were investigated together with CCL3L copy number (CN), for their role in HIV-1 disease. Hap-A1 was associated with protection from in utero HIV-1 infection: exposed uninfected (EU) infants had higher representation of wild type (WT)/Hap-A1 than infected infants (excluding intrapartum (IP)-infected infants), which maintained significance post maternal Nevirapine (mNVP) and viral load (MVL) correction (P=0.04; odds ratio (OR)=0.33). Mother-infant pair analyses showed the protective effect of Hap-A1 is dependent on its presence in the infant. Hap-A3 was associated with increased IP transmission: WT/Hap-A3 was increased in IP-transmitting vs non-transmitting (NT) mothers, and remained significant post mNVP and MVL correction (P=0.02; OR=3.50). This deleterious effect of Hap-A3 seemed dependent on its presence in the mother. Hap-2SNP was associated with lower CD4 count in the NT mothers (P=0.03). CCL3 Hap-A1 was associated with high CCL3L CN in total (P=0.001) and EU infants (P=0.006); the effect was not additive, however, having either Hap-A1 or high CCL3L CN was more significantly (P=0.0008) associated with protection from in utero infection than Hap-A1 (P=0.028) or high CCL3L CN (P=0.002) alone. Linkage disequilibrium between Hap-A1 and high CCL3L CN appears unlikely given that a Nigerian population showed an opposite relationship.

Passively transmitted gp41 antibodies in babies born from HIV-1 subtype C-seropositive women: correlation between fine specificity and protection.

HIV-exposed, uninfected (EUN) babies born to HIV-infected mothers are examples of natural resistance to HIV infection. In this study, we evaluated the titer and neutralizing potential of gp41-specific maternal antibodies and their correlation with HIV transmission in HIV-infected mother-child pairs. Specific gp41-binding and -neutralizing antibodies were determined in a cohort of 74 first-time mother-child pairs, of whom 40 mothers were infected with HIV subtype C. Within the infected mother cohort, 16 babies were born infected and 24 were PCR negative and uninfected at birth (i.e., exposed but uninfected). Thirty-four HIV-uninfected and HIV-unexposed mother-child pairs were included as controls. All HIV-positive mothers and their newborns showed high IgG titers to linear epitopes within the HR1 region and to the membrane-proximal (MPER) domain of gp41; most sera also recognized the disulfide loop immunodominant epitope (IDE). Antibody titers to the gp41 epitopes were significantly lower in nontransmitting mothers (P < 0.01) and in the EUN babies (P < 0.005) than in HIV-positive mother-child pairs. Three domains of gp41, HR1, IDE, and MPER, elicited antibodies that were effectively transmitted to EUN babies. Moreover, in EUN babies, epitopes overlapping the 2F5 epitope (ELDKWAS), but not the 4E10 epitope, were neutralization targets in two out of four viruses tested. Our findings highlight important epitopes in gp41 that appear to be associated with exposure without infection and would be important to consider for vaccine design.

Transcranial Doppler quantification of residual shunt after percutaneous patent foramen ovale closure: correlation of device efficacy with intracardiac anatomic measures.

BACKGROUND: Percutaneous, mechanical closure of defects of the atrial septum fails to completely resolve shunting in up to 20% of cases. Little is known about the factors associated with device failure. METHODS: We measured the left atrial opening (X), right atrial opening (Z), tunnel length (Y), septum secundum, device-septum primum separation, and tunnel compressibility of the patent foramen ovale (PFO) in 301 patients with cryptogenic neurological events, PFO anatomy, and severe Valsalva shunting (Spencer Grade 5-5+). All patients then underwent percutaneous closure with the GORE®HELEX Septal Occluder device and were evaluated at 3 months for residual shunt by transcranial Doppler (TCD). RESULTS: Severe residual Valsalva shunt (TCD Grade 5-5+) was found at 3 months in 21 of 301 (7%) patients. X, Y, and Z were associated with failure with a high degree of statistical significance, whereas the width of the septum secundum, device-septum primum separation, and tunnel compressibility were not. An unanticipated finding was that 14 of 35 (40%) patients sized with a large balloon failed compared with 9 of 280 (3%) sized with a small balloon (P < 0.0001). In the multivariate logistic regression model, X (P = < 0.0001) and balloon size (P < 0.0001) were both strong predictors of failure. CONCLUSIONS: In an intracardiac echocardiography-defined PFO population, characterized by severe baseline Valsalva shunt and a high incidence of persistent (rest) shunting, association of six intracardiac measurements to closure device failure by multivariate logistic regression showed that the width of the left atrial opening was a strong predictor of residual shunting. An unanticipated finding was that use of a large sizing balloon was also strongly associated with failure.

Population-level risk factors for vertical transmission of HIV in the national prevention of mother-to-child transmission programme in South Africa: An ecological analysis.

BACKGROUND: Although South Africa has an overall mother-to-child transmission (MTCT) of HIV rate <5%, case rates remain high. OBJECTIVES: To identify population-level predictors of MTCT to inform targeted interventions to further reduce paediatric HIV incidence. METHODS: The study was an ecological analysis of routine laboratory HIV-related test data from a synthetic cohort of women of reproductive age living with HIV (WRLHIV), identified from the National Health Laboratory Service's Corporate Data Warehouse between 2016 and 2017. Criteria based on syphilis screening and timing of HIV-related tests were used to identify pregnant and non-pregnant WRLHIV. Pregnant WRLHIV were followed from cohort entry at the first antenatal care (fANC) visit, through delivery to exit at the latest viral load (VL) or 15 months post delivery. Follow-up for non-pregnant WRLHIV started at cohort entry on 1 January 2016 to exit at the latest VL or 31 December 2018. HIV VL tests performed at cohort entry, delivery and cohort exit described viraemia (VL ≥50 copies/mL) at subdistrict level. A negative binomial regression model determined the association between MTCT cases and the number of viraemic WRLHIV at different time points, controlling for number of WRLHIV aged <25 years at cohort entry and other routine HIV-related indicators at subdistrict level. RESULTS: Of 3 386 507 WRLHIV identified, 178 319 (5.3%) met criteria for pregnancy. Median (interquartile range (IQR)) proportions of women with fANC booking <20 weeks' gestation, maternal HIV seroprevalence during antenatal care (ANC) and antiretroviral therapy (ART) coverage during ANC were 68.2% (62.9 - 72.8), 31.5% (23.4 - 35.7) and 94.8% (89.7 - 97.8), respectively. Viraemia was consistently higher in pregnant v. non-pregnant WRLHIV at median proportions of 42.9% (38.3 - 59.3) v. 35.0% (25.9 - 49.0) at cohort entry (p<0.001) and 36.3% (25.0 - 48.4) v. 29.6% (21.0 - 42.6) at cohort exit (p<0.001). In total, 4 535 children aged <24 months tested HIV polymerase chain reaction-positive, representing a median subdistrict-level case rate of 1 372 (914 - 2 077) per 100 000 live births. Maternal viraemia postpartum, maternal HIV seroprevalence and ART coverage during ANC positively correlated with cases of MTCT, while higher proportions of women with fANC booking <20 weeks' gestation were associated with a decline in MTCT cases. CONCLUSIONS: Findings suggest that maternal viraemia postpartum, geographical areas with a higher burden of maternal HIV, women initiating ART late in pregnancy and/or incident maternal HIV during pregnancy are significant population-level predictors of MTCT in the national prevention of MTCT programme. Scale-up of HIV prevention services is required to lower maternal HIV prevalence, while expanded access to HIV testing will fast-track ART initiation among WRLHIV. Increased VL monitoring is critical to improve VL suppression rates for elimination of MTCT.

Transcranial doppler quantification of residual shunt after percutaneous patent foramen ovale closure: efficacy of the GORE(®) HELEX septal occluder.

BACKGROUND: Ideally, percutaneous, mechanical closure of defects of the atrial septum should completely resolve shunt. To achieve this goal, more information is needed about the factors associated with device failure. METHODS: Consecutive patients with cryptogenic neurological events who had severe baseline Valsalva shunt (Spencer Grade 5-5+) and intracardiac echocardiography (ICE) defined patent foramen ovale (PFO) who underwent percutaneous PFO closure with the GORE(®) HELEX Septal Occluder device were evaluated for residual 3-month shunt by transcranial Doppler (TCD). RESULTS: We closed 315 PFO patients with the HELEX devices: 15, 20, 25, 30 mm devices in 19, 138, 150, and 8 patients, respectively. Severe residual Valsalva shunt (TCD Grade 5-5+) at 3 months occurred in 23 of 315 (7%) of all patients and in 2 of 108 (2%), 5 of 86(6%), and 16 of 121 (13%) patients with none, Grade 4, and Grade 5-5+ baseline rest shunt, respectively (P = 0.002). At 3 months, rest shunting was essentially abolished by closure. The percent of patients with severe residual Valsalva shunt was also related to device size: 15 mm (0%), 20 mm (4%), 25 mm (10%), and 30 mm (25%) (P = 0.008) and to atrial septal aneurysm. All of these variables were independent predictors of failure by multivariate logistic regression. CONCLUSIONS: In an ICE-defined PFO population characterized by severe baseline Valsalva shunt and a high incidence of persistent (rest) shunting, the GORE(®) HELEX Septal Occluder device effectively reduces both provoked and persistent shunt. The causes of device failure are multifactorial. Larger devices perform less reliably suggesting the need for size-specific modifications to improve closure of more severe defects. (J Interven Cardiol 2011;24:366-372).

Maternal HIV viral load testing during pregnancy and postpartum care in Gauteng Province, South Africa.

BACKGROUND: Pregnant and breastfeeding women living with HIV (WLHIV) are a target population for elimination of mother-to-child transmission of HIV (eMTCT). However, there are limited data on maternal virological responses during pregnancy and the postpartum period in South Africa (SA). OBJECTIVES: To review compliance of viral load (VL) testing with national guidelines and suppression rates during pregnancy and up to 9  months postpartum among WLHIV delivering in four tertiary hospitals in Gauteng Province, SA. METHODS: All women who had a point-of-care HIV VL test using Xpert HIV-1 VL (Cepheid, USA) at delivery in four tertiary obstetric units in Gauteng between June 2018 and February 2020 were included. HIV VL tests of eligible women performed up to 9 months before and after delivery were extracted from the National Health Laboratory Service's Corporate Data Warehouse. Proportions of women delivering who had antenatal and postpartum VL tests performed and their suppression rates were determined and expressed as percentages. RESULTS: Of 4 989 eligible WLHIV (median age 31.1 years), 917 (18.4%) had a VL performed during the antenatal period; of these, 335 (36.5%) had a VL ≥50 copies/mL and 165 (18.0%) a VL ≥1 000 copies/mL. At delivery, 1 911 women (38.3%) had a VL ≥50 copies/mL and 1 028 (20.6%) a VL ≥1 000 copies/mL. Among 627 women (12.6%) with a VL test postpartum, 234 (37.3%) had a VL ≥50 copies/mL and 93 (14.8%) a VL ≥1 000 copies/mL. Overall, having a VL test performed during the antenatal period was associated with viral suppression at delivery and receiving a VL test postpartum (p<0.001). Women with a VL ≥50 copies/mL at delivery were more likely to be younger and to remain virally unsuppressed postpartum (p<0.001) compared with women with a VL <50 copies/mL. CONCLUSIONS: Fewer than 5% of WLHIV with a VL at the time of delivery received VL monitoring during the antenatal and postpartum periods in accordance with national guidelines. More than 80% of WLHIV delivering had no evidence of VL monitoring during the antenatal period, and they were more likely than women who received monitoring during the antenatal period to be virally unsuppressed at delivery and to receive no VL monitoring postpartum. Women with a high VL at delivery were likely to remain virally unsuppressed postpartum. These results emphasise the need for closer monitoring of and rapid reaction to high maternal VLs during pregnancy, at delivery and postpartum for attainment of eMTCT.

Evaluating the performance of the GeneXpert HIV-1 qualitative assay as a consecutive test for a new early infant diagnosis algorithm in South Africa.

BACKGROUND: The proportion of HIV-exposed infants and young children infected with HIV in South Africa (SA) has declined markedly over the past decade as a result of the country's comprehensive prevention of mother-to-child transmission programme. This decrease has in turn reduced the positive predictive value (PPV) of diagnostic assays, necessitating review of early infant diagnosis (EID) algorithms to ensure improved accuracy. OBJECTIVES: To evaluate the performance of the GeneXpert HIV-1 qualitative assay (Xpert EID) as a consecutive test for infants with an 'HIV-detected' polymerase chain reaction screening test at birth. METHODS: We retrospectively analysed a longitudinal cohort of HIV-exposed infants on whom birth testing was performed, using whole-blood ethylenediaminetetra-acetic acid samples, from four tertiary sites in Gauteng Province between June 2014 and December 2019. Birth samples from all infants with a Cobas AmpliPrep/Cobas TaqMan HIV-1 Qualitative Test v2.0 (CAP/CTM v2.0) HIV-detected screening test, a concurrent Xpert EID test and a subsequent confirmatory CAP/CTM v2.0 test on a separate specimen were included. Performance of the Xpert EID in predicting final HIV status was determined as proportions with 95% confidence intervals (CIs). A comparison of indeterminate CAP/CTM v2.0 results, as per National Health Laboratory Service resulting practice, with discordant CAP/CTM v2.0 v. Xpert EID results was performed. RESULTS: Of 150 infants who met the inclusion criteria, 6 (3.9%) had an Xpert EID result discordant with final HIV status: 5 (3.3%) were false negatives and 1 (0.7%) was false positive. As a consecutive test, the Xpert EID yielded a sensitivity of 96.5% (95% CI 92 - 98.9), specificity of 85.7% (95% CI 42.1 - 99.6), PPV of 99.3% (95% CI 95.7 - 99.9), negative predictive value of 54.5% (95% CI 32.5 - 74.9) and overall accuracy of 96.1% (95% CI 91.5 - 98.5). Using discordant CAP/CTM v2.0/Xpert EID results as criteria to verify indeterminate results instead of current practice would have reduced the number of indeterminate screening results by 42.1%, from 18 (12.6%) to 11 (7.2%), without increasing the false-positive rate. CONCLUSIONS: Addition of the Xpert EID as a consecutive test for specimens with an HIV-detected PCR screening result has the potential to improve the PPV and reduce the indeterminate rate, thereby reducing diagnostic challenges and time to final status, in SA's EID programme.

Quality and turnaround times of viral load monitoring under prevention of mother-to-child transmission of HIV Option B+ in six South African districts with a high antenatal HIV burden.

BACKGROUND: Barriers to monitoring maternal HIV viral load (VL) and achieving 90% viral suppression during pregnancy and breastfeeding still need to be understood in South Africa (SA). OBJECTIVES: To measure quality of VL care and turnaround times (TATs) for returning VL results to women enrolled in the prevention of mother-to-child transmission of HIV (PMTCT) programme in primary healthcare facilities. METHODS: Data were obtained from a 2018 cross-sectional evaluation of the PMTCT Option B+ programme in six SA districts with high antenatal and infant HIV prevalence. Quality of VL care was measured as the proportion of clients reporting that results were explained to them. TATs for VL results were calculated using dates abstracted from four to five randomly selected facility-based client records to report overall facility 'short TAT' (≥80% of records with TAT ≤7 days). Logistical regression and logit-based risk difference statistics were used. RESULTS: Achieving overall short TAT was uncommon. Only 50% of facilities in one rural district, zero in one urban metro district and 9 - 38% in other districts had short TAT. The significant difference between districts was influenced by the duration of keeping results in facilities after receipt from the laboratory. Expected quality of VL care received ranged between 66% and 85%. Client-related factors significantly associated with low quality of care, observed in two urban districts and one rural district, included lower education, recent initiation of antiretroviral treatment and experiencing barriers to clinic visits. Experiencing clinic visit barriers was also negatively associated with short TATs. CONCLUSIONS: We demonstrate above-average quality of care and delayed return of results to PMTCT clients. Context-specific interventions are needed to shorten TATs.

Transcranial Doppler quantification of residual shunt after percutaneous patent foramen ovale closure. Comparison of two devices.

BACKGROUND: Recurrent paradoxical embolism after catheter-based closure of right-to-left shunt (RLS) can be related to residual RLS. To improve closure success, we need a better understanding of the anatomic and device-related factors associated with closure efficacy. METHODS: Patients with cryptogenic neurologic events and severe RLS (Valsalva Spencer transcranial Doppler [TCD] grade 5/5+) who underwent patent foramen ovale (PFO) closure by either central pin (Amplatzer(®) PFO [A-PFO]) or central occluding (Amplatzer(®) SO [A-SO]) devices were evaluated for residual shunt by quantitative TCD evaluation at 3 months. The findings were correlated with atrial septal aneurysm (ASA), device type, and device size. RESULTS: We closed 628 consecutive patients with either the A-PFO (n = 327) or A-SO (n = 301) device. The frequency of large defects, small defects, and ASA was 12%, 88%, and 44% of cases, respectively. Severe residual shunt was detected in 13% of A-PFO and 7% of A-SO recipients (P = 0.005). This difference was attributable to a much higher frequency of severe residual shunt among patients with large defects closed with the A-PFO compared to the A-SO device (12 out of 29 [41%] vs. 3 out of 42 [7%], respectively; P < 0.001). There was no significant difference in device failure frequency for small defects. The presence of ASA increased the frequency of severe residual shunt compared to those without this feature (36 out of 275 [13%] vs. 28 out of 353 [8%], respectively; P = 0.046) but did not influence device-related differences. CONCLUSIONS: (1) Both noncentering and central occluding closure devices effectively reduce RLS after PFO closure. (2) Large PFO defects with or without ASA have lower residual shunt grades at 3 months when closed by central occluding devices.

Transient neurological symptoms during contrast transcranial Doppler right-to-left shunt testing in patients with cryptogenic neurological disease.

BACKGROUND: Paradoxical embolization from right-to-left shunt (RLS) resulting in neurological events is well described and patients with cryptogenic neurological disease are commonly evaluated for this condition. In the course of testing for RLS by bubble contrast transcranial Doppler (TCD), we observed that some patients developed transient neurological symptoms. This report describes our findings. METHODS: We performed diagnostic TCD on 445 consecutive patients with cryptogenic neurological disease (cerebral vascular accident, 21%; transient ischemic attack, 30%; migraine, 48%; and abnormal magnetic resonance brain imaging, 68%). Immediately following the procedure, patients were questioned about neurological symptoms. RESULTS: One hundred and sixty-three (37%) of the 445 patients had absent or minimal shunting (Spencer grades 0-1) and 233 of 445 (52%) had severe RLS (Spencer grades 4-5+). One or more TCD-associated neurological symptoms (TCD-SX) developed in 95 of 445 (21%) of the patients. Compared to patients with absent or minimal shunting, patients with shunt grades 2-5+ were two and one half times more likely to develop TCD-SX (18/164 [11%] vs. 77/283 [27%], P < 0.001). TCD-SX were fourfold more common among patients with a history of migraine compared to history-negative subjects (35 vs. 8.7%, P < 0.0001). CONCLUSIONS: Diagnostic bubble-contrast TCD provoked transient neurological symptoms. The symptoms correlated with the severity of RLS and were more common in migraine patients, suggesting that migraine patients are sensitized to chemical and/or microembolic shunt factors. There was no significant residual morbidity, and bubble-contrast echocardiograph continues to be a safe and valuable diagnostic procedure.

Venus: radar determination of gravity potential.

We describe a method for the determination of the gravity potential of Venus from multiple-frequency radar measurements. The method is based on the strong frequency dependence of the absorption of radio waves in Venus' atmosphere. Comparison of the differing radar reflection intensities at several frequencies yields the height of the surface relative to a reference pressure contour; combination with measurements of round-trip echo delays allows the pressure, and hence the gravity potential contour, to be mapped relative to the mean planet radius. Since calibration data from other frequencies are unavailable, the absorption-sensitive Haystack Observatory data have been analyzed under the assumption of uniform surface reflectivity to yield a gravity equipotential contour for the equatorial region and a tentative upper bound of 6 x 10(-4) on the fractional difference of Venus' principal equatorial moments of inertia. The minima in the equipotential contours appear to be associated with topographic minima.

Monitoring Protocols for Cochlear Toxicity.

The need for monitoring hearing and auditory function during drug therapy and other treatments that have the potential to cause hearing loss is well documented. Besides the main purpose of ototoxic monitoring, which is to provide feedback to the attending physician about the effects the treatment is having on the auditory system, it is also helpful in setting expectations for the patient and his/her family about the communication issues that may result from the drug therapy. This article will review tests available to an audiologist, both subjective and objective, that can be used to effectively monitor hearing levels and auditory function during treatment. Published guidelines and various ototoxic monitoring protocols are reviewed regarding tests administered, what constitutes a significant change in test results and how these findings are reported, and the impact significant changes may have on the course of treatment. Test protocols from different institutions are compared for both similarities and contrasts. Effective scheduling and test location are key to a successful monitoring program. Finally, the need to streamline ototoxic monitoring of hearing and auditory function to reduce test time and make it less stressful and tiresome on the patient will be considered.

Monitoring diagnosis, retention in care and viral load suppression in children testing HIV polymerase chain reaction-positive in two districts in South Africa.

BACKGROUND: Retention in care is associated with improved virological control and survival among HIV-infected children. However, retention of children in HIV care remains a challenge. OBJECTIVES: To describe, using routine laboratory HIV test data, the retention-in-care and virological outcomes of HIV-infected children aged <18 months in two districts in South Africa. METHODS: HIV polymerase chain reaction (PCR)-positive results of children from uMkhanyakude and Tshwane districts in KwaZulu-Natal and Gauteng provinces, respectively, tested between April 2015 and May 2016, were extracted from the National Health Laboratory Service's Corporate Data Warehouse (CDW). HIV-related tests (PCR, viral load (VL), CD4+) were documented longitudinally for each child for ≥13 months after the first positive PCR result by manually searching demographics within the CDW, supplemented by an automated patient-linking algorithm. Test sets were linked if two or more demographics (surname, name, date of birth, folder number) matched exactly. Programmatic indicators assessed included age at first positive PCR test, presumed confirmatory test rates, retention in care, and VL suppression at 6 and 12 months. RESULTS: Ninety-four and 304 children tested HIV PCR-positive in uMkhanyakude and Tshwane, respectively. The median age at diagnosis was 3.6 months (interquartile range (IQR) 1.4 - 7.1) for uMkhanyakude and 2.3 months (IQR 0.1 - 6.7) for Tshwane. In uMkhanyakude, confirmed in utero infections accounted for 18.1% of transmissions (n=17), compared with 29.6% (n=90) in Tshwane. Presumed confirmatory test rates following an initial positive PCR result were 77.7% and 71.7% for uMkhanyakude and Tshwane, respectively. Within 6 months of starting antiretroviral therapy, 43 children (58.9%) were lost to follow-up in uMkhanyakude compared with 160 (73.4%) in Tshwane. Of those retained in care at 6 months with a VL measurement, 15 (60.0%) from uMkhanyakude had a VL <1 000 copies/mL, compared with 24 (48.0%) in Tshwane. For both districts, a third of all HIV PCR-positive children were retained in care at the end of follow-up, with 29 (30.9%) in uMkhanyakude and 99 (32.5%) in Tshwane. Of these, 12 (41.4%) had a VL <1 000 copies/mL in uMkhanyakude compared with 28 (28.3%) in Tshwane. CONCLUSIONS: We demonstrate the value of routine laboratory data in monitoring diagnosis, retention and VL suppression in HIV-infected children. This approach is scalable, can be reported near real-time, is relatively inexpensive to implement, and provides a tool for improving paediatric HIV services until clinical databases can assume this role.

The impact of health programmes to prevent vertical transmission of HIV. Advances, emerging health challenges and research priorities for children exposed to or living with HIV: Perspectives from South Africa.

Over the past three decades, tremendous global progress in preventing and treating paediatric HIV infection has been achieved. This paper highlights the emerging health challenges of HIV-exposed uninfected (HEU) children and the ageing population of children living with HIV (CLHIV), summarises programmatic opportunities for care, and highlights currently conducted research and remaining research priorities in high HIV-prevalence settings such as South Africa. Emerging health challenges amongst HEU children and CLHIV include preterm delivery, suboptimal growth, neurodevelopmental delay, mental health challenges, infectious disease morbidity and mortality, and acute and chronic respiratory illnesses including tuberculosis, pneumonia, bronchiectasis and lymphocytic interstitial pneumonitis. CLHIV and HEU children require three different categories of care: (i) optimal routine child health services applicable to all children; (ii) routine care currently provided to all HEU children and CLHIV, such as HIV testing or viral load monitoring, respectively, and (iii) additional care for CLHIV and HEU children who may have growth, neurodevelopmental, behavioural, cognitive or other deficits such as chronic lung disease, and require varying degrees of specialised care. However, the translation thereof into practice has been hampered by various systemic challenges, including shortages of trained healthcare staff, suboptimal use of the patient-held child's Road to Health book for screening and referral purposes, inadequate numbers and distribution of therapeutic staff, and shortages of assistive/diagnostic devices, where required. Additionally, in low-middle-income high HIV-prevalence settings, there is a lack of evidence-based solutions/models of care to optimise health amongst HEU and CLHIV. Current research priorities include understanding the mechanisms of preterm birth in women living with HIV to optimise preventive interventions; establishing pregnancy pharmacovigilance systems to understand the short-, medium- and long-term impact of in utero ART and HIV exposure; understanding the role of preconception maternal ART on HEU child infectious morbidity and long-term growth and neurodevelopmental trajectories in HEU children and CLHIV, understanding mental health outcomes and support required in HEU children and CLHIV through childhood and adolescence; monitoring HEU child morbidity and mortality compared with HIV-unexposed children; monitoring outcomes of CLHIV who initiated ART very early in life, sometimes with suboptimal ART regimens owing to medication formulation and registration issues; and testing sustainable models of care for HEU children and CLHIV including later reproductive care and support.

Leveraging the Road to Health booklet as a unique patient identifier to monitor the prevention of mother-to-child transmission programme.

BACKGROUND: Currently there is no unique patient identification system in the South African public health sector. Therefore, routine laboratory data cannot effectively be de-duplicated, thereby hampering surveillance of laboratory-diagnosed diseases such as mother-to-child transmission of HIV. OBJECTIVES: To determine the uptake of Road to Health booklet (RTHB) identifiers at HIV polymerase chain reaction (PCR) birth test and describe their performance in linking follow-up test results in the early infant diagnosis programme. METHODS: Between May 2016 and May 2017, Tshwane District Clinical Services implemented a unique patient identifier pilot project in which a sticker-page of unique, readable, barcoded patient identifiers was incorporated in the patient-retained immunisation record (the RTHB) before distribution. Uptake of RTHB identifiers at birth was calculated as the proportion of HIV PCR tests in infants aged <6 days registered with an RTHB identifier over the total number of registered HIV PCR tests. Descriptive analysis of demographic details was performed among infants with two registered HIV PCR tests linked by the RTHB identifier, and performance of the National Health Laboratory Service Corporate Data Warehouse (NHLS CDW)-linking algorithm in matching RTHB-linked results was calculated using a 2 × 2 table. RESULTS: A total of 5 309 HIV PCR birth tests registered with an RTHB identifier were extracted from the NHLS CDW over the 13-month period of the pilot project. The number of registered RTHB identifiers increased from 24 (2% of birth PCR tests) in May 2016, peaking at 728 (56% of birth PCR tests) in May 2017. Among infants with a registered RTHB identifier at birth, 635 (12%) had a subsequent linked HIV PCR test, as indicated by the same RTHB number registered for a later specimen. Demographic details at the time of birth and subsequent PCR test were compared, demonstrating that <4% of infants had exact matches for name, surname, date of birth and sex; 74% of birth tests had variations such as 'born to' or 'baby of ' in place of a first name; surnames matched exactly in 61% of cases; 18% (n=116) of infants had both tests performed at the same facility, of which only 27% (n=31) had the same patient folder number on both test results. CONCLUSIONS: Leveraging RTHBs as unique patient identifiers, even if used temporarily until linkage to other future national unique identifiers, promises to be an effective scalable approach to laboratory-based surveillance, facilitating healthcare provider access to all test results from birth.

Near-real-time tracking of gaps in prevention of mother-to-child transmission of HIV in three districts of KwaZulu-Natal Province, South Africa.

BACKGROUND: Identifying and addressing gaps in the prevention of mother-to-child transmission of HIV (PMTCT) is required if South Africa (SA) is to achieve targets for eliminating MTCT (eMTCT). Potential PMTCT gaps that increase MTCT risk include late maternal HIV diagnosis, lack of or delayed antiretroviral therapy (ART) during pregnancy and breastfeeding, and lack of effective prophylaxis for HIV-exposed infants. OBJECTIVES: To investigate, in near real time, PMTCT gaps among HIV-infected infants in three districts of KwaZulu-Natal Province, SA. METHODS: Between May and September 2016, PMTCT co-ordinators from eThekwini, uMgungundlovu and uMkhanyakude districts received daily email notification of all HIV polymerase chain reaction (PCR)-positive results. Co-ordinators reviewed facility records for each infant to identify gaps in PMTCT care, including maternal age, timing of maternal HIV diagnosis, maternal treatment history and maternal viral load (VL) monitoring. Data were submitted via the mobile phone SMS (text message) service using Rapid Pro technology and analysed in Stata 14. RESULTS: Data on PMTCT gaps were received for 367 (91.8%) of 400 infants with HIV PCR-positive results, within a median time of 12.5 days (interquartile range (IQR) 6 - 23). The median maternal age was 25 years (IQR 22 - 30), with 48 teenage mothers (15 - 19 years). The sample size was too small to determine whether there were significant differences in PMTCT gaps between the 48 teenage mothers and 293 older (20 - 34 years) mothers. Of the mothers, 220 (60.0%) were first diagnosed prior to conception or at their first antenatal care (ANC) visit, and 127 (34.6%) at or after delivery; 137 (37.3%) transmitted HIV to their infants despite receiving >12 weeks of ART. VL results were unavailable for 70.0% of women. Only 41 (17.5%) of women known to be HIV-positive during ANC had confirmed virological suppression. No statistically significant differences in PMTCT gaps were observed between districts, owing to small sample sizes in uMgungundlovu and uMkhanyakude. CONCLUSIONS: The findings highlight the need to improve services during ANC, in particular prioritising maternal VL monitoring. We intend to use improved technology to streamline data collection and reporting towards eMTCT.

Evaluation of a physiatrist-directed prehabilitation intervention in frail patients with colorectal cancer: a randomised pilot study protocol.

INTRODUCTION: Prehabilitation interventions have shown efficacy in the orthopaedic and cardiothoracic surgical populations, but there has been limited evidence for general surgical patients. We present the protocol for a pilot trial of a novel prehabilitation intervention, consisting of a physiatrist-directed preoperative assessment and treatment programme. METHODS AND ANALYSIS: This is a single-centre pilot randomised controlled trial investigating physiatrist-directed prehabilitation for a 4 to 6-week preoperative period. We will block randomise 40-50 participants awaiting surgery for colorectal cancer to prehabilitation versus control. Participants in the prehabilitation arm will undergo assessment by a physiatrist and enrol in a supervised exercise programme. The control group will not undergo any prehabilitation interventions in the preoperative period. Our primary outcome is feasibility, measured by examining recruitment, refusal, retention and adherence rates as well as participant satisfaction and feedback. Secondary outcomes include physical fitness, functional ability, health-related quality of life, postoperative complications, mortality, readmissions, length of stay, prehabilitation interventions performed and exercise complications. ETHICS AND DISSEMINATION: This study has been approved by the Hamilton Integrated Research Ethics Board (HIREB reference number 2015-0090-GRA). The results of this pilot study will be used to design a full-scale study and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02531620; Pre-results.

Biological substrates of anatomic asymmetry.

Asymmetric cortical areas differ in volume and in the number of neurons. There are also differences between asymmetric and symmetric areas. As asymmetry increases, the total area of the region decreases, suggesting that when a brain is symmetric, it is the result of two large sides rather than two small sides. Also, these volume differences are caused by changes in the number of cells, not changes in cell-packing density. The ontogenetic basis for this difference in cell numbers likely relates to events that occur quite early in corticogenesis before final mitosis of proliferative units, but definitive proof is lacking. Finally, the pattern and degree of callosal connections differ between symmetric and asymmetric brains, with differential axonal pruning being implicated as the likely mechanism.

Correlations between cancer incidence rates from the Canadian National Cancer Incidence Reporting System, 1969-78.

Incidence rates for 19 cancers in females and 16 cancers in males have been computed from data reported by 8 Canadian provinces to the National Cancer Incidence Reporting System between 1969 and 1978. The rates, very similar in absolute and relative magnitude to those reported by the U.S. Third National Cancer Survey, have been used to examine patterns of correlation between various cancers within the 8 provinces. There is strong evidence of positive associations between a number of cancers, including a number of associations that have been reported in other similar correlational studies. Correlations that may be of particular interest in suggesting etiologic factors in common include clusters of smoking-related cancers (buccal cavity with pharynx, larynx, lung, and bladder), female sexual cancers (breast, corpus uteri, and ovary), and a group of cancers that have shown correlation in other studies (i.e., cancers of the pancreas and kidney, leukemias, lymphomas, and cancer of the prostate gland). Organs in the gastrointestinal tract (esophagus, stomach, colon, and rectum) anatomically close to each other show a high positive correlation in both females and males, but the further apart the organs are the lower is the correlation; these observations are consistent with other evidence of varying dietary etiologies. Two individual correlations of particular interest are those between female brain tumors and female bladder cancer (two cancers for which little is known of the etiology for a large percentage of them) and those between female breast cancer and female lung cancer. This study, the largest correlational study of incidence data reported to date, demonstrates the utility of such simple correlational analyses.