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Abstract: Little is known about the factors that influence providers' perceptions of patient risk for aberrant opioid use. Patient gender may interact with previous opioid misuse to influence these perceptions. We asked 131 physicians to view videos and vignettes for 8 virtual patients with chronic pain. Gender (male/female) and previous prescription opioid misuse (present/absent) varied across patients; the vignettes were otherwise balanced on demographic and clinical characteristics. For each patient, providers assessed 4 risk domains: opioid-related adverse events, opioid misuse or abuse, opioid addiction, and opioid diversion. Results indicated a significant gender-by-misuse interaction for risk of opioid misuse orabuse. When previous misuse behaviors were absent, providers rated men at higher risk; there was no gender difference when previous misuse behaviors were present. A significant gender-by-misuse interaction was found for risk of opioid-related adverse events. Providers perceived men to be at higher risk when previous misuse behaviors were absent; there was no gender difference when previous misuse behaviors were present. A significant gender-by-misuse interaction was found for risk of opioid addiction. Providers rated women at higher risk when previous misuse behaviors were present and men at higher risk when previous misuse behaviors were absent. There were significant main effects of gender and misuse for risk of opioid diversion. Providers rated men and those with previous misuse behaviors at higher risk. These results demonstrate that patient gender and previous opioid misuse have unique and interactive effects on provider perceptions of prescription opioid-related risks. Studies are needed to identify the mechanisms underlying these effects, such as gender-based stereotypes about risk-taking and drug abuse., (Copyright © 2021 International Association for the Study of Pain.)

Race disparities in pain care are well-documented. Given that most black patients are treated by white providers, patient-provider racial discordance is one hypothesized contributor to these disparities. Research and theory suggest that providers' trait-level intergroup anxiety impacts their state-level comfort while treating patients, which, in turn, impacts their pain treatment decisions. To test these hypothesized relationships, we conducted a planned secondary analysis of data from a randomized controlled trial of a perspective-taking intervention to reduce pain treatment disparities. Mediation analyses were conducted on treatment decision data from white providers for black virtual patients with chronic pain. Results indicated that white providers with higher trait-level intergroup anxiety reported lower state-level comfort treating black patients and were thereby more likely to recommend opioid (indirect effect = 0.76, 95% confidence interval [CI]: 0.21-1.51) and pain specialty (indirect effect = 0.91, 95% CI: 0.26-1.78) treatments and less likely to recommend nonopioid analgesics (indirect effect = -0.45, 95% CI: -0.94 to -0.12). Neither trait-level intergroup anxiety nor state-level comfort significantly influenced provider decisions for physical therapy. This study provides important new information about intrapersonal and interpersonal contributors to race disparities in chronic pain care. These findings suggest that intergroup anxiety and the resulting situational discomfort encroach on the clinical decision-making process by influencing white providers' decisions about which pain treatments to recommend to black patients. Should these findings be replicated in future studies, they would support interventions to help providers become more aware of their trait-level intergroup anxiety and manage their state-level reactions to patients who are racially/ethnically different from themselves.

This article presents a hypothetical case of a patient with multiple sclerosis (MS), reviewing the use of clinical practice guidelines and incorporation of quality measures into practice. Appropriate diagnosis of MS is important to avoid the cost and consequences of a misdiagnosis. Ensuring that treatment discussion occurs when a patient with MS is receptive is good clinical practice and a guideline recommendation from the American Academy of Neurology. Continuing dialogue about disease-modifying therapy and ongoing monitoring are important for patient care and improved outcomes. Ultimately, cost-effective care in MS relates to using appropriate medicines in patients with active MS, ensuring adherence, and careful monitoring.

Objectives: To explore which clinic-level factors influence treatment outcomes in a multisite antiretroviral therapy (ART) programme in South Africa., Design: Retrospective cohort study using 36 clinics., Methods: We used random effects modelling to investigate clinic-level factors influencing ART outcomes, adjusting for patient-level factors and accounting for clustering at clinic level. Outcomes were unsuppressed viral load (>400 copies/ml) at 24 months after ART start and time to loss to follow-up., Results: At clinic level, the mean proportion of patients with unsuppressed viral load at 24 months was 16% (range 8-33%). Loss to follow-up was also highly variable across clinics ranging from 3.5 to 23.4/100 person-years. Unsuppressed viral load was associated with a lower doctor-patient ratio [for every 500 patients, compared with >2.6 doctors: <0.7 doctors: adjusted odds ratio (OR) 1.52, 95% confidence interval (CI) 1.04-2.21; 0.7-2.6 doctors, OR 1.33, CI 0.91-1.93, P trend 0.04] after adjustment for patient factors. Combinations of psychosocial support interventions were weakly associated with reduced loss to follow-up [>6 interventions vs. <4 interventions: hazard ratio 0.39 (CI 0.15 - 1.04), P = 0.11]. Flexibility of services, integration of services, staff motivation, staff leadership and location of clinic were not consistently associated with improved outcomes., Conclusion: The dominant clinic-level influences on patient outcomes were doctor : patient ratio, and combination interventions to reduce loss to follow-up. Further research is needed to define optimum staffing levels that are required to roll out ART and the combination intervention that is most effective to reduce loss to follow-up.

Purpose of Review: In multiple sclerosis (MS), symptoms vary widely from patient to patient. Certain events in MS are well recognized (eg, optic neuritis, brainstem and spinal cord relapses) and do not lead to much clinical confusion. However, other events that occur in MS may be less expected and may be underrecognized by some clinicians and may lead to an extensive and potentially unnecessary investigation for what is a known problem in MS., Recent Findings: This article reviews Lhermitte sign, Pulfrich phenomenon, Uhthoff phenomenon, and the useless hand of Oppenheim, along with the underrecognized phenomena of transient neurologic events (including tonic spasms). Disorders of temperature regulation in MS (likely based on hypothalamic involvement) which can present with bizarre behavioral change and evade diagnosis, are also discussed. The article concludes with a review of epilepsy and sleep disorders in MS, both of which appear to occur at an increased frequency in the MS population and may have implications for therapy., Summary: This article is meant to help clinicians recognize and treat this fascinating set of underrecognized phenomena in MS and perhaps save patients trips to the emergency department, extraneous testing, and ineffective intervention.

A variety of changes in the eye can occur during pregnancy. These can be physiological, pathologic related to the pregnancy, or pathologic unrelated to the pregnancy. Pregnancy also can affect preexisting conditions. Pregnant women often discuss changes in their health first with their obstetrician; therefore, knowledge of common ophthalmic complaints during pregnancy is of particular concern for the practicing obstetrician. We reviewed the literature for ophthalmic and neuro-ophthalmic conditions that occur during pregnancy or in the postpartum period. Results are presented anatomically, first discussing general ophthalmologic conditions, then neuro-ophthalmic conditions follow. Effects of ocular medications on the fetus are reviewed.

Objective: To describe a programme of community education and mobilization to promote uptake in a cluster-randomized trial of tuberculosis preventive therapy offered to all members of intervention clusters., Setting and Participants: Gold mines in South Africa, where tuberculosis incidence is extremely high, despite conventional control measures. All employees in intervention clusters (mine shaft and associated hostel) were invited to enrol., Main Outcome Measure: Cumulative enrolment in the study in intervention clusters., Results: Key steps in communicating information relevant to the study included extensive consultation with key stakeholders; working with a communication company to develop a project 'brand'; developing a communication strategy tailored to each intervention site; and involving actors from a popular television comedy series to help inform communities about the study. One-to-one communications used peer educators along with study staff, and participant advisory groups facilitated two-way communication between study staff and participants. By contrast, treatment 'buddies' and text messaging to promote adherence proved less successful. Mean cumulative enrolment in the first four intervention clusters was 61.9%, increasing to 83.0% in the final four clusters., Conclusion: A tailored communication strategy can facilitate a high level of enrolment in a community health intervention.

Objectives: Despite good evidence that isoniazid preventive therapy (IPT) reduces incidence of tuberculosis among people with HIV infection, implementation of IPT is low. This study aimed to describe barriers to IPT implementation from healthcare provider and patient perspectives in a donor-funded HIV care programme in Gauteng province, South Africa, in which IPT is recommended, but delivery is variable., Design: A qualitative study using in-depth interviews and a focus group discussion., Methods: We conducted interviews with 22 clinic staff and 20 patients from 10 purposively selected HIV clinics, and a staff focus group discussion. Staff were questioned on their knowledge and experience of IPT, and asked about barriers to its use. Patients were asked for their opinions about taking IPT., Results: Healthcare workers reported the primary barrier to IPT use was lack of knowledge and experience. Prescribers were unaware of the benefits of IPT and unclear about guidelines. The belief that existing screening tools are inaccurate in HIV-infected individuals and the need to refer patients to separate clinics for tuberculosis screening also emerged as barriers. No patients had heard of IPT., Conclusion: Barriers to the widespread use of IPT primarily derived from healthcare workers, in particular, lack of experience among physicians. In addition to overcoming operational barriers, a change in healthcare worker perception is needed if IPT is to be widely used; we suggest local clinical opinion leaders could help achieve this.

Objective: This analysis describes the prevalence of and risk factors for tuberculosis at screening prior to isoniazid preventive therapy (IPT); the additional yield of tuberculosis using chest radiography versus symptoms alone, and risk factors for tuberculosis missed by screening., Design: Cross-sectional analysis of a trial of community-wide IPT in South African gold mines., Methods: Participants were screened for tuberculosis prior to starting IPT using symptoms (cough >2 weeks, weight loss, night sweats) and chest radiography. Tuberculosis suspects had sputum collected for mycobacterial investigations. Those with a positive smear or culture with no speciation or culture identified as Mycobacterium tuberculosis were classified as having probable or definite tuberculosis, respectively. Among participants who were dispensed IPT, we defined a 'missed' case of active tuberculosis as one identified within 90 days of the enrolment screen., Results: Between July 2006 and December 2008, among 23,286 participants with complete data, the prevalence of undiagnosed tuberculosis [definite (284) and probable (31)] was high (315/23 286; 1.4%). The addition of chest radiography to symptom screening increased the number of definite tuberculosis cases detected by 2.5-fold (113 to 281 cases). Among 19,609 individuals correctly screened for tuberculosis who started IPT and had more than 90 days of follow-up, only 39 (0.2%) active tuberculosis cases were missed. Risk factors for tuberculosis missed by screening included increasing age [adjusted odds ratio (aOR) 1.66/10 year increase, 95% confidence interval (CI) 1.07-2.56], non-South African, in HIV care (aOR 4.80, 95% CI 1.63-14.1), lower weight (aOR 2.07/10 kg decrease, 95% CI 1.23-3.49) and alcohol use (aOR 2.52, 95% CI 1.31-4.86), which were similar to risk factors for tuberculosis detected by screening., Conclusion: Tuberculosis screening prior to IPT detects a substantial burden of tuberculosis and misses very few cases. Chest radiography significantly increased the yield of tuberculosis cases detected.

Objective: To describe the association between isoniazid preventive therapy (IPT) and mortality among individuals starting antiretroviral therapy (ART) in a workplace programme in South Africa where tuberculosis (TB) incidence is very high., Methods: ART-naive individuals starting ART from January 2004 to December 2007 were followed for up to 12 months. Deaths were ascertained from clinic and human resource data. The association between IPT and mortality was assessed using Cox regression., Results: A total of 3270 individuals were included (median age 45; 93% men; median baseline CD4 cell count 155 cells/μl (interquartile range 87-221); and 45% with WHO stage 3/4]. Nine hundred twenty-two (28%) individuals started IPT either prior to or within 3 months of starting ART. Individuals who started IPT tended to have less advanced HIV disease at ART initiation. Two hundred fifty-nine (7.9%) deaths were observed with overall mortality rate 8.9 per 100 person-years [95% confidence interval (CI) 7.9-10.6]. The unadjusted mortality rate was lower among those who received IPT compared with those who did not [3.7/100 vs. 11.1/100 person-years, respectively, hazard ratio 0.34 (95% CI 0.24-0.49)]; this association remained after adjustment for age, baseline CD4 cell count, baseline WHO stage, year of ART start, and individual company (hazard ratio 0.51, 95% CI 0.32-0.80). In sensitivity analyses restricted to those with no previous history of TB (n = 3036) or with no TB symptoms at ART initiation (n = 2251), IPT remained associated with reduced mortality [adjusted hazard ratios 0.51 (95% CI 0.32-0.81) and 0.48 (95% CI 0.24-0.96), respectively]., Conclusion: Mortality was lower among individuals receiving IPT with or prior to ART start. These results support routine use of IPT in conjunction with ART.

Objectives: We describe isoniazid-related adverse events in Thibela TB, a cluster-randomized study of community-wide isoniazid preventive therapy (IPT) among gold miners in South Africa, where HIV prevalence is estimated at 30%., Methods: Consenting employees were screened prior to IPT for active tuberculosis and increased risk of isoniazid toxicity using a questionnaire and chest radiograph. Study-defined IPT-related adverse events were sought at each study visit: liver function tests were only performed if clinically indicated. In a substudy, we questioned consecutive participants at baseline and months 1, 3, and 6 concerning minor IPT-related adverse events., Results: Among 24,221 participants (95.2% men, median age 40 years), 130 individuals had 132 study-defined adverse events (0.54%); 61 (0.25%) possible hypersensitivity rash, 50 (0.21%) peripheral neuropathy, 17 (0.07%) clinical hepatotoxicity, and four (0.02%) convulsions. Four events (two hepatotoxicity, one fatal, and two convulsions) fulfilled criteria for seriousness. Clinical hepatotoxicity was associated with consumption of alcohol [0.11 vs. 0.03% if no alcohol consumed, odds ratio 3.9 (95% confidence interval 1.2-12.1)], but not with sex, age, weight, or concurrent antiretroviral therapy. In the substudy, 324 of 498 (65.1%) participants reported better health since starting IPT; 180 of 324 (55.6%) reported that this was because of increased appetite. The frequency of specific minor symptoms was low among those taking IPT, and all symptoms were reported less often than at baseline., Conclusion: The risk of adverse events, particularly hepatotoxicity, was very low in this population. Our data suggest that clinical criteria can safely be used for screening prior to and monitoring during IPT.

Objective: To assess the effectiveness of cotrimoxazole preventive therapy (CPT) among individuals with CD4 cell count above 200 cells/microl and varying WHO clinical stages in reducing mortality during combination antiretroviral therapy (cART)., Design: A cohort study., Methods: Using proportional hazards modeling, we compared mortality during the first 12 months after cART initiation among patients receiving CPT with patients not receiving CPT. We adjusted for clinic level confounding throughout., Results: We included 14 097 patients starting cART between January 2003 and January 2008, 62% of whom were men, the median CD4 cell count was 132 cells/microl, and 1289 died (11%). The baseline median CD4 cell count was lower (118 vs. 153 cells/microl) among the 7508 patients who received CPT compared with the 6589 patients who did not. In adjusted multivariate modeling, stratifying for baseline CD4 cell count and WHO stage, CPT reduced mortality overall (hazard ratio 0.64, P < 0.001) and for all individuals with CD4 cell count below 200 cells/microl or WHO clinical stage 3 or 4 conditions but did not reduce mortality for patients with both CD4 cell count above 200 cells/microl and WHO clinical stage 1 or 2., Conclusion: We demonstrated a 36% reduction in mortality extending to patients associated with CPT when used with cART that extended to patients with CD4 cell count above 350 cells/microl in a setting with minimal malaria and high rates of cotrimoxazole-resistant bacteria. This provides important additional data toward efforts to increase CPT provision among all cART initiators in resource limited settings.

Objective: Despite World Health Organization recommendations, concerns about promoting resistance have impeded implementation of isoniazid preventive therapy (IPT) for tuberculosis (TB). We describe characteristics of TB in individuals previously exposed to IPT as part of 'Thibela TB', a cluster-randomized trial of community-wide IPT in gold miners in South Africa., Design: Case series including participants who were dispensed IPT, attended at least one follow-up visit and were subsequently treated for TB., Methods: TB episodes were detected through surveillance and through follow-up if IPT was stopped early. Drug susceptibility data were compared with TB episodes detected through surveillance in control clusters (where IPT use was minimal) and a laboratory substudy of mycobacterial sputum culture from TB suspects in control clusters., Results: Among 126 eligible individuals (125 men, median age 43 years), median time from starting IPT to TB treatment was 316 days (interquartile range 174-491). Ninety-four of the 126 (75%) were first episodes. Eighty-nine of 103 (86%) tested HIV-infected, with the median CD4 cell count of 196 cells/microl (n = 51). Sixty-four of 108 (59%) with known treatment outcomes were cured or completed treatment. Among 71 isolates with drug susceptibility results available, 12.1% [95% confidence interval (CI) 5.0-23.3] and 7.7% (95% CI 0.2-36.0) from first and retreatment episodes, respectively, had isoniazid resistance, compared with 6.0% (95% CI 3.1-10.2) and 18.7% (95% CI 10.6-29.3) in control clusters and 11.8% (95% CI 8.2-16.3) among first TB episodes in the laboratory substudy., Conclusion: TB after recent IPT has prevalence of drug resistance similar to background and treatment outcomes typical of this setting. These data support wider implementation of IPT.

Objective: To investigate the incidence of, and risk factors for, tuberculosis among HIV clinic attendees in the United Kingdom., Design and Methods: Observational cohort study of 27 868 individuals in the United Kingdom Collaborative HIV Cohort collaboration, 1996-2005., Results: Among individuals not taking combination antiretroviral therapy (cART), tuberculosis incidence was considerably higher among individuals of black African vs. white or other ethnicities {incidence rates 9.9 [95% confidence intervals (CIs) 7.2, 12.6], 2.5 [95% CI 1.8, 3.0] and 4.4 [95% CI 2.7, 6.0] episodes per 1000 person-years, respectively}. Tuberculosis incidence decreased with time after starting cART; among black Africans, incidence was consistently higher and remained substantial (5.3 per 1000 person-years) at 24 months and longer after starting cART. The strongest independent risk factors for tuberculosis after cART start were most recent CD4 cell count: adjusted rate ratios (aRR) 10.65 (95% CI 6.11, 18.57), 3.40 (95% CI 2.05, 5.65), 1.77 (95% CI 1.06, 2.96) and 1.84 (95% CI 1.09, 3.12) for individuals with CD4 cell counts less than 50, 50-199, 200-349 and 350-499 cells/microl, respectively, compared with at least 500 cells/microl; and black African vs. white ethnicity [aRR 2.93 (95% CI 1.89, 4.54)]. HIV risk group, shorter time on cART, later calendar period and unsuppressed viral load were also independently associated with incident tuberculosis., Conclusions: Tuberculosis incidence among people attending UK HIV clinics is substantial, particularly among those with non-white ethnicity and low CD4 cell counts, even after starting cART. Earlier HIV diagnosis is needed in order to implement interventions to prevent tuberculosis; tuberculosis preventive therapy should be considered in addition to cART.

In 2007, the WHO recommended a maximum stavudine dose of 30 mg. We compared virologic suppression among patients weighing more than 60 kg and receiving stavudine 30 mg (n = 110) versus 40 mg (n = 508) in community HIV clinics in South Africa, before and after guidelines changed. At 6 months, HIV RNA less than 400 copies/ml was achieved in 79% and 81% receiving 30 and 40 mg stavudine, respectively (chi2, P = 0.6). In regression modeling, including baseline HIV RNA and nonnucleoside reverse transcriptase inhibitor agent, stavudine dose remained unassociated with suppression.

Objective: To assess the performance of WHO clinical and CD4 cell count criteria for antiretroviral treatment (ART) failure among HIV-infected adults in a workplace HIV care programme in South Africa., Design: Cohort study., Methods: We included initially ART-naive participants who remained on first-line therapy and had an evaluable HIV viral load result at the 12-month visit. WHO-defined clinical and CD4 cell count criteria for ART failure were compared against a gold standard of virological failure., Results: Among 324 individuals (97.5% men, median age 40.2, median starting CD4 cell count and viral load 154 cells/mul and 47,503 copies/ml, respectively), 33 (10.2%) had definite or probable virological failure at 12 months, compared with 19 (6.0%) and 40 (12.5%) with WHO-defined CD4 and clinical failure, respectively. CD4 criteria had a sensitivity of 21.2% and a specificity of 95.8% in detecting virological failure, and clinical criteria had sensitivity of 15.2% and specificity of 88.1%. The positive predictive value of CD4 and clinical criteria in detecting virological failure were 36.8 and 12.8%, respectively. Exclusion of weight loss or tuberculosis failed to improve the performance of clinical criteria., Conclusion: WHO clinical and CD4 criteria have poor sensitivity and specificity in detecting virological failure. The low specificities and positive predictive values mean that individuals with adequate virological suppression risk being incorrectly classified as having treatment failure and unnecessarily switched to second-line therapy. Virological failure should be confirmed before switching to second-line therapy.

Objective: To describe the safety and tolerability of zidovudine, lamivudine, and efavirenz in a low-income setting., Design: We conducted a prospective cohort study in a workplace HAART programme in South Africa, which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring 6-monthly pre-HAART and at 2, 6, 12, 24, 36, 48 weeks during HAART., Methods: We assessed the incidence of specified clinical and laboratory events (AIDS Clinical Trials Group grade 3 or higher) and associated regimen changes, hospitalizations, and deaths one year before HAART initiation and one year on-HAART using person-year analysis., Results: Between November 2002 and October 2005, 853 subjects (98% male, median age 40 years, and median CD4 cell count at HAART initiation 186 cells/mul) met enrollment criteria. The incidence of events on-HAART was higher than pre-HAART for neutropenia and nausea/vomiting. Dizziness was common early after HAART initiation (not evaluated pre-HAART). Of those with neutropenia, 88% had no apparent clinical consequences. The incidence of anemia, hepatotoxicity, peripheral neuropathy, and rash was similar or higher pre-HAART than on-HAART. Mean hemoglobin rose during the time on-HAART and was higher at 24 and 48 weeks than at baseline (P < 0.001)., Discussion: This regimen was well tolerated with a short-term increase in neutropenia, nausea, and probably neurocerebellar events. Most significantly, in contrast to reports from high-income countries, we observed a long-term improvement in the hemoglobin concentration.

Objective: Hepatotoxicity is a significant complication of antiretroviral therapy (ART). We assessed the incidence of and risk factors for hepatotoxicity among HIV-infected individuals on ART in South Africa., Design: We conducted a retrospective cohort study in a workplace HIV care program in South Africa which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring., Methods: We included subjects with baseline and follow-up alanine transaminase and aspartate aminotransferase tests. Severe hepatotoxicity cases were identified during the first 12 months of ART. Potential risk factors, including concomitant medication use, tuberculosis, and hepatitis B and C, were determined from clinical records, database queries, and serological testing. Associations with hepatotoxicity were investigated using Cox proportional hazards modeling., Results: Of the 868 subjects (94% male, median age 41 years), the median nadir CD4 cell count was 136/microl, 25% received concomitant tuberculosis treatment during ART, and 17% of a randomly selected subset were positive for hepatitis B surface antigen (HBsAg). We identified 7.7 episodes of severe hepatotoxicity per 100 person-years. Tuberculosis treatment increased risk 8.5 fold, positive HBsAg 3.0 fold, and nadir CD4 cells count < 100/microl 1.9 fold. Importantly, the fraction of patients with severe hepatotoxicity on ART (4.6%) was similar to the fraction with liver enzyme elevations > 5 times the upper limit of normal before starting ART (4%)., Conclusions: In this African ART cohort, we found a low incidence of and minimal morbidity due to hepatotoxicity. HBsAg and concomitant tuberculosis therapy significantly increased the risk of hepatotoxicity.

Adrenomedullin (AM) levels are elevated in cardiovascular disease, but little is known of the role of specific receptor components. AM acts via the calcitonin receptor-like receptor (CLR) interacting with a receptor-activity-modifying protein (RAMP). The AM1 receptor is composed of CLR and RAMP2, and the calcitonin gene-related peptide (CGRP) receptor of CLR and RAMP1, as determined by molecular and cell-based analysis. This study examines the relevance of RAMP2 in vivo. Transgenic (TG) mice that overexpress RAMP2 in smooth muscle were generated. The role of RAMP2 in the regulation of blood pressure and in vascular function was investigated. Basal blood pressure, acute angiotensin II-raised blood pressure, and cardiovascular properties were similar in wild-type (WT) and TG mice. However, the hypotensive effect of IV AM, unlike CGRP, was enhanced in TG mice (P<0.05), whereas a negative inotropic action was excluded by left-ventricular pressure-volume analysis. In aorta relaxation studies, TG vessels responded in a more sensitive manner to AM (EC50, 8.0+/-1.5 nmol/L) than WT (EC50, 17.9+/-3.6 nmol/L). These responses were attenuated by the AM receptor antagonist, AM(22-52), such that residual responses were identical in all mice. Remaining relaxations were further inhibited by CGRP receptor antagonists, although neither affected AM responses when given alone. Mesenteric and cutaneous resistance vessels were also more sensitive to AM in TG than WT mice. Thus RAMP2 plays a key role in the sensitivity and potency of AM-induced hypotensive responses via the AM1 receptor, providing evidence that this receptor is a selective target for novel therapeutic approaches.

Objective: To determine the efficacy of secondary preventive therapy against tuberculosis (TB) among gold miners working in South Africa., Design: An observational study., Setting: Health service providing comprehensive care for gold miners., Methods: The incidence of recurrent TB was compared between two cohorts of HIV-infected miners: one cohort (n = 338) had received secondary preventive therapy with isoniazid (IPT) and the other had not (n = 221)., Results: The overall incidence of recurrent TB was reduced by 55% among men who received IPT compared with those who did not (incidence rates 8.6 and 19.1 per 100 person-years, respectively; incidence rate ratio, 0.45; 95% confidence interval 0.26-0.78). The efficacy of isoniazid preventive therapy was unchanged after controlling for CD4 cell count and age. The number of person-years of IPT required to prevent one case of recurrent TB among individuals with a CD4 cell count < 200 x 106 cells/l, and > or = 200 x 106 cells/l was 5 and 19, respectively., Conclusion: Secondary preventive therapy reduces TB recurrence: the absolute impact appears to be greatest among individuals with low CD4 cell counts. International TB preventive therapy guidelines for HIV-infected individuals need to be expanded to include recommendations for secondary preventive therapy in settings where TB prevalence is high.

Between 1994 and 1998, seven adolescents underwent hip arthrodesis with the use of an external fixator. Mean time of follow-up was 24.0 months after surgery. The duration of fixation and time to fusion were 6.6 months (range, 5-9.5 months) and 8.0 months (range, 5.2-15 months), respectively. At most recent follow-up, there was a significant improvement in the mean modified Harris hip score, in which the maximum score is 91 points after omitting 9 points for hip range of motion and deformity, from 25.7 before surgery to 66.7 after surgery (p < 0.01). The advantages of this procedure include (i) the ease and accuracy of obtaining the proper position for fusion, (ii) the ability to lengthen the affected leg at the same time, (iii) the diminished likelihood of compromising future hip operations, and (iv) the ability to ambulate and bear weight throughout the treatment course. We recommend this method of hip arthrodesis with external fixation for patients with intractable hip pain necessitating this procedure.

Background: A laboratory method has been developed that detects recent HIV infection and allows incidence to be estimated by testing single stored antibody-positive specimens. A theoretical exploration of the method's surveillance utility was carried out., Methods: Using various data sources, HIV incidence rates were postulated. The confidence intervals (CI) for these postulated incidences were calculated using the expected number of recent infections for each postulated incidence, the actual number tested for HIV, and the known number of HIV-1 positives. A test for trend was used to determine when an important change in incidence could be recognized., Results: If the incidence was 5% per annum (p.a.) in homosexual/bisexual men attending sexually transmitted diseases (STD) clinics in London, 64 recent infections would be expected in the 392 HIV-seropositive specimens and, if observed, would result in a 95% CI of 3.1-7.9% p.a. for the incidence rate. An incidence of 1% p.a. in pregnant women would be most unlikely as this would require detection of 193 recent infections, 26 more than the total 167 HIV-seropositive specimens found in 1997. In African women attending STD clinics in London, 30% of prevalent infections would be classified as recent if the incidence was 5% p.a. Further, if the incidence in homosexual/bisexual men were to fall by 50% over 3 years, a decrease of this magnitude would be recognized as significant within 2 years., Conclusions: The detuned assay will increase the information from HIV serosurveys even where prevalence and incidence are relatively low. Existing surveillance systems should be redesigned to take full advantage of the method.

Congenital pseudoarthrosis of the tibia remains one of the most difficult conditions to treat in orthopedic surgery. Seven cases were treated in our hospital by different methods. Three out of seven patients were healed, two of these refractured. At follow-up, the success rate was 14% (one out of seven cases). It is our recommendation that early primary amputation with an appropriate prosthesis should be considered, and that the final evaluation should not be based on obtaining bone union, but on the level of function of the lower extremity.

Objectives: To describe the spectrum of opportunistic disease in HIV-infected patients admitted to hospital in Abidjan, Côte d'Ivoire, and to describe the level of immunosuppression at which these diseases occur., Design: Cross-sectional study., Setting: In-patient wards of the University Hospital Infectious Diseases Unit., Patients: A total of 250 adult patients recruited by systematic sampling at the point of hospital admission., Main Measures: HIV status; CD4 count; diagnoses, confirmed by microbiological/radiological investigations whenever possible; and outcome of hospitalization (death or discharge)., Results: Overall, 79% patients were HIV-positive. The most frequent diagnoses in HIV-positive patients were septicaemia (20%, with non-typhoid salmonellae, Escherichia coli and Streptococcus pneumoniae the most common organisms), HIV wasting (16%), meningitis (14%), tuberculosis (TB; 13%), isosporiasis (10%), cerebral toxoplasmosis (7%) and bacterial enteritis (7%). Most HIV-positive patients had evidence of severe immunosuppression: 39% had CD4 counts < 50 x 10(6)/l, 17% had 50-99 x 10(6)/l, and 20% had 100-199 x 10(6)/l. In-hospital mortality among HIV-positive patients was 38% compared with 27% among HIV-negative patients [age-adjusted odds ratio (OR), 1.5; 95% confidence interval (CI), 0.7-2.9]. Among HIV-positive patients, the highest case-fatality rates were among patients with meningitis, toxoplasmosis and TB: in a multivariate analysis the strongest independent risk factors for death were an abnormal level of consciousness (OR, 9.3; 95% CI, 3.5-24.6), a haemoglobin concentration below 8 g/dl (OR, 4.2; 95% CI, 1.4-12.8) and age > 40 years (OR, 3.9; 95% CI, 1.5-10.2)., Conclusions: Our data show that, as in industrialized countries, most HIV-infected individuals admitted to and dying in hospital in Abidjan are profoundly immunosuppressed. Potentially preventable infections are the main causes of in-hospital morbidity and mortality among HIV-infected persons in Abidjan, and the evaluation of appropriate primary prophylactic regimes is a priority.

Progression from seroconversion to the development of AIDS in Africa may be shorter than in industrialized countries, but there are insufficient data to be certain. Although the data are not always directly comparable, survival after an AIDS diagnosis appears to be substantially shorter in African countries and this may be partly because of later diagnosis of AIDS in Africa, but may also be because of environmental factors such as increased exposure to pathogens of high virulence and lack of access to care. Tuberculosis and bacterial infections are the most important causes of morbidity and mortality among hospitalized patients. Bacteraemia is frequent, particularly due to non-typhoid salmonellae and S. pneumoniae. Cryptosporidia and I. belli are the most frequently isolated pathogens in patients with diarrhoea; non-typhoid salmonellae and Shigella species are also commonly isolated when stool cultures are performed. Cerebral toxoplasmosis, and meningitis due to Cryptococcus, tuberculosis and bacterial pathogens are the most frequent neurological infections and cognitive changes are frequently identified when specifically looked for. Infections with atypical mycobacteria and Pneumocystis carinii are rare, as is CMV retinitis. In women, HIV infection is associated with cervical human papillomavirus and with SIL, although there is currently no evidence for an association with invasive cervical cancer. Individuals infected with HIV-2 progress to AIDS and to death more slowly than those infected with HIV-1, but seem to experience the same spectrum of opportunistic disease when they reach the stage of advanced disease. The limited data available suggest that HIV-infected individuals in Africa develop opportunistic disease at broadly the same level of immunosuppression as do individuals in industrialized countries, but death occurs at a higher range of CD4 counts, although still in the range consistent with advanced disease. Data are still lacking concerning the aetiology of common clinical presentations of HIV disease and the relative frequencies of specific opportunistic diseases in different regions, particularly from southern Africa. Tuberculosis is the single most important HIV-related opportunistic infection in African countries, but diagnosis, particularly of extrapulmonary disease, remains difficult. The lack of laboratory facilities makes the diagnosis of bacterial infections difficult in many parts of the continent and, since this situation is unlikely to change in the near future, clinical algorithms for syndromic management need to be evaluated. More information is needed about gynaecological disease in HIV-infected women. The most important research questions concern the development and evaluation of cost-effective regimes for prophylaxis and treatment of opportunistic disease in order to prolong healthy life in HIV-infected individuals.

Orthoses are used by patients with neuromuscular disorders to control their ankle and foot position. Heel contact inside an orthosis is difficult to determine. A simple, inexpensive device was constructed that could be positioned between the heel and the inside of the orthosis. It consists of a thin, single-cell pressure sensor connected to a low-cost, digital multimeter. The resistance reading was used to determine the presence or absence of heel contact during a controlled standing protocol. The device was evaluated in 23 patients. The majority of patients did not weightbear on their heels. The heel contact of five patients was reassessed by using a computerized F-scan system, which determines plantar weightbearing forces. A 100% agreement was found between the single-cell sensor and the F-scan system. This single-cell sensor is a simple, inexpensive, and easily used device to determine the presence or absence of heel contact within an orthosis.

We screened all head-injured trauma patients admitted to Lehigh Valley Hospital during a 2-year period. From 725 screened patients, 69 patients in a coma on the second day after trauma were entered into this study. During the first week, these patients underwent electroencephalography (EEG), evoked potentials, ocular pneumoplethysmography, and transcranial Doppler (TCD) sonography. Clinical examinations were undertaken 2 and 7 days after trauma. Test results were correlated with functional clinical outcome at 6 months. In a multiple regression analysis, EEG was the major independent variable that significantly predicted 6-month outcome based on Glasgow Outcome Scale score. Transcranial Doppler sonography contributed a small additional component. Though EEG was the most significant predictive factor in this neurophysiological battery, it did not add significantly to the predictive power of Glasgow Coma Scale score determined at day 7. These findings suggest that in neurophysiologic testing in this type of patient is not useful in improving predictive outcome data.

Background and Purpose: Redundant internal carotid arteries have been considered a risk factor in tonsillectomy, adenoidectomy, and surgical treatment of peritonsillar abscess and also a potentially treatable cause of stroke. However, an association between internal carotid artery redundancy and spontaneous dissection has not yet been clearly demonstrated., Methods: We reviewed, for spontaneous carotid artery dissection, records of all patients admitted to our institution during the period from 1986 through 1992 with the diagnosis of stroke or transient ischemic attack. We also reviewed 108 percutaneous cerebral arteriograms performed between September 1992 and December 1992 for presence of carotid artery redundancies., Results: Thirteen patients exhibited spontaneous dissection. Of these, 8 of 13 (62%) patients and 13 of 20 (65%) internal carotid arteries, viewed to the siphon, had significant redundancies, kinks, coils, or loops. Of 108 consecutive arteriograms of patients without dissection, in which 187 internal carotid arteries were viewed to the siphon, there were 20 (19%) patients and 22 (12%) of 187 vessels with significant redundancy. Five patients in the dissection group and 2 in the nondissection group had bilateral internal carotid artery redundancy (P = .0019 and P = .0001, respectively)., Conclusions: We found a significant correlation between internal carotid artery redundancy and dissection, particularly if redundancy is present bilaterally.

A bicenter study was conducted to compare the results of treatment in developmental dysplasia of the hip (DDH) with Frejka splint versus Pavlik harness. Eighty-four dislocated hips were treated by the Frejka splint, and 48 dislocated hips were treated by the Pavlik harness. Failure of reduction was 10% with the Frejka splint and 12% with the Pavlik harness. Avascular necrosis (AVN, mostly type 1) was detected in 7% of Frejka patients versus 6% in Pavlik patients. The Frejka splint is simpler to use and if properly applied may be as safe as the Pavlik harness for DDH treatment.

In a series of 20 EEGs from 15 patients, well-defined brief attenuations occurred interspersed among the background activity. These episodic low-amplitude events (ELAEs) typically lasted 0.5-4 s. They were hemispheric or bisynchronous and occurred in patients with coma of various etiologies, including status epilepticus. The episodes of attenuation were brief and no bursts of activity were present, distinguishing this finding from burst-suppression. Prognosis was poor in the patients with coma due to entities other than status epilepticus. In the setting of status epilepticus, the prognosis depended on the etiology. This pattern may be an ictal phenomenon, or a product of waveform simplification. ELAEs are a manifestation of seriously abnormal EEG activity and correlate with a 50% mortality.

An angle within the femoral arch is defined, and its line is described in selecting the osteotomy site and the position of the fixation device in performing a femoral varus osteotomy. This neck metaphyseal angle was measured with varying degrees of rotation on seven pediatric femurs; it was also studied on 283 randomly selected hip radiographs. The angle varied 25-40 degrees in 90% of the patients and was not age related. The angle is stable within 5 degrees as long as the landmarks, base of the great trochanter, and medial metaphysis of the femoral neck are definable (0-30 degrees of rotation).

Equinus deformity, due to a contracture of the triceps surae, is a frequent problem in cerebral palsy. The authors present a retrospective analysis of the functional status of 27 patients (39 feet) of equinus deformity seen in a 10-year follow-up study. When either a Hoke or White tendo Achillis surgical lengthening procedure was combined with a postoperative management program of night-bracing, the recurrence of equinus deformity was significantly reduced.