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Study Design: Retrospective study of a prospective multicenter database., Objective: The purpose of this study was to identify predictors of lower total surgery costs at 3 years for adult spinal deformity (ASD) patients., Summary of Background Data: ASD surgery involves complex deformity correction., Methods: Inclusion criteria: surgical ASD (scoliosis ≥20°, sagittal vertical axis [SVA] ≥5 cm, pelvic tilt ≥25°, or thoracic kyphosis ≥60°) patients >18 years. Total costs for surgery were calculated using the PearlDiver database. Cost per quality-adjusted life year was assessed. A Conditional Variable Importance Table used nonreplacement sampling set of 20,000 Conditional Inference trees to identify top factors associated with lower cost surgery for low (LSVA), moderate (MSVA), and high (HSVA) SRS Schwab SVA grades., Results: Three hundred sixtee of 322 ASD patients met inclusion criteria. At 3-year follow up, the potential cost of ASD surgery ranged from $57,606.88 to $116,312.54. The average costs of surgery at 3 years was found to be $72,947.87, with no significant difference in costs between deformity groups (P > 0.05). There were 152 LSVA patients, 53 MSVA patients, and 111 HSVA patients. For all patients, the top predictors of lower costs were frailty scores <0.19, baseline (BL) SRS Activity >1.5, BL Oswestry Disability Index <50 (all P < 0.05). For LSVA patients, no history of osteoporosis, SRS Activity scores >1.5, age <64, were the top predictors of lower costs (all P < 0.05). Among MSVA patients, ASD invasiveness scores <94.16, no past history of cancer, and frailty scores <0.3 trended toward lower total costs (P = 0.071, P = 0.210). For HSVA, no history of smoking and body mass index <27.8 trended toward lower costs (both P = 0.060)., Conclusion: ASD surgery has the potential for improved cost efficiency, as costs ranged from $57,606.88 to $116,312.54. Predictors of lower costs included higher BL SRS activity, decreased frailty, and not having depression. Additionally, predictors of lower costs were identified for different BL deformity profiles, allowing for the optimization of cost efficiency for all patients.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Retrospective review of a prospectively enrolled multicenter Adult Spinal Deformity (ASD) database., Objective: Investigate invasiveness and outcomes of ASD surgery by frailty state., Summary of Background Data: The ASD Invasiveness Index incorporates deformity-specific components to assess correction magnitude. Intersections of invasiveness, surgical outcomes, and frailty state are understudied., Methods: ASD patients with baseline and 3-year (3Y) data were included. Logistic regression analyzed the relationship between increasing invasiveness and major complications or reoperations and meeting minimal clinically important differences (MCID) for health-related quality-of-life measures at 3Y. Decision tree analysis assessed invasiveness risk-benefit cutoff points, above which experiencing complications or reoperations and not reaching MCID were higher. Significance was set to P < 0.05., Results: Overall, 195 of 322 patients were included. Baseline demographics: age 59.9 ± 14.4, 75% female, BMI 27.8 ± 6.2, mean Charlson Comorbidity Index: 1.7 ± 1.7. Surgical information: 61% osteotomy, 52% decompression, 11.0 ± 4.1 levels fused. There were 98 not frail (NF), 65 frail (F), and 30 severely frail (SF) patients. Relationships were found between increasing invasiveness and experiencing a major complication or reoperation for the entire cohort and by frailty group (all P < 0.05). Defining a favorable outcome as no major complications or reoperation and meeting MCID in any health-related quality of life at 3Y established an invasiveness cutoff of 63.9. Patients below this threshold were 1.8[1.38-2.35] (P < 0.001) times more likely to achieve favorable outcome. For NF patients, the cutoff was 79.3 (2.11[1.39-3.20] (P < 0.001), 111 for F (2.62 [1.70-4.06] (P < 0.001), and 53.3 for SF (2.35[0.78-7.13] (P = 0.13)., Conclusion: Increasing invasiveness is associated with increased odds of major complications and reoperations. Risk-benefit cutoffs for successful outcomes were 79.3 for NF, 111 for F, and 53.3 for SF patients. Above these, increasing invasiveness has increasing risk of major complications or reoperations and not meeting MCID at 3Y.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Retrospective review of a prospective database., Objective: The aim of this study was to identify demographic, surgical, and radiographic factors that predict superior recovery kinetics following cervical deformity (CD) corrective surgery., Summary of Background Data: Analyses of CD corrective surgery use area under the curve (AUC) to assess health-related quality of life (HRQL) metrics throughout recovery., Methods: Outcome measures were baseline (BL) to 1-year (1Y) health-related quality of life (HRQL) (Neck Disability Index [NDI]). CD criteria were C2-7 Cobb angle >10°, coronal Cobb angle >10°, C2-C7 sagittal vertical axis (cSVA) >4 cm, TS-CL >10°, or chin-brow vertical angle >25°. AUC normalization divided BL and postoperative outcomes by BL. Normalized scores (y axis) were plotted against follow-up (x axis). AUC was calculated and divided by cumulative follow-up length to determine overall, time-adjusted recovery (Integrated Health State [IHS]). IHS NDI was stratified by quartile, uppermost 25% being "Superior" Recovery Kinetics (SRK) versus "Normal" Recovery Kinetics (NRK). BL demographic, clinical, and surgical information predicted SRK using generalized linear modeling., Results: Ninety-eight patients included (62 ± 10 years, 28 ± 6 kg/m2, 65% females, Charlson Comorbidity Index: 0.95), 6% smokers, 31% smoking history. Surgical approach was: combined (33%), posterior (49%), anterior (18%). Posterior levels fused: 8.7, anterior: 3.6, estimated blood loss: 915.9ccs, operative time: 495 minutes. Ames BL classification: cSVA (53.2% minor deformity, 46.8% moderate), TS-CL (9.8% minor, 4.3% moderate, 85.9% marked), horizontal gaze (27.4% minor, 46.6% moderate, 26% marked). Relative to BL NDI (Mean: 47), normalized NDI decreased at 3 months (0.9 ± 0.5, P = 0.260) and 1Y (0.78 ± 0.41, P < 0.001). NDI IHS correlated with age (P = 0.011), sex (P = 0.042), anterior approach (P = 0.042), posterior approach (P = 0.042). Greater BL pelvic tilt (PT) (SRK: 25.6°, NRK: 17°, P = 0.002), pelvic incidence-lumbar lordosis (PI-LL) (SRK: 8.4°, NRK: -2.8°, P = 0.009), and anterior approach (SRK: 34.8%, NRK: 13.3%; P = 0.020) correlated with SRK. 69.4% met MCID for NDI (<Δ-15) and 63.3% met substantial clinical benefit for NDI (<Δ-10); 100% of SRK met both MCID and substantial clinical benefit. The predictive model for SRK included (AUC = 88.1%): BL visual analog scale (VAS) EuroQol five-dimensional descriptive system (EQ5D) (odds rario [OR] 0.96, 95% confidence interval [CI]: 0.92-0.99), BL swallow sleep score (OR: 1.04, 95% CI: 1.01-1.06), BL PT (OR: 1.12, 95% CI: 1.03-1.22), BL modified Japanese Orthopedic Association scale (mJOA) (OR: 1.5, 95% CI: 1.07-2.16), BL T4-T12, BL T10-L2, BL T12-S1, and BL L1-S1., Conclusion: Superior recovery kinetics following CD surgery was predicted with high accuracy using BL patient-reported (VAS EQ5D, swallow sleep, mJOA) and radiographic factors (PT, TK, T10-L2, T12-S1, L1-S1). Awareness of these factors can improve decision-making and reduce postoperative neck disability.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Parents and families of children with cancer and blood disorders increasingly turn to social media to connect with families facing similar challenges. These multidirectional interactions on social media are not only sources of psychosocial support but frequently sources of medical information. Consequently, such interactions have the potential to meaningfully impact the relationships between parents, children, and pediatric hematology/oncology providers. The 3 case studies analyzed here illustrate the spectrum of ethical and communication issues that arise when families' use of social media enters the pediatric clinical space, including questions related to trust and mistrust, misinformation, patient privacy and confidentiality, and allocation of resources, including time. Ideal approaches to resolving dilemmas related to parental social media use are those that maintain respect, build trust, and acknowledge the changing culture. Social media use is now the norm. Promoting transparent discussions of its use between families and health professionals is, therefore, the key to optimizing health outcomes for children whose parents turn to social media. Mutual respect, collaboration, and long-term relationships are also potential antidotes to the spread of misinformation and mistrust through social media.

Study Design: Retrospective review of a prospective database., Objective: The aim of this study was to evaluate postop clinical recovery among adult spinal deformity (ASD) patients between frailty states undergoing primary procedures SUMMARY OF BACKGROUND DATA.: Frailty severity may be an important determinant for impaired recovery after corrective surgery., Methods: It included ASD patients with health-related quality of life (HRQLs) at baseline (BL), 1 year (1Y), and 3 years (3Y). Patients stratified by frailty by ASD-frailty index scale 0-1(no frailty: <0.3 [NF], mild: 0.3-0.5 [MF], severe: >0.5 [SF]). Demographics, alignment, and SRS-Schwab modifiers were assessed with χ/paired t tests to compare HRQLs: Scoliosis Research Society 22-question Questionnaire (SRS-22), Numeric Rating Scale (NRS) Back/Leg Pain, Oswestry Disability Index (ODI). Area-under-the-curve (AUC) method generated normalized HRQL scores at baseline (BL) and f/u intervals (1Y, 3Y). AUC was calculated for each f/u, and total area was divided by cumulative f/u, generating one number describing recovery (Integrated Health State [IHS])., Results: A total of 191 patients were included (59 years, 80% females). Breakdown of patients by frailty status: 43.6% NF, 40.8% MF, 15.6% SF. SF patients were older (P = 0.003), >body mass index (P = 0.002). MF and SF were significantly (P < 0.001) more malaligned at BL: pelvic tilt (NF: 21.6°; MF: 27.3°; SF: 22.1°), pelvic incidence and lumbar lordosis (7.4°, 21.2°, 19.7°), sagittal vertical axis (31 mm, 87 mm, 82 mm). By SRS-Schwab, NF were mostly minor (40%), and MF and SF markedly deformed (64%, 57%). Frailty groups exhibited BL to 3Y improvement in SRS-22, ODI, NRS Back/Leg (P < 0.001). After HRQL normalization, SF had improvement in SRS-22 at year 1 and year 3 (P < 0.001), and NRS Back at 1Y. 3Y IHS showed a significant difference in SRS-22 (NF: 1.2 vs. MF: 1.32 vs. SF: 1.69, P < 0.001) and NRS Back Pain (NF: 0.52, MF: 0.66, SF: 0.6, P = 0.025) between frailty groups. SF had more complications (79%). SF/marked deformity had larger invasiveness score (112) compared to MF/moderate deformity (86.2). Controlling for baseline deformity and invasiveness, SF showed more improvement in SRS-22 IHS (NF: 1.21, MF: 1.32, SF: 1.66, P < 0.001)., Conclusion: Although all frailty groups exhibited improved postop disability/pain scores, SF patients recovered better in SRS-22 and NRS Back. Despite SF patients having more complications and larger invasiveness scores, they had overall better patient-reported outcomes, signifying that with frailty severity, patients have more room for improvement postop compared to BL quality of life., Level of Evidence: 3.

Objectives: To determine significant associations between patient frailty status and odontoid fractures across common traumatic mechanisms of injuries (MOIs) in the elderly., Design: Retrospective review., Setting: Single, academic-affiliated hospital with full surgical services., Patients/participants: Patients 65 years or older with traumatic odontoid fractures were included., Intervention: Nonoperative management (soft/hard collar, halo, traction tongs, and Minerva) and/or operative fixation., Main Outcome Measurements: Modified frailty index (mFI), MOI, concurrent injuries, inpatient length of stay (LOS), reoperation, and mortality rates., Results: Seventy patients were included (80.6 ± 8.5 years, 60% F, 88% European, 10% Maori/Pacific, 1.4% Asian, Charlson Comorbidity Index 5.3 ± 2.2, mFI 0.21 ± 0.15). The most common MOIs were falls (74.3%), high-speed motor vehicle accidents (MVAs) (17.1%), low-speed MVAs (5.7%), and pedestrian versus car (2.9%). Patients with traumatic falls exhibited significantly higher mFI scores (0.25) compared with low-speed MVAs (0.16), high-speed MVAs (0.08), and pedestrian versus car (0.01) (P = 0.003). Twenty-seven patients with odontoid fractures were frail, 33 were prefrail, and 10 were robust. Ninety-two percent of frail patients had a traumatic fall as their MOI, as opposed to 73% of prefrail and 30% of robust patients (P < 0.001). Prefrail and frail patients were 4.3 times more likely than robust patients to present with odontoid fractures through traumatic fall [odds ratio (OR): 4.33 (1.47-12.75), P = 0.008], and frailty increased likelihood of reoperation [OR: 4.2 (1.2-14.75), P = 0.025] and extended LOS [OR: 5.71 (1.05-10.37), P = 0.017]. Frail patients had the highest 30-day (P = 0.017) and 1-year mortality (P < 0.001) compared with other groups., Conclusion: Patients with traumatic odontoid fractures from falls were significantly more frail in comparison with any other MOIs, with worse short- and long-term outcomes., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Study Design: Retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database years 2010 to 2015., Objective: Investigate which short-term outcomes differ for cervical laminoplasty and laminectomy and fusion surgeries., Summary of Background Data: Conflicting reports exist in spine literature regarding short-term outcomes following cervical laminoplasty and posterior laminectomy and fusion. The objective of this study was to compare the 30-day outcomes for these two treatment groups for multilevel cervical pathology., Methods: Patients who underwent cervical laminoplasty or posterior laminectomy and fusion were identified in National Surgical Quality Improvement Program (NSQIP) based on Current Procedural Terminology (CPT) code: laminoplasty 63,050 and 63,051, posterior cervical laminectomy 63,015 and 63,045, and instrumentation 22,842. Propensity-adjusted multivariate regressions assessed differences in postoperative length of stay, adverse events, discharge disposition, and readmission., Results: Three thousand seven hundred ninety-six patients were included: 2397 (63%) underwent cervical laminectomy and fusion and 1399 (37%) underwent cervical laminoplasty. Both groups were similar in age, sex, body mass index (BMI), American Society of Anesthesiologist Classification (ASA), Charleston Comorbidity Index (CCI), and had similar rates of malnutrition, chronic kidney disease, diabetes, chronic obstructive pulmonary disease, and history for steroid use. Age more than 70 and age less than 50 were not associated with one treatment group over the other (P > 0.05). Compared with laminoplasty patients, laminectomy and fusion patients had increased lengths of stay (LOS) (4.5 vs. 3.7 d, P < 0.01) and increased rates of adverse events (41.7% vs. 35.9%, P < 0.01), discharge to rehab (16.4% vs. 8.6%, P < 0.01), and skilled nursing facilities (12.2% vs. 9.7%, P = 0.02), and readmission (6.2% vs. 4.5%, P = 0.05). Both groups experienced similar rates of death, pulmonary embolus, deep vein thrombosis, deep and superficial surgical site infection, and reoperation (P > 0.05 for all)., Conclusion: Posterior cervical laminectomy and fusion patients were found to have increased LOS, readmissions, and complications despite having similar pre-op demographics and comorbidities. Patients and surgeons should consider these risks when considering surgical treatment for cervical pathology., Level of Evidence: 3.

Objectives: Tuberculosis (TB) is common in people living with HIV, leading to worse clinical outcomes including increased mortality. We investigated risk factors for developing TB following HIV diagnosis., Design: Adults aged at least 15 years first presenting to health services for HIV care in England, Wales or Northern Ireland from 2000 to 2014 were identified from national HIV surveillance data and linked to TB surveillance data., Methods: We calculated incidence rates for TB occurring more than 91 days after HIV diagnosis and investigated risk factors using multivariable Poisson regression., Results: A total of 95 003 adults diagnosed with HIV were followed for 635 591 person-years; overall incidence of TB was 344 per 100 000 person-years (95% confidence interval 330-359). TB incidence was high for people who acquired HIV through injecting drugs [PWID; men 876 (696-1104), women 605 (365-945)] and black Africans born in high TB incidence countries [644 (612-677)]. The adjusted incidence rate ratio for TB amongst PWID was 4.79 (3.35-6.85) for men and 6.18 (3.49-10.93) for women, compared with MSM. The adjusted incidence rate ratio for TB in black Africans from high-TB countries was 4.27 (3.42-5.33), compared with white UK-born individuals. Lower time-updated CD4 cell count was associated with increased rates of TB., Conclusion: PWID had the greatest risk of TB; incidence rates were comparable with those in black Africans from high TB incidence countries. Most TB cases in PWID were UK-born, and likely acquired TB through transmission within the United Kingdom. Earlier HIV diagnosis and quicker initiation of antiretroviral therapy should reduce TB incidence in these populations.

Background: We characterize engagement with HIV care in South Africa in 2012 to identify areas for improvement towards achieving global 90-90-90 targets., Methods: Over 3.9 million CD4 cell count and 2.7 million viral load measurements reported in 2012 in the public sector were extracted from the national laboratory electronic database. The number of persons living with HIV (PLHIV), number and proportion in HIV care, on antiretroviral therapy (ART) and with viral suppression (viral load <400 copies/ml) were estimated and stratified by sex and age group. Modified Poisson regression approach was used to examine associations between sex, age group and viral suppression among persons on ART., Results: We estimate that among 6511 000 PLHIV in South Africa in 2012, 3300 000 individuals (50.7%) accessed care and 32.9% received ART. Although viral suppression was 73.7% among the treated population in 2012, the overall percentage of persons with viral suppression among all PLHIV was 23.8%. Linkage to HIV care was lower among men (38.5%) than among women (57.2%). Overall, 47.1% of those aged 0-14 years and 47.0% of those aged 15-49 years were linked to care compared with 56.2% among those aged above 50 years., Conclusion: Around a quarter of all PLHIV have achieved viral suppression in South Africa. Men and younger persons have poorer linkage to HIV care. Expanding HIV testing, strengthening prompt linkage to care and further expansion of ART are needed for South Africa to reach the 90-90-90 target. Focus on these areas will reduce the transmission of new HIV infections and mortality in the general population.

Objective: To investigate whether HIV-infected individuals diagnosed with tuberculosis (HIV-TB) around the time of starting antiretroviral therapy (ART) have impaired CD4 cell responses to treatment., Design: Analysis of a national cohort of HIV-infected adults, linked to the national TB surveillance system for England, Wales and Northern Ireland, including individuals starting ART from 2005 to 2009., Methods: We compared CD4 cell responses in HIV-infected individuals starting ART with a TB diagnosis ('HIV-TB cohort') with those not known to have TB ('TB-free cohort'). The TB-free cohort was frequency-matched to the HIV-TB cases for sex, age strata, baseline CD4 strata and ethnicity. Median change in CD4 cell count from baseline (ΔCD4) was calculated at 6-monthly intervals until 36 months., Results: There were 593 and 1779 individuals in the HIV-TB and TB-free cohorts, respectively (median follow-up 3.8 years). In both cohorts, median age was 36 years, 49.2% were women and 74.9% were black-African. Median baseline CD4 at the start of treatment was similar in the HIV-TB and TB-free cohorts (74 vs. 80 cells/μl). Median ΔCD4 was similar in HIV-TB and TB-free cohorts at all time points [294 (inter-quartile range 198-424) cells/μl in HIV-TB cohort; 296 (inter-quartile range 196-431) cells/μl in TB-free cohort after 3 years of ART]. A higher proportion of the HIV-TB cohort than the TB-free cohort died during follow-up (4.2 vs. 2.2%; P = 0.01); 78.5% of all individuals who died had a baseline CD4 cell count below 100 cells/μl., Conclusions: Long-term CD4 cell recovery during ART appears similar in HIV-TB and TB-free patients. Significant mortality in both cohorts highlights the need for earlier HIV diagnosis and ART initiation.

Objective: HIV-1 subtype B infections are associated with MSM in the UK. Yet, around 13% of subtype B infections are found in those reporting heterosexual contact as transmission route. Using phylogenetics, we explored possible misclassification of sexual exposure among men diagnosed with HIV in the UK., Design: Viral gene sequences linked to patient-derived information were used to identify phylogenetic transmission chains., Methods: A total of 22,481 HIV-1 subtype B pol gene sequences sampled between 1996 and 2008 were analysed. Dated phylogenies were reconstructed and transmission clusters identified as clades of at least two sequences with a maximum genetic distance of 4.5%, a branch support of at least 95% and spanning 5 years. The characteristics of clusters containing at least one heterosexually acquired infection were analysed., Results: Twenty-nine percent of the linked heterosexuals clustered exclusively with MSM. These were more likely to be men than women. Estimated misclassification of homosexually acquired infections ranged between 1 and 11% of the reported male heterosexuals diagnosed with HIV. Black African heterosexual men were more often phylogenetically linked to MSM than other ethnic group, with an estimated misclassification range between 1 and 21%., Conclusion: Overall, a small proportion of self-reported heterosexual men diagnosed with HIV could have been infected homosexually. However, up to one in five black African heterosexual men chose not to disclose sex with men at HIV diagnosis and preferred to be identified as heterosexual. Phylogenetic analyses can enhance surveillance-based risk information and inform national programmes for monitoring and preventing HIV infections.

Cetuximab, a monoclonal antibody specific for epidermal growth factor receptor, is increasingly used off-label and in early-phase trials for pediatric malignancies. Here, we report a patient with metastatic medulloblastoma receiving therapy with cyclophosphamide, vinblastine, and cetuximab. During evaluation for possible seizures, he was noted to be severely hypocalcemic, hypokalemic, and hypomagnesemic, a consequence of the blockade of renal epidermal growth factor receptor expression. His symptoms rapidly abated with intravenous electrolyte repletion. This case highlights the clinical heterogeneity of tetany and the importance of careful laboratory screening for known adverse effects of chemotherapy, particularly when newer biological agents are used off-study in combination chemotherapeutic regimens.

The WHO guidelines recommend antiretroviral therapy (ART) begins when CD4 cell counts reach less than 500 cells to reduce HIV transmission. In the UK, 96 000 people were living with HIV (PLWHIV) in 2011, ART coverage was 84% among the diagnosed population and 42% of PLWHIV had detectable viraemia. Using published methods, we estimate starting ART at below 500 CD4 cells could have reduced the proportion of PLWHIV with detectable viraemia from 42% to 38%, whereas halving the undiagnosed population could have led to a decrease to 28%. In the UK, it is unlikely early treatment will reduce HIV transmission unless the undiagnosed population is substantially reduced.

Objectives: To examine invasive pneumococcal disease (IPD) incidence, the impact of the 7-valent pneumococcal conjugate vaccines (PCV7s) programme on the distribution of Streptococcus pneumoniae serotypes and risk factors for IPD among HIV-positive adults., Methods: We analysed adults (aged ≥15 years) reported to the HIV and IPD national datasets in England and Wales (2000-2009). Through data-linkage, changes in IPD incidence and serotype distribution were examined. Risk factors for IPD among HIV-positive adults were assessed using a case-control study., Results: Among 63,109 HIV-positive adults, 951 were co-infected with IPD. The average annual incidence of IPD was 245 episodes per 100,000 HIV-positive adults and 246 of 100,000 among those aged 15-44 years. Incidence was higher among those not on antiretroviral therapy (ART) (281 of 100,000) and those with severe immunosuppression (563 of 100,000). Among 9283 adults aged 15-44 at IPD diagnosis, 2.4% were living with undiagnosed HIV. The proportion of IPD episodes in HIV-positive adults with serotypes covered by PCV7 was 23% in 2009, a 54% proportional reduction compared with pre-PCV7 (2000-2006); the reduction in adults of unknown HIV status was 70%. The proportion of IPD episodes among HIV-positive adults caused by serotypes covered by PCV13 was 61%. Significant risk factors for IPD in multivariate analysis included older aged (≥65 years), a lower nadir CD4 cell count and no previous ART., Conclusion: An HIV test should be offered and recommended to adults aged 15-44 years without other obvious IPD risk factors. Our study provides an evidence base to policy makers regarding the use of the new PCV13 in HIV-positive adults.

Objectives: Describe the epidemiology and impact of late diagnosis among older adults living with HIV and estimate age at infection., Methods: Comparative national analyses between individuals diagnosed when aged 50 years and over with individuals diagnosed prior to 50 years. Age at infection was estimated using CD4 cell count at diagnosis., Results: A total of 8255 older adults accessed HIV care in England, Wales and Northern Ireland in 2007, a 3.5-fold increase compared to 2000; with one in 10 individuals newly diagnosed in 2007. When compared with younger adults at diagnosis, older adults were significantly more likely to be men (74 vs. 58%; P < 0.001), infected through sex between men (40 vs. 34%; P < 0.001) and of white ethnicity (60 vs. 38%; P < 0.001). Older heterosexual adults were more likely to be infected within the UK (16 vs. 12%; P < 0.001), with evidence of travel abroad among white heterosexual men. Almost half (48%) of older adults were late presenters vs. a third (33%) of younger adults. Older late presenters were 14 times more likely to die within a year of diagnosis compared with older adults who were not diagnosed late (14 vs. 1%; P < 0.001) and had 2.4 times the risk of dying than younger late presenters. We estimate that nearly half (48%) of older adults diagnosed between 2000 and 2007 acquired their infection at age 50 and over., Conclusion: Our study provides evidence of HIV transmission, high rates of late presentation and an increased risk of short-term mortality among older adults. These findings highlight the need for increased targeted prevention efforts and strategies to increase HIV testing among older adults at risk of HIV.

Objectives: To identify biological factors associated with HIV transmission in men who have sex with men (MSM)., Design: A longitudinal phylogenetic analysis of HIV-1 from an MSM cohort, incorporating clinical and epidemiological data., Methods: Potential individuals were HIV-infected MSM attending a sexual health clinic between 2000 and 2006. Individuals were classified such that they could move from recent to chronic infection categories. HIV-1pol gene sequences were obtained from plasma virus or proviral DNA and clusters estimated by maximum likelihood and conservative genetic distance differences. The single most likely transmitter generating each recent infection was ascertained and risk factors around time of likely transmission explored using Poisson regression modelling., Results: Out of 1144 HIV-infected MSM, pol sequence data were obtained for 859 (75%); 159 out of 859 (19%) were recently HIV infected at diagnosis. A single most likely transmitter was identified for 41 out of 159 (26%), of which 11 were recently infected (27%) and 30 chronically infected. Factors associated with transmission in multivariable analysis were: younger age {rate ratio per 5 years older 0.68 [95% confidence interval (CI) 0.54-0.86], P=0.0009}, higher viral load [rate ratio per log higher 1.61 (95% CI 1.15-2.25), P=0.005], recent infection [rate ratio 3.88 (95% CI 1.76-8.55), P=0.0008] and recent sexually transmitted disease [rate ratio 5.32 (95% CI 2.51-11.29), P=0.0001]. HAART was highly protective in a univariable model, RR 0.14 (95% CI 0.07-0.27, P=0.0001)., Conclusion: Onward transmission of HIV among MSM is significantly associated with recent infection, sexually transmitted diseases and higher viral load, and reduced by effective HAART. The majority of new infections appear to occur from individuals whose infection was undiagnosed at the time of transmission.

To obtain a better understanding of the evolving HIV-1 epidemic in Thailand, we utilized antibody to hepatitis C virus (HCV) to indicate the mode of HIV-1 transmission. Although the proportion of men with HCV co-infection increased between 1995 and 2000, the prevalence was similar, whereas the prevalence of men not co- infected decreased (1.93-0.46%). This suggests that HIV-1 infection associated with parenteral transmission has been stable despite a dramatic reduction in the sexual transmission of HIV-1.

Objectives: To study the association between hepatitis C virus (HCV) and HIV-1, and HCV seropositivity as an indicator of HIV-1 risk behavior for HIV vaccine preparatory cohorts in Thailand., Design: Cross-sectional study of HIV-1-infected persons identified at screening for potential HIV vaccine trial cohort studies., Methods: Sera from HIV-1-infected and uninfected volunteers was matched by age, sex, and community, and tested for HCV reactivity. Logistic regression methods were used to measure associations between HIV-1, HCV and other risk factors for HIV infection., Results: The prevalence of HCV among HIV-negative controls was 8.3% (6/72) for men and 4.2% (5/118) for women. Co-infection with HIV and occurred in 50.7% (37/73) of men and 3.4% (4/118) of women. Among men who reported injection drug use (IDU), 96.4% (27/28) were HCV seropositive. No women reported IDU. HCV was associated with HIV infection [odds ratio (OR), 11.3; 95% confidence interval (CI), 4.4-29.3] and IDU (OR, 12.0; 95% CI, 3.4-41.9) among men, but not women (OR, 0.8; 95% CI, 0.2-3.0). After adjustment for potential confounding, HCV, but not IDU, remained strongly associated with HIV-1 infection among men (OR, 9.4; 95% CI, 2.7-32.6)., Conclusions: The strong associations between HCV seropositivity, HIV-1 infection, and IDU history suggest that IDU was reported accurately in this study. The surprisingly high prevalence of HCV among HIV-1-infected young men may assist health policy makers in the choice of behavioral interventions for this important subgroup of the population.

Persons attending sexually transmitted disease clinics at three sites in Thailand were recruited to participate in a 1-year study of HIV-1 incidence. Between September 1995 and February 1996, 31% (371 of 1205) of eligible men and 24% (161 of 659) of eligible women agreed to participate. At enrollment, HIV-1 seropositivity was 3.8% among men and 2.5% among women. Follow-up of the 514 participants who were seronegative at baseline was 78% at the 12-month visit. During the study period, 53% of men reported 2 or more sexual partners, 31% reported sex with a commercial sex worker (CSW), and 33% with a casual partner. Of those visiting CSWs, 72% reported consistent condom use. Among women, 11% reported 2 or more sexual partners. Decreased HIV risk behaviors among men were observed during the study. Four incident infections occurred in men (1.4/100 person-years, 95% confidence interval [CI] = 0.4-3.6) and none among women. Based on the observed HIV-1 incidence, HIV vaccine efficacy trials in such populations would have to be larger than previously planned or more selective of high risk subgroups for recruitment.

Purpose: This report describes the incidence of septic shock in pediatric hematology-oncology patients with positive blood cultures and investigates parameters of potential use in early diagnosis of gram-negative (GN) bacteremia and septic shock., Patients: In a 12-month period, 140 consecutive episodes of septicemia (135 bacterial and 5 fungal) were seen in 100 patients. The absolute neutrophil count (ANC) was > 500/microl in 89 episodes (65%)., Results: Septic shock developed in patients with positive blood cultures with an overall incidence of approximately 19%. Of the 12 bacteremic patients who required transfer to the intensive care unit, 83% had a GN isolate recovered. The incidence of septic shock was not significantly lower in the group of patients with ANC > 500/microl. Low serum bicarbonate correlated with GN infection in patients with bacteremia., Conclusions: GN organisms were the major cause of septic shock in a group of pediatric hematology-oncology patients with positive blood cultures although they were recovered less frequently than gram-positive organisms. In our study, non-neutropenic patients with indwelling catheters were at approximately the same risk for GN shock as neutropenic patients. Monitoring blood carbon dioxide content may be useful in the early diagnosis of GN infection.

Objective: To determine the relative frequencies of HIV-1 p24 antigen and culture positivity in white and black patients., Design: Volunteers in the US military's HIV natural history study were 46% white, 44% black, 7% Hispanic and 3% other. Focusing on the comparable groups of whites and blacks, a retrospective analysis was performed of the results of virologic assays collected over a 2-year period., Methods: p24 antigen was quantitated in sera with and without immune complex dissociation (ICD); viral isolation was performed by coculture of peripheral blood mononuclear cells., Results: Results of the two virologic assays were very similar in the two racial groups, both overall and after stratification by CD4 cell count. As reported previously, the concentration of serum immunoglobulin G was found to be greater in black than white subjects. In contrast to results with ICD, sera tested without ICD resulted in differing (higher) rates of antigenemia in whites than blacks (P = 0.002)., Conclusions: The frequencies of p24 antigen and culture positivity were found to be independent of race. Previously observed racial differences in antigen positivity were likely to be due to more extensive antibody binding in blacks than in whites.

The potential of lymph node fine-needle aspiration (LNFNA) for sampling viral load was evaluated in excised, peripheral lymph nodes from five patients with early-stage human immunodeficiency virus type 1 HIV-1 disease (asymptomatic, CD4 cells > 300/mm3). The preponderance (> 80%) of viral RNA was within follicular germinal centers as noted by in situ hybridization on lymph node frozen sections (LNFSs) as well as within cohesive groups of 10-20 lymphoid cells (microfragments) in LNFNA preparations. Quantification of cells expressing HIV-1 RNA by in situ hybridization, quantification of HIV-1 gag RNA and gag DNA per 10(5) cells by polymerase chain reaction, and measurement of p24 antigen per 10(5) cells yielded similar values for LNFNA, lymph node mononuclear cells (LNMCs) from tissue homogenates by Ficoll-Hypaque separation, and LNFS. Sampling of lymph node viral load by LNFNA appears to capture viral components associated with both individual expressing cells and follicular germinal centers. Due to the advantages in terms of patients' morbidity, repeatability, and cost, assessment of lymphoid tissue viral load by LNFNA warrants an in vivo feasibility trial as an alternative to lymph node biopsy.

Previous reports of F. oryzihabitans sepsis involving central venous access devices reveal a relatively high rate of complications, including device removal, despite a course of broad-spectrum anti-microbials with compatible in vitro susceptibility results. In the present report of 22 cases of F. oryzihabitans sepsis treated at Memorial Sloan-Kettering Cancer Center from February 1986 through September 1993, the majority of CVAD-related infections with F. oryzihabitans were successfully treated with a 14-day course of antimicrobials with antipseudomonal activity, and removal of the device was usually not required. Factors that may complicate successful treatment of CVAD-related sepsis caused by F. oryzihabitans include polymicrobial infections and premature discontinuation of antibiotic therapy.

Objective: This study was performed to evaluate the effect of a silver-impregnated cuff on the incidence of catheter-related bacteremia/fungemia or tunnel tract infection in cancer patients with chronic dual-lumen tunneled venous access catheters., Summary Background Data: Infection is a frequent and potentially life-threatening complication of tunneled chronic cuffed silastic central venous access catheters in cancer patients. Recent experience with antimicrobial silver-impregnated cuffs placed on nontunneled percutaneously inserted central venous catheters suggests that such a cuff may render the catheter less prone to infection., Methods: The authors prospectively randomized 200 cancer patients to receive either a dual-lumen 10 French tunneled cuffed silastic central venous access catheter or the same catheter with a second more proximal subcutaneous silver-impregnated cuff. All patients then were followed prospectively for infectious morbidity until the device was removed or the patient died., Results: The hazard rate for infection/day (95% confidence limits) was 0.0022 (0.0015 to 0.0030) for standard catheters compared with 0.0027 (0.0019 to 0.0037) for catheters with silver-impregnated cuffs (p = not significant). Regression analysis of infection-free interval of both catheter types shows no difference over the lifetime of catheter as well as the over the first 48 days after insertion., Conclusions: The study indicated no effect of a silver-impregnated cuff in decreasing the incidence of catheter-related bacteremias/fungemias, tunnel infections, or the spectrum of causative microorganisms involved in cancer patients with tunneled chronic venous access catheters.