P Yeates

J T Costello

E T Kennedy

Charged Particle Dynamics in a 'High Pressure' Laser Ion Source

Keywords: laser ion source, ion bunch, beam transport, simulation, SIMION PACS: 52.38.-r (Laser Plasma) 52.50.-Dg (Ion Sources)

published or not. The documents may come

Charged particle dynamics in a high-pressure laser ion source

Introduction

Charged particle systems take many forms. Laser ion sources (LIS) [1][2][3], radiofrequency (RF) [4,5] or microwave sources [6,7], insertion devices like wigglers and undulators and related free electron laser (FEL) devices [8][9][10], linear particle accelerators (LINAC) [11,12] and e -guns [13,14] amongst others. To usefully employ the resultant electron or ion bunches, electrostatic and/or magnetic optics for transport and manipulation are often essential. Common optical elements include einzel lenses [15][16][17], ion energy analyzers (IEA) [18][19][20], quadrapoles [21], Wien [22] filters, charged grids and bending magnets.

Electrostatic optics are utilized for numerous applications such as collimation (for beam transport), focusing, energy (velocity) and charge selection, energy (velocity) compression (usually termed 'energy focusing'), space -charge force compensation and particle acceleration (or deceleration). All electrostatic optics however can be labelled filters, essentially creating differing path lengths (linear) or trajectories (radial) due to a charge or kinetic energy differential between charged particles. Einzel lenses are one of the most widely utilized electrostatic optical elements, especially in the case of laser ion sources where extensive reports on the design, analysis and simulation of einzel lenses have been published [23][24][25][26][27][28].

A primary concern for electrostatic lens designers is to ensure that the lens parameters are constant over a range of bias values. Lenses can be two element systems [29][30][31] however such designs do not permit a constant 'image' size to be achieved for varying bias values. Three element lenses have been studied in great detail [32][33][START_REF] Grivet | Electron Optics[END_REF][START_REF] Hawkes | Focusing of Charged Particles[END_REF][START_REF] Paszkowski | Electron Optics[END_REF][START_REF] Read | [END_REF][START_REF] Klemperer | Electron Optics[END_REF] with regard to focusing properties, zoom range and magnification control. The above mentioned 'einzel' lens is a particular category of three element lenses, in that the central element is biased while the outer two are not (or are similarly biased). The unique property of such lenses is that the initial energy of the particle under influence is not modified [START_REF] El -Kareh | [END_REF][40][41][42] and the image position is constant. However, the magnification is not. Four element lenses can produce both a fixed image position and a constant image size [43][44][45][46]. Multiple elements are also possible, e.g., Correa et al in a recent publication [47] studied the concept of multiple electrostatic elements in series. Both, single 'wall', parallel plate and ring units were analytically studied and simulated for possible electrostatic trapping in lieu of magnetic bottles.

In a 'high -pressure' LIS, the divergence of the beam is very high due to the average charge state and the high ion density within the extracted plume. Combined, these two effects result in strong lateral beam expansion within the drift tube, driven by strong space -charge forces and the fast flow velocity of the primary plasma plume from which the ions are subsequently extracted. The latter originates from the explosive nature of laser plasma generation.

As the extraction voltage (V ext ) increases the bias required to compensate for beam divergence increases. Experimental [48][49][50] studies on our system indicated that the electrostatic optical system must be biased to ~ 45 -60% of V ext for efficient ion transportation and capture. The system is designed to be a compact LIS. Thus we utilize drift tubes of moderate radius (80 mm). This in turn leads to einzel cylindrical elements of diameter ~ 50 mm. Consequently, strong focusing of the rapidly expanding beam leads to strong divergence after each focus point. LIS systems need long drift tubes (D > 1 m) to ensure a long enough time -of -flight (TOF) separation of differently charged ions. Such a condition requires continuous refocusing of the injected ion bunches for optimum system throughput. Experimentally, traditional three element einzel units have been found to be unsatisfactory when applied to a high -pressure LIS [48]. It becomes necessary to test experimentally the concept of a multiple element electrostatic system [47].

In this paper, we expand upon the performance of the DCU laser ion source (LIS) [48]. Specifically, we present experimental data and detailed ion electrodynamic simulations on a beam transport system that we term a 'continuous einzel array (CEA)'. Individual sections of the CEA can be biased separately, allowing the effective 'length' of this beam transport system to be varied. We have also studied the source operational performance with three element and five element lenses and compared them with the performance of the ion source with the full multiple element CEA.

System design

The DCU -LIS [48][49][50] employs a range of extraction voltages both DC (5-18 kV) and pulsed (15-50 kV). Laser intensities used to generate plasma ions range from ~10 9 -10 11 Wcm -2 via a Q -switched Ruby laser (τ ~35 ns, λ = 694 nm). The short field free region in our system (L = 48 mm) means that strong space -charge forces result in pronounced beam expansion and divergence upon injection into the drift tube. To minimize the beam divergence and concomitant beam loss a unique electrostatic transport system, which we term a 'continuous einzel array (CEA)' was designed and integrated into the drift tube. In combination with high extraction bias at the source, the 36 element CEA results in a number of significant gains in system performance. The specific parameters affected include the temporal duration of the collected ion bunches, the uniformity of the velocity distributions within each ion bunch and the radial properties of each charged resolved ion bunch. The total system throughput is also improved by the CEA, albeit the gain is charge dependent.

A detailed description of the electrostatic lens system design and specifications is given elsewhere [48]. The initial electrostatic transport system employed in the DCU -LIS consisted of three einzel lens units (each unit was composed of three hollow cylinders, a central element which was positively biased and two grounded cylinders, one located on either side of the central ring). These compound lens 'units' were placed at the entrance, midpoint and exit of the 2.16m long drift tube. The second and more effective system comprised the continuous einzel lens array (CEA) placed along the whole length of the drift tube. The final section of the CEA could be biased separately from the other sections of the CEA and was composed of five elements in total (two biased and three grounded).

Measurement and simulations

To thoroughly diagnose the effects of the CEA on the LIS performance we compared experimental data with results from detailed SIMION TM simulations, focussing on three specific aspects of the system performance. Firstly, in section 3.1 we present data on the modification of the velocity distribution within the extracted Cu + ion bunch, at the end of the CEA. We observe a two component distribution when the CEA is biased to the high values required when the source potential, V ext is high. Secondly, in section 3.2 we demonstrate strong variations in the radial focusing properties of the CEA which results in preferential focusing of ion bunches of one charge state over its neighbouring states of ionization. This is presented both experimentally and through simulations. Lastly in section 3.3, the total system throughput with the CEA, is presented, and a quantitative comparison between the CEA performance and that of the more traditional 3 and 5 -element einzel lens systems is discussed in detail.

TOF velocity group formation

The TOF signal recorded by a Faraday cup [48] for all extraction voltages (V ext ) clearly indicated a two component distribution in the current trace for charge states from Cu + to Cu 5+ when the CEA was employed to enhance beam transportation and collection. To further investigate this aspect of the extracted ion beam electrodynamics the system was simulated in SIMION TM . A range of initial energies E 0 for each charge state in the simulation, corresponding to values obtained from the Langmuir probe diagnostic of the copper plasma plume within the extraction gap, were used as input to the code. The experiment [48] was performed with a laser intensity I p ~1.13×10 11 Wcm -2 and fluence F ~3.97 kJcm -2 and the measured Maxwell -Boltzmann kinetic energy distribution of the plasma ions ranged from ~5 -55 eV (with a peak at ~28 eV).

A series of simulations of the DCU -LIS for initial ion energies (E 0 ) ranging from 5 eV to 55 eV, in steps of 0.81 eV, for ion bunches composed of 500 Cu + ions were performed. These energy groups were 'launched' from the planar copper target surface. Thus sixty -one different energy groups were simulated. The diameter of each monoenergetic plasma plume at creation was set to 2 mm (parallel to the simulated target surface), in accordance with the plasma plume radius upon laser pulse termination, as predicted by the MEDUSA [51,[START_REF] Djaoui | Calculation of the time -dependent excitation and ionization in laser -produced plasma[END_REF] laser plasma code and the Narayan and Singh [53] analytical, Eulerian 2D fluid code for our conditions. These codes utilized initial parameters which closely reproduced our experimental plasma plume [48]. The extraction bias (V ext ) and CEA bias values were set to those values employed experimentally. The ions were launched parallel to each other, however the Columbic repulsion factor in SIMION TM was set to 5×10 -14 C. This value was used to obtain a plasma plume which expanded through a ±30 0 cone relative to the target normal.

For each simulated initial energy, the time of flight (TOF) was recorded upon arrival of the extracted ions at the end of the drift tube. The results are plotted in figure 1, for a number of initial energies (E 0 ). The upper inset (a) in figure 1 To experimentally quantify the observed two component behaviour of the extracted ion bunches, the measured TOF trace from the Cu + ion bunch was deconvoluted to generate two Gaussian functions centred at the two observed signal peaks in the Cu + ion bunch, for the data sets for V ext = 5 -15 kV and F = 3.97 kJcm -2 . Figure 2 displays the measured peak voltage for each deconvoluted velocity group plotted against the extraction voltage (V ext ). The upper inset (a) in figure 2 shows the TOF of the deconvoluted peaks for both velocity groups.

The lower inset (b) displays the experimental TOF current trace for Cu + for F = 3.97 kJcm -2 and V ext = 5 kV.

Comparing figure 1 and2 (simulation versus experiment) we make the following observations. Ions launched close to the system axis (i.e. ion '250', bunch centre in figure 1, lower inset -b) exhibit the shortest simulated TOF, as expected. In comparison, ions launched at large angles relative to the system optic axis follow a more complex set of ion trajectories (main figure, figure 1). Experimentally this can be seen in figure 2 as the 'leading group' and the 'trailing group'. The leading group exhibit shorter TOF values (upper inset -a, figure 2) and also a moderate contribution to the total recorded Cu + bunch signal as V ext increases. The longer TOF of the trailing velocity group is due to the diversity of trajectories taken by this ion group as they traverse the drift tube. Ions travelling along the most divergent trajectories experience the greatest electrostatic focusing by the CEA resulting in an extended path length and hence TOF from source to Faraday cup. Furthermore, as V ext increases, the contribution of the trailing edge group to the total detected signal in figure 2 grows rapidly. This result demonstrates the beneficial compensation effect in having a high source potential (V ext ).

To obtain a more quantitative measure of these effects, the number of simulated ions arriving within a 4 ns integration time at the Faraday cup were calculated (corresponding to the integration time on the oscilloscope). The simulation results are plotted in figure 3. The two component velocity distribution is evident with a clearly defined peak -to -peak separation. The inset in figure 3 shows the actual experimental data for F = 3.97 kJcm -2 for V ext = 5 kV. Superimposed on this trace is a two peak Gaussian fit, identifying the TOF location of each peak. The simulated results display a large signal contribution from the leading edge group while the experimental results indicate a larger contribution from the trailing velocity group. This difference in the relative signal magnitudes between the leading edge and trailing edge velocity groups for the simulation versus actual results may be partly attributed to the absence of various loss mechanisms which SIMION is unable to include, e.g. ion -gas collisions. A second limitation is the simulations' approximation of the columbic inter -ion space -charge forces which broaden the beam during transport. This occurs three dimensionally and is an extremely complex process.

In a previous publication [49] the extraction efficiency (actual beam kinetic energy versus expected kinetic energy for a particular value of V ext ) was determined to be ~55 -65% depending upon the laser fluence and extraction voltage used. Thus a discrepancy in the absolute TOF values between the simulation and experiment was expected. The difference is related to Debye shielding of the plasma bulge at the anode within the extraction gap [48,49], leading to inefficient coupling of the electric field lines to the extracted ions. However, despite this discrepancy, the peak -to -peak separations for both data sets are in good agreement given the limitations of the simulation process. This two component temporal distribution behaviour was observed for all recorded charge resolved ion bunches (Cu + -Cu 5+ ), for high extraction voltages. Thus while utilization of the CEA dramatically improves the system throughput both in terms of the peak recorded current and the highest recorded charge state, it gives rise to a broadening of the temporal distribution of each ion bunch.

Many applications utilizing highly charged ions require good yield (ion density) per 'event', and mono -energetic ion bunches are generally preferred. For implantation studies, extracted ion bunches from the DCU -LIS, if directed at a target would implant over a range of depths. For efficient and discrete implanted layer formation, energy compression (termed energy focusing) would be required. Our experiments confirm that the contribution to the overall signal from the 'trailing velocity group' increases with V ext increases (figure 2).

In contrast, the portion of the TOF trace (from the 'leading velocity group' saturates for V ext > 12 kV. As V ext (often termed the source potential) increases, it tends to compensate for the space -charge forces which underlie the observed beam divergence. For ions travelling almost paraxially in the drift tube, this improved beam transport process can only be applied to the extent that inter -ion repulsive forces will allow. In comparison, ions undergoing strong divergence must be strongly refocused if successful transport of this group is be achieved. Thus increased source potential must be matched by increased bias on the CEA and in combination these two actions ensure efficient transport of highly diverging ions along the drift tube.

Radial behaviour and beam focusing

The diagnostic chamber at the end of the drift tube was equipped with a range of detectors including a scanning planar probe. Orientated in the vertical plane, and facing the oncoming ion beam, the planar probe was 3 mm wide and 35 mm long. It could scan the transported ion beam radially to determine the signal response across the beam diameter.

Minimum beam diameters of ~ 6 mm were recorded under optimum focusing conditions [48].

It was observed that optimum beam transport and focusing bias on the CEA for a particular ion bunch reduced the detected peak current for neighbouring charged states (an effect most pronounced for the more highly charged ions). The extent of this preferential response to different charge states is clear from figure 4. Here the radial dependence of the detected signal trace for V ext = 7 kV, F = 3.97 kJcm -2 , under conditions which optimized the collected Cu 2+ ion signal via the Faraday cup, is displayed. Beam transport conditions result in a double peak structure in the radial dependence for Cu 2+ but not for other charge states. However, these conditions did not result in optimal signals for more highly charged ions, nor did they minimize the Cu 2+ bunch diameter at the end of the drift tube, as is clear from figure 4.

To investigate this aspect of the system performance, simulated bunches of 400 Cu 2+ ions were launched with energies between E 0 = 5 and 55 eV, in intervals ΔE = 5 eV. The values of the source potential and einzel bias used, were determined by experiment for a) optimum throughput (T p ) and b) best focus conditions (minimum beam diameter). The radial positions of the ions upon arriving at a position in the drift tube corresponding to the position of the scanning planar probe were recorded. These results are displayed in figure 5a and5b where the experimentally determined radial dependence of the probe peak voltage signal for Cu 2+ ion bunch is superimposed on the results of simulations for the same charge state. The differences in the focusing properties of the CEA are clearly evident in both the experimental and simulation results. The agreement between the experimental and simulation results is better for the system when optimised for best focus. The results provide further insight into the behaviour observed earlier [48,49] from our system regarding optimized transport. This analysis is also relevant to current density measurements, J (equal to collected current divided by beam area, ~Ic /A). Many systems minimize the diameter of the aperture to their detector to prevent or minimize secondly electron emission. For beam diameters that are not matched to the detector entrance aperture, varying degrees loss of beam may result.

The challenge in balancing the desire to minimize beam diameters (and thus maximize the collected current density, J) versus charge dependent optimised system throughput (T p ) was also present in our system. Generally system throughput is defined in terms of peak collected current of the charge state. For optimized Cu 2+ transport and focusing conditions we noted that the Cu 3+ collected signal decreased by ~20 -30% and the beam diameter was not minimized. These observations are directly linked to the electrostatic lens limitations, as the bias and/or charge state changes. Such behaviours are of particular relevance to systems which rely on charge dependent TOF separation for accurate classification and quantification of ion yields. There is a limit on the length of a drift tube, dictated by loss mechanisms, especially vacuum constraints. Consequently, a charge resolved ion train will arrive at a detector within a window of typically a few microseconds and as it will usually require beam focusing, it will encounter the problem of preferential, charge dependent ion bunch focusing and transport. Thus the utilization of a variable circular aperture in concert with a CEA can act as a charge filter.

Beam transport

Efficient transport of extracted charged particles can be obtained at high source potential (to offset space -charge forces) and/or high ion or electron initial energies, or by employing electrostatic optics. The latter mechanism controls the flow of the extracted particles through the electric forces experienced by those particles, from multiple electric field sources/sinks, as they take diverse trajectories along the drift tube. This is especially true for an electrostatic transport system which is composed of many elements. While presenting a significant challenge, such transport systems have a number of inherent advantages. For example, laser energies and system extraction bias values have limited practical operational ranges. In comparison, a multi -component electrostatic transport system can dramatically enhance system throughput, with only minor increases in individual element bias since optical properties vary non -linearly with the applied voltages.

To investigate the main features of the transport system in the DCU -LIS, we simulated its throughput. This was achieved by launching bunches of 400 Cu 2+ ions with a range of initial energies E 0 from 2.5 -59 eV in increments ΔE = 2.5 eV, for an extraction voltage V ext = 7 kV. We carried through this analysis for the three different electrostatic lens systems, briefly described in the introduction. The first of these was the set of three -element compound lens 'units' placed at the entrance, midpoint and exit of the drift tube. The second system comprised the full 36 element "continuous" einzel lens array (CEA) placed along the whole length of the drift tube. The final section of the CEA could be biased separately from the other sections of the CEA and was composed of five elements in total (two biased and three grounded), which when operated alone constituted the third system examined.

Figure 6a displays the simulated percentage throughput of ions (number of ions which entered the simulated Faraday cup as a percentage of the total launched) for a source potential V ext = 7 kV and a range of initial energies (E 0 ) of Cu 2+ ions. The simulated electrostatic element biases were set to those utilized experimentally. In each case, the simulated ion transport systems demonstrated some losses. The CEA displayed superior beam transport for all initial energies (E 0 ). The full CEA and the 5 -element einzel lens displayed relatively stable increases in T p (throughput) with E 0 . This is in stark contrast to the relatively unstable T p profile for the 3 -element transport system, reflecting the difficulty in optimizing such a system. This is related to components of each ion bunch, which cannot be efficiently transported with a simple 3 -element lens transport system, largely due to the fact that the distance between each 3 -element lens unit is greater than 0.5 m. These electrostatic 'gaps' can give rise to significant beam losses along the drift tube. As mentioned in previous work [48], bias values for the CEA were set to optimize the collected Cu 2+ signal (as this was the largest signal). Such bias values however were not always optimum for the efficient transport of other charge states. Figure 6b displays the simulated throughput of the CEA for the charge states Cu + to Cu 3+ for E 0 = 5 -55 eV (ΔE = 5 eV) and highlights the charge dependent behaviour of the throughput for the CEA system. Charge state selective beam transport was most pronounced when the kinetic energy of the extracted ions was increased. The differences in the efficiency of the transport systems are obvious from figure 7. Here the measured TOF signal for V ext = 7 kV, F = 3.96 kJcm -2 detected at the end of the drift tube with the Faraday cup is plotted for 1) the traditional 3 -element einzel lens units, 2) the 5 -element einzel array at the end of our drift tube (which is part of the CEA) and finally the TOF signal utilizing the entire CEA. The greatest differences in the collected signals occur for the highest charge states (Cu 3+ -Cu 5+ ) and also for the slower 'tail' regions in the TOF signals of each ion group.

Highly charged ions experience strong transverse expansion and also possess a larger kinetic energy (K E ) gained from the extraction voltage so that they diverge most strongly. Hence, upon entering the drift tube they must be subjected to strong electrostatic focusing (which in practice occurs at numerous points along the drift tube) to ensure efficient transport of these ions from source to detector. Only the CEA can efficiently and continuously transport highly charged ions over the extended drift tube. Also notable is the changing duration and signal amplitude within a particular ion group. The superior efficiency of the CEA for all ion groups is reflected in the amplitude of the trailing edge velocity group and its contribution to the total signal at the Faraday cup which registers as a large increase in ion bunch signal duration at the tail of the pulse (figure 7, t ~16 -21 μs region for Cu + ).

For TOF based methods of charge identification, the associated long drift tubes thus require continuous electrostatic optics if efficient beam transport, for all charge states is to be achieved. As remarked earlier, while extraction of plasma ions close to the target surface (at 'high -pressure') yields higher peak currents, higher average charge states and shorter current pulse durations, it also presents numerous challenges. These challenges are most acute for high source potentials. Table 1 shows the experimentally measured charge yields for Cu + -Cu 3+ for a range of fluences at fixed source potential V ext = 5 kV, for all three tested beam transport systems. Table 2 displays the charge yields for Cu + -Cu 3+ for a range of source potentials at a fixed laser fluence (F = 3.9 kJcm -2 ). Table 1. Fluence resolved charge yield for the three beam transport systems tested experimentally. The 3 -element einzel lens system (3 Einzel ), the 5 -element einzel lens (5 Einzel ) and the full CEA (CEA) for Cu + -Cu 3+ at V ext = 5 kV. Figure 8a shows graphically the experimental charge yield versus F (for a fixed V ext = 5 kV) for Cu 2+ and figure 8b shows the Cu 2+ charge yield versus V ext (at a fixed laser flux F = 3.9 kJcm -2 ). As stated above, the largest differences in system T p occur at high energies i.e.

F(kJcm

high initial energy, E 0 or high source potential (V ext ). Figures. 8a and 8b provide interesting insight into the ion beam dynamics after injection into the drift tube. More efficient beam transport and capture as V ext is increased is clearly evident in figure 8b, particularly for the CEA. This may be interpreted in terms of the 'plasma bulge' present at the anode. Debye shielding at the anode distorts the extraction field lines. Ions may be accelerated along diverging trajectories, which for high source potentials would have associated high kinetic energies. This can best be compensated for with strong electrostatic focusing throughout the ion flight times. This is only possible with the CEA. While the 5 -element einzel lens displays reasonable charge yield per kV of extraction voltage, the yield profile is no more than half of the total achieved with the CEA. In comparison, the 3 -element lens transport system displays relatively poor system throughput and declining performance as V ext is increased, this trend is evident in figure 8b. At a relatively low source potential of 5 kV, the 3 -element lens transport system can, with some success, compensate for beam expansion at the entrance to the drift tube. For 5 kV, the 5 -element array and the CEA systems are only moderately superior to the 3 -element lens system. The differences become increasingly clear as the extraction voltage increases (figure 8b). Furthermore the enhanced performance of the CEA is also evidenced in figure 8a which shows a continuously increasing T p for increasing fluence, in clear contrast with the others.

The differences in performance are also evidenced in the increasing changes in charge yield values in Table 2 for Cu 3+ as V ext increases. For V ext = 5kV the Cu 3+ yield ratio between the three beam transport systems is 1: 1.9 : 10.5. However at V ext = 13 kV this yield ratio increases to 1: 6.2 : 141. It is thus clear, that to access the benefits of a LIS configured for 'high -pressure' operation that space -charge force compensation via electrostatic optics must be utilized early and throughout the TOF of the extracted ion, as is the case for the CEA.

Summary

The majority of LIS systems utilize field free regions which generally exceed L ~0.5 m. This reduces the extracted plasma plume density and ensures thermalization of the ion kinetic energies [2,3] At this point the plasma plume is a collection of neutrals and charged particles moving at uniform velocities and displaying a small velocity gradient from front to back. While this reduces the challenges of high voltage extraction and beam transport, it strongly limits the peak current and charge state which can be extracted. By minimizing the length of the field free region and consequently extracting ions at 'high -pressure' we have maximized the extracted current and charge state from the laser generated plasma. This also ensures short bunch duration, resulting in a high peak current. In doing so, a number of mechanisms dominate the extracted ion bunches dynamics. For optimum performance these ions for the three beam transport systems tested experimentally.

  figure 1 points to a diversity of paths taken by the ions in the drift tube resulting in a

Figure 1 .

 1 Figure 1. Simulated TOF times to the Faraday cup detector of separate bunches of 500 mono

Figure 2 .

 2 Figure 2. Measured peak voltage of the two velocity groups detected in the Cu + ion bunch

Figure 3 .

 3 Figure 3. Simulated TOF times of all mono -energetic ion groups displaying a two component velocity distribution for V ext = 5 kV (Time interval for each bin, Δt = 4 ns). Inset:

Figure 4 .

 4 Figure 4. Experimental radial dependence of the ion beam at the end of the drift tube (V ext = 7 kV, F = 3.97 kJcm -2 ). Inset: Typical TOF signal from the planar probe, displaying the

Figure 5 .

 5 Figure 5. Cu 2+ radially resolved scanning probe peak voltage, and simulated ion count for

Figure 6 . 5 -

 65 Figure 6. (a) Simulated percentage throughput (T p ) for traditional einzel 3 -element

Figure 7 .

 7 Figure 7. Experimental TOF signal (via the Faraday cup) for V ext = 7 kV, F = 3.96 kJcm -2 , for

Figure 8 .

 8 Figure 8. Fluence dependent (a) and Source potential (b) dependent, charge yields of Cu 2+

-2 ), V ext =5 kV

			Cu + (pC)			Cu 2+ (pC)			Cu 3+ (pC)
		3 Einzel	5 Einzel	CEA	3 Einzel	5 Einzel	CEA	3 Einzel	5 Einzel	CEA
	910	72	184	198	216	293	419	6.15	13.2	20.6
	1238	85	265	266	277	432	507	14.6	30.6	37.2
	2123	112	294	337	344	489	724	25.7	66.0	76.9
	3060	140	317	414	396	529	774	32.3	69.4	164
	3970	172	326	392	425	544	998	34.4	71.5	236
	4860	208	305	433	458	525	1051	36.4	99.5	378
	5790	254	307	495	471	542	1085	42.1	118	500
	6650	281	297	604	476	507	1133	47.4	83.8	604
	7610	300	260	658	494	496	1165	44.8	95.5	550
	8520	289	247	819	450	509	1212	25.6	184	648

Table 2 .

 2 Charge yield versus V ext for the three beam transport systems tested experimentally.The three unit einzel lens transport system (3 Einzel ), the five einzel lens (5 Einzel ) and the CEA (CEA) for Cu + -Cu 3+ at F = 3.9 kJcm -2 .

	V ext		Cu + (pC)			Cu 2+ (pC)			Cu 3+ (pC)
	( F= 3.9 kJcm -2 ) 3 Einzel 5 Einzel	CEA	3 Einzel	5 Einzel	CEA	3 Einzel	5 Einzel	CEA
	5	149	370	392	385	636	998	22.4	42.0	236
	7	167	536	599	435	1104	1403	24.6	69.2	385
	9	183	662	794	479	1680	2190	29.6	85.2	700
	11	153	800	971	345	1900	2963	23.2	82.6	1282
	13	102	840	1235	267	1920	3228	10.9	67.8	1540
	15	90.0	725	1245	225	1810	3504	8.10	46.1	1468
	17	88.0	588	924	212	1433	2620	6.20	19.8	1050

must be minimized if beam extraction, transport and collection are to be successful. It is clear from the work reported here that under such conditions electrostatic optics are crucial components of a LIS. The extent of the increase observed in figure 7 for the CEA clearly indicates the requirement for more sophisticated transport systems in a LIS when initial conditions, prior to extraction (i.e. the plasma density and charge state at the anode) deviate strongly from those normally reported in the literature. To better access the superior performance which results from extraction at 'high -pressure' utilizing a short field -free region, requires a concomitant increase in the complexity and size of secondary systems (i.e. electrostatic optics), as achieved here with the CEA system.

ACKNOWLEDGMENTS:

The authors wish to thank Enterprise Ireland for financial support in this project (grant No: SC/2003/0180).


Kristina Åhsberg

Weimin Ye

Yunxia Lu

Zongli Zheng

Dr Christer Staël

Von Holstein

C Staël Von Holstein
email: christer.stael_von_holstein@med.lu.se

Hospitalization of and mortality from bleeding peptic ulcer in Sweden. A nation-wide time-trend analysis

Keywords: Peptic ulcer disease < Disease-based, Non-variceal bleeding < Topics, Stomach and duodenum < Organ-based, Epidemiology peptic ulcer, bleeding, incidence, mortality

Hospitalization of and mortality from bleeding peptic ulcer in Sweden. A nation-wide time-trend analysis.

(1-6) probably due to a cohort phenomenon with decreasing prevalence of Helicobacter pylori (H. pylori) infection [START_REF] Loffeld | Changes in prevalence of Helicobacter pylori infection in two groups of patients undergoing endoscopy and living in the same region in the Netherlands[END_REF][START_REF] Roosendaal | Helicobacter pylori and the birth cohort effect: evidence of a continuous decrease of infection rates in childhood[END_REF] and modern ulcer treatment with histamin-2-receptor antagonists and proton pump inhibitors as well as eradication therapies against H. pylori.

However, during the last two decades, the prescriptions of low dose aspirin (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) as well as selective serotonin reuptake inhibitors (SSRIs) have increased several fold in our country [START_REF] Silwer | Patterns of drug use during a 15 year period: data from a Swedish county, 1988--2002[END_REF] These drugs interfere with the defense mechanisms of the gastric mucosa and/or influence with the haemostasis and may therefore promote peptic ulcer bleeding [START_REF] De Abajo | Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based casecontrol study[END_REF][START_REF] James | Assessment of non-steroidal anti-inflammatory drug (NSAID) damage in the human gastrointestinal tract[END_REF].

There are divergent results in nation-wide population-based time-trend analyses of incidence of and mortality from peptic ulcer bleeding during the last decades. In Finland ) [START_REF] Paimela | Current features of peptic ulcer disease in Finland: incidence of surgery, hospital admissions and mortality for the disease during the past twenty-five years[END_REF] and England (1989England ( -1999) ) [START_REF] Higham | Recent trends in admissions and mortality due to peptic ulcer in England: increasing frequency of haemorrhage among older subjects[END_REF] hospitalization rates increased for ulcer hemorrhage, especially among the elderly. In Scotland (3) a general declining trend was found, but among the elderly the admission rates increased, especially for duodenal ulcer (DU) hemorrhage. In the Netherlands (5) a gender difference was seen as female gastric ulcer (GU) and DU bleeding increased, whereas among men bleeding from DU decreased and GU bleeding was stable. In not nation-wide but regional population based studies from Denmark (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002) [START_REF] Lassen | Complicated and uncomplicated peptic ulcers in a Danish county 1993-2002: a population-based cohort study[END_REF], the Netherlands (1993-2000) [START_REF] Van Leerdam | Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000[END_REF] and Germany (1990-2000) [START_REF] Ohmann | Timetrends in the epidemiology of peptic ulcer bleeding[END_REF] the incidence of ulcer hemorrhage was found unchanged.

Mortality rates from bleeding ulcer have been reported as being stable [START_REF] Van Leerdam | Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000[END_REF][START_REF] Lim | The outcome of suspected upper gastrointestinal bleeding with 24-hour access to upper gastrointestinal endoscopy: a prospective cohort study[END_REF][START_REF] Fiore | Changes in characteristics and outcome of acute upper gastrointestinal haemorrhage: a comparison of epidemiology and practices between 1996 and 2000 in a multicentre French study[END_REF]. In Scotland case fatality rates were decreasing after GU bleeding and increasing after DU hemorrhage [START_REF] Kang | Recent trends in hospital admissions and mortality rates for peptic ulcer in Scotland 1982-2002[END_REF] . Mortality rates have ranged between 5 and 15 per cent in different studies from the last decades [START_REF] Kang | Recent trends in hospital admissions and mortality rates for peptic ulcer in Scotland 1982-2002[END_REF][START_REF] Van Leerdam | Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000[END_REF][START_REF] Lim | The outcome of suspected upper gastrointestinal bleeding with 24-hour access to upper gastrointestinal endoscopy: a prospective cohort study[END_REF][START_REF] Fiore | Changes in characteristics and outcome of acute upper gastrointestinal haemorrhage: a comparison of epidemiology and practices between 1996 and 2000 in a multicentre French study[END_REF][START_REF] Rockall | Incidence and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage[END_REF]. This study is the first detailed nation-wide analysis of The 9th and 10th revision of International Classification of Diseases were used to identify the ulcer cohort in the Swedish Hospital Discharge Registry and the following diagnoses were included; bleeding gastric ulcer (GU); 531A, 531E, K25.0, K25.4, bleeding duodenal ulcer (DU); 532A, 532E K26.0, K26.4, bleeding gastroduodenal ulcer (without specified location); 533A, 533E, K27.0, K27.4, perforated gastric ulcer 531B, 531C, 531F, 531G, K25.1, K25.2, K25.5, K25.6, perforated duodenal ulcer 532B, 532C, 532F, 532G, K26.1, K26.2, K26.5, K26.6, perforated gastroduodenal ulcer 533B, 533C, 533F, 533G, K27.1, K27.2, K27.5, K27.6, unspecified (not bleeding, not perforated) gastric ulcer (UNS) 531D, 531H, 531X, K25.3, K25.7, K25.9, duodenal ulcer UNS 532D, 532H, 532X, K26.3, K26.7, K26.9 and gastroduodenal ulcer UNS 533D, 533H, 533X, K27.3, K27.7, K27.9. Ulcers classified as both bleeding and perforated were assigned to the perforated ulcers. Gastrojejunal ulcers 534 and K28 were not included in this study.

In the preliminary calculations we found a sudden increase of hospitalizations for ulcer UNS after 1997, and at the same time point there was a large drop in hospitalizations for bleeding and perforated ulcers. These changes in hospitalization rates coincided with the introduction of the ICD-10 classification system in Sweden. A validation study was performed and data extrapolated according to the results from that study (please see online chapter Validation study).

Annual hospitalization rates per 100 000 inhabitants of total ulcer, bleeding ulcer, perforated ulcer and ulcer UNS were calculated. Further calculations of bleeding ulcer were performed with reference to ulcer location, gender and age groups. Bleeding ulcer fatality rate within 30 days after admission date was calculated by Life table method and standardized to the gender and age distribution of total bleeding hospitalization episodes in Sweden from 1987 to 2005. Negative binomial regression model was used to compare hospitalization and mortality rates among sub-groups. Logarithm of the number at risk (population in hospitalization rate and effective sample size in mortality) was used as offset. Validity of negative binomial regression models were justified by deviance value divided by degree of freedom.

The study was approved by the Regional Ethical Review Board, Lund, Sweden.

Results

Hospitalizations for peptic ulcer

Admission rates are expressed as hospitalizations per 100 000 inhabitants per year. The hospitalization rate for peptic ulcer in total decreased from 102.1 to 54.8 during the study period 1987 to 2005. Hospitalizations for bleeding ulcer decreased from 63.9 to 35.3, for perforated ulcer from 11.9 to 7.7 and for ulcer UNS from 26.3 to 11.8 (All rates p<0.0001) (Figure 1).

The declining trend of bleeding ulcer from 1987 to 2005 was significant for both sexes (p<0.0001) but more pronounced for men (80.4 to 40.9) than for women (47.7 to 29.7) (Figure 2) and the male to female ratio decreased from 1.69 to 1.37 during the study period.

Median age increased for both men (67 to 73 years) (p<0.0001) and women (74 to 78 years) (p<0.0001). The hospitalization rates were much higher among the elderly and the decrease in hospitalization rates was lower among the elderly compared to that of the younger age groups though the decrease was significant in all age groups (p<0.0001) (Table 1).

Hospitalization rates for gastric ulcer was higher than for duodenal ulcer hemorrhage during the entire study period (p<0.0001). Both gastric and duodenal ulcer bleeding decreased from 1987 to 2005 (Figure 3). Admissions for gastric ulcer bleeding decreased among men from 35.6 to 20.2 and among women from 26.3 to 17.1 and the decrease was more pronounced 3 online). Hospitalizations for duodenal ulcer hemorrhage decreased in males from 40.5 to 20.1 and in females from 18.9 to 12.3. The hospitalization rates for duodenal ulcer hemorrhage decreased in all age groups (p<0.0001) except among women over 85 years of age where the rate was stable (p=0.0942) (Table 4 online). The male hospitalization rate was significantly higher than the female rate for both gastric and duodenal ulcer bleeding during the whole study period (p<0.0001).

Mortality from bleeding ulcer

Mortality rates are presented in text and tables as the means of 1987/1988 and 2004/2005 in order to reduce the effects of inter-annual variations.

Standardized total mortality within 30 days after admission for an episode of bleeding ulcer increased during the study period from 5.3 to 6.2 percent (Figure 4) mostly due to an increased mortality after duodenal ulcer bleeding. Table 2 presents 30-day mortality by gender and age. Men had an overall higher mortality than women (p=0.0023) and mortality increased in both sexes from 1987 to 2005.

After gastric ulcer bleeding the mortality was stable from 1987 to 2005 (Table 2) but men had a higher mortality than women during the entire study period (p=0.0071). Mortality in duodenal ulcer bleeding increased among both men and women and in most age groups during the study period (Table 2). The mortality rate after duodenal ulcer bleeding among men was not different from that among women. Mortality was not higher after an episode of duodenal ulcer than gastric ulcer hemorrhage during the entire study period. The greatest decrease in our study appears between the years 1992 to 1999. During the years before and after this period the curves are fairly stable. The decline approximately coincides in time when you could expect a more wide spread effect of the introduction of proton pump inhibitors and eradication therapies against H. pylori.

Discussion

For bleeding ulcer we found decreasing admission rates for both GU and DU hemorrhage, among both men and women and in every age-group except in the oldest women (>85 years) with bleeding duodenal ulcer where the hospitalization rate was stable. The decrease was greater in young people and lesser in the elderly. This might be explained by lower prevalence of H. pylori infection in the younger population [START_REF] Loffeld | Changes in prevalence of Helicobacter pylori infection in two groups of patients undergoing endoscopy and living in the same region in the Netherlands[END_REF][START_REF] Roosendaal | Helicobacter pylori and the birth cohort effect: evidence of a continuous decrease of infection rates in childhood[END_REF] and the influence of low dose aspirin, other NSAIDs and SSRI more and more commonly prescribed to the elderly [START_REF] Silwer | Patterns of drug use during a 15 year period: data from a Swedish county, 1988--2002[END_REF]. Decreased incidence of peptic ulcer complications after 1988 in Sweden has recently been published [START_REF] Hermansson | Decreasing incidence of peptic ulcer complications after the introduction of the proton pump inhibitors, a study of the Swedish population from 1974-2002[END_REF] and the same trend has been shown in a local hospital study from Southern Sweden [START_REF] Sadic | Bleeding peptic ulcer -time trends in incidence, treatment and mortality in Sweden[END_REF]. Declining admission rates for bleeding ulcers are previously only found in Scotland [START_REF] Kang | Recent trends in hospital admissions and mortality rates for peptic ulcer in Scotland 1982-2002[END_REF]. In most other countries with studies of time trend for bleeding ulcer during the last decades the admission rates have been stable or have increased [START_REF] Post | Declining incidence of peptic ulcer but not of its complications: a nation-wide study in The Netherlands[END_REF][START_REF] Paimela | Current features of peptic ulcer disease in Finland: incidence of surgery, hospital admissions and mortality for the disease during the past twenty-five years[END_REF][START_REF] Higham | Recent trends in admissions and mortality due to peptic ulcer in England: increasing frequency of haemorrhage among older subjects[END_REF][START_REF] Lassen | Complicated and uncomplicated peptic ulcers in a Danish county 1993-2002: a population-based cohort study[END_REF][START_REF] Van Leerdam | Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000[END_REF][START_REF] Ohmann | Timetrends in the epidemiology of peptic ulcer bleeding[END_REF]. Although the studies are all from Western Europe they still show quite different results. There could be several reasons to this finding. The prevalence of H. pylori differ between countries [START_REF] Rothenbacher | Burden of Helicobacter pylori and H. pylorirelated diseases in developed countries: recent developments and future implications[END_REF].

Immigration patterns vary a lot between the European countries and immigrants in Western countries are shown to have high H. pylori infection rates [START_REF] Loffeld | Changes in prevalence of Helicobacter pylori infection in two groups of patients undergoing endoscopy and living in the same region in the Netherlands[END_REF][START_REF] De Vries | Migrant communities constitute a possible target population for primary prevention of Helicobacter pylori -related complications in low incidence countries[END_REF][START_REF] Heuberger | Helicobacter pylori infection in Swiss adolescents: prevalence and risk factors[END_REF][START_REF] Staat | A population-based serologic survey of Helicobacter pylori infection in children and adolescents in the United States[END_REF]. Socio-economic differences might also play a role as low socio-economic class and crowded living conditions in childhood are shown to be related to H. pylori infection [START_REF] Staat | A population-based serologic survey of Helicobacter pylori infection in children and adolescents in the United States[END_REF][START_REF] Malaty | Importance of childhood socioeconomic status on the current prevalence of Helicobacter pylori infection[END_REF][START_REF] Mendall | Childhood living conditions and Helicobacter pylori seropositivity in adult life[END_REF]. Prescription patterns of both ulcer healing and ulcer promoting drugs could be a factor, as well as compliance to medication due to costs for medication for the patient. Most studies have evaluated the admission rates for peptic ulcer, and varying medical traditions and probably more importantly differences in reimbursement for hospitalizations may affect differences in indications for hospital admission, though this probably is a minor problem when studying ulcer complications. Finally, differences in diagnostic efforts cannot be ruled out nor those of diagnostic coding.

The standardized 30-day mortality in bleeding ulcer increased in our study from 5.3 to 6.2 per cent despite the supposed improvements in the care of these patients with both new endoscopic and pharmacologic treatments as well as better intensive care during the last decades. Other population-based studies have reported of higher in-hospital or 30-day mortality between 10 to 14 per cent after ulcer bleeding [START_REF] Lassen | Complicated and uncomplicated peptic ulcers in a Danish county 1993-2002: a population-based cohort study[END_REF][START_REF] Van Leerdam | Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000[END_REF][START_REF] Rockall | Incidence and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage[END_REF]. The difference in mortality seen for ulcer hemorrhage might be due to variations in case mix with different proportions of elderly and co-morbid patients with different nutritional and socio-economic backgrounds in the studies. The lower mortality in Sweden may reflect a better general heath situation in the population in our country. Variations in quality of therapy and care could also play a role.

Thirty-day mortality after bleeding ulcer was higher in the older age groups which is in line with other reports [START_REF] Kang | Recent trends in hospital admissions and mortality rates for peptic ulcer in Scotland 1982-2002[END_REF][START_REF] Van Leerdam | Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000[END_REF][START_REF] Lim | The outcome of suspected upper gastrointestinal bleeding with 24-hour access to upper gastrointestinal endoscopy: a prospective cohort study[END_REF][START_REF] Rockall | Incidence and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage[END_REF] and to be expected due to probably higher co-morbidity and medicine usage among the elderly. The mortality was also increasing during the study period among the elderly patients while it was stable among patients younger than 65 years. We found an increased mortality among men compared to woman. This might reflect a worse general health condition among men which could be attributed to several factors for example a higher frequency of smoking and smoking related diseases and higher alcohol consumption.

In contrast to the findings by Rockall et al. [START_REF] Rockall | Incidence and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage[END_REF], we did not find a higher mortality among patients already hospitalized for another reason at the start of bleeding in comparison to those who started to bleed at home. However register studies are not an appropriate setting to In our study we found 30-day mortality to be stable after gastric ulcer bleeding but it increased after duodenal ulcer hemorrhage, which is in line with the findings in the Scottish study where case fatality rates after gastric ulcer declined but it increased after duodenal ulcer hemorrhage (3). Most bleeding ulcer patients are subjected to endoscopic procedures nowadays and most bleedings cease on endoscopic treatment. Duodenal ulcers are often more difficult to reach for the endoscopist with optimal therapy and the rebleeding rate is higher, especially if the ulcer has eroded the gastroduodenal artery, which might explain the increasing mortality rate for duodenal ulcers. For these cases emergency surgery is the rescue therapy and mortality after surgery in these situations is high. As elective ulcer surgery has virtually vanished during the last two decades the impact of decreased experience among surgeons cannot be ruled out.

The strength of our study is the large national sample size covering all significant ulcer bleedings in the country. This was reached by analyzing all hospitalizations with a discharge diagnosis of bleeding ulcer from the departments with primary responsibility of gastrointestinal bleeding, validated by a questionnaire to all emergency hospitals in Sweden.

Another strength is that we noted the misclassification problem of bleeding ulcer as ulcer UNS after the introduction of ICD-10 and conducted a validation study with a very high response rate of 96.8 per cent. The extrapolation of the results from the validation study to the ulcer cohort during the analyzed years 1993/1994 and 1999/2000 is thus considered to be fairly accurate. The accuracy of the extrapolation may however decline with time from the index years, and individual annual hospitalization rates must therefore be interpreted with caution although we believe that the overall trends are correct. In summary, the hospitalization rate for bleeding peptic ulcer has decreased by more than 40 per cent in Sweden from 1987 to 2005. This is probably due to a decreasing prevalence of H. pylori in the population. An increase in 30-day mortality after peptic ulcer bleeding was observed during the same time period mostly due to an increased mortality after duodenal ulcer bleeding. This might reflect more frequent serious co-morbidity in the elderly population with corresponding increased use of ulcer and bleeding promoting drugs, but differences in care cannot be ruled out.

Validation study

In the preliminary calculations we found a sudden increase of hospitalizations for ulcer UNS after 1997, and at the same time point there was a large drop in hospitalizations for bleeding and perforated ulcers. We considered this finding to be medically doubtful, as the reason to hospitalization for ulcer disease in modern time in the majority of cases is because of ulcer complications (hemorrhage, perforation or obstruction). These changes in hospitalization rates In cooperation with the National Board of Health and Welfare, questionnaires were sent to the departments where the patients had been hospitalized, for evaluation of the medical records to

Extrapolation of data

The percentage of misclassified bleeding or perforated ulcers found in the validation study was subtracted from the crude rate of hospitalizations for ulcer UNS in the cohort. The result from the period 1993-1994 was used for 1987-1996 (before the introduction of ICD-10) and

Introduction

  Hospitalization rates for peptic ulcer have declined in most Western countries from the 1950´s

  rates due to peptic ulcer hemorrhage in Sweden during the last two decades.MethodHealth care in Sweden is provided to all citizens by public funding at public hospitals under the audit of the National Board of Health and Welfare. Discharge data are registered for all patients in the National Hospital Discharge Register as well as cause of death data in the Cause of Death Registry. Every citizen has an individual ten-digit personal identification number which facilitates registration and follow-up in the national registries.All hospitalizations in Sweden from 1987 to 2005 at departments with primary responsibility for patients with peptic ulcer hemorrhage (main-or co-diagnosis at discharge) were retrieved from the Swedish Hospital Discharge Register. Patients with gastrointestinal bleeding have traditionally always been admitted to Departments of Surgery and surgeons are doing the great majority of all diagnostic and therapeutic endoscopic procedures in bleeding ulcer patients in Sweden as medical gastroenterologists, although increasing, still are few in numbers. In order to make an updated identification of the hospital departments with primary responsibility for peptic ulcer bleeding a questionnaire was sent to all emergency hospitals in Sweden in December 2005. In 60 out of totally 63 emergency hospitals in Sweden at that time, patients with bleeding ulcer were handled at Departments of Surgery. In only three hospitals bleeding ulcer patients were hospitalized at another department (Department of Medicine, Gastroenterology and Emergency conditions, respectively). This search strategy thus included all significant ulcer bleeds in all emergency hospitals in Sweden during the time period.The study period started in 1987 as this was the first year the Swedish Hospital Discharge Register had a 100 per cent national coverage. The cohort consisted of totally 129 687 ulcer of which 58 445 hospitalizations were coded as bleeding ulcer.

  was used to test secular trends of hospitalization and mortality rates.

  although hospitalization rates declined in all age groups (p<0.0001) (men over 85 years, p=0.0002) (Table

  wide study covering all emergency hospitals in Sweden we found a highly significant decrease in hospital admissions due to bleeding ulcers between 1987 and 2005.

  as there is a lack of control for patients who start to bleed at the department with primary responsibility for gastrointestinal bleeding, although they are admitted for something else.

11 A

 11 weakness of the study includes the problems with potential errors in registry data though we believe that the Swedish Hospital Discharge Register do not contain more errors than similar National Registers in other countries. The Swedish individual ten-digit personal identification number facilitates registration and follow-up and all emergency hospitals are under public control and audit and patients living within the hospital catchment area are in a very high percentage referred to their local hospital.

Figure 1 .Figure 2 .Figure 3 .*

 123 Figure 1. Annual hospitalisation rates for ulcer in Sweden, 1987 -2005

  coincided with the introduction of the ICD-10 classification system in Sweden. In the short alphabetic version of diagnostic codes published by the National Board of Health and Welfare, usually used by doctors, there was no longer a specification of 4 th position of the diagnostic code. The fourth position is required to give information of the presence of bleeding or perforation and to retrieve this information after 1997 the more comprehensive systematic version had to be explored. An increased rate of misclassifications could thus be suspected. A validation study was therefore conducted in order to calculate the suspected rate of misclassified ulcer complications (bleeding and perforations) as ulcer UNS after 1997. A random sampling of totally 400 emergency hospitalizations at Departments of Surgery, with a discharge diagnosis of ulcer UNS were drawn from the Swedish Hospital Discharge Register, 200 from the period 1993-1994 and 200 from 1999-2000. The sampling number was chosen after the following calculations: With an assumption of a base-line misclassification of diagnoses in the Swedish Hospital Discharge Register of around 10 per cent, 195 individuals in each group were required to detect an increase to around 20 per cent of misclassified ulcer complications as ulcer UNS after the introduction of ICD-10 (80 per cent power, two-sided test, α= 0.05).

  misclassification of a perforated or bleeding ulcer. The response rate was 96.8 per cent (387/400). Data were unidentified before further processing and analyzing.The criteria of a misclassified bleeding ulcer was either a) operation for bleeding ulcer or b) symptoms/history of bleeding at admission together with an endoscopically verified ulcer with no other bleeding source or c) an endoscopically verified bleeding ulcer. The criteria of a misclassified perforated ulcer were either operation for perforated ulcer or in another way verified perforated ulcer.In the validation study the median age increased from 69 to 74 years (p=0.0132). Symptoms or patient history of bleeding (hematemesis or melena) at time for admission increased by 53 per cent and was much more frequent in the latter period (52.3 per cent compared to 34.2 per cent, p=0.000047, Fisher's exact test). Diagnostic endoscopy was frequently performed during both periods (84.0 and 89.2 per cent, ns). The diagnosis of ulcer disease was verified (through surgery, endoscopy, radiology or autopsy) to a higher extent in the latter period (81.0 and 88.8 per cent respectively, p=0.033). The verification of bleeding was made in about 20 per cent of patients (blood in stomach, ongoing bleeding, visible vessel, hematin coloured spot or blood clot covering ulcer base) and did not change between periods.In summary, 65/190 patients met the criteria of a misclassified bleeding ulcer before the introduction of ICD-10 in comparison with 98/197 patients after the introduction of ICD-10, an increase from 34.2 to 49.7 per cent (p=0.002). The misclassification of perforated ulcer increased from 1/190 (0.5 per cent) to 12/197 (6.1 per cent) (p=0.003).

  1999-2000 was used for 1997-2005 (after the introduction of ICD-10) (In one Swedish region the introduction of ICD-10 took place in 1998). The number of hospitalizations subtracted from the ulcer UNS cases was then added to the bleeding or perforated ulcer cases in the cohort. Chi-square tests showed no difference regarding the distribution in age, gender and ulcer location between the misclassified bleeding cases in the validation study and the UNS cases in the cohort. The same extrapolation percentage was therefore applied across all subgroups of age, gender and ulcer location.

Table 1 .

 1 Hospitalization rates for bleeding ulcer / 100 000 inhabitants / year and difference in per cent between 1987 and 2005.

		1987	1996	2005	% diff
	Men
	<45 years	20.0	10.5	4.7	-77	*
	45-54 years	84.2	45.1	28.5	-66	*
	55-64 years	131.4	80.8	62.2	-53	*
	65-74 years	219.0	172.9	97.4	-56	*
	75-84 years	363.6	268.9	214.5	-41	*
	>84 years	428.8	433.4	343.1	-20	*
	Women
	<45 years	6.6	3.9	2.7	-59	*
	45-54 years	39.5	23.8	15.4	-61	*
	55-64 years	60.0	34.7	26.3	-56	*
	65-74 years	113.0	78.6	63.2	-44	*
	75-84 years	205.4	177.9	139.2	-32	*
	>84 years	242.3	242.2	189.2	-22	*
	Total
	<45 years	13.4	7.3	3.7	-72	*
	45-54 years	62.2	34.6	22.0	-65	*
	55-64 years	94.8	57.6	44.3	-53	*
	65-74 years	162.2	122.3	79.6	-51	*
	75-84 years	269.6	215.3	170.9	-37	*
	>84 years	301.0	301.8	239.0	-21	*
	p value for trend by linear regression from 1987 to 2005
	* <0.0001

Table 2 .

 2 30 day mortality (%) after ulcer bleeding.

	Standardized by age and gender wherever applicable.
		1987/1988 2004/2005 p-value
				for trend
	Total ¤ #	5.3%	6.2%	0.0014
	<65 years #	1.0%	2.8%	0.054
	65-74 years #	3.7%	5.9%	0.020
	>74 years #	9.4%	9.6%	0.0092
	Men total ¤	5.9%	6.1%	0.019
	<65 years	0.8%	2.2%	0.24
	65-74 years	3.8%	5.7%	0.046
	>74 years	10.2%	9.7%	0.065
	Women total ¤	4.9%	6.6%	0.015
	<65 years	1.4%	3.7%	0.069
	65-74 years	3.6%	6.3%	0.048
	>74 years	8.1%	9.4%	0.030
	Men GU total ¤	5.1%	5.2%	0.57
	<65 years	0.8%	2.3%	0.72
	65-74 years	3.5%	3.3%	0.54
	>74 years	8.6%	9.1%	0.26
	Women GU total ¤	4.2%	5.5%	0.22
	<65 years	0.5%	3.8%	0.27
	65-74 years	2.6%	4.9%	0.16
	>74 years	7.8%	6.9%	0.62
	Men DU total ¤	6.0%	6.1%	0.023
	<65 years	0.6%	2.6%	0.042
	65-74 years	2.8%	6.3%	0.030
	>74 years	11.2%	9.1%	0.14
	Women DU total¤	5.9%	7.6%	0.013
	<65 years	1.9%	4.7%	0.010
	65-74 years	4.8%	8.2%	0.16
	>74 years	9.3%	10.3%	0.019
	Linear regression was used to test for secular trend.
	Abbreviations: GU=gastric ulcer, DU=duodenal ulcer
	¤ Standardized to the age distribution of bleeding
	ulcer hospitalizations in Sweden 1987-2005
	# Standardized to the gender distribution of bleeding
	ulcer hospitalizations in Sweden 1987-2005

Table 3 .

 3 Hospitalisation rates for bleeding gastric ulcer / 100 000 inhabitants / year and difference in per cent between 1987 and 2005.

		1987	1996	2005	% diff
	Men
	<45 years	7.6	4.8	2.2	-72	*
	45-54 years	35.2	22.1	14.9	-58	*
	55-64 years	55.7	43.6	30.0	-46	*
	65-74 years	98.5	83.7	47.2	-52	*
	75-84 years	176.1	145.7	105.2	-40	*
	>84 years	213.2	232.9	181.0	-15	**
	Women
	<45 years	3.1	2.0	1.5	-53	*
	45-54 years	19.1	13.4	8.4	-56	*
	55-64 years	30.2	19.6	15.1	-50	*
	65-74 years	68.4	44.5	35.6	-48	*
	75-84 years	116.3	110.4	82.1	-29	*
	>84 years	132.4	140.9	110.3	-17	*
	Total
	<45 years	5.4	3.4	1.8	-67	*
	45-54 years	27.3	17.8	11.7	-57	*
	55-64 years	42.6	31.5	22.6	-47	*
	65-74 years	82.4	62.7	41.1	-50	*
	75-84 years	140.6	124.9	91.9	-35	*
	>84 years	157.9	169.6	133.2	-16	*
	p values for trend by linear regression from 1987 to
	2005
	* <0.0001, ** =0.0002

Table 4 .

 4 Hospitalisation rates for bleeding duodenal ulcer / 100 000 inhabitants / year and difference in per cent between 1987 and 2005.

		1987	1996	2005	% diff
	Men
	<45 years	11.4	5.6	2.4	-79	*
	45-54 years	44.9	22.7	13.6	-70	*
	55-64 years	66.1	37.7	32.6	-51	*
	65-74 years	110.3	88.2	48.9	-56	*
	75-84 years	166.8	123.3	104.3	-38	*
	>84 years	190.9	196.4	152.7	-20	*
	Women
	<45 years	3.1	1.6	1.0	-66	*
	45-54 years	19.4	10.2	6.6	-66	*
	55-64 years	26.2	14.8	10.7	-59	*
	65-74 years	40.8	32.2	28.4	-30	*
	75-84 years	76.7	64.1	55.9	-27	*
	>84 years	89.2	95.6	77.5	-13	ns
	Total
	<45 years	7.3	3.7	1.7	-76	*
	45-54 years	32.3	16.5	10.1	-69	*
	55-64 years	45.7	26.2	21.8	-52	*
	65-74 years	73.0	58.1	38.2	-48	*
	75-84 years	113.3	88.4	76.3	-33	*
	>84 years	121.2	127.0	101.8	-16	*
	p values for trend by linear regression from 1987 to 2005
	* <0.0001, ns =0.0942

Acknowledgements

We are very grateful to Annika Edberg at the Swedish National Board of Health and Welfare for valuable cooperation with the validation study and to Peter Höglund at Lund University Hospital for support with the statistics in the same part of this study. We also want to acknowledge the Bengt Ihre Foundation and the Erik and Angelica Sparre Foundation for financial support.

We want to acknowledge the Bengt Ihre Foundation and the Erik and Angelica Sparre Foundation for financial support.