Delayed and significant hypercalcaemia due to teriparatide therapy: a case report and review.

INTRODUCTION: Transient hypercalcaemia due to teriparatide occurs in up to 11% of patients though delayed hypercalcaemia (> 24 h post injection) is rare. We report the case of a female who developed significant delayed hypercalcaemia after teriparatide treatment for osteoporosis and review other cases in the literature to date. CASE REPORT: A 72-year-old female on teriparatide for the treatment of osteoporosis was found to have hypercalcaemia (3.30 mmol/l) on routine testing approximately 3 months after starting therapy. Serum calcium pretreatment was normal at 2.39 mmol/l. She was admitted to the hospital for investigations which identified a serum 25-hydroxyvitamin D of 94 nmol/l, a low parathyroid hormone of 6.0 pg/ml, and normal test results for 1,25 dihydroxyvitamin D (115 pmol/l), parathyroid hormone-related peptide (< 1.4 pmol/ml), serum electrophoresis and angiotensin-converting enzyme (39 IU/l). CT abdomen, pelvis, and thorax revealed no evidence of malignancy and an isotope bone scan ruled out skeletal metastases. Serum calcium normalised (2.34 mmol/l) several days after stopping teriparatide and calcium supplements and administering intravenous fluid. On restarting teriparatide, delayed hypercalcaemia reoccurred and treatment was switched to denosumab. DISCUSSION: Delayed moderate to severe hypercalcaemia (serum calcium > 3.0 mmol/l) due to teriparatide is rare but may lead to therapy withdrawal. The underlying predisposing risk factors remain unclear and highlight the importance of a routine serum calcium assessment on therapy.

Treatment Challenges When Stopping Denosumab.

Introduction Denosumab is commonly used to treat osteoporosis. However, discontinuation results in rebound bone loss and increased vertebral fracture risk. We report a clinical case series, illustrating the dilemma in deciding the best treatment should denosumab be stopped. Cases In eight patients aged 56-89 years, zolendronic acid after stopping denosumab resulted in BTM rises and BMD decline.  In a 68-year-old, two years of oral bisphosphonate after three years of denosumab resulted in elevated bone turnover markers (BTM) and decline in bone mineral density (BMD), necessitating a switch to zoledronic acid.  In a 79-year-old, two annual doses of zolendronic acid after three years of denosumab failed to suppress high BTM, with BMD dropping and denosumab being restarted.  In a 60-year-old, on stopping denosumab after 10 years of oral bisphosphonate, BMD remained stable despite no further therapy. Conclusion Drug holidays are not an option with denosumab, with a risk of bone loss even on transitioning to bisphosphonates. Risk is greater with longer duration of treatment6 and may be mitigated by prior bisphosphonate use. Standard dose zoledronic acid does not prevent bone loss in a significant proportion of patients. BTM may help in monitoring treatment and need for further bisphosphonates.

Greater yogurt consumption is associated with increased bone mineral density and physical function in older adults.

In this cohort of community dwelling older adults (>60 years), we observed significant positive associations between the frequencies of yogurt intake with measures of bone density, bone biomarkers, and indicators of physical function. Improving yogurt intakes could be a valuable health strategy for maintaining bone health in older adults. INTRODUCTION: The associations of yogurt intakes with bone health and frailty in older adults are not well documented. The aim was to investigate the association of yogurt intakes with bone mineral density (BMD), bone biomarkers, and physical function in 4310 Irish adults from the Trinity, Ulster, Department of Agriculture aging cohort study (TUDA). METHODS: Bone measures included total hip, femoral neck, and vertebral BMD with bone biochemical markers. Physical function measures included Timed Up and Go (TUG), Instrumental Activities of Daily Living Scale, and Physical Self-Maintenance Scale. RESULTS: Total hip and femoral neck BMD in females were 3.1-3.9% higher among those with the highest yogurt intakes (n = 970) compared to the lowest (n = 1109; P < 0.05) as were the TUG scores (-6.7%; P = 0.013). In males, tartrate-resistant acid phosphatase (TRAP 5b) concentrations were significantly lower in those with the highest yogurt intakes (-9.5%; P < 0.0001). In females, yogurt intake was a significant positive predictor of BMD at all regions. Each unit increase in yogurt intake in females was associated with a 31% lower risk of osteopenia (OR 0.69; 95% CI 0.49-0.96; P = 0.032) and a 39% lower risk of osteoporosis (OR 0.61; 95% CI 0.42-0.89; P = 0.012) and in males, a 52% lower risk of osteoporosis (OR 0.48; 95% CI 0.24-0.96; P = 0.038). CONCLUSION: In this cohort, higher yogurt intake was associated with increased BMD and physical function scores. These results suggest that improving yogurt intakes could be a valuable public health strategy for maintaining bone health in older adults.

Physical and mental health of older people while cocooning during the COVID-19 pandemic.

BACKGROUND: Cocooning or shielding, i.e. staying at home and reducing face-to-face interaction with other people, was an important part of the response to the COVID-19 pandemic for older people. However, concerns exist regarding the long-term adverse effects cocooning may have on their physical and mental health. AIM: To examine health trajectories and healthcare utilization while cocooning in a cohort of community-dwelling people aged ≥70 years. DESIGN: Survey of 150 patients (55% female, mean age 80 years and mean Clinical Frailty Scale Score 4.8) attending ambulatory medical services in a large urban university hospital. METHODS: The survey covered four broad themes: access to healthcare services, mental health, physical health and attitudes to COVID-19 restrictions. Survey data were presented descriptively. RESULTS: Almost 40% (59/150) reported that their mental health was 'worse' or 'much worse' while cocooning, while over 40% (63/150) reported a decline in their physical health. Almost 70% (104/150) reported exercising less frequently or not exercising at all. Over 57% (86/150) of participants reported loneliness with 1 in 8 (19/150) reporting that they were lonely 'very often'. Half of participants (75/150) reported a decline in their quality of life. Over 60% (91/150) agreed with government advice for those ≥70 years but over 40% (61/150) reported that they disliked the term 'cocooning'. CONCLUSIONS: Given the likelihood of further restrictions in coming months, clear policies and advice for older people around strategies to maintain social engagement, manage loneliness and continue physical activity and access timely medical care and rehabilitation services should be a priority.

Dairy Intakes in Older Irish Adults and Effects on Vitamin Micronutrient Status: Data from the TUDA Study.

BACKGROUND: Consumption of dairy products has been associated with positive health outcomes including a lower risk of hypertension, improved bone health and a reduction in the risk of type 2 diabetes. The suggested dairy intake for health in older adults is three servings per day but recent analysis of the NHANES data for older adults reported 98% were not meeting these recommendations. No studies have investigated the consequences of such declines in the dairy intakes of Irish older adults and the subsequent effects on vitamin micronutrient status. OBJECTIVES: To study the daily dairy intakes of older Irish adults and to examine how the frequency of dairy food consumption affects vitamin micronutrient status. METHODS: Participants (n 4,317) were from the Trinity Ulster Department of Agriculture (TUDA) Study, a large study of older Irish adults (aged >60 yrs) designed to investigate gene-nutrient interactions in the development of chronic diseases of aging. The daily intake portion for milk, cheese and yoghurt was calculated from food frequency questionnaire (FFQ) responses. Blood samples were analysed for vitamin biomarkers as follows: vitamin B12 (total serum cobalamin and holotranscobalamin (holoTC)), folate (red cell folate (RCF) and serum folate), vitamin B2 (erythrocyte glutathione reductase activation coefficient (EGRac)), vitamin B6 (serum pyridoxal phosphate) and vitamin D (serum 25(OH)D). RESULTS: The mean total reported dairy intake was 1.16 (SD 0.79) portions per day with males consuming significantly fewer total dairy portions compared to females (1.07 vs 1.21 respectively) (P<0.05). There was no significant difference in total daily dairy serving intakes by age decade (60-69, 70-79, >80 yrs). Overall, only 3.5% of the total population (n 151) achieved the recommended daily dairy intake of three or more servings per day. A significantly higher proportion of females (4%) compared to males (2.4%) met these dairy requirements (P=0.011). Blood concentrations of vitamin B12 biomarkers, RCF, vitamin B2 and vitamin B6 were significantly worse in those with the lowest tertile of dairy intake (0-0.71 servings) compared to those in the highest tertile (1.50-4.50 servings) (P<0.05). CONCLUSION: This study found that more than 96% of the older adults sampled did not meet current daily dairy intake recommendations. The study is the largest to-date examining dairy intakes in older Irish adults, and provides evidence that daily dairy intakes (in particular yogurt) contribute significantly to the B-vitamin and vitamin D biomarker status of older adults. These results suggest that older adults who are already vulnerable to micronutrient inadequacies, are forgoing the nutritional advantages of vitamin-rich dairy products.

Comparison of rizatriptan and other triptans on stringent measures of efficacy.

OBJECTIVE: To compare the efficacy of oral rizatriptan 10 mg with oral doses of sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures. METHODS: Retrospective analysis of data from five randomized, placebo-controlled, double-masked clinical trials in which oral rizatriptan was directly compared with oral sumatriptan 100 mg (n = 772), 50 mg (n = 1116), 25 mg (n = 1183), naratriptan 2.5 mg (n = 413), and zolmitriptan 2.5 mg (n = 580) for the acute treatment of a moderate or severe migraine attack. OUTCOME MEASURES: Percentage of patients pain-free at 2 hours, symptom-free at 2 hours (no pain, nausea, photophobia, phonophobia, vomiting, or functional disability), 24-hour sustained pain-free (no headache at 2 hours, no recurrence, and no additional antimigraine medications for 24 hours). RESULTS: More patients taking rizatriptan 10 mg were pain-free at 2 hours than were patients taking sumatriptan 100 mg (40% vs 33%, p = 0.019), sumatriptan 50 mg (40% vs 35%, p = 0.009), sumatriptan 25 mg (38% vs 27%, p < 0.001), naratriptan 2.5 mg (45% vs 21%, p < 0.001), and zolmitriptan 2.5 mg (43% vs 36%, p = 0.041). More patients taking rizatriptan 10 mg were symptom-free at 2 hours than were patients taking sumatriptan 100 mg (31% vs 22%, p = 0.002), sumatriptan 50 mg (33% vs 28%, p = 0.003), sumatriptan 25 mg (33% vs 24%, p < 0.001), naratriptan 2.5 mg (30% vs 11%, p < 0.001), and zolmitriptan 2.5 mg (31% vs 24%, p = 0.042). More patients taking rizatriptan 10 mg had a 24-hour sustained pain-free response than did patients taking sumatriptan 100 mg (27% vs 23%, p = 0.112), sumatriptan 50 mg (30% vs 26%, p = 0.015), sumatriptan 25 mg (27% vs 20%, p = 0.005), naratriptan 2.5 mg (29% vs 17%, p = 0.004), and zolmitriptan 2.5 mg (32% vs 24%, p = 0.013). CONCLUSION: Oral rizatriptan 10 mg was more effective than oral sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures of pain-free response at 2 hours, symptom-free response at 2 hours, and 24-hour sustained pain-free response.

Within-patient consistency of response of rizatriptan for treating migraine.

OBJECTIVE: To determine the within-patient consistency of response for rizatriptan, a 5-HT(1B/1D) receptor agonist for the acute treatment of migraine. METHODS: Post hoc analysis was performed on data from a randomized, double-blind, placebo-controlled clinical trial. Four hundred seventy-three patients with migraine diagnosed according to the criteria of the International Headache Society were randomly assigned to one of five sequence groups in which each patient was scheduled to treat four separate moderate or severe migraine attacks. Patients in four groups received 10 mg of rizatriptan for three of four attacks and placebo for the remaining attack; patients in the fifth group received 10 mg of rizatriptan for all four attacks. Headache severity, functional disability, and associated migraine symptoms were measured immediately before dosing and at regular intervals up to 4 hours after the dose. The analysis was based on efficacy at 2 hours after dosing, the last time point before escape medications were allowed. The percentages of patients who responded in a specified number of attacks after treatment with rizatriptan were calculated. The analysis was descriptive, and no formal statistical testing was performed. RESULTS: Of the evaluable patients who treated three migraine attacks with 10 mg of rizatriptan (with an additional interspersed placebo-treated attack in most patients), 216 of 252 (86%) had pain relief (reduction of pain to mild or none), 122 of 252 (48%) were pain free, 211 of 250 (84%) had no nausea, 163 of 251 (65%) had no photophobia, 182 of 252 (72%) had no phonophobia, 136 of 249 (55%) had no functional disability, and 233 of 252 (92%) had no need for escape medications at 2 hours after dosing in at least two of three attacks. CONCLUSION: The response to 10 mg of oral rizatriptan within individual patients was consistent over three attacks on a range of measures.

Correlative imaging of the liver and hepatobiliary system.

Many imaging techniques can be used to assess the liver and hepatobiliary system. Each modality has individual strengths and limitations, which usually vary depending on the specific clinical situation. This review discusses several specific common clinical situations where imaging of the liver and biliary system is necessary and describes the various imaging options. Space-occupying liver lesions are discussed, and particular attention is paid to the assessment of liver metastasis, hepatoma, and incidentally discovered liver lesions such as hemangioma, adenoma, and focal nodular hyperplasia. The value of ultrasound, computed tomography, magnetic resonance imaging, and scintigraphic techniques in this patient population is described. Isolated sulfur colloid hepatic scintigraphy is not of great value in the evaluation of these patients. Therefore, this review describes in some detail the value of physiological liver scintigraphy, including gallium and iminodiacetic acid (IDA) scanning as well as dynamic flow imaging of the liver such as hepatic artery perfusion scintigraphy and tagged red cell scintigraphy. Imaging of the biliary tree also is described. The roles of ultrasound and scintigraphy are compared and contrasted as related to the diagnosis of acute cholecystitis, common duct obstruction, and postoperative complications.

Low dose famotidine in the prevention of sleep disturbance caused by heartburn after an evening meal.

AIM: To determine whether, in a susceptible population, dosing with 10 mg famotidine 1 h before an evening meal could decrease the interference with sleep caused by heartburn. METHODS: Patients with a history of frequent heartburn (n = 309) were randomized to receive 10 mg famotidine or placebo 1 h before an evening meal likely to induce symptoms. Patients assessed the efficacy of the treatment in preventing heartburn after the meal, at bedtime and during the night. The number of awakenings due to heartburn and the consumption of antacid tablets taken to alleviate symptoms were also recorded. RESULTS: Treatment groups were well matched and data from 302 patients were available for analysis. Compared to placebo, famotidine treated patients had: less heartburn after the meal (P < 0.0001 mean global scores), less interference with getting to sleep (P = 0.0156 mean global scores), fewer awakenings (P = 0.0001 difference in mean number) and better control of heartburn during the night (P < 0.0001 mean global scores). They were also almost three times less likely to need antacid treatment than the placebo group during the night (relative odds for no antacid 2.78 (95% CI: 1.29-5.96). Only four patients in each group suffered adverse events. CONCLUSION: Taking a 10 mg dose of famotidine 1 h before an evening meal appears to be a successful and well tolerated strategy for preventing post-prandial heartburn and avoiding the associated interference with sleep.

Resident interpretation of emergency computed tomographic scans.

Our busy, urban emergency room is staffed by radiology residents after working hours. To determine the accuracy of our residents' interpretations of emergency cranial computed tomographic (CT) scans, the authors reviewed the preliminary reports of our residents for a two-month period. A total of 289 cranial CT scans were retrospectively reviewed and the resident interpretation judged acceptable, minor error, moderate error, or major error. Six of 289 neurologic examinations (2%) had moderate (4) or major (2) errors. The mistakes all involved misinterpretation of cerebral hemorrhage. The 98% accuracy in interpretation of cranial CT is higher than the accuracy reported with emergency plain film (PF) interpretation.

Rizatriptan in the treatment of menstrual migraine.

OBJECTIVE: To determine the efficacy of oral rizatriptan 10 mg and 5 mg for treating menstrually associated migraine attacks. METHODS: Data from two large clinical trials with identical designs were included in a retrospective analysis. The studies were randomized, double-masked, placebo-controlled, incomplete block, two-period, crossover designs. Women with migraines were randomly assigned to one of five treatment sequences for the treatment of two migraine attacks. Only data from the first attack in women with migraines who were treated with rizatriptan or placebo were included in the analysis. A menstrually associated attack was defined as one that occurred within 3 days before or after the onset of the last menstrual period. RESULTS: In the subgroup of 335 women with menstrually associated migraine, rizatriptan was effective compared with placebo. At 2 hours after dosing, 68% of 139 women taking rizatriptan 10 mg and 70% of 115 women taking rizatriptan 5 mg with a menstrually associated migraine had pain relief compared with 44% of 81 patients taking placebo (P <.05). In all women, rizatriptan was as effective in treating menstrual as well as nonmenstrual migraine: 68% of 139 patients taking rizatriptan 10 mg with a menstrually associated migraine had pain relief at 2 hours after dosing compared with 69% of 393 patients with nonmenstrually associated attacks (test of menstrual association = nonsignificant; the analysis had 80% power to detect a difference of six percentage points between groups). Similar results were found for rizatriptan 5 mg (menstrual = 70%, nonmenstrual = 66%; not statistically significant). CONCLUSION: Rizatriptan is effective in the treatment of menstrually associated migraine attacks.

Comparative study of ibuprofen lysine and acetaminophen in patients with postoperative dental pain.

This single-dose, double-blind, parallel-group, single-site study compared ibuprofen lysine 400 mg with acetaminophen 1000 mg and placebo in 240 patients with moderate-to-severe postoperative dental pain. The relative onset of analgesic response, overall analgesic efficacy, duration of effect, and safety were assessed over a 6-hour postdose period. Analgesic efficacy was assessed by patient self-rating of pain intensity, pain relief, time to meaningful pain relief, need for additional analgesic medication, and patient global evaluation. Both ibuprofen lysine 400 mg and acetaminophen 1000 mg were significantly (P < or = 0.05) more effective than placebo. Ibuprofen lysine had a significantly (P < or = 0.05) faster onset of action with greater peak and overall analgesic effect than did effect than did acetaminophen. All treatments were generally well tolerated.

Rizatriptan: pharmacological differences from sumatriptan and clinical results.

Rizatriptan and sumatriptan are selective 5-HT(1B/1D) receptor agonists for theacute treatment of migraine. For oral formulations, the time to maximum plasma concentration is reached earlier with rizatriptan than with sumatriptan (1 h versus 2-2.5 h) and rizatriptan has greater bioavailability than sumatriptan (45% versus 15%). These pharmacological advantages appear to translate into a faster onset of action and a better overall response for oral rizatriptan versus oral sumatriptan. The two drugs have been directly compared in randomized, double-blind, placebo-controlled clinical trials of patients with moderate or severe migraine attacks. Rizatriptan 10 mg was generally superior to sumatriptan on a measure of time-to-pain-relief within 2 h, where pain relief was defined as a reduction of pain to mild or none (odds ratio for rizatriptan versus sumatriptan 100 mg = 1.21; odds ratios for rizatriptan 10 mg versus sumatriptan 50 mg = 1.14 and 1.10 in two studies). Rizatriptan 10 mg was also superior to sumatriptan on the International Headache Society recommended endpoint of the percentage of patients pain free at 2 h (40% for rizatriptan 10 mg, 33% for sumatriptan 100 mg, and 35% for sumatriptan 50 mg). Further advantages for rizatriptan were seen on stringent outcome measures of the percentage of patients who were completely free of all symptoms at 2 h, patient satisfaction with medication at 2 h, and 24-h sustained pain-free response. 5-HT(1B/1D) receptor agonists are contraindicated in patients with coronary artery disease because of their potential to cause vasoconstriction. In clinical trials which excluded such patients, rizatriptan and sumatriptan were both well-tolerated. The most common side-effects on both drugs occurred in <10% of patients and consisted of dizziness, drowsiness, and asthenia/fatigue. The adverse events were usually mild or moderate in severity and short-lasting.

Accuracy of detecting screw penetration of the acetabulum with intraoperative fluoroscopy and computed tomography.

BACKGROUND: The purpose of this study was to determine the accuracy of computed tomography and fluoroscopy in assessing joint penetration by periacetabular screws. METHODS: A 3.5-mm acetabular periarticular screw was inserted in each of thirty-nine cadaveric hemipelves. Twenty screws were intentionally directed to violate the articular surface, whereas nineteen screws were positioned to avoid the articular surface. Using two fluoroscopic views (tangential and axial) in a manner simulating the clinical setting, an examiner blinded to the actual screw location determined whether each screw was violating the articular surface. In addition, each hemipelvis was examined with computed tomography with use of two different techniques: (1) a 1-mm slice thickness at 1-mm intervals, and (2) a 4-mm slice thickness at 3-mm intervals. Each scan was evaluated by another examiner who was blinded to the actual screw location. Sensitivity, specificity, and percent correct interpretations were then calculated for each method. RESULTS: The sensitivity, specificity, and percent correct interpretations were 95%, 84%, and 90%, respectively, for axial fluoroscopy; 85%, 89%, and 87% for tangential fluoroscopy; 100%, 84%, and 92% for the computed tomography scans with a 1-mm slice thickness at 1-mm intervals; and 100%, 58%, and 79% for the computed tomography scans with a 4-mm slice thickness at 3-mm intervals. Tangential fluoroscopy was found to be more specific than the computed tomography scans with a 4-mm slice thickness at 3-mm intervals (p = 0.02). No other significant differences were found. CONCLUSIONS: Fluoroscopy and computed tomography are equally accurate for determining intra-articular screw penetration. Computed tomography scans with thick slices (4 mm at 3-mm intervals) have a low specificity. Their use postoperatively may lead to a false-positive interpretation of the scan and unnecessary exploration of a hip for screw penetration.

Vocal cord paralysis resulting from neck injections in the intravenous drug use population.

Intravenous drug use patients present to the head and neck surgeon when injections are directed "in the pocket," or more appropriately, toward the internal jugular vein in the neck. The more common complications of this practice include the development of cellulitis, abscess, and venous thrombophlebitis and, potentially, pulmonary embolism and pseudoaneurysm of the carotid and subclavian arteries. Vocal cord paralysis as a result of neck injection in the intravenous drug-using population is rarely described, and a review of the literature has yielded only two reports addressing this uncommon phenomenon. During a 7 1/2-year period between October 1981 and June 1989, nine patients presented to Detroit Medical Center with hoarseness, upper-airway obstruction, or both following the injection of heroin or related substances into the neck. Otolaryngologic evaluation demonstrated unilateral or bilateral vocal cord paralysis coincident with recent neck injections. The clinical signs and symptoms, location of the injections, acute management, and subsequent complications are catalogued. Acute management of these patients consisted of airway assurance via tracheotomies when indicated and observation for the development of cellulitis, abscess, or more life-threatening neurovascular complications. Follow-up laryngeal examinations ranged from 4 months to 4 1/2 years and found no demonstrable return of vocal cord function in any of the nine patients.

Lung disorders due to drug abuse.

Drug-related diseases of the lungs have been noted with increasing frequency in urban patients. These entities are also being seen in smaller urban and suburban settings, however. The spectrum of pathology is also changing coincident with the marked increase in crack cocaine use. The incidence of abnormal chest radiographs in cocaine users admitted with pulmonary complaints has ranged from 12% to 55%. Findings have included focal air space disease, atelectasis, pneumothorax, pneumomediastinum, and pulmonary edema. Pulmonary complications related to injections of illicit drugs have included pulmonary infection, pulmonary edema, particulate embolism, and talcosis. The "pocket shot" places the patient at risk for a unique set of complications. Radiologists should be aware of this wide spectrum of pulmonary disease that may be related to this increasingly frequent social problem.

Discharge of patients to long-term care from a large acute hospital over a 12-year period.

BACKGROUND: Several factors may be important in determining the discharge of patients to long-term care from the acute hospital. AIMS: We aimed to look at factors associated with discharge to long-term care from St. James's Hospital, Dublin between 1997 and 2008. METHODS: Data obtained from a long-term care database within the geriatric service were analysed. This service is responsible for assessing and listing all patients for long-term care within the hospital. RESULTS: 3,107 patients were listed and 2,520 discharged to long-term care during the period. Mean age was 81.7±7.3 years and 64.1% were female. The number listed increased since 1997, but there was no change in age or gender. Median time to discharge was 52 days, but varied by year and was longer for public versus private facilities (mean difference=18 days, P=0.006). Mortality of those awaiting long-term care was 17.0%, but varied significantly by year and ranged form 9.3-29.0%. Mortality was higher in males, in those of older age and during the winter months. CONCLUSIONS: Variation in the time to discharge appears to be associated with changes in the provision of publicly funded private nursing home beds.

Ertapenem versus cefepime for initial empirical treatment of pneumonia acquired in skilled-care facilities or in hospitals outside the intensive care unit.

The study presented here compared the efficacy and safety of ertapenem and cefepime as initial treatment for adults with pneumonia acquired in skilled-care facilities or in hospital environments outside the intensive care unit (ICU). Non-ventilated patients developing pneumonia in hospital environments outside the ICU, in nursing homes, or in other skilled-care facilities were enrolled in this double-blind non-inferiority study, stratified by APACHE II score (15) and randomized (1:1) to receive cefepime (2 g every 12 h with optional metronidazole 500 mg every 12 h) or ertapenem (1 g daily). After 3 days of parenteral therapy, participants demonstrating clinical improvement could be switched to oral ciprofloxacin or another appropriate oral agent. Probable pathogens were identified in 162 (53.5%) of the 303 randomized participants. The most common pathogens were Enterobacteriaceae, Streptococcus pneumoniae, and Staphylococcus aureus, isolated from 59 (19.5%), 39 (12.9%), and 35 (11.6%) participants, respectively. At the test-of-cure assessment 7-14 days after completion of all study therapy, pneumonia had resolved or substantially improved in 89 (87.3%) of 102 clinically evaluable ertapenem recipients and 80 (86%) of 93 clinically evaluable cefepime recipients (95% confidence interval for the difference, -9.4 to 11.8%), fulfilling pre-specified criteria for statistical non-inferiority. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. In this study population, ertapenem was as well-tolerated and efficacious as cefepime for the initial treatment of pneumonia acquired in skilled-care facilities or in hospital environments outside the ICU.

Adverse effects of left ventricular hypertrophy in the reduction of endpoints in NIDDM with the angiotensin II antagonist losartan (RENAAL) study.

AIMS/HYPOTHESIS: We explored the impact of baseline left ventricular hypertrophy (LVH) and losartan treatment on renal and cardiovascular (CV) events in 1,513 patients from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial, which studied the effects of losartan on the progression of renal disease and/or death in patients with type 2 diabetes and nephropathy. MATERIALS AND METHODS: LVH was assessed using ECG criteria (Cornell product and/or Sokolow-Lyon voltage). The risk of renal or CV events was determined by a proportional hazards model fit with treatment allocation and presence of LVH. Covariates at baseline included age, sex, systolic BP, mean arterial pressure, pulse, proteinuria, serum creatinine, albumin and haemoglobin. RESULTS: A total of 187 subjects (12%) had LVH at baseline. Treatment with losartan resulted in a significant decrease in the Cornell product (-6.2%) and Sokolow-Lyon voltage (-6.3%). LVH was shown to be significantly associated with the primary endpoint, which was a composite of doubling of serum creatinine (DSCR), endstage renal disease (ESRD) or death (hazard ratio [HR]=1.44, p=0.011), as well as with the composite renal endpoint of DSCR/ESRD (HR=1.42, p=0.031) and CV events (HR=1.68, p=0.001). Losartan treatment of patients with LVH decreased the CV as well as renal risk to a level similar to that of patients without LVH. CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes and nephropathy, LVH is associated with significantly increased risk of CV events and the progression of kidney disease. Importantly, in patients with LVH, losartan reduced the CV as well as the renal risk to a level similar to that seen in subjects without LVH.

Sum of Pain Intensity Differences (SPID) in migraine trials. A comment based on four rizatriptan trials.

Sum of Pain Intensity Difference (SPID) is an outcome measure that summarizes treatment response over a clinically relevant period. SPID is widely reported in clinical trials of analgesics but has been little used in migraine trials. We compared SPID over 2 h with the standard migraine outcome measures of pain-free at 2 h and headache relief at 2 h using data from four published clinical trials of rizatriptan in migraine patients. In assessing treatment response (rizatriptan and sumatriptan versus placebo, rizatriptan versus sumatriptan, within-treatment dose effects), SPID usually yielded similar results to the more easily understood pain-free measure.