Weaning practices in phenylketonuria vary between health professionals in Europe.

BACKGROUND: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. METHODS: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. RESULTS: Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and < 17 weeks in 3% (n = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. CONCLUSIONS: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Early feeding practices in infants with phenylketonuria across Europe.

BACKGROUND: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. METHODS: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. RESULTS: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and < 17 weeks in 3%. DISCUSSION: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.

Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach.

BACKGROUND: There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. RESULTS: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). CONCLUSIONS: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.

Clinical outcome 1 year after transurethral vaporization and resection of the prostate.

OBJECTIVES: To evaluate the 1-year safety and effectiveness of transurethral vaporization of the prostate (TUVP) compared with transurethral resection of the prostate (TURP) in alleviating outflow obstruction. METHODS: Two experienced surgeons performed 26 TUVPs and 28 TURPs. The intraoperative blood loss was measured by photometry and fluid absorption by the ethanol method. The treatments were evaluated by means of the International Prostate Symptom Score (IPSS), quality-of-life score, transrectal ultrasound, prostate-specific antigen level, urinary flow rate, and postvoid residual urine volume. RESULTS: After TUVP, the median IPSS decreased from 22 to 4.5 and the quality-of-life score from 4.5 to 1.5. The corresponding data for TURP were from 25 to 5.5 and from 4.0 to 1.0. The median urinary flow rate increased from 4 to 10 mL/s after TUVP and from 2 to 11 mL/s after TURP. The postvoid residual urine volume decreased to 35% (TUVP) and 15% (TURP) of the preoperative volume. The blood loss was larger during TURP (P <0.04), but complications during follow-up were more frequent after TUVP (P <0.02). Patients with fluid absorption during surgery had a lower quality-of-life score at follow-up (P <0.02) and tended to have a smaller reduction in prostate size (to 79%) than those without absorption (to 67% of baseline). CONCLUSIONS: TUVP and TURP were both effective in alleviating outflow obstruction, but the outcome appeared to be slightly better for TURP.

Operative course of transurethral resection of the prostate and progression of prostate cancer.

Surgery has the potential to disseminate cancer cells, and we therefore hypothesized that extensive transurethral resections of the prostate (TURP) would be followed by a worse prognosis than minor ones. For this purpose, the association between the extent of surgery, disease progression, and mortality was studied in 138 patients with prostatic cancer who had undergone TURP. The results show that a large bleed (> or = 275 ml) indicated a slightly increased relative risk of general progression of the cancer (relative risk (RR) = 1.9, 95% confidence interval (CI) = 0.9-4.1) and death (RR = 1.5, CI = 0.6-3.3). Other parameters of extensive surgery, such as the operating time and fluid absorption, were not associated with increased risk. Patients with a medical disease, however, such as hypertension and congestive heart failure, had a significantly higher relative risk of general progression (RR = 2.7, CI = 1.2-6.1) and death from prostatic cancer (RR = 4.6, CI = 2.0-10.7) in addition to an increased relative risk of death from other causes (RR = 3.7, CI = 1.3-10.5). We conclude that concurrent medical disease, but not an extensive TURP, worsened the prognosis of patients with prostatic cancer who underwent TURP.

Free and total prostate-specific antigen serum concentrations do not help to detect prostate cancer in patients with urinary outlet obstruction.

OBJECTIVES: To determine whether different molecular forms of prostate-specific antigen (PSA) obtained before transurethral resection of the prostate (TURP) indicate the presence of prostate cancer. PATIENTS AND METHODS: The free, total and free-to-total PSA levels were measured in 261 patients scheduled for TURP, 20 of whom had known prostate cancer. The tissue histology was compared with the PSA levels and the patients were followed for 5 years. RESULTS: Prostate cancer was detected in 23 of the patients (9%) who were thought to have benign disease. Normal ranges for the distribution of the PSA levels were established based on the patients with a benign histology, but these ranges did not detect most of the unknown cancers. The sensitivity of the total PSA test in detecting cancer was 38% and the specificity 90%. The discrimination was no better when considering the free fraction or the free-to-total PSA level. However, none of the 14 patients whose cancer was missed showed general progression of the disease during the 5-year follow-up and only one died from prostate cancer. In contrast, eight of the 20 patients with a known prostatic malignancy showed general progression, and six died from the disease. CONCLUSION: PSA testing of patients with outlet obstruction often failed to detect prostate cancer, but the prognosis was moderately good in those patients in whom it was missed.

Complications during transurethral vaporization of the prostate.

OBJECTIVES: To review adverse events during transurethral vaporization of the prostate (TVP) and to compare them with those occurring during transurethral resection of the prostate (TURP). METHODS: One experienced surgeon performed 26 consecutive TVPs and 100 TURPs. We monitored blood loss by photometry, fluid absorption by the ethanol method, and hemodynamic stability with a blood pressure manometer. RESULTS: Total blood loss and the rate of blood loss were significantly lower during TVP. Fluid absorption occurred during most TVPs, but it was mostly small volumes. No sudden drop in arterial pressure was recorded during TVP, but this did occur in 11% of the TURPs. Complications that would normally require medical attention (blood loss greater than 800 mL, fluid absorption greater than 500 mL, or hemodynamic instability) were more infrequent during TVP than during TURP (P = 0.012). CONCLUSIONS: Transurethral vaporization of the prostate was associated with fewer intraoperative complications than was TURP.

Femoral vein blood flow during transurethral resection of the prostate.

OBJECTIVE: To determine whether bladder distension affects venous haemodynamics during transurethral resection of the prostate (TURP) such that irrigating fluid is more easily absorbed. PATIENTS AND METHODS: The right common femoral vein was examined using an ultrasound Doppler blood-flow scanner in 10 patients (mean age 73 years, range 63-80) undergoing TURP. Measurements of blood flow were performed before, during and after the bladder was filled with irrigating solution. Fluid absorption was measured by the ethanol method. RESULTS: Measurements before, half-way through and immediately after the resection all showed that the luminal diameter and the cross-sectional area of the femoral vein increased significantly when the bladder was filled with irrigating fluid. Furthermore, a decrease in the normal variation of blood flow with breathing often occurred when the bladder was filled, indicating that proximal venous obstruction was the cause of the increase in vessel diameter. However, there was no apparent association between these changes and the absorption of irrigating fluid. CONCLUSIONS: Filling the bladder with irrigating fluid with the patient in the lithotomy position during TURP was followed by signs of iliac venous obstruction but this did not correlate with the absorption of irrigating fluid.

Large-sized bladders reduce intravesical pressure and fluid absorption during TURP using the suprapubic trocar.

We studied whether the height of the irrigating fluid bags above the operating table and the capacity of the bladder influence intravesical pressure and fluid absorption during transurethral resection of the prostate (TURP) when evacuation is performed with Reuter's trocar. For this purpose, the intravesical pressure was recorded continuously, and the fluid absorption was measured by the ethanol method during 30 TURP procedures. The bags were placed between 60 and 95 cm above the operating table, and the bladder capacity was measured before surgery started. The results show that the bladder capacity, but not the bag height, correlated with the intravesical pressure and the fluid absorption. Large-sized bladders were associated with lower pressures and smaller absorption. Rapid absorption (>30 ml/min) occurred at a maximum pressure of 2-3 kPa and a mean pressure of between 1 and 2 kPa. In conclusion, the size of the bladder is important to the intravesical pressure and to the fluid absorption during TURP when using the suprapubic trocar.

Operative factors and the long-term incidence of acute myocardial infarction after transurethral resection of the prostate.

We studied the association between the operative course of transurethral resection of the prostate (TURP) and the morbidity of acute myocardial infarction (AMI) in a cohort comprising 846 patients who underwent this operation between 1983 and 1992. Up to the end of 1993, a total of 69 patients had developed AMI, of which 10 patients had a reinfarction. The relative risk associated with absorption of 500 ml or more of the irrigating medium during surgery was 1.6 [95% confidence interval (CI) = 0.9-3.0] for a first-time AMI after TURP, 6.1 (95% CI = 1.8-20.7) for a reinfarction, and 2.2 (95% CI = 1.3-3.9) for a first-time or a reinfarction combined. A blood loss of 275 ml or more was associated with a decreased relative risk (RR = 0.4; 95% CI = 0.2-0.8) of a first-time AMI after TURP. Patients who lost less than 275 ml of blood and absorbed 500 ml or more of irrigating fluid during surgery had 4.4 times the risk of having an acute myocardial infarction (RR = 4.4; 95% CI = 1.7-11.8). These results appear to indicate that the operative course of TURP is important to the development of AMI over an extended period of time.

Fluid absorption during transurethral bladder surgery.

We report 2 patients who absorbed large amounts of irrigating fluid during transurethral resection of bladder tumours (TURB). Ethanol indication facilitated diagnosis of this complication and showed that absorption had occurred by the extravascular route. Symptoms occurred in one case but they resolved when hypertonic saline and furosemide were given.

Effects of bladder capacity and height of fluid bag on intravesical pressure during transurethral resection of the prostate.

We studied the intravesical pressure profile and the fluid absorption in 30 men undergoing transurethral resection of the prostate with the irrigating fluid bags placed 55-60, 70-75, 80-85 or 90-100 cm above the operating table. The maximum intravesical pressure, but not the mean pressure or the period of time during which there was excessive pressure (> 2 kPa), increased when the fluid bags were placed higher. The urologist consistently reached about half the possible maximum pressure as indicated by the bag height at the end of each intermittent filling of the bladder. A large bladder capacity promoted lower maximum and mean pressures and shortened the period of excessive intravesical pressure. However, neither bag height nor bladder capacity correlated with the absorption of irrigating fluid.

Continuous versus intermittent flow irrigation in transurethral resection of the prostate.

OBJECTIVE: We compared fluid absorption, blood loss, and immediate postoperative complications in transurethral resection of the prostate (TURP) performed with the continuous flow and the intermittent flow irrigation techniques. We also studied pressure conditions under which fluid absorption occurs when continuous flow irrigation is used. METHODS: One experienced urologic surgeon performed TURP in 40 patients using suprapubic drainage of the bladder and in 40 other patients using the intermittent-filling technique. Fluid absorption was measured by the ethanol method every ten minutes. The intravesical pressure was recorded continuously in 23 of the patients with suprapubic drainage. RESULTS: Fluid absorption was more common when suprapubic drainage was used (P < 0.004). There were no differences in operating time, blood loss, postoperative complications, or in the period of hospitalization. Low-degree absorption occurred during minor elevations of the intravesical pressure, and massive fluid absorption was associated with pressures between 1.0 and 2.5 kPa (10 and 25 cm H2O). CONCLUSIONS: Continuous flow irrigation promoted fluid absorption, which occurred at lower pressures than commonly believed. With respect to other parameters, we found no superiority of one irrigating technique over the other.

Absorption of irrigating fluid and height of fluid bag during transurethral resection of the prostate.

The purpose of this study was to examine the relationship between the static pressure and the absorption of irrigating fluid during transurethral resection of the prostate. We measured the absorption by the ethanol method in 550 operations during which the fluid bags were placed randomly at distances of 60-65, 70-75, 80-85 or 90-100 cm above the operating table. There was no difference in the volume of irrigant absorbed at different bag heights or any association between fluid height and absorption when different ranges of fluid absorption were analyzed. This suggests that irrigant absorption cannot be prevented by placing the fluid bags at a certain height within the range of 60 to 100 cm above the operating table.

Patterns of irrigating fluid absorption during transurethral resection of the prostate as indicated by ethanol.

The absorption of irrigating fluid was measured by the ethanol method every 10 minutes during the course of 700 transurethral prostatic resections. The total blood loss was also measured using a photometer method. We found that ethanol determination is a convenient method of monitoring irrigating fluid absorption in daily practice. Absorption in excess of 150 ml. was detected in 46% of the operations. The volume of irrigant absorbed increased with the weight of the removed prostatic tissue, operating time and blood loss. The uptake of fluid usually started midway through the operation. Once absorption had started, there was an 87% probability that it would continue through the next 10 minutes with the exception of the last 10 minutes of surgery, when there was a 67% probability. A sudden decrease in arterial pressure coincided with the onset of fluid absorption 3.7 times more often than expected by chance. The absorption was no different in the 114 patients with a cancerous histology, compared to those with benign prostatic hyperplasia.

Blood loss during transurethral resection of the prostate as measured by the HemoCue photometer.

Blood loss was measured with the portable HemoCue photometer and the absorption of irrigating fluid was assessed by the ethanol method during 700 transurethral resections of the prostate. The blood loss ranged between 10 and 3,825 ml (median 300 ml). The weight of the resected prostatic tissue and the operating time were independent predictors of the amount of blood lost. General anaesthesia (n = 82) and malignant histology (n = 114) were associated with a smaller blood loss. In the patients who were given regional anaesthesia (n = 618), an mean systolic blood pressure of 100 mmHg or less resulted in a smaller bleed. Large-scale irrigating fluid absorption was typically associated with a blood loss of medium size and ranged between 500 and 1,000 ml. The incidence of such absorption was negligible in the patients in whom the blood loss per gram of resectate was less than 10 ml/g. Blood loss was also measured every 10 min during the course of another 110 operations, from which 20 patients with operating times in excess of 60 min were selected. Our analysis showed that no excessive blood loss occurred after 60 min of surgery.

Effects of 1.5% glycine solution with and without 1% ethanol on the fluid balance in elderly men.

Ten male patients scheduled for transurethral prostatic resection (aged 57-79) were given irrigating fluid by intravenous infusion at 50 ml.min-1 over 20 min. Each patient was subjected to two infusions: 1.5% glycine in water on one occasion, and the same solution but with 1% ethanol added on the other. Urine and blood samples were collected at regular intervals for up to 2 h after infusion, and the changes in the distribution of water and electrolytes between fluid compartments were calculated. Transient prickling skin sensations were frequently reported effects of the infusions. Two patients experienced visual disturbances. There were no changes in the blood ammonia and plasma vasopressin levels. During the infusions, the estimated blood volume and the total plasma sodium and potassium content increased. The solutions produced osmotic diuresis with increased urinary excretion of water and electrolytes. After ending the fluid administration, blood volume was rapidly restored. Over the following 120 min the irrigant water was redistributed intracellularly or removed by urinary excretion. The addition of ethanol did not alter the overall effects of glycine solution on the fluid balance.

Acute arterial occlusion.

During the years 1969--1976, 66 patients were subjected to surgery for acute arterial occlusion. Arterial occlusion was due to emboli in 67% of the patients, and to acute thrombosis in 33%. There was no difference in the mean age for the two groups. More than 50% of the occlusions, embolic as well as thrombotic, were located in the femoral artery. In the embolic group limb salvage rate was 93% and patient survival rate 82%. The corresponding figures for the thrombotic group were both 73%. There was no direct correlation between the number of amputations and the time interval from occlusion to operation in either of the two groups. In the embolic group, adequate backflow was reestablished in 82%, while the corresponding figure in the thrombotic group was only 45%.