Reduction in unplanned hospitalizations associated with a physician focused intervention to reduce potentially inappropriate medication use among older adults: a population-based cohort study.

BACKGROUND: A multimodal general practitioner-focused intervention in the Local Health Authority (LHA) of Parma, Italy, substantially reduced the prevalence of potentially inappropriate medication (PIM) use among older adults. Our objective was to estimate changes in hospitalization rates associated with the Parma LHA quality improvement initiative that reduced PIM use. METHODS: This population-based longitudinal cohort study was conducted among older residents (> 65 years) using the Parma LHA administrative healthcare database. Crude and adjusted unplanned hospitalization rates were estimated in 3 periods (pre-intervention: 2005-2008, intervention: 2009-2010, post-intervention: 2011-2014). Multivariable negative binomial models estimated trends in quarterly hospitalization rates among individuals at risk during each period using a piecewise linear spline for time, adjusted for time-dependent and time-fixed covariates. RESULTS: The pre-intervention, intervention, and post-intervention periods included 117,061, 107,347, and 121,871 older adults and had crude hospitalization rates of 146.2 (95% CI: 142.2-150.3), 146.8 (95% CI: 143.6-150.0), and 140.8 (95% CI: 136.9-144.7) per 1000 persons per year, respectively. The adjusted pre-intervention hospitalization rate was declining by 0.7% per quarter (IRR = 0.993; 95% CI: 0.991-0.995). The hospitalization rate declined more than twice as fast during the intervention period (1.8% per quarter, IRR = 0.982; 95% CI: 0.979-0.985) and was nearly constant post-intervention (IRR: 0.999; 95% CI: 0.997-1.001). Contrasting model predictions for the intervention period (Q1 2009 to Q4 2010), the intervention was associated with 1481 avoided hospitalizations. CONCLUSION: In a large population of older adults, a multimodal general practitioner-focused intervention to decrease PIM use was associated with a decline in the unplanned hospitalization rate. Such interventions to reduce high risk medication use among older adults warrant consideration by health systems seeking to improve health outcomes and reduce high-cost acute care utilization.

Inappropriate prescribing in a large community-dwelling older population: a focus on prevalence and how it relates to patient and physician characteristics.

WHAT IS KNOWN AND OBJECTIVE: The prescription of potentially inappropriate medications (PIMs) for older adults is a well-known population health concern. Updated country-specific estimates of inappropriate prescribing in older adults using germane explicit criteria are needed to facilitate physician-tailored quality improvement strategies. Therefore, we sought to determine the prevalence of PIMs for older adults in Emilia-Romagna, Italy, using the updated Maio criteria. We also evaluated patient and general practitioner (GP) characteristics related to inappropriate prescribing. METHODS: Older adults (≥ 65) in 2012 were evaluated in a one-year retrospective study using administrative health care data. The 2011 Maio criteria includes 25 medications reimbursed by the Italian National Formulary, in the following categories in terms of severity: 16 medications that 'should always be avoided,' 3 that are 'rarely appropriate,' and 6 that have 'some indications although they are often misused.' To evaluate the extent of associations between patient and GP related characteristics, we used generalized estimating equations with an exchangeable covariance design to fit robust logistic regression models. RESULTS AND DISCUSSION: A total of 865,354 older adults were in the cohort and 28% had at least one PIM. Of the entire cohort, 8%, 10%, and 14% of individuals were prescribed at least one medication that 'should always be avoided,' is 'rarely appropriate,' and has 'some indications but are often misused,' respectively. Older patients (≥ 75) and females were more likely to be exposed to PIMs. 2,923 GPs were identified in the region, each having prescribed at least one PIM, of which older GPs (≥ 56), male GPs, and solo practice GPs were more likely to prescribe PIMs to their older patients. WHAT IS NEW AND CONCLUSION: The high prevalence of PIM exposure among older adults is a substantial issue in the region. Knowing how patient and GP characteristics relate to PIMs exposure may improve the design and targeting of initiatives for improving prescribing safety in this population.

Evaluating sustained quality improvements: long-term effectiveness of a physician-focused intervention to reduce potentially inappropriate medication prescribing in an older population.

WHAT IS KNOWN AND OBJECTIVES: Although quality improvement initiatives targeting physician practice patterns have been effective, evidence is lacking on their long-term sustainability. We previously demonstrated the success of a population-wide, physician-focused quality improvement intervention targeting potentially inappropriate prescribing (PIP) in an aged population of the Local Health Authority (LHA) of Parma, Italy. We sought to assess whether the decrease in PIP incidence rates achieved during the intervention was sustained after discontinuation of the intervention, and which factors modified the effectiveness of the intervention. METHODS: Using a regional administrative claims database, we assessed changes in quarterly PIP exposure incidence rates for each phase [pre-intervention (2005 Q1-2007 Q3), intervention (2007 Q4-2009 Q4) and post-intervention (2010 Q1-Q4)] of the study for both all and newly PIP-exposed patients. Piecewise-linear longitudinal logistic regression was used to model the odds of PIP exposure. RESULTS: 299 GPs (98·7%) serving 111,282 older patients were included. PIP incidence rates declined from 7·1% (pre-intervention) to 4·9% (intervention), and to 4·3% (post-intervention). There was no significant change in odds of PIP exposure following the intervention period (P = 0·52), and the rates of change in PIP exposure odds during pre-intervention and post-intervention periods were not significantly different (P = 0·39). The intervention was attributed to an 18% long-term reduction in the odds of PIP exposure. No assessed patient or GP characteristics modified this effect. Results among patients newly exposed to PIP were similar to results among all patients exposed to PIP. WHAT IS NEW AND CONCLUSION: The significant reduction in the odds of PIP exposure achieved during the intervention was sustained after its discontinuation. Because the intervention showed success across the spectrum of patients and providers, it shows promise for generalizability to other healthcare settings.

Appropriate medication prescribing in elderly patients: how knowledgeable are primary care physicians? A survey study in Parma, Italy.

WHAT IS KNOWN AND OBJECTIVE: Increasing attention is being paid to inappropriate medication prescribing for the elderly. A growing body of studies have detected a prevalence of inappropriate prescribing ranging from 12% to 40% worldwide, including Regione Emilia-Romagna, Italy. To improve quality of prescribing, a multi-phase pilot project in the Local Health Unit (LHU) of Parma, Regione Emilia-Romagna, was established. This phase aimed to assess primary care physicians' knowledge of appropriate prescribing in elderly patients. METHODS: In total, 155 primary care physicians (51% of the total), convened by the LHU of Parma for an educational session, were asked to complete anonymously a 19-item paper survey. Knowledge of inappropriate medication use in the elderly was assessed using seven clinical vignettes based on the 2002 Beers Criteria. Topics tested included hypertension, osteoarthritis, arrhythmias, insomnia and depression. Data regarding physician's perceived barriers to appropriate prescribing for elderly patients were also collected. To evaluate the relationship between physician knowledge scores and physician characteristics, physicians were classified as having a 'low score' (three or below) or a 'high score' (six or more) with respect to their knowledge of prescribing for the elderly. RESULTS AND DISCUSSION: All physicians completed the survey. Most physicians (88%) felt confident in their ability to prescribe appropriate medications for the elderly. Thirty-nine physicians (25%) received a 'high score' compared to 26 (17%) who received a 'low score'. 'Lower score' respondents had been in practice for a longer time (P < 0·05) than 'higher score' respondents. Perceived barriers to appropriate prescribing included potential drug interactions (79% of respondents) and the large number of medications a patient is already taking (75%). WHAT IS NEW AND CONCLUSION: The study results show an unsatisfactory knowledge of appropriate prescribing among primary care physicians in the LHU of Parma, especially among older physicians. Educational strategies tailored to primary care physicians should be establish to enhance knowledge in this area and improve quality of prescribing.

Using explicit criteria to evaluate the quality of prescribing in elderly Italian outpatients: a cohort study.

BACKGROUND AND OBJECTIVE: Inappropriate prescribing in the elderly population is a well-recognized problem in public health. The Beers criteria have been widely used to evaluate the quality of prescribing for the elderly. However, because the Beers criteria were developed in the United States, they are not fully applicable in Italy. The purpose of this study was to establish explicit criteria for potentially inappropriate medication prescribing (PIP) for the elderly and assess the prevalence of and factors associated with PIP among elderly residents in the Local Health Unit of Parma, Italy according to the developed criteria. METHODS: A nine-member expert panel was convened to identify a list of inappropriate medications reflecting the Italian prescribing habits. The panel decided to refine and update the 2002 Beers criteria. Consensus through a Nominal Group Technique was reached to classify the identified 23 inappropriate medications into three categories: 17 medications to be always avoided, three medications rarely appropriate, and three medications with some indications but often misused. A retrospective cohort study using the 2006 Parma Local Health Unit automated outpatient prescriptions database was conducted. The cohort comprised 91 741 elderly individuals >or=65 years with at least one prescription medication. PIP was defined as having a prescription claim for at least one inappropriate medication. RESULTS AND DISCUSSION: A total of 23 662 elderly in the cohort (25.8%) had at least one PIP. Of these, 14.1% received prescriptions for two medications of concern, and 2.0% for three or more. Using the expert panel's categories, 59.2% of the elderly receiving PIP had prescriptions for drugs that should always be avoided, 33.9% for rarely appropriate drugs, and 19.1% for drugs that have some indications but are often misused. Non-steroidal anti-inflammatory drugs (35.7% of subjects) were the most frequently occurring PIP, followed by ticlopidine (17.6%), doxazosin (15.5%), and amiodarone (13.6%). Female, older age, overall number of drugs prescribed, greater number of chronic conditions were factors associated with greater odds of receiving PIP. CONCLUSION: Via the developed criteria, the study corroborates that PIP among elderly outpatients is a substantial issue in Parma Local Health Unit, Italy. Knowledge of the prevalence of PIP and associated factors should gear efforts to develop strategies to reduce PIP in outpatient settings in Italy.

Hypercapnic-hypoxemic chronic obstructive pulmonary disease (COPD): influence of severity of COPD on nutritional status.

In 90 patients with hypercapnic-hypoxemic chronic obstructive pulmonary disease (COPD), noninvasive anthropometric and biochemical nutritional indices were measured to assess the prevalence and features of malnutrition in COPD and to analyze the relationship between nutritional depletion and the severity of the disease. A significant inverse relationship was found between PaCO2 and body weight; a parallel decrease of both somatic proteins and body-energy stores of fat appears to be paired with decreasing body weight. Deterioration of nutritional status occurred in the COPD patients considered despite seemingly adequate calorie and protein intakes, although in patients with more severe impairment of pulmonary gas exchange, calorie intake was significantly lower compared with basal energy expenditure. In the course of hypercapnic-hypoxemic COPD malnutrition is common, it is related to the severity of the disease as judged by the need for hospitalization and degree of impairment of gas exchange, and it may be present despite apparently adequate nutrient intake.

Skeletal muscle energetics, acid-base equilibrium and lactate metabolism in patients with severe hypercapnia and hypoxemia.

Quadriceps femoris muscle needle biopsies were performed in ten patients with chronic obstructive pulmonary disease and acute respiratory failure and in ten age- and sex-matched healthy control subjects. The main indices of skeletal muscle cell energy metabolism, intracellular acid-base equilibrium and lactate metabolism were evaluated. Reduced ATP and phosphocreatine content, intracellular acidosis related to hypercapnia, increased muscle lactate without alterations of the muscle lactate concentration gradient were observed in the skeletal muscle of the hypercapnic-hypoxemic COPD patients studied, in which group no correlation was found between hypoxia and energy or lactate metabolism parameters. These results suggest that an overall derangement of cell energy metabolism and acid-base equilibrium is present in severely hypercapnic-hypoxemic chronic obstructive pulmonary disease and that in this condition skeletal muscle seems to metabolize anaerobically-even though, in addition to hypoxia, other factors interfering with both cell energy and lactate metabolism are likely to be present.

A comparative clinical study on the effects of cardiopulmonary bypass with different flows and pressures on skeletal muscle cell metabolism in patients undergoing coronary bypass grafting.

This study compares the effects of cardiopulmonary bypass with different flows and pressures on intracellular energy metabolism, acid-base equilibrium, and muscle water compartments in two groups of patients undergoing coronary artery bypass grafting. Eighteen patients (16 men and two women aged 54 +/- 7 years, New York Heart Association class I-II) undergoing low flow (flow rate 1.5 L/min/m2 at 26 degrees C), low pressure (mean arterial pressure 40 to 60 mm Hg) cardiopulmonary bypass, as well as 10 age-matched and sex-matched patients undergoing normal flow (flow rate 2.2 L/min/m2 at 26 degrees C), normal pressure (mean arterial pressure 60 to 80 mm Hg) bypass were studied. Intracellular acid-base equilibrium (intracellular pH and intracellular bicarbonate), cell energetics (adenosine triphosphate, diphosphate, and monophosphate, phosphocreatine, and lactate), and muscle water compartments were evaluated in specimens of the quadriceps femoris muscle obtained by needle biopsy before and at the end of cardiopulmonary bypass. In both the low flow-low pressure and normal flow-normal pressure groups, adenosine triphosphate levels were unchanged at the end of bypass, whereas phosphocreatine concentration was decreased; muscle total water and extracellular water increased without variations of intracellular water; muscle and plasma lactate increased as intracellular bicarbonate decreased; intracellular pH values remained unchanged. The present study suggests the following: (1) Cardiopulmonary bypass is associated with the overall preservation of intracellular compartment metabolism in skeletal muscle (about 40% of body cell mass) of patients undergoing coronary bypass grafting, even though low phosphocreatine values and increased plasma and muscle lactate values found at the end of bypass could be an expression of cell functional reserve exhaustion; (2) the effects of cardiopulmonary bypass on cell metabolism are comparable, regardless of the flows and pressures used.

Muscle energy metabolism in uremia.

Energy-rich phosphagens were measured in 11 patients with end-stage chronic renal failure and 11 nonuremic subjects. A significant decrease of ATP, phosphocreatine, total adenine nucleotides, lactate, and energy charge was found. The present results can be referred both to glycolytic sequence disturbances and to the lack of substrates characteristic of uremia.

Effect of induced metabolic acidosis on intracellular pH, buffer capacity and contraction force of human skeletal muscle.

Five volunteers were studied before and after oral administration of NH4Cl (0.3 g/kg body wt.) given in order to create a moderate acidosis. The quadriceps femoris muscles were stimulated electrically for 75 s and muscle biopsies for determination of pH and metabolite content were taken before, at the end of contraction and after 10 min in the recovery period. Muscle pH at rest (mean 7.04) was not significantly decreased after acidification despite an extracellular pH decrease of 0.15 unit. After contraction muscle pH was significantly lower after NH4Cl. Mean values before and after acidification were 6.70 and 6.54 respectively. The buffer capacity calculated as the total capacity of the muscle to buffer H+ produced during the isometric contraction before and after NH4Cl ingestion was reduced from 68.6 sl to 54.5 sl. The force produced by contracting muscle was significantly lower at the end of the contraction period after NH4Cl ingestion, 44.6% of initial compared with 55.4% without NH4Cl.

Muscle and serum magnesium in pulmonary intensive care unit patients.

Muscle specimens by means of quadriceps femoris needle biopsy and blood samples were obtained in 32 patients consecutively admitted to a pulmonary ICU for chronic obstructive pulmonary disease and acute respiratory failure, and in 30 age and sex-matched healthy control subjects. Muscle magnesium (Mg) and potassium (K) content was assessed by atomic absorption spectrophotometry; serum electrolytes were also measured. The presence of clinical and biochemical correlates of low serum and muscle Mg was investigated. Three (9.4%) out of 32 patients had hypomagnesemia (Mgs less than or equal to 0.7 mmol/L) with normal muscle Mg values, whereas low muscle Mg values were found in 15 (47%) of 32 patients, with no alterations of serum Mg levels. Muscle Mg was decreased significantly in pulmonary ICU patients as compared to control subjects. No significant correlation was present between serum and muscle Mg, or between serum and muscle K. Significant relationships between muscle Mg and both muscle and intracellular K concentrations were also found. Lower values for muscle and intracellular K and a higher incidence of both more prolonged ICU stays and ventricular extrasystolic beats characterized the ICU patients with altered muscle Mg levels. We conclude that, given the serious complications of Mg metabolism derangements, the presence of altered cell Mg content should be taken into account in pulmonary ICU patients. Moreover, in these patients, serum Mg levels are of little value in the diagnosis of intracellular Mg deficits.

Intracellular acid-base and electrolyte metabolism in skeletal muscle of patients with chronic obstructive lung disease and acute respiratory failure.

Quadriceps femoris muscle needle biopsies were performed in 21 patients with chronic obstructive lung disease (COLD) and acute respiratory failure (ARF) and in 21 age-matched healthy control subjects. Muscle samples were analysed to obtain intracellular bicarbonate and pH values from total acid-labile carbon dioxide content. Muscle potassium, magnesium and sodium content were also determined, as well as water compartments. Skeletal muscle of COLD patients with ARF showed intracellular acidosis and reduced potassium and magnesium content. Total muscle water increase was linked to extracellular water increment. It was concluded that in COLD patients with ARF an overall derangement of skeletal muscle metabolism is present.

Uremic acidosis and intracellular buffering.

Skeletal muscle biopsies were performed in 16 controls and 15 non-dialysed end-stage chronic renal failure (CRF) patients presenting untreated metabolic acidosis. Intracellular bicarbonate, pH, water compartments and electrolytes were determined. In 8 of 15 patients muscle ATP and lactate were measured. Intracellular bicarbonate (HCO3i) and pH (pHi) were obtained by means of muscle total carbon dioxide method: a significant (p less than 0.001) reduction in both intracellular acid--base indexes was found in all patients (pHi 6.82 +/- 13 vs. 7.04 +/- 0.05; HCO3i 6.28 +/- 2.07 vs. 11.86 +/- 0.87). Total muscle as well as extracellular water was increased. Muscle sodium and chloride contents were also increased, while no change in potassium and magnesium was detected. A significant decrease of both muscle ATP and lactate was found. The data lead to the conclusion that chronic retention of acids in CRF results in a depletion of the muscle buffer pool and consequently in intracellular acidosis: the latter could be the main cause of the cell energy metabolism derangement described in uremia.

[Measurement of intracellular bicarbonate and pH: preliminary study using potentiometric determination of muscle acid-labile CO2]. / Misurazione del bicarbonato e del pH intracellulari: rilievi preliminari mediante determinazione potenziometrica della CO2 acido-labile muscolare.

A method is described for the determination of total acid-labile CO2 (TCO2) and intracellular bicarbonate concentration [HCO3-] in skeletal muscle samples. Surgical biopsies obtained from the quadriceps femoris muscle of 24 Wistar male rats were analyzed for acid-labile CO2 and extra and intracellular water, extracellular water was estimated from the muscle chloride content. TCO2 method utilizes a single diffusion step with absorption of extracted CO2 by sulphuric acid into barium hydroxide and subsequent potentiometric determination of muscle CO2 content. The measured total CO2 content in muscle was 12.01 +/- 1.06 mMol/Kg wet weight when the sample weight was kept in terms of 22-110 mg, assuming a normal membrane potential and a muscle pCO2 equal to femoral vein blood pCO2, calculated intracellular bicarbonate concentration was 12.58 +/- 1.08 mEq/1 H2O i.c. (X +/- D.S.) and intracellular pH was 7.03 +/- 0.04 (X +/- D.S.).

Cell metabolism response to cardiopulmonary bypass in patients undergoing aorto-coronary grafting.

The main parameters of muscle acid-base, water and energy metabolism were studied in ten patients undergoing low-flux (1.5 l/min/m2), low-pressure (40 to 60 mmHg) hypothermic (26 degrees C) cardiopulmonary bypass (CPB) for aortocoronary grafting; absolute gas exchange and haemodynamic data were also measured throughout the entire CPB period. At the end of CPB a substantial preservation of water and energy metabolic indexes was found; a condition of extracellular metabolic acidosis was apparently sustained by muscle cell anaerobic glycolysis enhancement with a consequent increase of both muscle and plasma lactate content. Subnormal cell phosphocreatine levels as well as reduced bicarbonate buffer stores and decreased intracellular pH, were detected. Direct limiting effects of hypothermia on tissue O2 delivery and muscle oxidative metabolism as well as vasoconstriction and arteriovenous shunting associated with CPB procedures are likely to be involved in the above mentioned alterations of cell metabolism.

Effects of low flux-low pressure cardiopulmonary bypass on intracellular acid-base and water metabolism.

In eight patients undergoing open heart surgery for elective myocardial revascularization, extra-intracellular acid-base and water metabolism parameters were studied before and after cardiopulmonary bypass procedures. All patients presented a different degree of metabolic acidosis related to plasma lactate increase. Intracellular acid-base indexes did not change significantly, though all but one patient showed an intracellular buffers consumption. Both total muscle and extracellular water increased, while intracellular water did not change. It was concluded that low flux-low pressure perfusion CPB was related to a substantial preservation of cell integrity.

Intracellular bicarbonate and pH of skeletal muscle in chronic renal failure.

In 11 controls and 10 patients suffering from untreated uraemic acidosis intracellular bicarbonate and skeletal muscle pH (needle biopsy) were determined. In all patients a significant intracellular acidosis, not related to any extracellular indices was found. It is concluded that the chronic proton load is able to effect intracellular buffer composition; moreover the action of other factors such as derangements of cell metabolism and nutritional imbalance could be operating.