Stay out of the hospital! Wherever you are in the world...

On 27 March 2001, Michael R. Cohen, MS, RPh, President of the Institute for Safe Medication Practices, testified before the Committee on Ways and Means of the Subcommittee on Health, Congress of the United States House of Representatives and made some recommendations to reduce error and improve the quality of medication use. He stated that "Medications are a blessing, but humans must safely prescribe, prepare, dispense, and administer these drugs. Yet humans are fallible, and as clearly articulated in the recent report ‘To Err is Human: Building A Safer Health System (Medical Errors)’ by the Institute of Medicine, errors and other adverse events occur and cause unbearable human and financial cost. Medication use has been further complicated by the large number of new drugs and technologies introduced every year, an increasing elderly population with chronic and acute conditions requiring complex treatment strategies, and the proliferation of over-the-counter products. In light of this fact, much can and should be done to enhance medication safety." The cited report arrived at the conclusion that in the USA between 48 000 and 98 000 deaths were related to medical error (which does not mean the physician only, as has been wrongly quoted, but the medical system). This enormous figure looks even worse if one considers that AIDS has killed 16 000 and car accidents 43 000 people. On 4 February 2002, the medical director of the Geneva University Hospital, a pharmacologist, announced that 10% of all patients admitted in 2001 had suffered from some form of drug usage error. Although electronic diaries have recently been introduced with programs alerting housestaff to potential interactions, an unresolved issue is the packaging of drugs by the Hospital, which results in the very uniform appearance of boxes, a major source of error. If one then realizes that the Geneva Cancer Statistics point out that patients diagnosed in the University Hospital have a worse outcome than patients diagnosed in town, one wants to stay away from that respected Institution. Fortunately, these data have not been misinterpreted in the lay press. Of course one understands that the size of the drug prescription problem is related to very stringent quality control criteria, which initially uncover lots of minor problems. The statistical bias towards a worse outcome in a major Hospital is related to the fact that patients in poor condition are admitted on an emergency basis to the University Hospital, while those who can easily tolerate an ambulatory or delayed diagnostic procedure are not admitted or are admitted to other centers of care.

Annals is doing well, but old issues are not yet freely accessible

Your Journal is doing well, thank you. You have sent us 824 manuscripts in 2001, compared with 722 in 2000, and the rejection rate also increased over that period. Why is the rejection rate going up? Because of changes in editorial policy, already mentioned to you by the Editor-in-Chief, which, we hope will further increase the quality of the journal (and raise its impact factor). The impact factor is already doing well; it was 3.249 in 2000, with nearly 600 institutional subscriptions (also an increase on the previous year, significant in a world of declining library budgets). ESMO member subscribers may wonder why they no longer have free access to the old issues of Annals. Regular readers of Annals News will understand a little of the complexity of the world of intellectual property. For now, suffice it to say that negotiations with our former publisher are ongoing to allow members to access their own Journal from past years.

The cowboy country thinks it will save the world but its citizens have a tough time

On 27 January 2002, one was appalled to read in USA Today (J. Appleby reporting) that some elderly and disabled cancer patients say they will forgo medical treatment because they can’t afford new payments required by their Medicare HMOs (health maintenance organizations, a type of insurance with numerous restrictions). Charges can run into thousands of dollars each month. Starting on 1 January 2002, many Medicare HMOs across the USA began charging steep co-payments for chemotherapy, dialysis, radiation therapy and hospitalization. Costing as much as $100 per day for radiation therapy, $25 for dialysis and $100–500 per chemotherapy drug; some patients require several drugs, several times a week. The new charges were approved late last year by Medicare officials, who required several insurers to lower their fees. Obviously the system needs some corrective action, such corrections are under discussion. For patients with cancer, average costs (lower in HMO than in regular Medicare) mean little. A case cited by the USA Today article is that of a woman, age 58, who was diagnosed with cancer in 2001, her monthly cancer costs hit $3184 after her HMO raised its co-payments, charging $150 per chemotherapy drug. After switching back to regular Medicare, her care will cost $1315 a month.

ImClone Systems Inc

In last month’s news, we reported on this company. While investigations continue, and all kinds of rumours exist, it is of interest to note that on 15 February 2002, Charles Icahn, a well known financier, bought US $500 million worth of ImClone shares, about 20% of the total value of the company on the market that day. This important ‘raid’ prompted immediate defensive moves on the part of the company’s management. More next month?

About failures in medical systems (continued)

The global increase in the number of elderly people is putting greater and greater constraints on our economies. R. Scott Martin of The New York Times reported on 19 February 2002 that more than 90% of the USA’s nursing homes have too few workers to take proper care of patients, according to a new federal study. But it seems that the Bush administration, citing the costs involved, says it has no plans to set minimum staffing levels for nursing homes, hoping instead that the problem will be resolved through market forces and more efficient use of existing nurses and nurse’s aides. As Europeans we sometimes wonder how this belief in ‘market forces’ can prevail when faced with the terrible disparities of treatment one can observe in the USA. The report, ordered by Congress and prepared by the Department of Health and Human Services, concludes that "it is not currently feasible" for the federal government to require that homes achieve a minimum ratio of nursing staff to patients, as many experts have recommended, largely because of cost. It would take $7.6 billion a year, an 8% increase over current spending, to reach adequate staffing levels, the report states. Instead of imposing new rules, the Bush administration plans to publish data on the number of workers at each nursing home, in the hope that "nurse staffing levels may simply increase due to the market demand created by an informed public". Patients in understaffed homes are more likely to experience bedsores, malnutrition, weight loss, dehydration, pneumonia and serious blood-borne infections, according to the official report. In most nursing homes a patient needs an average of 4.1 h of care each day, 2.8 h from nurse’s aides plus 1.3 h from registered nurses or licensed practical nurses. According to the New York Times, Dr John F. Schnelle, a co-author of the report, said the recommendations would require homes to have one nurse’s aide for every five or six residents from 7 a.m. to 11 p.m. Currently, he said, it is common for nursing homes to have one aide for every 8–14 residents. To reach the recommended staffing levels, the report said, nursing homes would have to hire 77 000–137 000 registered nurses, 22 000–27 000 licensed practical nurses and 181 000–310 000 nurse’s aides. This would increase overall demand for registered nurses by 5–9%, while the demand for nurse’s aides would rise 13–21%. Nursing home executives said they would have difficulty finding the additional workers. Not easy, of course, but the recently suggested increase in the military budget was $48 billion, while that of the Health and Human Service was $29 billion.

What one does not read in the news: a ‘legal’ note of caution

Here is an example of legal language that might also be used in news in the ‘lay’ press about the activity of new drugs: "The foregoing release contains forward-looking statements that can be identified by terminology such as ‘demonstrate’, ‘more effective’, ‘show’, ‘statistically significant difference’ and ‘concluded’, or similar expressions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with the cited drug to be materially different from any future results, performance or achievements expressed or implied by such statements. In particular, management’s expectations regarding further commercialization of the cited drug could be affected by, among other things, additional analysis of data; new data; unexpected clinical trial results; clinical trial results for competitor’s products; unexpected regulatory actions or delays or government regulation generally; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; and other risks and factors referred to in the Company’s current Form 20-F on file with the Securities and Exchange Commission of the United States. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected." Well, after such a statement, everything and its contrary can happen...

When TV shows are informative

Abigail Trafford from the Washington Post, reported on 29 January 2002 that Gleevec, "the hottest new agent in the war on cancer", played a major role in episodes of both ‘The West Wing’ and ‘Law and Order’ two US TV shows, leaving behind a trail of blood and broken dreams. She writes that Gleevec is a relatively unknown drug against a relatively uncommon leukemia, "but it is very, very hot in medical circles. On a scale of 10, "it’s a 7 or 8", said Anthony Murgo, who monitors drug development at the National Cancer Institute". In American television land, Gleevec is portrayed as the drug which can "cure cancer". In ‘Law and Order’, it appears as the only hope for a 9-year-old girl with chronic myeloid leukemia (CML) but a health insurance plan denies treatment with Gleevec, offering a bone marrow transplant instead. Ms Trafford correctly states that the "wicked health plan" is not completely off base in offering a bone marrow transplant; it is "the only treatment known to cure CML" according to a fact sheet from the National Cancer Institute. On ‘The West Wing’, Gleevec gives shape to a political dream. The president’s wife is having a group of physicians over for dinner. The talk turns to a "signal transduction inhibitor", which gives the President an idea for his upcoming State of the Union speech, "Why shouldn’t I stand up and say we are going to cure cancer in 10 years?" Then he gives a stirring monologue, "If we can land a man on the moon, why can’t we cure cancer?" reminiscent of a President a few years ago. So, now that Gleevec is FDA approved for the treatment of gastrointestinal stromal cancer, shall we have an episode about the abuse of antacids and the missed diagnosis of a rare type of gastric cancer?

Abigail Trafford can be reached by e-mail at trafforda{at}washpost.com

Perhaps not everyone knows that...

...a recent pooled analysis of case-control studies did not show any association between the use of fertility drugs and the risk of ovarian cancer. The data on infertility and fertility drug use were pooled from eight case-control studies conducted between 1989 and 1999 in the United States, Denmark, Canada and Australia, which included 5207 cases and 7705 controls. Results were adjusted for age, race, family history of ovarian cancer, duration of oral contraception use, tubal ligation, gravidity and education. Among nulliparous subfertile women, neither any fertility drug use [odds ration (OR) 1.60, 95% confidence interval (CI) 0.90–2.87] nor >12 months of use (OR 1.54, 95% CI 0.45–5.27) were associated with ovarian cancer. In nulligravid women, fertility drug use was associated with borderline serous tumors (OR 2.43, 95% CI 1.01–5.88) but not with any invasive histological subtypes [1].

...the immunosuppressant drug rapamycin may reduce the risk of subsequent tumor development while still effectively preventing immunologic rejection in organ transplantation, whereas older drugs such as cyclosporine may facilitate cancer growth. The increased tendency to develop either new or recurring cancers is currently a serious consequence of immunosuppressive therapy after transplantation, with some studies suggesting that transplant patients receiving immunosuppressive drugs have a 20- to 500-fold higher incidence of certain types of cancer. A study, from the University of Regensburg, has now shown that rapamycin inhibits metastatic tumor growth and angiogenesis in in vivo mouse models. Moreover, normal immunosuppressive doses of rapamycin effectively controlled the growth of established tumors while cyclosporine promoted tumor growth. The authors suggest that rapamycin shows antiangiogenic activities linked to a decrease in production of vascular endothelial growth factor (VEGF) and to a markedly inhibited response of vascular endothelial cells to stimulation by VEGF [2].

...the minimally invasive laparoscopic-assisted colectomy (LAC) procedure offers only minimal short-term quality of life (QOL) benefits compared with standard open colectomy. The safety and efficacy of LAC for colon cancer are still under investigation, but short-term QOL benefits have now been assessed by a multicenter randomized trial of the Clinical Outcomes of Surgical Therapy (COST) Study Group. Data from scores on the Symptoms Distress Scale, QOL Index and a single-item global rating scale at 2 days, 2 weeks and 2 months postoperative were provided, plus the duration of postoperative in-hospital analgesic use and length of stay, for 428 of 449 consecutive patients with clinically resectable colon cancer. In an intention-to-treat analysis comparing LAC with standard open colectomy the only significant difference observed between groups was the global rating scale score for 2 weeks postsurgery; they were 76.9 (median 80) for LAC, versus 74.4 (median 75) for open colectomy (P = 0.009) [3].

...percutaneous radio frequency ablation of small renal tumors is minimally invasive and well tolerated. These are the conclusions of a preliminary trial, from the US National Cancer Institute, in which 24 ablations were performed in 21 patients with renal tumors. All tumors were solid on computerized tomography (CT), 3 cm or less in diameter and enlarging for at least 1 year. Ablation, delivered with ultrasound and/or CT guidance, involved delivery of radio frequency energy from a 50 W, 460 kHz electrosurgical generator via a percutaneously placed 15 gauge coaxial probe. At least two, 10–12 min ablation cycles were applied to each lesion, with patients being observed overnight before discharge from hospital. Re-evaluation at 2 months postoperative showed that the mean tumor diameter had decreased from 2.4 [standard deviation (SD) ±0.4 cm] to 2.0 cm (SD ± 0.5 cm, P = 0.001) and a majority of tumors (19 of 24, 79%) ceased to be enhanced on contrast CT. Mean serum creatinine ±SD was unchanged during this interval. The authors warn, however, that the procedure must remain experimental until procedural and imaging parameters that correlate with tumor destruction are validated [4].

...children with cancer and other chronic illnesses often adapt to their conditions by repressing their emotions, covering over feelings of depression and anxiety. This is the conclusion of a study, from St Jude Children’s Research Hospital, Memphis, TN, which sought to confirm the results of previous studies of repression in children with cancer and to assess whether this repression was a general feature of chronic illnesses in children. Measures of defensiveness, trait anxiety and anger expression were obtained from three groups of children; those with cancer (n = 130), those with chronic illnesses (diabetes, cystic fibrosis and juvenile rheumatoid disorders, n = 121) and healthy control participants (n = 368). Based on their self-reports, participants were categorized as either high anxious, low anxious, defensive high anxious or repressor, with the prevalence of these categories being compared across the three groups. Children in the cancer and chronic illness groups both reported significantly higher levels of defensiveness and lower levels of anxiety than those in the healthy control group. The authors suggest that even if chronically ill children report no distress, further assessment using additional questions or additional screening may be indicated [5].

...the COMPARE algorithm, which allows comparison of compounds based on their mechanism of cell growth inhibition, and associated data, are freely available on the Web site of the US National Cancer Institute’s Developmental Therapeutics Program (DTP) http://dtp.nci.nih.gov/. It has been demonstrated previously that compounds with similar mechanisms of cell growth inhibition show similar patterns of activity in inhibiting the growth of human tumor cell lines in culture (NCI screen). COMPARE has been successfully used to predict mechanisms for a wide variety of compounds, and more recently it has been extended to associate patterns of cell growth inhibition by compounds with measurements of molecular entities (such as gene expression) in the cell lines in the NCI screen [6].

References

1. Ness RB, Cramer DW, Goodman MT et al. Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case-control studies. Am J Epidemiol 2002; 155: 217–224.[Abstract/Free Full Text]

2. Guba M, von Breitenbuch P, Steinbauer M et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nature Med 2002; 8: 128–135.[ISI][Medline]

3. Weeks JC, Nelson H, Gelber S et al. Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial. JAMA 2002; 287: 321–328.[Abstract/Free Full Text]

4. Pavlovich CP, Walther MM, Choyke PL et al. Percutaneous radio frequency ablation of small renal tumors: initial results. J Urol 2002; 167: 10–15.[Medline]

5. Phipps S, Steele R. Repressive adaptive style in children with chronic illness. Psychosom Med 2002; 64: 34–42.[Abstract/Free Full Text]

6. Zaharevitz DW, Holbeck SL, Bowerman C, Svetlik PA. COMPARE: a web accessible tool for investigating mechanisms of cell growth inhibition. J Mol Graph Model 2002; 20: 297–303.[ISI][Medline]





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