Trends in length of stay, living setting, functional outcome, and mortality following medical rehabilitation

Context  Changes in reimbursement have reduced length of stay (LOS) for patients receiving inpatient medical rehabilitation. The impact of decreased LOS on functional status, living setting, and mortality is not known. Objective  To examine changes in LOS, functional status, living setting, and mortality in patients completing inpatient rehabilitation. Design  Retrospective cohort study from 1994 through 2001 using information submitted to the Uniform Data System for Medical Rehabilitation. Setting and Participants  Data were analyzed from 744 inpatient medical rehabilitation hospitals and centers located in 48 US states. A total of 148 807 patient records from 5 impairment groups (stroke, brain dysfunction, spinal cord dysfunction, other neurologic conditions, and orthopedic conditions) were examined. Patients’ mean age was 67.8 (SD, 15.8) years; the sample was 59% female and 81% non-Hispanic white. Main Outcome Measures  Discharge setting, follow-up living setting, change in functional status, and mortality. Results  Median LOS decreased from 20 to 12 days (P<.001) from 1994 to 2001. The proportional decrease in median LOS was greatest (42%) for patients with orthopedic conditions. Mean days to follow-up remained constant from 89 in 1994 to 90 in 2001. Functional status was clinically stable, while efficiency (functional status change divided by LOS) increased significantly (P<.001). Rates of discharge to home and living at home at follow-up remained stable, ranging from 81% to 93%. However, mortality at 80- to 180-day follow-up increased from less than 1% in 1994 to 4.7% in 2001. Conclusions  Length of stay for inpatient rehabilitation decreased substantially from 1994 to 2001. Effectiveness as measured by change in functional status did not change clinically, and living setting did not change. Efficiency for functional outcomes improved but mortality at follow-up increased.      

Suicide trends in South Africa, 1968--90

AIMS: A study was undertaken to investigate suicide rates and proportional mortality trends in South Africa from 1968 to 1990. METHODS: Suicide rates per 100,000 population per year and suicide proportional mortality rates per year were calculated. The analyses were stratified by race, sex, and age group. Trends were interpreted using graphs depicting smoothed sex/race-specific suicide rates and proportional mortality rates over time. Regression models for suicide rates were fitted within specific age groups to test the effects of race, sex, and time. Further analysis was done within the specific age and race groups, if any interaction was found with time. RESULTS: There were increases in suicide rate in the young (particularly for white males) and for whites aged 65 years and above (particularly for males). CONCLUSIONS: The finding that suicide among the young and elderly in South Africa is increasing suggests that preventive efforts are indicated, especially for white males. Trends for young South Africans mirror those in Europe and the USA, and attention to trends in these countries may predict future trends in youth suicide in South Africa.     

Apnea and bradycardia due to anaphylaxis to tobacco glycoprotein in the infant rabbit

Prenatal and postnatal exposure to cigarette smoke is associated with an increased incidence of the sudden infant death syndrome, although the cause(s) for this is unknown. Tobacco glycoprotein (TGP), a group of proteins purified from cured tobacco leaves and present in cigarette smoke, have been shown to cause anaphylaxis in excised hearts and lungs of adult rabbits that were neonatally sensitized to TGP and later rechallenged. We sought to determine whether anaphylaxis occurred in live infant rabbits who were neonatally sensitized to TGP. At the age of 1 day, 12 animals were sensitized to TGP (0.1mg in 0.25 cc alum) via intraperitoneal injection (i.p.i.) followed by a booster ipi at the age of 30 days (TGP-S). Seven animals received i.p.i. of antigen-free alum only (controls). All animals underwent an intravenous TGP challenge at age 42+/-2 days. Heart rate (HR) and respiratory rate (RR) were recorded for 2 min prior to and 5 min after the challenge. Baseline HR (approximately 260) and RR (approximately 120) were similar in all animals. Seven TGP-S animals developed apnea (1.9-4.7s) within 60s of the challenge while none of the controls did. The TGP-S also became bradycardic (the lowest HR over 50 consecutive beats), with the HR decreasing from 260 to 220 vs the controls, whose HR remained constant (approximately 250). We conclude that some rabbits neonatally sensitized to TGP develop apnea and bradycardia upon further intravenous TGP challenge. These studies suggest that cigarette smoke exposure may be associated with a higher rate of SIDS via an anaphylactic mechanism.     

Diet-gene interactions in p53-deficient mice: insulin-like growth factor-1 as a mechanistic target

Progress in cancer prevention research is being facilitated by the use of animal models displaying specific genetic susceptibilities for cancer, such as mice deficient in one (+/-) or both (-/-) alleles of the p53 tumor suppressor gene. Our lab, which focuses on nutrition (particularly energy balance/obesity) and molecular carcinogenesis, has shown in p53-/- mice that calorie restriction (CR) increases the latency of spontaneous tumor development (mostly lymphomas) approximately 75%, decreases serum insulin-like growth factor (IGF)-1 and leptin levels, and induces apoptosis in immature (lymphoma-susceptible) thymocytes. In heterozygous p53-deficient (p53+/-) mice, CR and a one day/wk fast each significantly delay spontaneous tumor development (a mix of lymphomas, sarcomas, and epithelial tumors) and decreases serum IGF-1 and leptin levels, even when begun late in life. We are presently comparing and combining CR and exercise (treadmill and running wheel) to further elucidate the relationships between energy balance, p53, and tumorigenesis in these models. Furthermore, we have capitalized on the susceptibility of p53+/- mice to chronic, low-dose aromatic amine-induced bladder carcinogenesis to develop a model for evaluating bladder cancer prevention approaches. Using this model, we have established that IGF-1 mediates many of the anti-cancer effects of CR. We are currently conducting oligonucleotide microarray studies to further characterize diet-gene interactions underlying the anti-cancer effects of CR and to determine which of the CR-responsive genes are IGF-1 dependent.     

Framing the doctor-patient relationship in chronic illness: a comparative study of general practitioners' accounts

How family doctors conceptualise chronic illness in the consultation has important implications for both the delivery of medical care, and its experience by patients. In this paper, we present the results of a re-analysis of qualitative data collected in a series of studies of British family doctors between 1995 and 2001, to explore the ways in which the legitimacy and authority of medical knowledge and practice are organised and worked out in relation to three kinds of chronic illness (menorrhagia; depression; and chronic low back pain/medically unexplained symptoms). We present a comparative analysis of (a). the moral evaluation of the patient (and judgements about the legitimacy of symptom presentation); (b). the possibilities of disposal; and (c). doctors' empathic responses to the patient, in each of these clinical cases. Our analysis defines some of the fundamental conditions through which general practitioners frame their relationships with patients presenting complex but sometimes diffuse combinations of 'social', 'psychological' and 'medical' symptoms. These are fundamental to, yet barely touched by, the increasingly voluminous literature on how doctors should interact with patients. Moving beyond the individual studies from which our data are drawn, we have outlined some of the highly complex and demanding features of what is often seen as routine and unrewarding medical work, and some of the key requirements for the local negotiation of patients' problems and their meanings (for both patients and doctors) in everyday general practice.     

Effects on aqueous flow of dorzolamide combined with either timolol or acetazolamide

PURPOSE: To determine the effect on aqueous flow of topical dorzolamide 2%, topical timolol 0.5%, or oral acetazolamide 250 mg when used alone or when dorzolamide is combined with either timolol or acetazolamide. METHODS: In 30 patients with ocular hypertension, aqueous flow and intraocular pressure (IOP) were determined at baseline and on the following combinations of drugs in a crossover design: (1) vehicle alone, (2) dorzolamide alone, (3) acetazolamide alone, (4) timolol alone, (5) dorzolamide + acetazolamide, and (6) dorzolamide + timolol. Treated eyes were compared with control eyes and comparisons were made between treatments. RESULTS: Compared with baseline, significant (P < 0.04) IOP reductions in the order of efficacy were: dorzolamide + timolol > dorzolamide + acetazolamide = acetazolamide = timolol > dorzolamide. Aqueous flow was reduced more by dorzolamide + timolol than by each drug alone (P < 0.04) and more by dorzolamide + acetazolamide than by dorzolamide alone (P < 0.04). CONCLUSION: The combination of dorzolamide and timolol demonstrated significant aqueous flow additivity and had greater IOP efficacy than the combination of dorzolamide and acetazolamide.     

Anti-AIDS agents. 52. Synthesis and anti-HIV activity of hydroxymethyl (3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone derivatives

To enhance the water solubility and oral bioavailability of DCK analogues, 12 new mono- and disubstituted (3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogues were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 3-Hydroxymethyl-4-methyl-DCK (4c) exhibited significant anti-HIV activity in H9 lymphocytes and primary peripheral blood mononuclear cells with EC(50) values of 0.004 and 0.024 microM, respectively. Although this compound was not as potent as 4-methyl-DCK (2) and 3-bromomethyl-4-methyl-DCK (4a), it provides increased water solubility and possible linkage to other moieties. Of particular note, 4c exhibits moderate oral bioavailability (15%) when administered as a carboxymethylcellulose suspension to rats, whereas 2 is not orally bioavailable in the same formulation. Further studies on mechanism of action suggest that 4c inhibits the production of double-stranded viral DNA from the single-stranded DNA intermediate. In addition, 4a is the most potent compound in this series of new analogues, with EC(50) and TI values of 0.00011 microM and 189,600, respectively. Thus, further modification at the 3-position of the coumarin ring can improve the potency of new DCK analogues.     

Synthesis and biological evaluation of analogues of 7-chloro-4,5-dihydro-4- oxo-8-(1,2,4-triazol-4-yl)-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylic acid (TQX-173) as novel selective AMPA receptor antagonists

In recent papers (Catarzi, D.; et al. J. Med. Chem. 2000, 43, 3824-3826; 2001, 44, 3157-3165) we reported chemical and biological studies on 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates (TQXs) bearing different nitrogen-containing heterocycles at position-8. In particular, from these studies it emerged that both the 7-chloro-4,5-dihydro-4-oxo-8-(1,2,4-triazol-4-yl)-1,2,4-triazolo[1,5-a] quinoxaline-2-carboxylic acid TQX-173 (compound B) and its corresponding ethyl ester (compound A) were the most active and selective compounds of this series. In pursuing our investigation on the structure-activity relationships of these TQX derivatives, different electron-withdrawing groups (CF(3), NO(2)) were introduced at position 7 on the TQX ring system, replacing the 7-chloro substituent of B and of other selected 8-heteroaryltriazoloquinoxaline-2-carboxylates previously described. All the newly synthesized compounds were biologically evaluated for their binding at the Gly/NMDA, AMPA, and KA high-affinity receptors. Gly/NMDA binding assays were performed to assess the selectivity of the reported compounds toward the AMPA receptor. Compounds endowed with micromolar binding affinity for the KA high-affinity binding site were also evaluated for their binding at the KA low-affinity receptor. Some selected compounds were also tested for their functional antagonist activity at the AMPA and NMDA receptor-ion channel complex. The results obtained in this study have pointed out that 4,5-dihydro-7-nitro-4-oxo-8-(3-carboxypyrrol-1-yl)-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylic acid (9b) and its corresponding ethyl ester (9a) are the most potent and selective AMPA receptor antagonists reported to date among the TQX series.