Why multihospital systems will continue to grow

The limitations of federal and state spending on health care indicate difficult times are ahead for hospitals. Rising costs are challenging their continued existence. Construction and renovation, for example, are normally not feasible in light of the present economic situation. To meet this financial challenge, Multi-Institutional Arrangements ( MIAs ) are proliferating. This phenomenon, which is particularly prevalent in the Southern United States, seems to be increasing geometrically, principally because many of the officials who operate hospitals see such an affiliation as an answer to their serious fiscal problems. Faced with myriad financial problems resulting from overcommitment , hospital boards are looking for a way out of the quagmire . While the boards do not want to give up control of the hospital to an outside group, they are beginning to realize that it may be the price that must be paid for fiscal solvency (i.e., keeping the hospital open to serve the public). Hospital boards usually are favorably impressed by the promised benefits accruing from association with a MIA.     

Analysis of the seasonal pattern in suicide

BACKGROUND: Suicide has been attributed to social and psychological factors but also to geophysical effects. Of the latter, changes in solar radiation and geomagnetic activities may contribute to the frequency and the seasonal pattern of suicides. METHODS: We studied with a population-based, nationwide analysis all the individuals who committed suicide (n=27,469) in Finland during the period of 1979 to 1999. The daily data on the number of suicides, and the mean and maximum levels of geomagnetic activity were compiled and modelled with Poisson regression using the number of inhabitants in each province as the denominator. Time series analysis of monthly numbers of suicides was carried out using a seasonal-trend decomposition procedure. RESULTS: There was a strong seasonal effect on suicide occurrence (P<0.00001), the risk of suicide being greatest in spring. The seasonal effect was most pronounced when the number of suicides was relatively low. High levels of solar radiation activity were associated with the increased risk of suicide (P=0.00001), but the effect of geomagnetic activity was weak. LIMITATIONS: No individual data on alcohol consumption or mental disorders were available. CONCLUSIONS: Suicide occurrence varies markedly by season and needs attention where prevention is concerned.     

Hepatic arterial variations and liver-related diseases of 100 consecutive donors

We prospectively studied anatomical variations and diseases of the liver in 100 consecutive donor operations during a period of 1 year. The normal arterial anatomy with a single hepatic artery (HA) from the celiac trunk was seen in 76% of all cases. Seven of twelve different major variations of the HA may be considered as rare, one of which cannot be found in the earlier literature. During harvesting, 6% of the livers were discarded, 3% on the basis of infection and 1% because of a polycystic disease. Two cases were rejected as the liver was found to be severely hypoperfused or hypoxic in an otherwise stable donor. Severe steatosis was macroscopically and histologically diagnosed in 3% of the cases, and in three donors a benign tumour was found in the liver or in the gall bladder. Two primarily nonfunctioning livers in the present series of 94 recipient operations were retrieved from this group of severely steatotic livers. As the donor liver was totally normal in only 2 out of 3 of the cases, the present study underlines the importance of searching for extremely variable anomalies of the HA and for liver-related diseases during organ harvesting.     

Cancer incidence among Finnish seafarers, 1967–92

A cohort of 30,940 male and 11,529 female seafarers registered in the files of Seafarers' Pension Fund in Finland was followed up through the Finnish Cancer Registry for cancer in 1967–92. Among male seafarers, there were 1,199 cases of cancer, which corresponds to the average cancer incidence in Finnish men. There was a statistically significant excess of non-melanoma skin cancer (standardized incidence ratio [SIR]=1.8, 95 percent confidence interval [CI]=1.2–2.5) and mesothelioma (SIR=2.9, CI=1.2–5.6) in the follow-up category of 20 or more years since the first employment. Alcohol-related cancers were increased among seafarers (SIR for cancer of the mouth and pharynx = 1.; esophagus = 1.4; and liver = 1.5; combined CI=1.1–1.9). Deck crews had a significantly high risk of cancer of the pancreas (SIR=2.0) and also prostate after 10 years since first employment (SIR=1.6). Occupational asbestos exposure among seafarers is likely strong enough to cause excess cases of mesothelioma but not of lung cancer. Occupational exposures also may be associated with increased risk of cancers of the kidney, pancreas, prostate and old-age brain cancer in some of the main occupational categories. Cumulative ultraviolet radiation likely doubles the risk of nonmelanoma skin cancer among older men and repeated sunburns that of skin melanoma in ages below 30 (SIR among deck and engine crew = 4.6, CI=3.1–6.5). Female ship personnel had a significantly elevated total cancer risk (observed number of cases = 732) which increased over follow-up time (SIR in the category 20 years since the first employment was 1.3, CI=1.1–1.5). This excess was attributable primarily to lung cancer (SIR=2.6, CI=2.0–3.3). Also cancers of the cervix uteri, vulva, and vagina showed significant excess after 10 to 20 years since first employment aboard.Address correspondence to Dr Pukkala, Finnish Cancer Registry, Litsankatu 21 B, FIN-00170 Helsinki, Finland. The Finnish Work Environment Fund financially supported this project.Dr Pukkala is with the Finnish Cancer Registry, Helsinki, Finland. Dr Saarni is with the Regional Institute of Occupational Health, Turku, Finland.     

Prospective randomized comparison of endonasal endoscopic dacryocystorhinostomy and external dacryocystorhinostomy

Objectives and Study Design: The advent of the rigid endonasal endoscope and the development of functional endoscopic sinus surgery (FESS) technique have awakened interest in an endonasal endoscopic dacryocystorhinostomy (EESC-DCR) in treating nasolacrimal obstruction. This prospective, randomized study compares EESC-DCR with traditional external dacryocystorhinostomy (EXT-DCR) for their success rates, surgical duration, and postoperative symptoms. Patients and Methods: Sixty-four cases in 60 patients with primary acquired nasolacrimal sac or duct obstruction were divided into two subgroups by symptoms (simple epiphora/ chronic dacryocystitis). These patients were randomized within both subgroups into two operation groups. Altogether 32 EESC-DCRs and 32 EXT-DCRs were performed. The final follow-up visit was at 1 year. The patency of the lacrimal passage was investigated by irrigation and patients were questioned about their symptoms. Results: The success rate at 1 year after surgery was 75% for EESC-DCR and 91% for EXT-DCR after primary surgery. The difference was not statistically significant (P = .18). The success rate after secondary surgery with a follow-up time of 1 year was 97% in both study groups. The average duration for EESC-DCR was 38 minutes, and 78 minutes for EXT-DCR, (P < .001). Conclusions: EXT-DCR, when compared with EESC-DCR, appears to give a higher, although not statistically significant, primary success rate, but the secondary success rates are equal, indicating that these two different DCR techniques are acceptable alternatives.     

First trimester combined screening biochemistry in detection of congenital heart defects

Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs).

Methods: During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down’s syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland.

Results: Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively.

Conclusions: Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.     

Trastuzumab emtansine: mechanisms of action and drug resistance

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that is effective and generally well tolerated when administered as a single agent to treat advanced breast cancer. Efficacy has now been demonstrated in randomized trials as first line, second line, and later than the second line treatment of advanced breast cancer. T-DM1 is currently being evaluated as adjuvant treatment for early breast cancer. It has several mechanisms of action consisting of the anti-tumor effects of trastuzumab and those of DM1, a cytotoxic anti-microtubule agent released within the target cells upon degradation of the human epidermal growth factor receptor-2 (HER2)-T-DM1 complex in lysosomes. The cytotoxic effect of T-DM1 likely varies depending on the intracellular concentration of DM1 accumulated in cancer cells, high intracellular levels resulting in rapid apoptosis, somewhat lower levels in impaired cellular trafficking and mitotic catastrophe, while the lowest levels lead to poor response to T-DM1. Primary resistance of HER2-positive metastatic breast cancer to T-DM1 appears to be relatively infrequent, but most patients treated with T-DM1 develop acquired drug resistance. The mechanisms of resistance are incompletely understood, but mechanisms limiting the binding of trastuzumab to cancer cells may be involved. The cytotoxic effect of T-DM1 may be impaired by inefficient internalization or enhanced recycling of the HER2-T-DM1 complex in cancer cells, or impaired lysosomal degradation of trastuzumab or intracellular trafficking of HER2. The effect of T-DM1 may also be compromised by multidrug resistance proteins that pump DM1 out of cancer cells. In this review we discuss the mechanism of action of T-DM1 and the key clinical results obtained with it, the combinations of T-DM1 with other cytotoxic agents and anti-HER drugs, and the potential resistance mechanisms and the strategies to overcome resistance to T-DM1.