Howard H. Hiatt

Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I.

BACKGROUND As part of an interdisciplinary study of medical injury and malpractice litigation, we estimated the incidence of adverse events, defined as injuries caused by medical management, and of the subgroup of such injuries that resulted from negligent or substandard care. METHODS We reviewed 30,121 randomly selected records from 51 randomly selected acute care, nonpsychiatric hospitals in New York State in 1984. We then developed population estimates of injuries and computed rates according to the age and sex of the patients as well as the specialties of the physicians. RESULTS Adverse events occurred in 3.7 percent of the hospitalizations (95 percent confidence interval, 3.2 to 4.2), and 27.6 percent of the adverse events were due to negligence (95 percent confidence interval, 22.5 to 32.6). Although 70.5 percent of the adverse events gave rise to disability lasting less than six months, 2.6 percent caused permanently disabling injuries and 13.6 percent led to death. The percentage of adverse events attributable to negligence increased in the categories of more severe injuries (Wald test chi 2 = 21.04, P less than 0.0001). Using weighted totals, we estimated that among the 2,671,863 patients discharged from New York hospitals in 1984 there were 98,609 adverse events and 27,179 adverse events involving negligence. Rates of adverse events rose with age (P less than 0.0001). The percentage of adverse events due to negligence was markedly higher among the elderly (P less than 0.01). There were significant differences in rates of adverse events among categories of clinical specialties (P less than 0.0001), but no differences in the percentage due to negligence. CONCLUSIONS There is a substantial amount of injury to patients from medical management, and many injuries are the result of substandard care.

A rapidly labeled RNA in rat liver nuclei

[ 14 C]orotic acid was injected intraperitoneally into rats with normal and regenerating liver. At intervals thereafter the animals were killed, the livers were removed and fractionated into nuclear and cytoplasmic components, and the RNA was purified with phenol. A heterogeneous, rapidly labeled fraction, ranging in size from 6 to more than 30 s, was found in nuclei, but not in cytoplasm. The base composition of the rapidly labeled RNA in the nuclei differed from those of total nuclear RNA, and of DNA, and was suggestive of enrichment with respect to nucleolar RNA. The rapidly labeled fraction could be obtained in apparently intact fashion only when sodium dodecyl sulfate was present during phenol treatment. On the basis of its size, rate of labeling, and its distinctive base composition, this fraction resembles bacterial messenger RNA. Its apparent absence from cytoplasm has led to a consideration of the possibility that a rapidly renewable messenger may exist in liver nuclei, and a relatively stable template in cytoplasm.

A cytoplasmic particle bearing messenger ribonucleic acid in rat liver.

Rapidly labeled RNA first appears in. rat liver cytoplasm predominantly in association with a 45 s particle, which is probably a newly synthesized ribosomal subunit. Although most of the rapidly labeled RNA purified from the 45 s particle sediments with a coefficient of 18 s, much is degraded to 6 to 14 s material under conditions in which the ribosomal RNA is little affected. Similar 6 to 14 s RNA obtained from total cytoplasmic extracts has many characteristics of messenger, for it is stimulatory in an in vitro protein-synthesizing system, is differentially sensitive to cellular nucleases, and differs from ribosomal RNA in base composition. The unstable fraction appears to represent only a small proportion of total cytoplasmic messenger RNA. Our results are consistent with a model in which messenger RNA becomes associated with a 45 s ribosomal subunit in the nucleus and is then transferred with the subunit to the cytoplasm.

MESSENGER RIBONUCLEIC ACID IN RAT LIVER NUCLEI AND CYTOPLASM.

The sedimentation pattern of “pulse” labeled ribonucleic acid was investigated in rat liver nuclei and cytoplasm. In parallel studies biological activity was measured, as defined by capacity to stimulate amino acid incorporation by a protein synthesizing system derived from Escherichia coli . In the microsomal fraction, these two characteristics—early labeling and biological activity—are found principally in 18 s RNA. Nuclear RNA with these characteristics is much more heterogeneous than is microsomal RNA. The proportion of early labeled and of biologically active material relative to total RNA is much higher in the nuclear than in the microsomal fraction.

Identification of Adverse Events Occurring during Hospitalization: A Cross-Sectional Study of Litigation, Quality Assurance, and Medical Records at Two Teaching Hospitals

STUDY OBJECTIVES To estimate the efficacy of a medical record review for identifying adverse events and negligent case suffered by hospitalized patients. DESIGN Cross-sectional study comparing an objective medical record review with information available from hospital quality assurance records as well as risk management and litigation records. SETTING Two metropolitan teaching hospitals in the northeastern United States. MEASUREMENTS AND MAIN RESULTS Using the litigation and risk management records as a criterion standard, we found that the medical record review had a sensitivity of 80% (93 of 116; 95% CI, 73% to 88%) for discovering adverse events and a sensitivity of 76% (51 of 67; 95% CI, 66% to 86%) for discovering negligent care. We estimated that record review of a random sample of hospitalizations across a geographic region would have even higher sensitivity (adverse-event sensitivity, 84%; negligence sensitivity, 80%). Moreover, we found that the adverse events we failed to discover led to less costly malpractice claims. A significant number of adverse events (20 of 172) among hospitalizations never gave rise to litigation or risk management investigation. Six of the twenty were due to negligent care. Quality assurance efforts at the level of the clinical departments in one hospital led to review of only 12 out of 82 risk management records. CONCLUSIONS The overwhelming majority of adverse events and episodes of negligent care are discoverable with the methods we used to evaluate medical records. Quality assurance efforts using similar record review methods should be further evaluated.

Evaluation of medical practices. The case for technology assessment.

We believe that the systematic evaluation of medical practices, especially those that are risky or costly deserves more attention. Available methods are limited, and definitive assessments of innovative or controversial practices are infrequent. Nevertheless, some evaluations have successfully enhanced the use of effective practices and diminished the reliance on ineffective ones. Greater efforts at evaluation can improve the quality of patient care, avoid waste and promote the more rational use of health resources. The cost of assessing new practices should be viewed as an intrinsic part of the cost of medical care. Physicians and medical societies bear primary responsibility for recognizing the need for this evaluation, for enlisting other experts, participating in technology assessment and working to translate the results of evaluation into practice. The commitment of government agencies, insurance companies and teaching institutions is also essential to an effective program of evaluation.

Actinomycin D: An Effect on Rat Liver Homogenates Unrelated to Its Action on RNA Synthesis

Liver homogenates prepared from rats injected with high doses of actinomycin D show a decrease in polyribosome content and in amino acid incorporation. These effects are not observed in rat liver not subjected to homogenization and are independent of the inhibition of RNA synthesis caused by the antibiotic.

PROTEIN SYNTHESIS BY FREE AND BOUND RAT LIVER RIBOSOMES IN VIVO AND IN VITRO.

Sucrose density gradient centrifugation has been used to separate free ribosomes in the microsomal fraction of rat-liver cytoplasm from those bound to the lipoprotein membrane (endoplasmic reticulum). During in vivo labeling experiments, radioactive arginine becomes rapidly associated with membrane-bound ribosomes but not with free ribosomes. Further, in an in vitro protein synthesizing system membrane-bound ribosomes incorporate labeled phenylalanine while free ribosomes are virtually inert. These observations suggest that membrane-bound ribosomes are the major site of protein synthesis. The inactivity of the free ribosomes is presumably attributable to the absence of messenger RNA, for they readily incorporate phenylalanine in the presence of polyuridylic acid.

Pathways of Carbohydrate Metabolism in Normal and Neoplastic Cells

IN mammalian tissues carbohydrates not only constitute the major source of energy for work and anabolic processes but also provide the precursors for the formation of essential cell constituents, s...

Meeting cholera's challenge to Haiti and the world: a joint statement on cholera prevention and care.

Cholera in Haiti: Acute-on-Chronic Long before the devastating earthquake on January 12, 2010, Haiti struggled beneath the burdens of intractable poverty and ill health. The poorest country in the Western Hemisphere, Haiti also faces some of the highest rates of maternal and infant mortality—widely used indicators of the robustness of a health system—in the world ([S1] in Text S1; [2], [3]). The October 2010 cholera outbreak is the most recent of a long series of affronts to the health of Haitis population; it is yet another acute symptom of the chronic weakness of Haitis health, water, and sanitation systems. Water and sanitation conditions highlight these systemic weaknesses. In 2002, Haiti ranked last out of 147 countries for water security [4], [5]. Before the earthquake struck, only half of the population in the capital, Port-au-Prince, had access to latrines or other forms of modern sanitation, and roughly one-third had no access to tap water [6]. Across the country, access to sanitation and clean water is even more limited: only 17% of Haitians had access to adequate sanitation in 2008, and 12% received treated water [7]. Not surprisingly, diarrheal diseases have long been a significant cause of death and disability, especially among children under 5 years of age [6]. The cholera outbreak began less than a year after a 7.0-magnitude earthquake took the lives of more than 300,000 people and left nearly 1.5 million homeless [6]. Almost 1 million Haitians still live in spontaneous settlements known as internally displaced persons (IDP) camps [8]. While post-earthquake conditions in Haiti were ripe for outbreaks of acute diarrheal illness, cholera was deemed “very unlikely to occur” by the United States Centers for Disease Control and Prevention (CDC) and other public health authorities [9]. Cholera had never before been reported in Haiti [S2] [10], [11]; health providers were unprepared for an influx of patients presenting with acute watery diarrhea. The cholera epidemic has been most severe in rural areas and large urban slums. Rural communities were charged with hosting hundreds of thousands of displaced people after the earthquake, placing greater demands on their already-scarce resources, including water. Surface water drawn directly from the source or piped from rivers and streams constitutes the principal supply of drinking water in rural Haiti. The lack of adequate piping, filtration, and water treatment systems (including chlorination) made these rural regions vulnerable to the rapid spread of waterborne disease. While most IDP camps have been supplied with potable water, large urban slums have had to rely on existing water sources—some of them containing Vibrio cholerae—and have therefore been vulnerable to rapid disease spread. Most slums also have poor sanitation infrastructure. Since the first cases were reported in Saint-Marc and Mirebalais, cholera has spread to every department in Haiti, and to other countries, too [S3] [12]–[14]. Public suspicion (ultimately validated by genomic sequence analyses [15]) of the strains link to South Asia, home to a group of United Nations peacekeepers stationed in central Haiti, triggered blame and violence that interfered with response efforts. As we have learned from the global AIDS pandemic and other infectious disease epidemics, cycles of accusation can continue for years, diverting attention and resources from the delivery of care and prevention services [16]. Systemic problems that brought cholera to epidemic levels in Haiti will (unless addressed) continue to facilitate its spread. As a disease of poverty, cholera preys upon the bottom of the social gradient; international trade, migration, and travel—from South Asia or elsewhere—open direct channels for pathogens that follow social fault lines.