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Abstract Environmental cleaning is essential to patient and health worker safety, yet it is a substantially neglected area in terms of knowledge, practice, and capacity-building, especially in resource-limited settings. Public health advocacy, research and investment are urgently needed to develop and implement cost-effective interventions to improve environmental cleanliness and, thus, overall healthcare quality and safety. We outline here the CLEAN Group Consensus exercise yielding twelve urgent research questions, grouped into four thematic areas: standards, system strengthening, behaviour change, and innovation.

Objective: To compare growth of very low birth weight (VLBW) infants given standard total parenteral nutrition (TPN), providing 25kcal/g amino acids, and high calcium TPN, providing 30kcal/g amino acids. Energy to protein ratio affects protein catabolism. Regimens providing less than 30kcal/g amino acids increase protein catabolism, leaving insufficient for growth. Study Design: All VLBW infants given high calcium TPN during the first 44 months of its use were compared with all those given standard TPN over the previous 24 months. Growth was assessed from mineral retention on TPN and anthropometric measurements until discharge from paediatric follow up. Ignoring stools, mineral retention equaled TPN intake minus urine excretion measured from daily urine samples: Mineral excretion mmol/kg/day = Urine mineral/ urine creatinine x creatinine production Creatinine production μmol/kg/day = -2.07 + 2.34 x gestational age in weeks. Results: 16 infants fed standard TPN retained less than 1 mmol/kg/day of calcium and phosphate and developed high alkaline phosphatase. TPN increased their protein catabolism. Their neonatal growth in weight and head circumference was retarded affecting their childhood growth. 23 infants fed high calcium TPN retained minerals at optimal rates and maintained normal alkaline phosphatase. TPN did not increase their protein catabolism, unless they received dexamethasone, which improved their breathing, allowing more TPN that prevented nitrogen retention from falling. Their neonatal growth was normal and did not affect their childhood growth. 6 (26%) infants, all below 29 weeks, needed insulin to control hyperglycaemia while on TPN, with normal glucose control in more mature babies. Conclusion: High calcium TPN with 30kcal/g amino acids produces normal growth. Standard TPN with 25kcal/g amino acids increases protein catabolism compromising growth.

To establish how controversies in understanding acid base balance arose, the literature on acid base balance was reviewed from 1909, when Henderson described how the neutral reaction of blood is determined by carbonic and organic acids being in equilibrium with an excess of mineral bases over mineral acids. From 1914 to 1930, Van Slyke and others established our acid base principles. They recognised that carbonic acid converts into bicarbonate all non-volatile mineral bases not bound by mineral acids and determined therefore that bicarbonate represents the alkaline reserve of the body and should be a physiological constant. They showed that standard bicarbonate is a good measure of acidosis caused by increased production or decreased elimination of organic acids. However, they recognised that bicarbonate improved low plasma bicarbonate but not high urine acid excretion in diabetic ketoacidosis, and that increasing pCO2 caused chloride to shift into cells raising plasma titratable alkali. Both indicate that minerals influence pH. In 1945 Darrow showed that hyperchloraemic metabolic acidosis in preterm infants fed milk with 5.7 mmol of chloride and 2.0 mmol of sodium per 100 kcal was caused by retention of chloride in excess of sodium. Similar findings were made but not recognised in later studies of metabolic acidosis in preterm infants. Shohl in 1921 and Kildeberg in 1978 presented the theory that carbonic and organic acids are neutralised by mineral base, where mineral base is the excess of mineral cations over anions and organic acid is the difference between mineral base, bicarbonate and protein anion. The degree of metabolic acidosis measured as base excess is determined by deviation in both mineral base and organic acid from normal.

Objective: To determine how weight for gestational age affects urea and mineral excretion by preterm infants receiving total parenteral nutrition (TPN). Study Design: Daily urine samples were collected from all preterm infants given high calcium TPN, providing 30 kcal/g amino acids, during its first 44 months of use, and from all those given standard TPN, providing 25 kcal/g amino acids, over the previous 24 months. Urine urea and mineral excretion were measured as follows: Urea excretion mmol/kg/day = Urine urea/ urine creatinine X creatinine production Creatinine production μmol/kg/day = -2.07 + 2.34 X gestational age in weeks Results: High calcium TPN was evaluated in 52 infants. Urea excretion did not rise with increasing TPN intake. During the first week, urea excretion increased with weight for gestational age, with higher rates in above average than below average weight infants. It also increased with gestational age in above average but not below average weight infants. Below average weight infants had lower potassium and phosphate excretion than those above average. Standard TPN was evaluated in 20 infants. Urea excretion increased with TPN intake to higher levels than on high calcium, and also increased with weight for gestational age. Conclusion: Urea excretion was simple to measure, with remarkably consistent daily results in individuals. Below 30 weeks gestation infants on TPN providing 30 kcal/g amino acids had urea excretion < 0.1 g urea N/kg/day, < 3.5 mmol/kg/day if below average weight, and < 0.12 g urea N/kg/day, < 4.3 mmol/ kg/day if above average weight. Below average weight infants retained more potassium and phosphate during the first week than those above average, and their greater requirements were provided by the TPN.