Body mass index and noninfectious comorbidity in HIV-positive patients commencing antiretroviral therapy in Zimbabwe.

OBJECTIVES: The aim of the study was to describe the prevalence of elevated body mass index (BMI) in a cohort of treatment-naïve people living with HIV (PLWH) and to investigate the association of BMI with CD4 count and noninfectious comorbidities including hypertension and renal impairment. METHODS: A retrospective cohort study of 1598 PLWH at the Newlands Clinic in Harare, Zimbabwe was carried out. Data were extracted from the medical records at baseline and 6 months after initiation of treatment. The univariate association between BMI and CD4 count was assessed and multiple regression models were used to predict factors associated with loss of renal function and change in CD4 count at 6 months. RESULTS: Overweight and obesity (BMI ≥ 25 kg/m2 ) were prevalent in this cohort (34%), as was the presence of hypertension (18%). Higher BMI was associated with a higher CD4 count at baseline and 6 months (B = 0.28 and 0.24, respectively; P < 0.001 for both), adjusted for age and sex. The presence of hypertension independently predicted loss of renal function at 6 months (B = -15.31; P < 0.001), adjusted for BMI, CD4 count and sex. High BMI itself was also independently associated with a decline in renal function (B = -0.41; P = 0.003), adjusted for other significant variables. CONCLUSIONS: We demonstrate a high prevalence of overweight/obesity and hypertension in an urban cohort of PLWH in Zimbabwe. Higher BMI was associated with a higher CD4 count, both before and 6 months after commencing antiretroviral therapy; it was also associated with loss of renal function in this cohort.

Screening and management of renal disease in human immunodeficiency virus-infected patients in Australia.

BACKGROUND: Renal disease has become one of the most important comorbidities observed in the human immunodeficiency virus (HIV)-infected patient cohort. Data are lacking on the current screening and management of renal disease in patients with HIV. We evaluated HIV-infected Australian adults in primary care to determine current practices. METHODS: This prospective, multicentre observational study included two rounds of data collection; the first was followed by an educational programme. Outcomes included screening for renal disease; management of risk factors for kidney disease and other comorbidities associated with renal disease. RESULTS: Fifty-three general practitioners participated with 733 patients enrolled. Most were male (94%); almost 40% were 41-50 years of age, and 6% and 84% were receiving antiretroviral therapy. Comorbidities were common; 19% had hypertension, 5% were diabetic, 32% were dyslipidaemic, and 40% were smokers. Estimated glomerular filtration rate was commonly measured in both rounds of data collection (96% vs 95%). Proteinuria was assessed less frequently; this improved after education (48% vs 71%). Almost 10% of patients tested had proteinuria on urinalysis. Of the 45 patients (6%) with renal impairment (estimated glomerular filtration rate <60 mL/min), none was referred for assessment by a renal specialist. CONCLUSIONS: This large observational study provides important information on renal disease in HIV-infected patients, an area with a paucity of clinical data. Current screening and management practices fall short of suggested guidelines. Failure to refer patients to specialists is a major deficiency. Improvements with education suggest the need to promote awareness of guidelines in primary care doctors.

The impact of ultrasound in suspected acute appendicitis.

AIMS: To evaluate prospectively the impact of an appendix ultrasound (US) service on the clinical management of patients presenting with suspected acute appendicitis. MATERIALS AND METHODS: The referring clinician completed a proforma for patients presenting with suspected acute appendicitis. Two visual analogue scales assessed clinical suspicion before and after knowledge of laboratory results. The clinician also indicated if they intended to operate had US been unavailable. During a 3-year period, 327 patients were examined by graded-compression US and diagnosed "positive" or "negative" for acute appendicitis. Findings were correlated with histopathology results. The referring clinician completed a retrospective audit questionnaire to assess user satisfaction. RESULTS: Clinical suspicion was altered by knowledge of laboratory results. The decision to operate if US had been unavailable, was "yes" in 70 cases (group A), "no" in 231 (group B), and incomplete in 26 (group C). In group A, 31 patients (44.3%) had a negative US and 25 avoided surgery. US identified 39 cases of appendicitis and 37 appendicectomies confirmed appendicitis in 34 cases. In group B, 72 (31.2%) patients had a positive US and 66 appendicectomies confirmed 51 cases of appendicitis. The sensitivity of US was 94.7% in group A, 93.3% in group B and 93.8% overall. Specificity was 90.6% in group A, 91.2% in group B and 91.3% overall. US findings were contrary to intended surgical management in 103 cases. Management was altered in 97 cases (32.2%), with a positive outcome in 85 (28.2%). The referrers found US of appendix very useful in planning appropriate management. CONCLUSION: US of the appendix increases diagnostic accuracy, alters management and is more sensitive and specific than clinical impression, either alone, or in conjunction with laboratory results.

Mothers' recollections of the Paediatric Intensive Care Unit: associations with psychopathology and views on follow up.

The aim of this study was to establish rates of posttraumatic stress symptoms in mothers after a child's admission to a Paediatric Intensive Care Unit (PICU) and their views on the potential value of a follow up appointment with PICU staff. Thirty-four mothers completed the Parental Stressor Scale:PICU, the General Health Questionnaire (GHQ-28) and the Impact of Event Scale, 8 months after discharge. In total 18/34 (53%) scored > or =5 on the GHQ-28 and 6/32 (18%) of the sample scored in the severe range (>35) on the Impact of Event Scale. Distress was associated with retrospective reports of stress experienced during admission (p < 0.001) but not with other demographic or medical variables. Mothers who talked about their feelings at the time of the admission had lower posttraumatic stress scores at 8 months (p = 0.02) and 25/34 (74%) mothers would have appreciated the offer of a follow up appointment. Screening for distress during admission with the Parental Stressor Scale:PICU may identify those mothers in greatest need of psychological support. Mothers' recollections of the Paediatric Intensive Care Unit: Associations with psychopathology and views on follow up.

Post-ICU weaning from mechanical ventilation: the role of long-term facilities.

A review of the largest observational studies on post-ICU weaning from prolonged mechanical ventilation yields evidence that more than half of such patients can be successfully liberated from mechanical ventilation. Success is likely to fall within a 3-month window, with late successes and partial ventilator independence still possible thereafter. There is a uniformity of practice in finishing difficult weaning with self-breathing trials of increasing duration.

The chronic ventilator-dependent unit: a lower-cost alternative to intensive care.

OBJECTIVE: To evaluate the fixed costs and patient outcomes of a specialty hospital unit for medically stable ventilator-dependent patients. The chronic ventilator-dependent unit (CVDU) was established to facilitate early dismissal from costly intensive care unit (ICU) hospitalization for patients requiring continued specialized care. PATIENTS AND METHODS: We carried out a cost analysis of the various ICUs that transferred patients to the CVDU by year from 1993 through 1998. In addition, direct and indirect costs for the CVDU were established by year for the same period. We then calculated the cost effect of transferring these patients for care from each high-cost ICU to the lower-cost CVDU. Ventilator weaning and mortality rates were also determined. RESULTS: During the 6 years of this study, $4,832,551 in patient care costs were saved by transferring care for 964 patients from ICUs to the CVDU. Ventilator weaning was successful in 64% of 549 patients, and mortality was 7% in the same patient group. CONCLUSIONS: Care in the CVDU yielded lower fixed costs per patient-day, and CVDU care was comparable to ICU hospitalization.

PD-135,158, a cholecystokinin(B) antagonist, enhances latent inhibition in the rat.

The antipsychotic potential of cholecystokinin (CCK)-related compounds stems from CCK's colocalization with dopamine (DA). CCK demonstrates excitatory and inhibitory effects on DA in the mesolimbic pathway. Such diverse actions might be mediated by different receptor subtypes (CCK(A) or CCK(B)). Multiple hypotheses have emerged regarding the clinical application of CCK-based drugs. Administering selective nonpeptide antagonists within animal models relevant to schizophrenia would help delineate CCK receptor involvement. One animal model simulating a cognitive dysfunction of schizophrenia is latent inhibition (LI). An animal repeatedly exposed to a stimulus that is devoid of consequence is subsequently inhibited in making new associations with that stimulus. This reflects a process of learning to ignore irrelevant stimuli. The present study examined the effects of the selective CCK(B) antagonist PD-135,158 (0.001, 0. 01, and 0.1 mg/kg) using a conditioned suppression of drinking procedure in rats. For purposes of comparison the effects of haloperidol (0.1 mg/kg) were also investigated. PD-135,158 (0.1 mg/kg), similar to haloperidol (0.1 mg/kg), elicited a clear LI effect under conditions that did not lead to LI in control rats (low number of preexposures). These findings highlight the antipsychotic potential of CCK(B) antagonists, and further illustrate the LI paradigm's capacity to detect novel, antipsychotic-like, drug activity.

Enhancement of latent inhibition in the rat by the CCK antagonist proglumide.

The behavioral paradigm of latent inhibition (LI) involves the retardation of conditioning to a stimulus when paired with reinforcement, if preexposure to that stimulus with no significant consequence has occurred. This phenomenon is believed to reflect a process of learning to ignore stimuli as irrelevant. Disruption in LI can be considered to be an attentional deficit observed in schizophrenia. The neuropeptide cholecystokinin (CCK), which coexists with dopamine (DA) in some brain regions, has been implicated in the pathophysiology of schizophrenia. The present study examined the effects of the nonselective CCK antagonist proglumide on LI (0.25, 0.5, and 1.0 mg/kg) using a conditioned suppression of drinking procedure in rats. For purposes of comparison the effects of haloperidol (0.1 mg/kg) were also investigated. Administration of 1.0 and 0.5 mg/kg, but not 0.25 mg/kg, proglumide was found to reduce suppression of drinking behavior in animals preexposed (PE) to a flashing light stimulus. These animals developed LI under conditions where preexposed control animals exhibited suppression of drinking behavior similar to that of nonpreexposed (NPE) control animals. These findings for proglumide were comparable to the effects on drinking behavior of 0.1 mg/kg haloperidol. The enhancement of LI by proglumide may be interpreted in terms of CCK dopamine interactions. Because CCK may modulate dopamine, the results reported here for proglumide strengthen the argument for the investigation of CCK-based drugs as potential antipsychotic agents.

Options for long-term ventilatory support.

Long-term mechanical ventilator support for patients with chronic respiratory failure is becoming more common. This article reviews the common causes for chronic ventilator dependence, and offers an approach to weaning these patients from the ventilator. In addition, the details for preparing these patients for prolonged mechanical ventilation outside of the acute-care hospital setting are discussed. Appropriate education of the patient's caregivers is key to the success of long-term ventilatory support outside of the acute-care hospital.

The Mayo Ventilator-Dependent Rehabilitation Unit: a 5-year experience.

OBJECTIVE: To describe the outcomes of 206 patients admitted to the Mayo Ventilator-Dependent Rehabilitation Unit (VDRU) during a 5-year study period. DESIGN: We analyze the patient data for 1990 through 1994, which had been prospectively entered into a computer database for a cohort of 206 patients who had become ventilator dependent during their current hospitalization. MATERIAL AND METHODS: Patients in the VDRU were classified into one of six categories that reflected the reasons for ventilator dependence. Ability to be weaned from mechanical ventilation, duration of hospital stay and ventilator dependence, outcome, disposition, demographics, and long-term survival were analyzed. The VDRU patient group was compared for hospital and follow-up outcomes with a group of historical control patients previously described by us. RESULTS: The Mayo VDRU was established in January 1990. During the first 5 years of its operation, 206 newly ventilator-dependent patients were admitted to the VDRU, 190 (92%) of whom survived to be dismissed; 16 patients (8%) died in the hospital. Of the 190 patients dismissed, 77% were able to return to their homes. Overall, 153 patients were liberated from mechanical ventilation, whereas 37 remained either completely or partially ventilator dependent. Of these 37 patients, 27 (73%) were receiving nocturnal mechanical ventilation only. The 4-year survival was 53%. CONCLUSION: The Mayo VDRU has been highly successful in liberating newly ventilator-dependent patients from mechanical ventilation. The long-term survival after management in the VDRU has been excellent. In addition, the medical charges for care in the VDRU are less than intensive-care unit charges.

Differential effects of CGS 12066B and CP-94,253 on murine social and agonistic behaviour.

Although it has been previously proposed that 5-HT1B agonism specifically attenuates rodent agonistic behaviour, more recent investigations have indicated that such influences may be ancillary to an anxiogenic effect. The present study examined the influences of two 5-HT1B agonists, CGS 12066B and CP-94,253, on murine agonistic behaviour. In a resident-intruder paradigm, CGS 12066B (0.5-5.0 mg/kg) decreased resident offensive aggression, social interest, and exploration while dose-dependently enhancing defensive behaviours across the dose range tested. CP-94,253 (2.5-10.0 mg/kg) also reduced elements of resident offensive behaviour whereas defensive behaviours were largely unchanged. Some elements of resident nonsocial and social behaviour were enhanced at 2.5 and 5.0 mg/kg but decreased at 10.0 mg/kg. The behavioural profile of CP-94,253, but not CGS 12066B, supports the proposal that 5-HT1B receptors inhibit agonistic behaviour without concomitant sedative or anxiogenic effects. Findings are discussed in relation to 5-HT1A/1B/2C receptors involved in agonistic behaviour and anxiety.

Outcome of patients cared for in a ventilator-dependent unit in a general hospital.

We describe our initial experience with the admission of 129 patients for 132 episodes of ventilator-dependence to a self-contained ventilator-dependent unit (VDU) in a general hospital and present a survival comparison between VDU patients and a historic control population from the same institution. Forty-three patients were screened and denied admission to the VDU because long-term ventilator dependence was not felt to be a probable outcome (56%); they were medically unstable, often requiring electrocardiographic monitoring (19%), they had poor rehabilitation potential because of markedly depressed mental status (13%), or they preferred to be treated closer to their homes (12%). Thirteen (9.8%) of the VDU patients died in the hospital compared to 44 (42%) in the historic control group. After exclusion of patients with multiorgan failure (who made up 26% of the control group) and using a proportional hazard model to adjust for group differences in age and disease class, the difference in hospital mortality remained highly significant (p < or = 0.01). Ninety-one of the 119 VDU patients (77%) were ultimately able to return home; 16 (13%) continued to use a ventilator intermittently at night; 26 patients (22%) were permanently placed in nursing homes, all off of the ventilator. Overall, 88% of the 119 patients discharged had been liberated from mechanical ventilation. Ninety-seven (82%) and 86 (72%) remain alive 1 and 2 years after discharge, respectively. Some of the survival benefits may be directly attributed to the VDU. Others reflect a change in treatment philosophy, which was nevertheless reinforced by our VDU experience.

The clinical spectrum of critical illness polyneuropathy.

OBJECTIVE: To describe the entity of critical illness polyneuropathy and review our experience with six cases. DESIGN: We present case reports of six patients with polyneuropathy associated with critical illness, who received medical care at the Mayo Clinic between 1992 and 1994, and discuss similar cases from the literature. RESULTS: Critical illness may damage peripheral nerves. In previous studies, sepsis and multiorgan failure have been found to trigger a peripheral neuropathy. Of our six patients with critical illness polyneuropathy, all had a preceding severe bacterial infection or septic shock. In one patient who had long-term administration of vecuronium bromide and had received massive intravenous doses of corticosteroids, sural nerve and quadriceps muscle biopsy specimens were available; they revealed axonal neuropathy and notable myopathic changes, respectively. The outcome was good in patients who survived the critical illness. CONCLUSION: Polyneuropathy in critically ill patients may be a cause of severe generalized limb weakness and occurs in the setting of a sepsis syndrome. The long-term outcome is good in patients who recover from the underlying critical illness. Compression neuropathies may be a cause of permanent sequelae.

Interrupter mechanics of patients admitted to a chronic ventilator dependency unit.

We analyzed the results of interrupter mechanics tests of 73 consecutive patients who were admitted to a chronic ventilator dependency unit. The purposes of this study were (1) to establish guidelines for grading the severity of airway obstruction based on interrupter mechanics measurements; (2) to estimate the prevalence of airway obstruction in this population; (3) to compare interrupter test results with the clinical assessment of airway function; and (4) to characterize the distribution of bronchodilator-induced changes in isorecoil flow. Measurements from 65 of 73 patients (89%) were considered technically adequate. Of 65 patients, 29 (45%) showed signs of flow limitation during passive expiration. All patients with severe obstruction documented with spirometry during clinical stability were flow-limited and achieved maximal flows < or = 0.45 L/s at recoil pressures of 10 cm H2O. In contrast to measures of expiratory dynamics, the inspiratory resistance of the respiratory system was a poor index of severity of obstruction. In seven of 12 patients, interrupter testing failed to substantiate a clinical diagnosis of severe obstruction while revealing unsuspected obstruction in six of 25 (24%) patients. The administration of 270 micrograms of albuterol increased flows at comparable recoil pressures by > or = 0.1 L/s in 29% of 41 patients. Changes in flow were unimodally distributed and were not correlated with severity of obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Serological detection of HBeAg and anti-HBe using automated microparticle enzyme immunoassays.

Fully automated microparticle enzyme immunoassays (EIA) were developed for the detection of HBeAg (IMx HBe) and antibodies against HBeAg (IMx anti-HBe), respectively. Specimens from blood donors, diagnostic and hospital patients and individuals with a variety of infectious and immune diseases were tested both in house and at four clinical sites. The overall agreement between IMx HBe and Abbott HBe RIA/EIA was 99.7% (2985 of 2994) and between IMx anti-HBe and anti-HBe RIA/EIA was 95.8% (2330 of 2432). Almost all anti-HBe discordant specimens (94.1%, 96 of 102) were reactive by IMx anti-HBe but negative by anti-HBe RIA/EIA. off anti-HBe discordant specimens were also reactive for anti-HBc. The IMx anti-HBe assay was 2- to 4-fold more sensitive than the current RIA as determined by serial dilution of anti-HBe reactive specimens. The ability of these IMx assays to detect HBeAg and anti-HBe in 199 HBsAg reactive specimens was also evaluated. 43.7% (87 of 199) and 66.3% (132 of 199) specimens were reactive for HBeAg and anti-HBe by IMx, respectively. Only one specimen was negative for both IMx assays compared to 14 (7.0%) non-reactive for both HBe and anti-HBe RIA. There were 24 specimens (12.1%) positive for both HBeAg and anti-HBe by IMx compared to 1 (0.5%) positive by the corresponding RIAs. This increased detectability of anti-HBe in HBsAg carriers using IMx anti-HBe may result from increased sensitivity for 'free' anti-HBe and/or increased ability to detect anti-HBe in immune complex. IMx anti-HBe also detected more reactives among volunteer blood donor specimens reactive for anti-HBc but negative for HBsAg (55.5%, 86 of 155), compared to RIA (38.7%, 60 of 155). IMx anti-HBe may be useful in confirming prior exposure to HBV in blood screened positive by Corzyme.