Burden of Haemophilus influenzae type b disease in Pakistani children.

Estimates of the burden of Haemophilus influenzae type b (Hib) in children in Pakistan are limited. A prospective surveillance was set up in 8 sentinel sites in Karachi and Hyderabad in January 2004. A total of 1481 children aged < 5 years underwent lumbar puncture for suspected acute bacterial meningitis. Specimens from 237 (16.0%) children met the criteria for probable bacterial meningitis, and Hib was detected in 45 of them (19.0%). The minimum detected incidence of Hib meningitis in the Hyderabad area was 7.6 per 100 000 in children < 5 years of age, and 38.1 per 100 000 children < 1 year. Hib vaccination is justified for inclusion in Pakistan's expanded programme of immunization.

Burden of Haemophilus influenzae type B disease in Pakistani children

Estimates of the burden of Haemophilus influenzae type b [Hib] in children in Pakistan are limited. A prospective surveillance was set up in 8 sentinel sites in Karachi and Hyderabad in January 2004. A total of 1481 children aged < 5 years underwent lumbar puncture for suspected acute bacterial meningitis. Specimens from 237 [16.0%] children met the criteria for probable bacterial meningitis, and Hib was detected in 45 of them [19.0%]. The minimum detected incidence of Hib meningitis in the Hyderabad area was 7.6 per 100 000 in children < 5 years of age, and 38.1 per 100 000 children < 1 year. Hib vaccination is justified for inclusion in Pakistan's expanded programme of immunization

Iatrogenic adverse events in the coronary care unit.

BACKGROUND: Although our understanding of medical adverse events has increased substantially over the last decade, little is known about iatrogenic adverse events (IAEs) in the coronary care unit (CCU). We sought to determine the frequency and potential preventability of IAEs in the CCU of a tertiary care center. METHODS AND RESULTS: We undertook a retrospective cohort study evaluating the hospital charts of consecutive patients admitted to the CCU at Hamilton General Hospital (Ontario, Canada) from November 1, 2005, to January 1, 2006. We used a priori developed definitions to determine whether patients suffered an IAE and whether it was potentially preventable. We included 194 patients, and 99 (51%; 95% CI, 44% to 58%) patients had at least 1 IAE, of which 45 (45%; 95% CI, 36% to 55%) were judged potentially preventable. Bleeding (14/51, 27%; 95% CI, 17% to 41%) was the most common potentially preventable IAE and was more common than recurrent ischemic events (4/51, 8%; 95% CI, 3% to 19%). Of the patients who died in the hospital, 9 of 17 (53%; 95% CI, 31% to 74%) had an IAE that was causally related to their death, of which 6 (67%; 95% CI, 35% to 88%) were judged potentially preventable. CONCLUSIONS: The present study suggests that IAEs, especially bleeding, are common in the CCU setting and more frequent than recurrent ischemic events. These results suggest the need for large multicenter studies to evaluate in CCUs the rates of IAEs, their causes, and potential preventability.

Does the clinical examination predict lower extremity peripheral arterial disease?

CONTEXT: Lower extremity peripheral arterial disease (PAD) is common and associated with significant increases in morbidity and mortality. Physicians typically depend on the clinical examination to identify patients who need further diagnostic testing. OBJECTIVE: To systematically review the accuracy and precision of the clinical examination for PAD. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: MEDLINE (January 1966 to March 2005) and Cochrane databases were searched for articles on the diagnosis of PAD based on physical examination published in the English language. Included studies compared an element of the history or physical examination with a reference standard of ankle-brachial index, duplex sonography, or angiogram. Seventeen of the 51 potential articles identified met inclusion criteria. Two of the authors independently extracted data, performed quality review, and used consensus to resolve any discrepancies. DATA SYNTHESIS: For asymptomatic patients, the most useful clinical findings to diagnose PAD are the presence of claudication (likelihood ratio [LR], 3.30; 95% confidence interval [CI], 2.30-4.80), femoral bruit (LR, 4.80; 95% CI, 2.40-9.50), or any pulse abnormality (LR, 3.10; 95% CI, 1.40-6.60). While none of the clinical examination features help to lower the likelihood of any degree of PAD, the absence of claudication or the presence of normal pulses decreases the likelihood of moderate to severe disease. When considering patients who are symptomatic with leg complaints, the most useful clinical findings are the presence of cool skin (LR, 5.90; 95% CI, 4.10-8.60), the presence of at least 1 bruit (LR, 5.60; 95% CI, 4.70-6.70), or any palpable pulse abnormality (LR, 4.70; 95% CI, 2.20-9.90). The absence of any bruits (iliac, femoral, or popliteal) (LR, 0.39; 95% CI, 0.34-0.45) or pulse abnormality (LR, 0.38; 95% CI, 0.23-0.64) reduces the likelihood of PAD. Combinations of physical examination findings do not increase the likelihood of PAD beyond that of individual clinical findings. However, when combinations of clinical findings are all normal, the likelihood of disease is lower than when individual symptoms or signs are normal. A PAD scoring system, which includes auscultation of arterial components by handheld Doppler, provides greater diagnostic accuracy. CONCLUSIONS: Clinical examination findings must be used in the context of the pretest probability because they are not independently sufficient to include or exclude a diagnosis of PAD with certainty. The PAD screening score using the hand-held Doppler has the greatest diagnostic accuracy.

Hydrochlorothiazide-induced noncardiogenic pulmonary edema: an underrecognized yet serious adverse drug reaction.

Noncardiogenic pulmonary edema is a rare but potentially life-threatening complication of hydrochlorothiazide therapy. We describe three patients who developed this serious adverse reaction. A 64-year-old woman developed dypsnea and hypotension within 60 minutes of taking a single dose of hydrochlorothiazide 25 mg. She was admitted to the critical care unit with acute respiratory failure and subsequent multiple-organ dysfunction. The second patient was a 56-year-old woman who experienced sudden onset of shortness of breath that developed 10 minutes after taking a single dose of hydrochlorothiazide 25 mg. The third was a 59-year-old woman who developed sudden onset of shortness of breath, nausea, vomiting, and diarrhea after her first dose of hydrochlorothiazide-triamterene. All three women had a history of a similar, albeit minor, reaction to a thiazide diuretic. Review of the literature identified 36 additional cases of noncardiogenic pulmonary edema after thiazide use. The patients developed symptoms 10-150 minutes after ingestion of hydrochlorothiazide or another thiazide. Symptoms can occur on first exposure to the drug or in patients taking the drug intermittently. Of interest, 90% of documented cases occurred in women. With the increasing use of thiazide diuretics in the treatment of hypertension, clinicians need to be aware of the possible association of these drugs with the development of noncardiogenic pulmonary edema.

Venous thromboembolism prophylaxis in medical inpatients: a retrospective chart review.

BACKGROUND: Venous thromboembolic disease (VTE) is a major cause of morbidity and mortality in hospitalized patients. Most hospitalized patients with a fatal pulmonary embolism are medical patients who do not have a history of recent surgery [BMJ 302 (1991) 709; J. R. Soc. Med. 82 (1989) 198]. There is evidence suggesting that VTE prophylaxis is indicated in many high risk medical patients [Chest 119 (2001) 132S; NEJM 341 (1999) 793]. However, previous studies have shown that only about one third of high risk medical patients receive VTE prophylaxis [Ann. Intern. Med. 115 (1991) 591; Chest 106 (1994) 13; Chest 107 (1995) 296]. The objective of this study was to determine the frequency of use of VTE prophylaxis in medical inpatients at two teaching hospitals in Hamilton, Ontario. METHODS: A retrospective chart review of consecutive patients admitted to medical wards at two acute care sites of McMaster University affiliated teaching hospitals between October 10, 2001 and December 11, 2001 was performed. For each patient, demographic data, risk factors for VTE, method of VTE prophylaxis and contraindications to VTE prophylaxis were recorded. RESULTS: 756 patient charts were reviewed and 310 (41%) were excluded because the primary diagnosis required anticoagulation, the patients were being treated with anticoagulation (warfarin or heparin) before admission or the patient was admitted to the intensive care unit. Of the remaining 446 patients, 146 (33%) received some form of VTE prophylaxis. Of the patients receiving prophylaxis, 4% had early ambulation, 9% wore anti-embolic stockings (AES), 1% used intermittent pneumatic compression, 23% used unfractionated heparin and 3% used low molecular weight heparin. Two hundred five (46%) patients had one identifiable VTE risk factor and 63 (14%) had two or more risk factors. Patients with more VTE risk factors were more likely to receive prophylaxis. INTERPRETATION: One third of medical inpatients at two teaching hospitals in Hamilton received some form of VTE prophylaxis.

Kinetic and pharmacological properties of cloned human equilibrative nucleoside transporters, ENT1 and ENT2, stably expressed in nucleoside transporter-deficient PK15 cells. Ent2 exhibits a low affinity for guanosine and cytidine but a high affinity for inosine.

We stably transfected the cloned human equilibrative nucleoside transporters 1 and 2 (hENT1 and hENT2) into nucleoside transporter-deficient PK15NTD cells. Although hENT1 and hENT2 are predicted to be 50-kDa proteins, hENT1 runs as 40 kDa and hENT2 migrates as 50 and 47 kDa on SDS-polyacrylamide gel electrophoresis. Peptide N-glycosidase F and endoglycosidase H deglycosylate hENT1 to 37 kDa and hENT2 to 45 kDa. With hENT1 being more sensitive, there is a 7000-fold and 71-fold difference in sensitivity to nitrobenzylthioinosine (NBMPR) (IC(50), 0.4 +/- 0.1 nM versus 2.8 +/- 0.3 microM) and dipyridamole (IC(50), 5.0 +/- 0.9 nM versus 356 +/- 13 nM), respectively. [(3)H]NBMPR binds to ENT1 cells with a high affinity K(d) of 0.377 +/- 0.098 nM, and each ENT1 cell has 34,000 transporters with a turnover number of 46 molecules/s for uridine. Although both transporters are broadly selective, hENT2 is a generally low affinity nucleoside transporter with 2.6-, 2.8-, 7. 7-, and 19.3-fold lower affinity than hENT1 for thymidine, adenosine, cytidine, and guanosine, respectively. In contrast, the affinity of hENT2 for inosine is 4-fold higher than hENT1. The nucleobase hypoxanthine inhibits [(3)H]uridine uptake by hENT2 but has minimal effect on hENT1. Taken together, these results suggest that hENT2 might be important in transporting adenosine and its metabolites (inosine and hypoxanthine) in tissues such as skeletal muscle where ENT2 is predominantly expressed.