Lessons learned from the first 50 COVID-19 critical care transfer missions conducted by a civilian UK Helicopter Emergency Medical Service team.

BACKGROUND: The COVID-19 pandemic has placed exceptional demand on Intensive Care Units, necessitating the critical care transfer of patients on a regional and national scale. Performing these transfers required specialist expertise and involved moving patients over significant distances. Air Ambulance Kent Surrey Sussex created a designated critical care transfer team and was one of the first civilian air ambulances in the United Kingdom to move ventilated COVID-19 patients by air. We describe the practical set up of such a service and the key lessons learned from the first 50 transfers. METHODS: Retrospective review of air critical care transfer service set up and case review of first 50 transfers. RESULTS: We describe key elements of the critical care transfer service, including coordination and activation; case interrogation; workforce; training; equipment; aircraft modifications; human factors and clinical governance. A total of 50 missions are described between 18 December 2020 and 1 February 2021. 94% of the transfer missions were conducted by road. The mean age of these patients was 58 years (29-83). 30 (60%) were male and 20 (40%) were female. The mean total mission cycle (time of referral until the time team declared free at receiving hospital) was 264 min (range 149-440 min). The mean time spent at the referring hospital prior to leaving for the receiving unit was 72 min (31-158). The mean transfer transit time between referring and receiving units was 72 min (9-182). CONCLUSION: Critically ill COVID-19 patients have highly complex medical needs during transport. Critical care transfer of COVID-19-positive patients by civilian HEMS services, including air transfer, can be achieved safely with specific planning, protocols and precautions. Regional planning of COVID-19 critical care transfers is required to optimise the time available of critical care transfer teams.

Effect of online diabetes training for hospitalists on inpatient glycaemia.

AIM: An online diabetes course for medical residents led to lower patient blood glucose, but also increased hypoglycaemia despite improved trainee confidence and knowledge. Based on these findings, we determined whether an optimized educational intervention delivered to hospitalists (corresponding to an Acute Physician or Specialist in Acute Hospital Medicine in the UK) improved inpatient glycaemia without concomitant hypoglycaemia. METHODS: All 22 hospitalists at an academic medical centre were asked to participate in an online curriculum on the management of inpatient dysglycaemia in autumn 2009 and a refresher course in spring 2010. RESULTS: All hospitalists completed the initial intervention. Median event blood glucose decreased from 9.3 mmol/l (168 mg/dl) pre-intervention to 7.8 mmol/l (141 mg/dl) post-intervention and 8.5 mmol/l (153 mg/dl) post-refresher (P < 0.001 for both). Hospitalizations categorized as hyperglycaemia decreased from 83.3 to 55.6% (P = 0.014), with a trend towards euglycaemia (10-28.9%, P = 0.08) and no change in hypoglycaemia. Hyperglycaemic patient-days decreased from 72.0 to 57.3% (P = 0.004), with greater target glycaemia (27.3-39.4%, P = 0.016) and no change in hypoglycaemia. CONCLUSIONS: An optimized online educational intervention delivered to hospitalists yielded significant improvements in inpatient glycaemia without increased hypoglycaemia.

Updated survival and outcomes for older adults with inoperable stage III non-small-cell lung cancer treated with cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel: analysis of a phase III trial from the Hoosier Oncology Group (HOG) and US Oncology.

BACKGROUND: Concurrent chemoradiation with etoposide and cisplatin (EP/XRT) is standard treatment for inoperable stage III locally advanced non-small-cell lung cancer (LA-NSCLC). Consolidation docetaxel (D; Taxotere) after EP/XRT resulted in increased toxicity but no improvement in survival compared with observation (O). We report updated survival for the entire study population and include an analysis of efficacy and tolerability of EP/XRT with or without D in patients aged ≥ 70 years. PATIENTS AND METHODS: Hoosier Oncology Group LUN 01-24 enrolled 243 patients with LA-NSCLC and randomized 166 after EP/XRT to three cycles of D versus O. the trial was terminated after an analysis of the first 203 patients demonstrated futility of D. RESULTS: Median survival time (MST) for the overall study population was 21.5 months, and 3-, 4-, and 5-year survival rates were 30.7%, 18.0%, and 13.9%, respectively. No differences in MST or 3-year survival were noted between D and O arms. Older patients had similar MST (17.1 versus 22.8 months for younger patients, P = 0.15) but higher rates of grade 3/4 toxicity and hospitalization during induction. CONCLUSIONS: Consolidation docetaxel after EP/XRT does not improve survival in LA-NSCLC. Fit older adults with LA-NSCLC benefit from concurrent chemoradiation similarly as younger patients but experience higher rates of hospitalization and toxicity.

Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is increasing in incidence and the majority of patients are not candidates for radical therapies. Therefore, interest in minimally invasive therapies in growing. METHODS: A Phase I dose escalation trial was conducted at Indiana University to determine the feasibility and toxicity of stereotactic body radiation therapy (SBRT) for primary HCC. Eligible patients had Child-Turcotte-Pugh's Class (CTP) A or B, were not candidates for resection, had 1-3 lesions and cumulative tumour diameter less than or equal to 6 cm. Dose escalation started at 36 Gy in 3 fractions (12 Gy/fraction) with a subsequent planned escalation of 2 Gy/ fraction/level. Dose-limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events v3.0 grade 3 or greater toxicity. RESULTS: Seventeen patients with 25 lesions were enrolled. Dose was escalated to 48 Gy (16 Gy/fraction) in CTP-A patients without DLT. Two patients with CPC-B disease developed grade 3 hepatic toxicity at the 42-Gy (14 Gy/fraction) level. The protocol was amended for subsequent CTP-B patients to receive a regimen of 5 fractions starting at 40 Gy (8 Gy/fraction) with one patient experiencing progressive liver failure. Four additional patients were enrolled (one died of unrelated causes after an incomplete SBRT course) without DLT. The only factor related to more than one grade 3 or greater liver toxicity or death within 6 months was the CTP score (p=0.03). Six patients underwent a liver transplant. Ten patients are alive without progression with a median FU of 24 months (10-42 months), with local control/stabilisation of the disease of 100%. One and two-year Kaplan-Meier estimates for overall survival are 75% and 60%, respectively. CONCLUSIONS: SBRT is a non-invasive feasible and well tolerated therapy in adequately selected patients with HCC. The preliminary local control and survival are encouraging. A confirmatory Phase II trial is currently open to accrual.

Update on diabetes mellitus: prevention, treatment, and association with oral diseases.

Diabetes mellitus is a prevalent disease that affects millions of people worldwide and has paralleled the growing population of overweight and obese individuals. Early detection of prediabetes and diabetes, as well as lifestyle interventions including diet and exercise, are the overarching objectives in preventing and managing diabetes. For individuals who do not achieve glycemic control with lifestyle modification, there are newer medication classes that assist with weight loss, more physiologic insulins with convenient delivery systems, and old standbys like metformin and thiazolidinediones. Glycemic control along with blood pressure and cholesterol management reduce microvascular and macrovascular disease including cardiovascular events. Mounting evidence demonstrates that diabetes is a risk factor for periodontitis and possibly oral premalignancies and oral cancer. The systemic inflammatory response generated by inflamed periodontal tissue may in turn exacerbate diabetes, worsen cardiovascular outcomes, and increase mortality. Thus, oral medical and surgical physicians are vital in treating oral pathology, recognizing new cases of diabetes, and counseling people with diabetes to promote oral health. This article presents updates in the diagnosis, risk factors, prevention, management, and peri-oral complications of diabetes to assist oral health professionals in providing optimal care to patients with diabetes.

Phase I trial on the safety of topical rhVEGF on chronic neuropathic diabetic foot ulcers.

OBJECTIVE: To assess the safety/tolerability and perform a preliminary efficacy evaluation of a multiple-dosing regimen of recombinant human vascular endothelial growth factor (VEGF165 or rhVEGF; telbermin) applied topically to chronic diabetic neuropathic foot ulcers. METHOD: Subjects with type 1 or 2 diabetes mellitus were randomised to receive either topical applied telbermin (72 microg/cm2) (n=29) or placebo (n=26) treatment to the foot ulcer surface in conjunction with standard ulcer care. Subjects received treatment every 48 hours (maximum three doses per week) for up to six weeks. Weekly 35mm photography, quantitative planimetry and physical examinations documented the ulcer appearance, surface area and stage. Safety endpoints included incidence of clinically significant hypotension, adverse events and ulcer infection. Exploratory efficacy endpoints included percentage reduction in total ulcer surface area, incidence of complete ulcer healing and time to complete ulcer healing. RESULTS: Incidence of adverse events was comparable in the two treatment groups. None of the adverse events were attributed to study drug, and no hypotension was observed as a result of telbermin treatment. Occurrence of infected study ulcers appeared to be balanced between the treatment groups. Positive trends suggestive of potential signals of biological activity were observed for incidence of complete ulcer healing (41.4% telbermin versus 26.9% placebo at day 43 [P=0.39]) and time to complete ulcer healing (25th percentile of 32.5 days telbermin versus 43.0 days placebo [log-rank P=0.13]). CONCLUSION: The topical application of telbermin 72 microg/cm2 three times a week for up to six weeks appeared to be well tolerated. Further studies are required to characterise the safety/efficacy of telbermin more completely.

Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial.

BACKGROUND: Gefitinib has demonstrated activity in patients with non-small cell lung cancer (NSCLC). Clinical trials have not demonstrated a relationship between response to gefitinib and over-expression of the epidermal growth factor receptor (EGFR). Although, EGFR is not over-expressed in small cell lung cancer (SCLC), we postulated that gefitinib might affect tumor growth through other mechanisms. Agents that are active in NSCLC usually are also effective in SCLC. METHODS: The primary objective was to assess the clinical control rate: complete response (CR) partial response (PR) and stable disease (SD > 90 days), of gefitinib in patients with chemo-resistant and chemo-sensitive small cell cancers. Eligibility criteria included pathologic proof of a neuroendocrine tumor, especially small cell cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, prior treatment with one or two prior chemotherapy regimens and adequate end-organ function. Patients received gefitinib, 250 mg p.o. daily until disease progression or intolerable side effects. RESULTS: From April 2003 to March 2004, 19 patients were enrolled. Small cell lung cancer accounted for 18 of the 19 patients and one patient had metastatic Merkel cell carcinoma. Twelve patients (63%) had chemo-sensitive disease, defined as progression greater than three months from completion of prior chemotherapy; 7 (37%) had chemo-refractory disease; 13 (68%) had one prior chemotherapy regimen. Other patient characteristics: mean age 64 years (range 52-79 years); ECOG PS 0/1/2 = 7/9/3, M:F = 9:10. Grade 3 toxicities included: fatigue in three patients (15.8%), pulmonary toxicities in three (15.8%) and one patient (5.3%) each with hyperglycemia or pain. Four patients had grade four toxicities: one patient (5.3%) with fatigue and three patients (15.8%) with dyspnea. There were no patients with grade 3 or 4 rash or diarrhea. Two patients had stable disease (<90 days) and 17 had progressive disease as their best response. This study was a two-stage design and because the continuing criterion for stage one was not met, stage 2 was not performed. Median time to progression (TTP) was 50 days (95% CI = 21-58 days). One year overall survival (OS) was 21% (95% CI = 6-45.6%). CONCLUSION: Although gefitinib has activity in select patients with NSCLC, this study failed to demonstrate benefit in patients with small cell lung cancer.

Collaboration between an internal medicine residency program and a federally qualified health center: Norwalk Hospital and the Norwalk Community Health Center.

In 1999, Norwalk Hospital and an independent, community-based board collaboratively developed the Norwalk Community Health Center (the NCHC). The objectives of the affiliation were to (1) create a new, free-standing, high-quality community health center, (2) optimize grant and clinical revenue, (3) create an ideal venue for ambulatory care training for residents, and (4) replace the traditional and increasingly inefficient hospital-based primary care clinics. The hospital transferred all of its primary care clinical activity to the new community health center and provides an ongoing financial subsidy of the NCHC operations via a forgivable loan. In exchange, the NCHC granted Norwalk Hospital 24% of the seats on its board of directors and purchases all primary care provider services from the hospital. For adult medicine, the contract providers are exclusively Norwalk Hospital internal medicine residents and faculty. Contract charges are based not upon actual staffing but upon a standard formula relating full-time-equivalent providers to patient visits. The new 10,000 square-foot NCHC contains 2,500 square feet of additional integrated space, rented from the NCHC by Norwalk Hospital, which supports the residency education program. The NCHC opened in April 1999 and received FQHC status in November 1999. Adult medicine volume increased 30%, from 36.8 daily visits in the old hospital-based clinics to 48.0 at the NCHC. Resident and patient satisfaction are high. The NCHC now receives cost-based visit reimbursement from Medicaid and has received $1.8 million in state, federal, and local grants.

Obstetric anesthesia practice in Canada.

PURPOSE: To describe obstetric anesthesia in Canada as practiced in 1997: to identify practices at variance with the literature and the opinions of experts: and to identify questions for future research. METHODS: In 1997, a detailed postal questionnaire asking about the practice of obstetric anesthesia was mailed to all 1,539 specialist anesthesiologist members of the Canadian Anaesthetists' Society residing in Canada. Nonresponders were mailed a second questionnaire three months later RESULTS: There were 865 completed questionnaires returned for analysis (56.2%). Of these, 522 anesthesiologists practiced obstetric anesthesia (60.3%). The data were subdivided into those from anesthesiologists with a full or part-time university based practice (40.1%) and those from a community based practice (59.9%). University based and community-based anesthesiologists have very similar patterns of practice. Specific areas where anesthesia practice was different from current recommendations included: (1) information provided when obtaining consent for labour epidural analgesia, (2) use of opioids and local anesthetics for initiation of epidural analgesia, (3) use of coagulation testing in preeclampsia, (4) the common use of cutting spinal needles, (5) use of neuraxial morphine and nonsteroidal anti-inflammatory agents after Cesarean deliveries, (6) optimal treatment of neuraxial opioid side effects, (7) when to insert an endotracheal tube for general anesthesia after delivery, and (8) withdrawing epidural catheters through epidural needles. CONCLUSIONS: This survey presents reference data on the practice of obstetric anesthesia in Canada in 1997. Anesthesiologists with university affiliation have very similar practices to those without university affiliations.

Comparison of 0.25 mg and 0.1 mg intrathecal morphine for analgesia after Cesarean section.

PURPOSE: To test the hypothesis that 0.1 mg intrathecal morphine plus NSAIDs provides satisfactory analgesia post-Cesarean section with fewer side effects than 0.25 mg intrathecal morphine. METHODS: Sixty women, scheduled for elective Cesarean section under spinal anesthesia, were randomized to receive either 0.1 mg or 0.25 mg intrathecal morphine combined with hyperbaric bupivacaine 0.75% and 20 microg fentanyl. All patients received a 100 mg indomethacin suppository at the end of surgery and 500 mg naproxen p.o. b.i.d. was started the evening of surgery and continued until discharge. A blinded researcher recorded the pain, pruritus, and nausea scores, the time to first request for additional analgesics, a visual analogue scale (VAS) satisfaction score, and the use of additional opioids, antipruritics, and/or antiemetics. RESULTS: Of the 60 patients enrolled, two were not included in the data analysis because of protocol violations leaving 30 patients in the 0.1 mg group and 28 in the 0.25 mg group. There were no differences in the VAS pain scores or the number of women requesting an opioid other than codeine between the two groups. The VAS pruritus scores in the 0.1 mg group were lower throughout the 24 hr (P < 0.001). Fewer women in the 0.1 mg group (4/30 vs 12/28) requested nalbuphine to treat itching (P = 0.018). Nausea scores were lower in the 0.1 mg group (P < 0.001). CONCLUSION: The use of 0.1 mg intrathecal morphine plus NSAIDs provides analgesia of similar quality to 0.25 mg but with fewer undesirable side effects following Cesarean section.

Estimating effectiveness in an observational study: a case study of dornase alfa in cystic fibrosis. The Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis.

Patients with cystic fibrosis (CF) receiving dornase-alfa had improved pulmonary function relative to a control group in a large randomized phase III controlled study. We reviewed data from a large observational phase IV study to estimate the observed drug effect in patients receiving dornase alfa as part of their routine care. Patients 6 years or older and with a baseline forced expiratory volume in 1 second (FEV1) of at least 40% predicted who had been enrolled for at least 18 months were included (n = 283). The control group consisted of 2382 patients who had never received dornase alfa. Patients in the study had a baseline spirometry and a second spirometry recorded 12 months later; a baseline observation period of 6 months preceded the initial spirometry, and dornase alfa had to have been started after the baseline spirometry (within 3 months) and to have continued through the 12-month follow-up spirometry. Patients treated with dornase alfa had lower pulmonary functions, more bacterial colonization, and more exacerbations at baseline (FEV1 : 76.0% vs 87.6%, Pseudomonas aeruginosa : 64.1% vs 46.7%, pulmonary exacerbations during the previous 6 months: 56.4% vs 22. 2%). Mean values of FEV1 for patients treated with dornase alfa improved by 3.9% of predicted compared with a decline of 1.6% in the untreated cohort. Covariate adjustment provided an estimated benefit of dornase alfa of 4.3% predicted FEV1 (SE = 0.9, P <.0001). This analysis provides evidence for the effectiveness of dornase alfa therapy in clinical practice.

Mutant alleles of the Drosophila trithorax gene produce common and unusual homeotic and other developmental phenotypes.

trithorax (trx) encodes chromosome-binding proteins required throughout embryogenesis and imaginal development for tissue- and cell-specific levels of transcription of many genes including homeotic genes of the ANT-C and BX-C. trx encodes two protein isoforms that contain conserved motifs including a C-terminal SET domain, central PHD fingers, an N-terminal DNA-binding homology, and two short motifs also found in the TRX human homologue, ALL1. As a first step to characterizing specific developmental functions of TRX, I examined phenotypes of 420 combinations of 21 trx alleles. Among these are 8 hypomorphic alleles that are sufficient for embryogenesis but provide different levels of trx function at homeotic genes in imaginal cells. One allele alters the N terminus of TRX, which severely impairs larval and imaginal growth. Hypomorphic alleles that alter different regions of TRX equivalently reduce function at affected genes, suggesting TRX interacts with common factors at different target genes. All hypomorphic alleles examined complement one another, suggesting cooperative TRX function at target genes. Comparative effects of hypomorphic genotypes support previous findings that TRX has tissue-specific interactions with other factors at each target gene. Some hypomorphic genotypes also produce phenotypes that suggest TRX may be a component of signal transduction pathways that provide tissue- and cell-specific levels of target gene transcription.

The changing role of magnesium sulphate therapy.

Magnesium sulphate is not an effective tocolytic. Magnesium sulphate therapy was also linked to preterm neonatal deaths in one study, which was stopped before completion. Other studies suggest a possible neuroprotective effect of magnesium. Both of these issues require further study. Magnesium sulphate is clearly the drug of choice to prevent recurrent eclampsia and to treat severe pre-eclampsia.

Comparison of epidural lidocaine and fentanyl to intrathecal sufentanil for analgesia in early labour.

A randomized, double-blind study was undertaken comparing an epidural test dose of lidocaine followed by 100 microg fentanyl (E-LF, n = 19) to combined spinal epidural sufentanil 10 microg (CSE-S, n = 21) in low risk women in early labour. The primary outcome measured was the duration of analgesia; secondary outcomes included the quality of analgesia, incidence and severity of pruritus, lower limb motor blockade, and the ability to ambulate. A P < 0.05 was considered statistically significant. Baseline demographic characteristics, including parity, were similar between groups. CSE-S provided analgesia of longer duration than E-LF (126 +/- 61 min versus 83 +/- 37 min, P < 0.01). Visual analog scores (VAS) for pain were higher with E-LF throughout the study period (P < 0.05) although patients in both groups had clinically acceptable analgesia. The VAS for pruritus were higher in the CSE-S group (P < 0.05) but no patient requested treatment for pruritus. Mild motor weakness was more frequent in the E-LF group (5/19 versus 20/21, P < 0.05) and fewer patients in the E-LF group met criteria for ambulation (13/19 versus 20/21, P < 0.05). While both E-LF and CSE-S provide effective analgesia for women in early labour, the more rapid onset of analgesia, lower VAS pain scores, longer duration of action and lesser impact on ability to ambulate suggest advantages of CSE-S over E-LF.

Risk for intracranial hemorrhage after tissue plasminogen activator treatment for acute myocardial infarction. Participants in the National Registry of Myocardial Infarction 2.

BACKGROUND: The efficacy of thrombolytic therapy in reducing mortality from acute myocardial infarction has been unequivocally shown. However, thrombolysis is related to bleeding complications, including intracranial hemorrhage. OBJECTIVE: To determine the frequency of and risk factors for intracranial hemorrhage after recombinant tissue-type plasminogen activator (tPA) given for acute myocardial infarction in patients receiving usual care. DESIGN: Large national registry of patients who have had acute myocardial infarction. SETTING: 1484 U.S. hospitals. PATIENTS: 71073 patients who had had acute myocardial infarction from 1 June 1994 to 30 September 1996, received tPA as the initial reperfusion strategy, and did not receive a second dose of any thrombolytic agent. MEASUREMENT: Intracranial hemorrhage confirmed by computed tomography or magnetic resonance imaging. RESULTS: 673 patients (0.95%) were reported to have had intracranial hemorrhage during hospitalization for acute myocardial infarction; 625 patients (0.88%) had the event confirmed by computed tomography or magnetic resonance imaging. Of the 625 patients with confirmed intracranial hemorrhage, 331 (53%) died during hospitalization. An additional 158 patients (25.3%) who survived to hospital discharge had residual neurologic deficit. In multivariable models for the main effects of candidate risk factors, older age, female sex, black ethnicity, systolic blood pressure of 140 mm Hg or more, diastolic blood pressure of 100 mm Hg or more, history of stroke, tPA dose more than 1.5 mg/kg, and lower body weight were significantly associated with intracranial hemorrhage. CONCLUSIONS: Intracranial hemorrhage is a rare but serious complication of tPA in patients with acute myocardial infarction. Appropriate drug dosing may reduce the risk for this complication. Other therapies, such as primary coronary angioplasty, may be preferable in patients with acute myocardial infarction who have a history of stroke.

Response to growth hormone in attention deficit hyperactivity disorder: effects of methylphenidate and pemoline therapy.

OBJECTIVE: To determine whether treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate hydrochloride or pemoline diminishes the response to growth hormone (GH) therapy in patients with idiopathic GH deficiency (IGHD) or idiopathic short stature (ISS). METHODS: The National Cooperative Growth Study database was used to identify patients between 3 and 20 years of age with IGHD or ISS and those within these groups who were treated with methylphenidate or pemoline for ADHD. Their growth in response to GH treatment (change in height standard deviation score [SDS]) was compared with that of patients with IGHD or ISS who were not treated for ADHD, by using a stepwise multiple regression analysis. RESULTS: In the IGHD cohort, there were 184 patients who were being treated for ADHD and 2313 who were not. In the ISS cohort there were 117 patients who were being treated for ADHD and 1283 who were not. There was a higher percentage of males being treated for ADHD in both cohorts. In the IGHD cohort, the change in height SDS was positively associated with the number of years of GH treatment, parents' heights, body mass index, and GH injection schedule, and was negatively associated with height SDS at the initiation of GH therapy, age, and maximum stimulated GH level. The use of methylphenidate or pemoline had a negative effect on the change in height SDS, but the magnitude of the effect was small. Similar effects were noted in the ISS cohort, but body mass index and the use of methylphenidate or pemoline had no effect on the change in height SDS. CONCLUSIONS: Concurrent ADHD therapy is associated with a slight decrease in the change in height SDS during GH treatment in patients with IGHD but not in those with ISS. Even in IGHD, the magnitude of the effect is small and should not deter the use of such concurrent therapy.

Treatment of glucocorticoid-induced growth suppression with growth hormone. National Cooperative Growth Study.

Growth failure is common during long term treatment with glucocorticoids (GC) due to blunting of GH release, insulin-like growth factor I (IGF-I) bioactivity, and collagen synthesis. These effects could theoretically be reversed with GH therapy. The National Cooperative Growth Study database (n = 22,005) was searched for children meeting the following criteria: 1) pharmacological treatment with GC and GH for more than 12 months, 2) known type and dose of GC, and 3) height measurements for more than 12 months. A total of 83 patients were identified. Monitoring of glucose, insulin, IGF-I, IGF-binding protein-3, type 1 procollagen, osteocalcin, and glycosylated hemoglobin levels was performed in a subset of patients. Stimulated endogenous GH levels were less than 10 microg/L in 51% of patients and less than 7 microg/L in 37% of patients. The mean GC dose, expressed as prednisone equivalents, was 0.5 +/- 0.6 mg/kg day. Baseline evaluation revealed extreme short stature (mean height SD score = -3.7 +/- 1.2), delayed skeletal maturation (mean delay, 3.1 yr), and slowed growth rates (mean, 3.0 +/- 2.5 cm/yr). After 12 months of GH therapy (mean dose, 0.29 mg/kg x weeks), mean growth rate increased to 6.3 +/- 2.6 cm/yr, and height SD score improved by 0.21 +/- 0.4 (P < 0.01). During the second year of GH therapy (n = 44), the mean growth rate was 6.3 +/- 2.0 cm/yr. Prednisone equivalent dose and growth response to GH therapy were negatively correlated (r = -0.264; P < 0.05). Plasma concentrations of IGF-I, IGF-binding protein-3, procollagen, osteocalcin, and glycosylated hemoglobin increased with GH therapy, whereas glucose and insulin levels did not change. The following conclusions were reached. The growth-suppressing effects of GC are counterbalanced by GH therapy; the mean response is a doubling of baseline growth rate. Responsiveness to GH is negatively correlated with GC dose. Glycosylated hemoglobin levels increased slightly, but glucose and insulin levels were not altered by GH therapy.

Use of reperfusion therapy for acute myocardial infarction in the United States: data from the National Registry of Myocardial Infarction 2.

BACKGROUND: There is clear evidence that reperfusion therapy improves survival in selected patients with an acute myocardial infarction. However, several studies have suggested that many patients with an acute myocardial infarction do not receive this therapy. Whether this underutilization occurs in patients appropriate for such therapy remains unclear. METHODS AND RESULTS: We examined the use of reperfusion therapy in patients with an acute myocardial infarction hospitalized at 1470 hospitals participating in the National Registry of Myocardial Infarction 2. We identified 84 663 patients who were eligible for reperfusion therapy as defined by diagnostic changes on the initial 12-lead ECG, presentation to the hospital within 6 hours from symptom onset, and no contraindications to thrombolytic therapy. Twenty-four percent of these eligible patients did not receive any form of reperfusion therapy (7.5% of all patients). When multivariate analyses were used, left bundle-branch block (odds ratio [OR]=0.22; 95% CI=0.20 to 0.24), lack of chest pain at presentation (OR=0.22; 95% CI=0.21 to 0.24), age >75 years (OR=0.40, 95% CI=0.36 to 0.43), female sex (OR=0.88, 95% CI=0.83 to 0.92), and various preexisting cardiovascular conditions were independent predictors that the patient would not receive reperfusion therapy. CONCLUSIONS: Reperfusion therapy may be underutilized in the United States. Increased use of reperfusion therapy could potentially reduce the unnecessarily high mortality rates observed in women, the elderly, and other patient groups with the highest risk of death from an acute myocardial infarction.

Growth-hormone treatment of renal transplant recipients: the National Cooperative Growth Study experience--a report of the National Cooperative Growth Study and the North American Pediatric Renal Transplant Cooperative Study.

OBJECTIVE: To evaluate growth response and renal allograft measures after recombinant human growth-hormone (GH) treatment in pediatric renal transplant recipients. STUDY DESIGN: Data on GH-treated children in the National Cooperative Growth Study (NCGS) database were linked to the database of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Data were analyzed for growth rate, graft survival, graft function, acute rejection, and adverse events. Data on 2390 transplant recipients in the NAPRTCS who had at least 24 months of graft function were used in the comparisons. RESULTS: Fifty-nine patients were treated with GH after renal transplantation. One-year growth data were available for 42 of these; 2-year, for 31; and 3-year, for 13. Growth velocity increased from 2.47 +/- 1.83 cm/yr to 7.17 +/- 2.97 cm/yr after 1 year. Year-2 and -3 growth rates were 5.93 +/- 2.29 cm/yr and 6.31 +/- 2.32 cm/yr. Height standard deviation score immediately after transplantation was -3.26 +/- 1.44 and at the initiation of GH was -3.59 +/- 1.15; it increased to -3.18 +/- 1.06 at year 1 and to -3.16 +/- 0.92 at year 2 and was -3.31 +/- 1.00 at year 3. Five-year graft survival was 80% in the GH cohort and 85% in the NAPRTCS cohort. Acute rejection ratio was 1.44 and 1.43 episodes per patient in the GH and NAPRTCS cohorts, respectively. Calculated creatinine clearance at 6 years was 68 and 63 ml/min per 1.73 m2, respectively. CONCLUSIONS: Growth hormone increase growth velocity for up to 3 years without an apparent decrease in graft survival or renal function, and no relation between GH therapy and acute rejection is seen. A randomized, prospective study to evaluate further the safety and efficacy of this promising therapy is required.

Role of magnetic resonance imaging in assessing factors affecting healing in scaphoid nonunions.

This study evaluates the role of magnetic resonance imaging in assessing the factors affecting the rate and healing time in scaphoid nonunions after surgery. Nineteen patients were assessed before surgery by radiographs, tomography, and magnetic resonance imaging. Fifteen had viable bone marrow and 4 patients had nonviable bone marrow on magnetic resonance imaging. All patients with normal preoperative magnetic resonance imaging healed in an average time of 4.7 months. Of the 4 patients with abnormal magnetic resonance imaging, but normal plain radiographs, 2 went on to heal in 10.5 months. The remaining 2 patients with abnormal magnetic resonance imaging and abnormal plain radiographs did not heal by 24 months. This study suggests 3 groups of scaphoid nonunions. Group 1 has normal trabecular bone radiographically and vascular bone marrow on magnetic resonance imaging and should be expected to heal after surgery. Group 2 has normal trabecular bone radiographically but avascular marrow on magnetic resonance imaging and may be expected to eventually heal after surgery. Group 3 has abnormal radiographs suggestive of fibrous replacement of the scaphoid proximal pole by the presence of cystic changes and the loss of trabecular bone, and avascular bone, as shown on magnetic resonance imaging. This study failed to show healing in this group of patients. Magnetic resonance imaging may be of benefit in predicting the healing potential in patients presenting with scaphoid nonunion.