Israel Medical Association Journal

Background: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive.

Objectives: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward.

Methods: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function.

Results: A total of 140 patients participated in the study, 54 diabetic patients on chronic metformin treatment, 33 diabetic patients without metformin and 53 patients with no diabetes. Most participants were admitted for conditions that prohibit metformin use, such as heart failure, hypoxia and sepsis. Average lactate level was significantly higher in the diabetes + metformin group compared to the diabetes non-metformin group. Metformin treatment was not associated with higher than normal lactate level (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as the main diagnosis.

Conclusions: Chronic metformin treatment mildly increases lactate level, but does not induce hyperlactatemia or lactic acidosis in acute illness on the first day of admission to an internal medicine ward. These data support the expansion of metformin use.

Background: The number of cancer survivors has been increasing worldwide and is now approximately 32.6 million and growing. Cancer survivors present a challenge to health care providers because of their higher susceptibility to long-term health outcomes related to their primary disease and treatment.

Objective: To report on the number of cancer survivors and incident cancer cases in the period 1960–2009 in Israel, in order to provide data on the scope of the challenge Israel’s health care funds face.

Methods: The Israel National Cancer Registry (INCR) database was used to identify new cancer cases diagnosed during the period 1960–2009. Lifetable analysis was used to assess changes in cumulative survival and population prevalence of cancer survivors throughout the 50 year study period.

Results: Almost 600,000 invasive cancer cases were diagnosed during the period 1960–2009 (overall absolute survival rate 54%). Within this time period, the number of new patients diagnosed with cancer increased fivefold and that of cancer survivors ninefold. The absolute survival of cancer patients and the prevalence of cancer survivors in the general population significantly increased with time from 34% and 0.5%, respectively (1960–1969), to 62% and 1.9%, respectively (2000–2009). Cumulative absolute survival for 5, 10 and 15 years following diagnosis increased with time as well.

Conclusions: The INCR database is useful to assess progress in the war against cancer. The growing numbers of cancer survivors in Israel present a challenge to the national health and social services system.

Background: The prevalence and etiology of nephrolithiasis vary, depending on geography, gender and ethnicity. 

Objectives: To analyze the demographic data of return nephrolithiasis patients in a tertiary care center.

Methods: We retrospectively reviewed our prospective registry database of return patients seen at our outpatient clinic for nephrolithiasis. Data included gender, age at first visit, age at first stone event, body mass index (BMI), self-reported hypertension, diabetes mellitus (DM), and hyperlipidemia. All patients were seen at least twice and had undergone a metabolic workup. 

Results: A total of 260 return patients were seen during the period 2010–2015. The male:female ratio was 3.1:1. Mean age at the first stone event was 44.1 years. Median time elapsed since the first stone event to medical evaluation was 5 years (interquartile range 1–12 years). Hypertension was reported by 33.1% of the patients, DM by 23.5% and hyperlipidemia by 30.4%. All three diseases were reported by 11.5% of patients. The metabolic abnormalities detected were hypocitraturia (60%), low urine volume (LUV) (60%), hypercalciuria (40.8%), hyperoxaluria (24.2%), hyperuricosuria (16.5%) and hyperuricemia (13.5%). Stone compositions from most to least frequent were calcium-oxalate (81%), calcium-phosphate (11.9%) and uric acid (7.1%). We also found that 24.6% were obese (BMI ≥ 30 kg/m2) and showed higher rates of hypertension, DM, hyperlipidemia, hyperuricemia and hyperuricosuria compared with non-obese patients. Significantly higher rates of obesity and LUV were detected in females compared with males. Patients over age 45 had lower rates of hyperuricemia compared with patients ≥ 45 years old (P = 0.038).

Conclusions: Factors related to nephrolithiasis can potentially differ among populations and countries. Our findings emphasize the significance of individualized national health programs to address local issues.

 

Background: Legg-Calvé-Perthes disease (LCPD) is an idiopathic hip osteonecrosis prevalent in children < age 15 years. The etiology remains incompletely understood, partly because of multiple potential environmental risk factors and partly because of lack of genetic markers. It has been hypothesized that hyperactivity may induce mechanical stress and/or vascular damage at a fragile joint. 

Objectives: To assess children with LCPD for markers of attention deficit hyperactivity disorder (ADHD) relative to their unaffected comparably aged siblings to exclude the contribution of hyperactive behavior versus environmental and/or genetic factors in LCPD. 

Methods: All children followed in the Pediatric Orthopedic Clinic, and their comparably aged siblings, were recruited. ADHD was assessed using the TOVA computerized test and DSM-IV criteria. Quality of life and sleep disorders as ancillary tests were assessed using the Child Health Questionnaire (Parent Form 50), Pediatric Outcomes Data Collection Instrument, and Pediatric Daytime Sleepiness Scale.

Results: Sixteen children with LCPD (age 9.1 ± 3.3, 75% males) were compared with their closest-aged siblings (age 9.3 ± 2.6, 30% males). Mean TOVA scores of children with LCPD (-3.79 ± 2.6) and of their non-LCPD siblings (-3.6 ± 4.04) were lower relative to the general population (0 ± 1.8, P < 0.0001). Both group means were in the ADHD range (≤ -1.8) implying that 73% of this LCPD cohort and 53% of their non-LCPD siblings performed in the ADHD range, relative to 3.6% incidence expected in the general population (P < 0.0001). Other test results were similar in both groups. 

Conclusions: Our findings in a small cohort of children with LCPD and their comparably aged siblings do not support an association between LCPD and ADHD. ADHD markers were equally high in the LCPD children and siblings. 

 

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, impulsivity and hyperactivity. Recently, increases in ADHD prevalence and methylphenidate use have been reported. There is evidence that children and adolescents use ADHD medication only during the school year. 

Objectives: To investigate trends in methylphenidate dispensing over a period of 3 years (2010–2012) at the monthly level and to investigate whether there is any monthly variation, especially during the summer season.

Methods: The database of Clalit Health Services (the largest of the four health funds in Israel) was used to identify (i) patients aged 6–17 years with a diagnosis of ADHD, and (ii) methylpenidate dispensation during the period 2010–2012. 

Results: Among children aged 6–17 years diagnosed with ADHD, 43% were treated with methylphenidate. For the period 2010 to 2012 there was an annual drop in methylphenidate dispensing, beginning in June and continuing through the 2 months of summer vacation, with a 2.5-fold reduction from July as compared to May. This decline was consistently followed by a rise in medications dispensed starting August. A similar small drop was observed during the Passover school vacation. The summer drop decreased over the years.

Conclusions: Our findings showed a decrease in the number of methylphenidate prescriptions dispensed during the summer months and Passover as compared to the rest of the year. However, this phenomenon appears to be decreasing. Given that ADHD is a chronic disease state that can effectively be managed with pharmacotherapy, discontinuation of treatment may be harmful for patients and should be considered only on a patient-by-patient basis.

 

Background: Proteinuria and albuminuria are markers of kidney injury and function, serving as a screening test as well as a means of assessing the degree of kidney injury and risk for cardiovascular disease and death in both the diabetic and the non-diabetic general population.

Objectives: To evaluate the association between proteinuria below 300 mg/24 hours and albuminuria, as well as a possible association with kidney function in patients with diabetes mellitus (DM).

Methods: The medical files of patients with type 1 and type 2 DM with proteinuria below 300 mg/24 hours at three different visits to the Diabetic Nephropathy Clinic were screened. This involved 245 patient files and 723 visits. The data collected included demographics; protein, albumin and creatinine levels in urine collections; blood biochemistry; and clinical and treatment data. 

Results: The association between proteinuria and albuminuria is non-linear. However, proteinuria in the range of 162–300 mg/24 hours was found to be linearly and significantly correlated to albuminuria (P < 0.001, r = 0.58). Proteinuria cutoff, based on albuminuria cutoff of 30 mg/24 hours, was found to be 160.5 mg/24 hr. Body mass index (BMI) was the sole independent predictor of proteinuria above 160.5 mg/24 hr. Changes in albuminuria, but not proteinuria, were associated with changes in creatinine clearance. 

Conclusions: A new cutoff value of 160.5 mg/hr was set empirically, for the first time, for abnormal proteinuria in diabetic patients. It appears that proteinuria below 300 mg/24 hr is not sufficient as a sole prognostic factor for kidney failure. 

 

Background: Recently we observed patients with chronic liver disease (CLD) or chronic reflux symptoms (CRS) who developed gastric polyps (GPs) while undergoing surveillance gastroscopies for the detection of either esophageal varices or Barrett's esophagus, respectively.

Objectives: To identify risk factors for GP growth and estimate the gastric polyp growth rate (GPGR).

Methods: GPGR was defined as the number of days since the first gastroscopy (without polyps) in the surveillance program, until the gastroscopy when a GP was discovered.

Results: Gastric polyp growth rates in CLD and CRS patients were similar. However, hyperplastic gastric polyps (HGPs) were detected more often (87.5% vs. 60.5%, P = 0.051) and at a higher number (2.57 ± 1.33 vs. 1.65 ± 0.93, P = 0.021) in the CLD patients. Subgroup analysis revealed the following findings only in CLD patients with HGPs: (i) a positive correlation between the GPGR and the patient's age; the older the patient, the longer the GPGR (r = 0.7, P = 0.004). (ii) A negative correlation between the patient's age and the Ki-67 proliferation index value; the older the patient, the lower the Ki-67 value (r = -0.64, P = 0.02). No correlation was detected between Ki-67 values of HGPs in CLD patients and the presence of portal hypertension, infection with Helicobacter pylori, or proton pump inhibitor use.

Conclusions: In comparison with CRS patients, CLD patients developed HGPs more often and at a greater number. Young CLD patients may have a tendency to develop HGPs at a faster rate than elderly CLD patients.

Background: Admission glucose levels correlate with clinical outcome in patients with type 2 diabetes mellitus (T2DM) hospitalized in general medicine wards. 

Objective: To investigate whether in-hospital hyperglycemia alone and after adjustment for age, gender and lipidemia correlates with in- and out-of-hospital mortality.

Methods: Capillary glucose, serum lipids and diagnoses at discharge among patients with T2DM hospitalized in the general medical wards of our hospital were documented. Correlation with in- and out-of-hospital mortality was determined through uni- and multivariate analyses. 

Results: Of the 4607 patients included in the study 22% died while hospitalized. From a median of five capillary glucose tests obtained per patient, average capillary glucose level was significantly lower in those who survived than in those who died (174 ± 64 vs. 180 ± 65 mg/dl, P = 0.005). Overall, blood cholesterol was higher in those who survived than in those who died (P < 0.001). Multivariate analysis, however, including age, gender, lipidemia and glycemia, showed that only age and male gender correlated with mortality.

Conclusions: Hyperglycemia was associated with increased in- and out-of-hospital mortality on univariate analysis. However, it was not an independent risk factor when corrected for age, gender and hyperlipidemia.