Use of colony-stimulating factor primary prophylaxis and incidence of febrile neutropenia from 2010 to 2016: a longitudinal assessment

Background: Guidelines recommend primary prophylactic use of colony-stimulating factor (PP-CSF) when risk of febrile neutropenia (FN) – based on chemotherapy and patient risk factors – is high. Whether and how PP-CSF use may have changed over time (e.g. due to guideline revisions, increasing use of myelosuppressive regimens, controversy regarding inappropriate CSF use), and whether there has been a concomitant change in the incidence of FN, is unknown.

Methods: A retrospective cohort design and data from two US healthcare claims repositories were employed. The study population included patients who had non-metastatic cancer of the breast, colon/rectum, lung or ovaries, or non-Hodgkin’s lymphoma (NHL), and who received myelosuppressive chemotherapy regimens with an intermediate/high risk for FN. For each patient, the first cycle of the first course was characterized in terms of PP-CSF use and FN episodes. Crude incidence proportions for PP-CSF and FN during the first cycle were estimated by calendar quarter (2010–2016); multivariable logistic regression models were used to estimate quarter-specific adjusted mean probabilities of FN by PP-CSF use.

Results: The study population totaled 142,730 patients with breast cancer (61%), colorectal cancer (14%), NHL (11%), ovarian cancer (10%) or lung cancer (5%). PP-CSF use increased from 52% in 1Q2010 to 58% in 4Q2016; pegfilgrastim was the most commonly used agent (>96% across quarters). PP-CSF administration on the same day as chemotherapy ranged from 8 to 11% until 1Q2015, and increased to 64% by 4Q2016. Adjusted incidence proportions for FN in the first chemotherapy cycle ranged from 2.7% (95% CI: 2.3–3.0) to 3.7% (95% CI: 3.1–4.3) among those who did not receive PP-CSF, and was 2.6% (95% CI: 2.5–2.7) across quarters among those who received PP-CSF.

Conclusions: Although the use of PP-CSF is commonplace in current US clinical practice, underutilization in cancer patients receiving chemotherapy regimens with an intermediate/high risk for FN may still be an issue. Use of same-day PP-CSF increased markedly from the end of 2015, although this finding reflects (at least in part) increased uptake of pegfilgrastim delivered via an on-body injector as well as the recent change in clinical practice guidelines. Overall, patients receiving PP-CSF appear to have a lower risk of FN during the first cycle of chemotherapy.     

A comparison of placement methods using a two-in-one dentin pin

Experiments were performed to determine the effect of pin channel preparation with standard and reduction speed handpieces, and pin seating by hand and with motor drive. The greatest retention was achieved by preparation with a standard handpiece at 6000 rpm, and manual pin placement with a hand driver. The most consistent retention values were achieved using the reduction handpiece. All preparation and placement combinations examined produced a clinically acceptable result.     

Characterization of hindlimb motoneuron membrane properties in acute and chronic spinal cats

The purpose of this study was to determine if changes in hindlimb motoneuron membrane electrical properties occur 4–6 months after spinal transection in the adult animal. Eight acute and nine chronic animals were spinalized at T₁₂. Intracellular recordings from motoneurons innervating the triceps surae were performed. Membrane electrical properties, including resting potential, action potential peak amplitude, afterhyperpolarization duration, rheobasic current, input resistance and axonal conduction velocity were measured. There were no statistical differences found between group means or frequency distributions in the membrane properties of motoneurons assessed from acute and chronic spinal animals. Thus, alteration of motoneuron membrane properties does not appear to be a major contributing factor to the hyperexcitable hindlimb reflex activity demonstrated by chronic spinal animals.     

Depressive Symptoms Among HIV Positive Men: Life Stress,Coping, and Social Support1

The significance of life stress, coping, and social support was examined in relation to depressive symptomatology in a sample of 160 asymptomatic and mildly symptomatic HIV-antibody-positive (HIV+) men. The participants (mean age = 32 years) were interviewed about the life stress that they had experienced in the previous 6     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Evaluating New and Traditional Methods for Aminoglycoside Dosing in Patients With Various Degrees of Renal Function

Aminoglycosides are widely used, and clinicians continue to seek newer and better methods for initial dosing of these agents. Recently, three new methods were introduced: Thomson, Reesor Nimmo, and dosing in Tenopathy by easy-to-use multipliers (DREM). In comparing them with older, traditional dosing methods in patients with various degrees of renal function, the pharmacokinetic variables of gentamicin were determined from steady-state peak (C_max) and trough (C_min) serum concentrations using individualized regimens in 88 patients. Dosages were determined in each patient using the method of Hull-Sarubbi, rule of eights, and the three new methods, and the resultant C_max and C_min values were calculated from dosages generated by each method. The daily doses and C_max values derived with the Hull-Sarubbi, Thomson, and Reesor Nimmo methods were not significantly different (p>0.05). The Hull-Sarubbi was the most precise (root mean squared prediction error 1.3) and least biased (mean prediction error −0.05) of the five methods in predicting target gentamicin serum peak concentrations (C_max 6.5 mg/L). The Hull-Sarubbi (69%), Thomson (86%), and Reesor Nimmo (70%) methods yielded therapeutic C_max (5–8 mg/L) in a significantly higher percentage of patients than did the rule of eights (32%) and DREM (35%), (p<0.05). Therefore, if gentamicin serum concentrations are not available, the first three appear to be reasonable methods for initiating gentamicin dosage regimens, but the last two may not be desirable to use in a clinical setting. These conclusions are based on the assumption that patients are adults with stable renal function and relatively stable clinical conditions.     

In vivo induction of Ia expression in murine cornea after intravitreal injection of interferon-gamma

Intravitreal injection of interferon gamma (IFN-gamma) induces increased expression of Class II major histocompatibility complex (Ia) antigen expression on corneal endothelial cells and stromal fibroblasts. In contrast, IFN-gamma has no detectable effect on Ia antigen expression in epithelium. Induction of Ia antigen expression was rapid with increases detectable as early as 6-12 hours after a single injection of 1 x 10(5) units. Expression peaked at 24-48 hours and decreased to background levels by 120 hours. The Ia antigen expression increased in a dose-dependent manner, and IFN-gamma treatment also induced the synthesis of increased amounts of a 65-kilodalton (kD) protein in the cornea. Increased levels of this 65-kd protein are seen as early as 12 hours after treatment and can be induced with as little as 1 x 10(2) units of IFN-gamma. The function of the 65-kd protein is unknown. This model should be useful in studies on in vivo modulation of Ia antigen expression.     

Radiographic manifestations of bronchiolitis obliterans with organizing pneumonia vs usual interstitial pneumonia

The radiographic findings in 24 cases of bronchiolitis obliterans with organizing pneumonia and 16 cases of usual interstitial pneumonia were reviewed and compared. Some cases of bronchiolitis obliterans with organizing pneumonia have been mistaken for usual interstitial pneumonia, although the two diseases have distinct pathologic findings. Clinically, the diseases often have different manifestations. Bronchiolitis obliterans with organizing pneumonia has a better prognosis and often responds well to steroids. This study shows that the radiologic findings of bronchiolitis obliterans include alveolar opacities without lung-volume loss. Patients with usual interstitial pneumonia, however, have bilateral diffuse interstitial opacities with occasional honeycomb changes, and there is loss of lung volume in most patients. These findings suggest that the chest radiograph can aid in distinguishing the two diseases.