Long-term changes in bone metabolism, bone mineral density, quantitative ultrasound parameters, and fracture incidence after spinal cord injury: a cross-sectional observational study in 100 paraplegic men

To study the time course of demineralization and fracture incidence after spinal cord injury (SCI), 100 paraplegic men with complete motor loss were investigated in a cross-sectional study 3 months to 30 years after their traumatic SCI. Fracture history was assessed and verified using patients' files and X-rays. BMD of the lumbar spine (LS), femoral neck (FN), distal forearm (ultradistal part = UDR, 1/3 distal part = 1/3R), distal tibial diaphysis (TDIA), and distal tibial epiphysis (TEPI) was measured using DXA. Stiffness of the calcaneus (QUI.CALC), speed of sound of the tibia (SOS.TIB), and amplitude-dependent SOS across the proximal phalanges (adSOS.PHAL) were measured using QUS. Z-Scores of BMD and quantitative ultrasound (QUS) were plotted against time-since-injury and compared among four groups of paraplegics stratified according to time-since-injury (<1 year, stratum I; 1-9 years, stratum II; 10-19 years, stratum III; 20-29 years, stratum IV). Biochemical markers of bone turnover (deoxypyridinoline/creatinine (D-pyr/Cr), osteocalcin, alkaline phosphatase) and the main parameters of calcium phosphate metabolism were measured. Fifteen out of 98 paraplegics had sustained a total of 39 fragility fractures within 1,010 years of observation. All recorded fractures were fractures of the lower limbs, mean time to first fracture being 8.9 +/- 1.4 years. Fracture incidence increased with time-after-SCI, from 1% in the first 12 months to 4.6%/year in paraplegics since >20 years ( p<.01). The overall fracture incidence was 2.2%/year. Compared with nonfractured paraplegics, those with a fracture history had been injured for a longer time ( p<.01). Furthermore, they had lower Z-scores at FN, TEPI, and TDIA ( p<.01 to <.0001), the largest difference being observed at TDIA, compared with the nonfractured. At the lower limbs, BMD decreased with time at all sites ( r=.49 to.78, all p<.0001). At FN and TEPI, bone loss followed a log curve which leveled off between 1 to 3 years after injury. In contrast, Z-scores of TDIA continuously decreased even beyond 10 years after injury. LS BMD Z-score increased with time-since-SCI ( p<.05). Similarly to DXA, QUS allowed differentiation of early and rapid trabecular bone loss (QUI.CALC) vs slow and continuous cortical bone loss (SOS.TIB). Biochemical markers reflected a disproportion between highly elevated bone resorption and almost normal bone formation early after injury. Turnover declined following a log curve with time-after-SCI, however, D-pyr/Cr remained elevated in 30% of paraplegics injured >10 years. In paraplegic men early (trabecular) and persistent (cortical) bone loss occurs at the lower limbs and leads to an increasing fracture incidence with time-after-SCI.

Incidence and direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland

The objective of this study was to estimate the annual direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland. Days of hospital stay in 1992 were quantified using the casuistic of the medical statistics department of VESKA (Vereinigung Schweizerischer Krankenhäuser, the Swiss Hospital Association), which covers 43% of all hospital beds of that country. Number and incidence of total hospitalizations due to fractures were calculated by extrapolating to 100% the 43% VESKA-selected sample. To estimate number and incidence of hospitalizations due to osteoporotic fractures, internationally accepted age-specific osteoporosis attribution rates were applied. According to the latter the probability of a fracture being caused by osteoporosis increases with age. Mean length of stay for all fractures was calculated (= total hospital days divided by number of cases). By multiplying these mean lengths of stay by the number of osteoporosis-related fracture cases, the number of bed-days due to osteoporotic fractures was calculated. To compare the direct medical costs of hospitalization due to osteoporosis with those due to other frequent diseases, days of hospital stay caused by chronic obstructive pulmonary disease (COPD), stroke, acute myocardial infarction and breast cancer were estimated using the same methodology. A total estimate of 63,170 (f: 33,596, m: 29,574) hospitalizations due to fractures (and other osteoporosis-related diagnoses) was calculated, thus leading to overall annual incidence rates of hospitalizations for fractures of 950/100,000 women and 877/100,000 men. In women, 548,615 hospital days were found to be caused by osteoporosis, 353,654 days by COPD, 352,062 days by stroke, 200,669 days by breast carcinoma and 131,331 days by myocardial infarction. In men, COPD caused more hospitalization days (537,164) than myocardial infarction (196,793), stroke (180,524) or osteoporosis (152,857). Taking a mean price for a hospital day in Switzerland of 845 Swiss francs, the annual costs of acute hospitalizations due to osteoporosis and its complications were approximately 600 million Swiss francs (f: 464, m: 130 million Swiss francs) in 1992. We conclude that there is enough economic evidence to justify wide-scale interventions against osteoporosis in Switzerland.

Diseases in neonatal foals. Part 2: potential risk factors for a higher incidence of infectious diseases during the first 30 days post partum

REASON FOR PERFORMING STUDY: The development of clinical illness in foals is usually predetermined by perinatal history, management or stressful environmental conditions. OBJECTIVES: To determine potential risk factors for an increased incidence of infectious diseases during the first 30 days post partum. METHODS: The population consisted of Thoroughbred foals born on stud farms in the Newmarket (UK) area in 2005 (n = 1031). They were followed for their first 30 days. Factors suspected to influence the incidence of infectious neonatal diseases were examined in a logistic regression approach for each of the 3 outcomes (total infectious diseases, systemic disease with diarrhoea and total infectious diseases excluding diarrhoea). All 28 factors were either foal or mare or stud farm related. RESULTS: Several significant risk factors for a higher disease incidence, such as birth complications, colostrum intake by stomach tube and leucocytosis 12-48 h post partum were identified. The factor 'boarding stud' seemed to be protective against disease. CONCLUSION: Some factors, such as the mare's time at stud before foaling, the mare's rotavirus vaccination schedule and fibrinogen-values that empirically had been linked to the outcome previously were not confirmed as relevant. This included the reported useful prophylactic treatment with antimicrobial drugs. POTENTIAL RELEVANCE: Factors to be considered when evaluating newborn foals include: stud management, the birth process, route of colostrum intake, white and red blood cells, and the date of birth. These may help to detect foals at risk to develop an infection so that targeted prophylactic measures can be initiated.

Diseases in neonatal foals. Part 1: the 30 day incidence of disease and the effect of prophylactic antimicrobial drug treatment during the first three days post partum

REASONS FOR PERFORMING STUDY: Neonatal diseases have been grouped and analysed but up-to-date statistically significant information about the incidence and prevalence of diseases in foals is limited. Since the 1950s it has been a common management practice to administer a 3 day course of antimicrobial drugs to neonatal foals. This was shown to significantly reduce the incidence of infections (Platt 1977). Since then management practices have improved and it is widely believed that prophylactic antimicrobial drugs are no longer necessary in foal rearing. OBJECTIVES: To determine the 30 day incidences or prevalences (depending on case definition) of various diseases and conditions in the neonatal foal and ascertain the influence of a prophylactic 3 day treatment on the frequency of infections. METHODS: The population consisted of Thoroughbred foals born on stud farms in the Newmarket (UK) area in 2005 (n = 1031). Depending on the stud farm's practice in the use of prophylactic antimicrobial drugs, 2 groups of newborn foals (treated and untreated) were identified and followed for 30 days. RESULTS: The 30 day incidences of infectious diseases under study were between 0.2% (osteomyelitis) and 5.85% (systemic disease with diarrhoea). The overall incidence for 'total infectious diseases' was 8.27%. The most commonly observed noninfectious condition was limb deformities (12.11% of all foals). There was no significant difference in the incidence of infectious diseases between the 2 groups. CONCLUSION: Infectious diseases are still an important problem in neonatal foals requiring further investigation as to which factors other than antimicrobial prophylaxis are relevant for disease prevention. POTENTIAL RELEVANCE: The results provide an up-to-date overview about the frequencies of various neonatal foal diseases. They do not support the traditional prophylactic use of antimicrobials to prevent infectious diseases in healthy newborn foals. However, it should be noted that this study was not a randomised controlled trial and therefore does not provide the strongest possible evidence for this conclusion.

Prevalence and predictors of suicide attempt in an incidence cohort of 661 young people with first-episode psychosis

Studies investigating suicidal behaviour in psychosis rarely focus on incidence cohorts of first-episode patients. This is important, because patients who refuse study participation have higher rates of comorbid substance use disorders and longer duration of untreated psychosis as well as worse course illness, variables potentially linked to higher prevalence of suicidal behaviour. The aims of the present study were therefore to examine the prevalence and predictors of suicide and suicide attempt before and during the first 18-24 months of treatment.

Incidence and risk factors of homicide-suicide in Swiss households: National Cohort study

BACKGROUND Homicide-suicides are rare but catastrophic events. This study examined the epidemiology of homicide-suicide in Switzerland. METHODS The study identified homicide-suicide events 1991-2008 in persons from the same household in the Swiss National Cohort, which links census and mortality records. The analysis examined the association of the risk of dying in a homicide-suicide event with socio-demographic variables, measured at the individual-level, household composition variables and area-level variables. Proportional hazards regression models were calculated for male perpetrators and female victims. Results are presented as age-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI). RESULTS The study identified 158 deaths from homicide-suicide events, including 85 murder victims (62 women, 4 men, 19 children and adolescents) and 68 male and 5 female perpetrators. The incidence was 3 events per million households and year. Firearms were the most prominent method for both homicides and suicides. The risk of perpetrating homicide-suicide was higher in divorced than in married men (HR 3.64; 95%CI 1.56-8.49), in foreigners without permanent residency compared to Swiss citizens (HR 3.95; 1.52-10.2), higher in men without religious affiliations than in Catholics (HR 2.23; 1.14-4.36) and higher in crowded households (HR 4.85; 1.72-13.6 comparing ≥2 with <1 persons/room). There was no association with education, occupation or nationality, the number of children, the language region or degree of urbanicity. Associations were similar for female victims. CONCLUSIONS This national longitudinal study shows that living conditions associated with psychological stress and lower levels of social support are associated with homicide-suicide events in Switzerland.

New insights regarding the incidence, presentation and treatment options of aorto-oesophageal fistulation after thoracic endovascular aortic repair: the European Registry of Endovascular Aortic Repair Complications

OBJECTIVES To review the incidence, clinical presentation, definite management and 1-year outcome in patients with aorto-oesophageal fistulation (AOF) following thoracic endovascular aortic repair (TEVAR). METHODS International multicentre registry (European Registry of Endovascular Aortic Repair Complications) between 2001 and 2011 with a total caseload of 2387 TEVAR procedures (17 centres). RESULTS Thirty-six patients with a median age of 69 years (IQR 56-75), 25% females and 9 patients (19%) following previous aortic surgery were identified. The incidence of AOF in the entire cohort after TEVAR in the study period was 1.5%. The primary underlying aortic pathology for TEVAR was atherosclerotic aneurysm formation in 53% of patients and the median time to development of AOF was 90 days (IQR 30-150). Leading clinical symptoms were fever of unknown origin in 29 (81%), haematemesis in 19 (53%) and shock in 8 (22%) patients. Diagnosis could be confirmed via computed tomography in 92% of the cases with the leading sign of a new mediastinal mass in 28 (78%) patients. A conservative approach resulted in a 100% 1-year mortality, and 1-year survival for an oesophageal stenting-only approach was 17%. Survival after isolated oesophagectomy was 43%. The highest 1-year survival rate (46%) could be achieved via an aggressive treatment including radical oesophagectomy and aortic replacement [relative risk increase 1.73 95% confidence interval (CI) 1.03-2.92]. The survival advantage of this aggressive treatment modality could be confirmed in bootstrap analysis (95% CI 1.11-3.33). CONCLUSIONS The development of AOF is a rare but lethal complication after TEVAR, being associated with the need for emergency TEVAR as well as mediastinal haematoma formation. The only durable and successful approach to cure the disease is radical oesophagectomy and extensive aortic reconstruction. These findings may serve as a decision-making tool for physicians treating these complex patients.

Transcatheter aortic valve implantation and bleeding: incidence, predictors and prognosis

Peri-procedural bleeding complications are feared adverse events in patients undergoing transcatheter aortic valve implantation (TAVI). Little is known about the implications of peri-procedural bleeding on clinical outcome. In a prospective single-center registry of consecutive patients undergoing TAVI, we investigated incidence, predictors and clinical consequences of life-threatening and major bleeding as defined by the Valve Academic Research Consortium. Among 389 consecutive patients undergoing TAVI by a transfemoral (79.2%), transapical (19.6%) or trans-subclavian (1.3%) approach between July 2007 and October 2011, life-threatening or major peri-procedural bleeding events occurred in 64 (16.4%) and 125 patients (32.1%), respectively. Patients with peri-procedural bleeding events had a higher logistic EuroSCORE, more advanced renal disease, and were more symptomatic as assessed by New York Heart Association functional class at baseline as compared to patients with no bleeding. Life-threatening bleeding was associated with a higher all-cause (17.2 vs. 5.6 vs. 3.0%, p < 0.001) and cardiovascular mortality (10.9 vs. 5.6 vs. 2.5%, p = 0.02) at 30 days compared to patients with major bleeding or no bleeding. Multivariate analysis identified transapical access (OR 2.6, 95% CI 1.4-4.8; p = 0.002), glomerular filtration rate <30 ml/min (OR 2.3, 95% CI 1.1-4.7, p = 0.031), and diabetes (OR 1.8, 95% CI 1.001-3.2, p = 0.049) as independent predictors of life-threatening, peri-procedural bleeding. Life-threatening bleeding complications in patients undergoing TAVI are associated with increased mortality. Renal impairment, diabetes, and transapical approach were identified as independent risk factors for life-threatening bleeding events.

Incidence and treatment of developmental hip dysplasia in Mongolia: a prospective cohort study

BACKGROUND In Mongolia, adequate early diagnosis and treatment of developmental hip dysplasia (DDH) have been unavailable and its incidence was unknown. We determined the incidence of ultrasonographic DDH in newborns and established adequate procedures for diagnosis and treatment of DDH at the largest maternity hospital in Ulaanbaatar, Mongolia. METHODOLOGY/PRINCIPAL FINDINGS During one year (Sept 2010 - Aug 2011) we assessed the hips newborns using ultrasound and Graf's classification of DDH. 8,356 newborns were screened; median age at screening was 1 day. We identified 14,873 Type 1 (89.0%), 1715 Type 2a (10.3%), 36 Type 2c (0.2%), 70 Type D (0.4%), 14 Type 3 (0.08%), and 4 Type 4 hips (0.02%). Children with Type 1 hips (normal) were discharged. Children with Type 2a hips (physiologically immature) received follow-up ultrasounds at monthly intervals. Children with Type 2c to 4 (DDH; deformed or misaligned hip joint) hips were treated with a Tubingen hip flexion splint and also followed up. The hip abnormalities resolved to mature hips in all children who were followed up. There was no evidence for severe treatment related complications. CONCLUSION/SIGNIFICANCE This study suggests that the incidence of DDH in Mongolian neonates is comparable to that in neonates in Europe. Early ultrasound-based assessment and splinting treatment of DDH led to mature hips in all children followed up. Procedures are feasible and will be continued.

What is the incidence of intracranial bleeding in patients with mild traumatic brain injury? A retrospective study in 3088 Canadian CT head rule patients

OBJECTIVE Only limited data exists in terms of the incidence of intracranial bleeding (ICB) in patients with mild traumatic brain injury (MTBI). METHODS We retrospectively identified 3088 patients (mean age 41 range (7-99) years) presenting with isolated MTBI and GCS 14-15 at our Emergency Department who had undergone cranial CT (CCT) between 2002 and 2011. Indication for CCT was according to the "Canadian CT head rules." Patients with ICB were either submitted for neurosurgical treatment or kept under surveillance for at least 24 hours. Pearson's correlation coefficient was used to correlate the incidence of ICB with age, gender, or intake of coumarins, platelet aggregation inhibitors, or heparins. RESULTS 149 patients (4.8%) had ICB on CCT. No patient with ICB died or deteriorated neurologically. The incidence of ICB increased with age and intake of anticoagulants without clinically relevant correlation (R = 0.11; P < 0.001; R = -0.06; P < 0.001). CONCLUSION Our data show an incidence of 4.8% for ICB after MTBI. However, neurological deterioration after MTBI seems to be rare, and the need for neurosurgical intervention is only required in selected cases. The general need for CCT in patients after MTBI is therefore questionable, and clinical surveillance may be sufficient when CCT is not available.

Effects of Gender on the Incidence of Cardiac Tamponade Following Catheter Ablation of Atrial Fibrillation: Results from a Worldwide Survey in 34,943 AF Ablation Procedures.

BACKGROUND -Cardiac tamponade is the most dramatic complication observed during atrial fibrillation (AF) ablation and the leading cause of procedure-related mortality. Female gender is a known risk factor for complications during AF ablation; however, it is unknown whether women have a higher risk of tamponade. METHODS AND RESULTS -A systematic Medline search was used to locate academic electrophysiologic (EP) centers that reported cases of tamponade occurring during AF ablation. Centers were asked to provide information on cases of acute tamponade according to gender and their mode of management including any case of related mortality. Nineteen EP centers provided information on 34,943 ablation procedures involving 25,261 (72%) males. Overall 289 (0.9%) cases of tamponade were reported: 120 (1.24%) in females and 169 (0.67%) in males (odds ratio 1.83, P<0.001). There was a reciprocal association between center volume and the occurrence of tamponade with substantial lower risk in high volume centers. Most cases of tamponade occurred during catheter manipulation or ablation; females tended to develop more tamponades during transseptal catheterization. No gender difference in the mode of management was observed. However, 16% cases of tamponade required surgery with lower rates in high volume centers. Three cases of tamponade (1%) culminated in death. CONCLUSIONS -Tamponade during AF ablation procedures is relatively rare. Women have an almost twofold higher risk for developing this complication. The risk of tamponade among women decreases substantially in high volume centers. Surgical back-up and acute management skills for treating tamponade are important in centers performing AF ablation.

Late recurrent arrhythmias after ablation of atrial fibrillation: incidence, mechanisms, and treatment.

OBJECTIVES The aim of the study was to determine the incidence of atrial flutter and other arrhythmia recurrences (other than atrial fibrillation [AF]) during long-term follow-up after left atrial substrate modification by percutaneous radiofrequency (RF) ablation of AF. BACKGROUND RF ablation is an effective treatment for patients with AF. However, late recurrent arrhythmias may complicate the patient's course. METHODS One hundred fifty consecutive patients with paroxysmal or persistent AF were included in this prospective study. The incidence of arrhythmia recurrences after AF ablation was analyzed during long-term follow-up using repetitive 7-day ECG recording. RESULTS In 28 of 150 patients (18.7%), stable regular arrhythmias other than AF were detected during follow-up. Left atrial flutter observed in 10 patients (6.7%) was treated by recompletion of the ablation lines in all 10 patients. Left atrial flutter was associated with recurrence of AF in all 10 patients. Nine of 10 patients (90%) were free from atrial flutter and 6 of 10 patients were free from AF after the second intervention. Typical right atrial flutter occurred in 10 patients (6.7%) and was treated successfully by percutaneous RF ablation without recurrence in all patients. Additionally, atrial flutter was documented during follow-up in 7 patients (4.7%); however, invasive electrophysiologic evaluation was not performed due to various reasons. CONCLUSIONS Left atrial flutter is a relevant complication after RF catheter ablation of AF and was always associated with AF recurrence in our study population. Prevention of left atrial flutter can be achieved by induction of ablation lines as continuous and transmural as possible. However, left atrial flutter that does occur late after ablation is amenable to interventional treatment with good prospects of success.

Stable secondary arrhythmias late after intraoperative radiofrequency ablation of atrial fibrillation: incidence, mechanism, and treatment.

INTRODUCTION Intraoperative radiofrequency (RF) ablation is an effective treatment of atrial fibrillation (AF). However, secondary arrhythmias late after ablation may complicate the patient's course. We report on the incidence, mechanisms, and treatment of gap-related atrial flutter and other secondary arrhythmias during long-term follow-up. METHODS AND RESULTS In 129 patients who underwent intraoperative RF ablation with placement of left atrial linear lesions using minimally invasive surgical techniques, secondary arrhythmias were analyzed during long-term follow-up (20 +/- 6 months). Transient atrial arrhythmias during the first 3 postoperative months were excluded. In 8 (6.2%) of 129 patients, sustained stable secondary arrhythmias were documented. Left atrial, gap-related atrial flutter was observed in 4 patients (3.1%). The flutter was treated by percutaneous RF ablation in 3 patients (2.3%) and with drugs in 1 patient (0.8%). In 2 patients (1.6%), right atrial isthmus-dependent atrial flutter occurred and was treated successfully by percutaneous RF ablation. In 2 patients (1.6%), ectopic right atrial tachycardias occurred and were treated with percutaneous RF ablation. CONCLUSION Late after intraoperative RF ablation of atrial fibrillation, three types of stable secondary arrhythmias were observed in 6% of patients: left atrial gap-related atrial flutter, right atrial isthmus-dependent atrial flutter, and ectopic atrial tachycardia. Gaps after intraoperative RF ablation due to noncontinuous or nontransmural linear lesions may lead to stable left atrial macroreentrant tachycardias, requiring new interventional therapy.

Impact of Antiviral Preventive Strategies on the Incidence and Outcomes of Cytomegalovirus Disease in Solid Organ Transplant Recipients

We assessed the impact of antiviral prophylaxis and preemptive therapy on the incidence and outcomes of cytomegalovirus (CMV) disease in a nationwide prospective cohort of solid organ transplant recipients. Risk factors associated with CMV disease and graft failure-free survival were analyzed using Cox regression models. One thousand two hundred thirty-nine patients transplanted from May 2008 until March 2011 were included; 466 (38%) patients received CMV prophylaxis and 522 (42%) patients were managed preemptively. Overall incidence of CMV disease was 6.05% and was linked to CMV serostatus (D+/R− vs. R+, hazard ratio [HR] 5.36 [95% CI 3.14–9.14], p < 0.001). No difference in the incidence of CMV disease was observed in patients receiving antiviral prophylaxis as compared to the preemptive approach (HR 1.16 [95% CI 0.63–2.17], p = 0.63). CMV disease was not associated with a lower graft failure-free survival (HR 1.27 [95% CI 0.64–2.53], p = 0.50). Nevertheless, patients followed by the preemptive approach had an inferior graft failure-free survival after a median of 1.05 years of follow-up (HR 1.63 [95% CI 1.01–2.64], p = 0.044). The incidence of CMV disease in this cohort was low and not influenced by the preventive strategy used. However, patients on CMV prophylaxis were more likely to be free from graft failure.

The Incidence of AIDS-Defining Illnesses at a Current CD4 Count >=200 Cells/ L in the Post-Combination Antiretroviral Therapy Era

Background. Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. Methods. Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. Results. A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0–21.1 per 1000 PYFU) with current CD4 200–349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6–4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500–749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10–1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79–1.07), compared to a current CD4 of 750–999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25–1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01–1.25), comparing persons with a current CD4 of 500–749 cells/µL to 750–999 cells/µL. Discussion. The incidence of ADIs was higher in individuals with a current CD4 count of 500–749 cells/µL compared to those with a CD4 count of 750–999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.