Why training is the key to successful guideline implementation

The market for pharmacoeconomic analysis is rapidly expanding. Demand for experienced investigators seems to have outpaced the capacity of both the academic community and industry to train qualified practitioners. The result is that many professionals charged with producing and using cost-effectiveness and other drug-related economic evaluation studies may lack the basic skills required to carry out their duties. This, in turn, raises concerns regarding the credibility and integrity of the field as a whole. In our opinion, the adoption of self-imposed practice guidelines is a necessary first step in confronting these issues. However, the power of guidelines to promote responsible practice will be limited by the technical preparation of the analysts charged with adhering to them. A long term solution requires a collaborative commitment, on the part of both the academic community and the private sector, to targeted graduate training in pharmacoeconomic methods, and to the provision of ample opportunities for continuing professional education.     

Is there really a decrease in sperm parameters among healthy young men? A survey of sperm donations during 15 years

Purpose: Our purpose was to measure changes in semen quality and quantity in young healthy sperm donors in Jerusalem over time. Methods: A retrospective analysis of semen parameters over 15 years using linear regression analysis, in a single sperm bank in a tertiary university center. Study population consisted of 188 young, healthy medical students, aged 20 to 30 years, who donated sperm samples for Artificial insemination between 1980 and 1995. Results: There were no statistically significant changes in semen concentration and motility during the study period. The mean semen volume increased by 0.1 ml (5.1%) per year (P < 0.0001), with a concomitant mean rise of 5.8 × 10⁶ (7.7%) per year in total motile sperm count. The percentage normal morphology decreased by a mean of 1.04% per year during the entire period (P < 0.0001). Conclusions: During the past 15 years, there has been an increase in total motile sperm count, secondary to an increase in semen volume, and a decline in normal morphology that are independent of the age and the duration of abstinence in fertile men.     

Correction to: Predicting Risk for Early Breastfeeding Cessation in Israel

Maternal and Child Health Journal -     

Management of severe hypokalemia in hospitalized patients: a study of quality of care based on computerized databases

BACKGROUND: While administrative databases are used to assess general indicators of quality of care, a detailed audit of the process of clinical care usually requires review of hospital medical records. OBJECTIVE: To evaluate the feasibility of assessing the management of severe hypokalemia using computerized administrative and laboratory databases. METHODS: The study included all patients hospitalized in 1997 who experienced serum potassium levels of less than 3.0 mmol/L at Hadassah University Hospital, Jerusalem, Israel, a tertiary care center. Using the computerized databases, we measured the following: (1) whether a subsequent serum potassium test was performed, (2) time to the subsequent test and to normalization of the serum potassium level, (3) achievement of normokalemia, and (4) in-hospital mortality. In a random subsample of 100 patients, these measures were compared with the blinded assessment of the quality of medical management of hypokalemia, as determined from medical records, using predetermined criteria for adequate management. RESULTS: The computerized databases revealed that severe hypokalemia occurred in 866 patients (2.6% of the yearly hospitalizations): 55 patients (6.4%) had no subsequent serum potassium levels measured, and 260 (30.0%) were discharged from the hospital with a subnormal potassium level. The mean time to a subsequent test was 20 hours, and to normokalemia, 50 hours; both intervals varied by department. In-hospital mortality was 20.4%, or 10-fold that of the entire hospitalized population. A review of hospital medical records revealed inadequate clinical management of hypokalemia in 24%, which was associated with nonperformance of a subsequent test (likelihood ratio, 8.4), failure to normalize the serum potassium level (likelihood ratio, 4.2), discharge from the hospital with a subnormal potassium level (likelihood ratio, 2.1), and in-hospital death (likelihood ratio, 2.5), all of which could be determined by the computerized databases. CONCLUSIONS: The computerized laboratory database is useful in ascertaining the prevalence of severe hypokalemia and in assessing shortcomings in its management. Databases can be used to derive valid and efficient measures of the quality of the clinical management of electrolyte disorders.     

Prioritizing HIV comparative effectiveness trials based on value of information: generic versus brand-name ART in the US

Value of Information (VOI) analysis examines whether to acquire information before making a decision. We introduced VOI to the HIV audience, using the example of generic antiretroviral therapy (ART) in the US.

Methods and Findings:We used a mathematical model and probabilistic sensitivity analysis (PSA) to generate probability distributions of survival (in quality-adjusted life years, QALYs) and cost for three potential first-line ART regimens: three-pill generic, two-pill generic, and single-pill branded. These served as input for a comparison of two hypothetical two-arm trials: three-pill generic versus single-pill branded; and two-pill generic versus single-pill branded. We modeled pre-trial uncertainty by defining probability distributions around key inputs, including 24-week HIV-RNA suppression and subsequent ART failure. We assumed that, without a trial, patients received the single-pill branded strategy. Post-trial, we assumed that patients received the most cost-effective strategy. For both trials, we quantified the probability of changing to a generic-based regimen upon trial completion and the expected VOI in terms of improved health outcomes and costs. Assuming a willingness to pay (WTP) threshold of $100?000/QALY, the three-pill trial led to more treatment changes (84%) than the two-pill trial (78%). Estimated VOI was $48?000 (three-pill trial) and $35?700 (two-pill trial) per future patient initiating ART.

Conclusions:A three-pill trial of generic ART is more likely to lead to post-trial treatment changes and to provide more value than a two-pill trial if policy decisions are based on cost-effectiveness. Value of Information analysis can identify trials likely to confer the greatest impact and value for HIV care.     

Supernumerary intrathoracic rib,a rare congenital anomaly: Case report and review of the literature

A 17‐year‐old female who presented with cough, chest pain, dyspnea, and hemoptysis was found to have an intrathoracic rib. Patients who are diagnosed with intrathoracic ribs are most often asymptomatic and should undergo limited diagnostic workup. Intrathoracic ribs are rare congenital anomalies incidentally identified after chest radiography performed for another indication, as is the case with this patient. In this case, further evaluation was necessary due to persistent symptoms. Here, we used contrast‐enhanced ultrasound after chest radiography and computed tomography to further evaluate the fatty intrathoracic mass and exclude vascular features suggestive of a tumor.     

Hodgkin lymphoma patients in first remission: routine positron emission tomography/computerized tomography imaging is not superior to clinical follow‐up for patients with no residual mass

There is no consensus regarding optimal follow‐up mode for Hodgkin lymphoma (HL) patients that achieve complete remission following chemotherapy or combined chemo‐ and radiation therapy. Several studies demonstrated high sensitivity of positron emission tomography/computerized tomography (PET/CT) in detecting disease progression; however, these techniques are currently not recommended for routine follow‐up. This retrospective study conducted in two Israeli (N = 291) and one New Zealand academic centres (N = 77), compared a group of HL patients, followed‐up with routine imaging every 6 months during the first 2 years after achieving remission, once in the third year, with additional dedicated studies performed due to symptoms or physical findings (Group I) to a group of patients without residual masses who underwent clinically‐based surveillance with dedicated imaging upon relapse suspicion (Group II). Five‐year overall survival (OS) was 94% and median time to relapse was 8·6 months for both modes. Relapse rates in Groups I and II were 13% and 9%, respectively. During the first 3 years of follow‐up, 47·5 and 4·7 studies were performed per detected relapse in Groups I and II, respectively. The current study demonstrated no benefit in either progression‐free survival (PFS) or OS in HL patients followed by routine imaging versus clinical follow‐up. The cost was 10 times higher for routine imaging.     

Specific expiratory muscle training in COPD

BACKGROUND: There are several reports showing that expiratory muscle strength and endurance can be impaired in patients with COPD. This muscle weakness may have clinically relevant implications. Expiratory muscle training tended to improve cough and to reduce the sensation of respiratory effort during exercise in patients other than those with COPD. METHODS: Twenty-six patients with COPD (FEV(1) 38% predicted) were recruited for the study. The patients were randomized into two groups: group 1, 13 patients were assigned to receive specific expiratory muscle training (SEMT) daily, six times a week, each session consisting of 1/2 h of training, for 3 months; and group 2, 13 patients were assigned to be a control group and received training with very low load. Spirometry, respiratory muscle strength and endurance, 6-min walk test, Mahler baseline dyspnea index (before), and the transitional dyspnea index (after) were measured before and after training. RESULTS: The training-induced changes were significantly greater in the SEMT group than in the control group for the following variables: expiratory muscle strength (from 86 +/- 4.1 to 104 +/- 4.9 cm H(2)O, p < 0.005; mean difference from the control group, 24%; 95% confidence interval, 18 to 32%), expiratory muscle endurance (from 57 +/- 2.9% to 76 +/- 4.0%, p < 0.001; mean difference from the control group, 29%; 95% confidence interval, 21 to 39%), and in the distance walked in 6 min (from 262 +/- 38 to 312 +/- 47 m, p < 0.05; mean difference from the control group, 14%; 95% confidence interval, 9 to 20%). There was also a small but not significant increase (from 5.1 +/- 0.9 to 5.6 +/- 0.7, p = 0.14) in the dyspnea index. CONCLUSIONS: The expiratory muscles can be specifically trained with improvement of both strength and endurance in patients with COPD. This improvement is associated with increase in exercise performance and no significant change in the sensation of dyspnea in daily activities.     

Ethnic ancestry and increased paternal age are risk factors for breast cancer before the age of 40 years.

To study the risk factors associated with breast cancer in women younger than 40 years, a cohort study (The Jerusalem Perinatal Study) of 42 822 female offspring born in hospitals in West Jerusalem during 1964-1976 was carried out. Hazard ratios of potential parental and perinatal risk factors for early breast cancer were measured. The overall incidence of breast cancer was 5.2/100 000 person-years. The highest incidence was found among Jewish women of West Asian ancestry (8.6/100 000 person-years), specifically those whose maternal grandfathers were born in Iraq, Iran or Afghanistan (9.5/100 000 person-years). Using Cox models we found independent risk factors for early breast cancer to be paternal age (relative risk/year=1.06, 95% confidence interval=1.02-1.10, P=0.005), and ancestry from Iraq/Iran/Afghanistan (relative risk=3.1, 95% confidence interval=1.50-6.52, P=0.002). The study confirms a previously observed effect of advanced paternal age on the occurrence of early breast cancer and identifies a novel population group at increased risk for the disease. The excess risk of early breast cancer associated with ancestry from Iraq, Iran and Afghanistan suggests involvement of genetic determinants, environmental exposures and/or lifestyle factors and mandates further investigation.